Chronic plaque psoriasis in adults: Treatment of disease requiring phototherapy or systemic therapy

INTRODUCTION — 

Psoriasis is a multisystem chronic inflammatory disorder with multiple clinical presentations. Chronic plaque psoriasis, the most common presentation of psoriasis, classically presents with well-defined plaques on the skin (picture 1A-H). The major treatment modalities for chronic plaque psoriasis include topical therapy, systemic therapy, and phototherapy.

The clinical presentation and other factors influence the approach to treatment. Although some presentations can be adequately managed with topical therapy, other presentations, such as extensive skin involvement, may be most effectively managed with phototherapy or systemic therapy. (See "Chronic plaque psoriasis in adults: Overview of management".)

The approach to treatment selection for chronic plaque psoriasis that will be treated with phototherapy or systemic therapy will be reviewed here. Selection of the preferred mode of treatment, general treatment principles, and the therapeutic approach to disease that is amenable to topical therapy are reviewed separately.

●(See "Chronic plaque psoriasis in adults: Overview of management".)

●(See "Chronic plaque psoriasis in adults: Treatment of disease amenable to topical therapy".)

The management of other presentations of psoriasis is reviewed separately.

●(See "Guttate psoriasis", section on 'Treatment'.)

●(See "Nail psoriasis", section on 'Treatment'.)

●(See "Erythrodermic psoriasis in adults", section on 'Management'.)

●(See "Pustular psoriasis: Management".)

●(See "Treatment of psoriatic arthritis".)

●(See "Treatment of peripheral psoriatic arthritis".)

The management of chronic plaque psoriasis in special populations is also reviewed separately.

●Children (see "Psoriasis in children: Management of chronic plaque psoriasis")

●Pregnant individuals (see "Management of psoriasis in pregnancy")

●Individuals with hepatitis, human immunodeficiency virus (HIV) infection, latent tuberculosis, or malignancy (see "Treatment selection for moderate to severe plaque psoriasis in special populations")

IDENTIFYING DISEASE APPROPRIATE FOR PHOTOTHERAPY OR SYSTEMIC THERAPY — 

Treatment options for chronic plaque psoriasis include topical therapies, phototherapy, and systemic therapies (table 1A-B). Selection of the primary mode of therapy is an individualized decision that considers the extent and location of skin involvement, disease complications, patient abilities and preferences, patient comorbidities (eg, psoriatic arthritis), and treatment availability (algorithm 1). (See "Chronic plaque psoriasis in adults: Overview of management", section on 'Selecting the primary mode of therapy'.)

Phototherapy and systemic therapy are generally considered when:

●The extent or location of skin involvement would make topical therapy less feasible.

●The patient has comorbidities requiring systemic antipsoriatic therapy (eg, psoriatic arthritis).

●The response to topical therapy is inadequate.

The extent and locations of disease that should prompt use of phototherapy or systemic therapy are not strictly defined and may vary among patients. Clinical experience suggests that disease involving more than 3 to 5 percent of the body surface seems to reduce the feasibility of topical therapy for many patients. In addition, plaques involving the genitals, palms, soles, scalp, intertriginous skin, or face and plaques scattered across multiple body areas can be more challenging to manage with topical therapy. (See "Chronic plaque psoriasis in adults: Overview of management", section on 'Extent and location of skin involvement' and "Chronic plaque psoriasis in adults: Overview of management", section on 'Patient ability and preference'.)

Systemic treatments for some comorbid inflammatory disorders, such as psoriatic arthritis, have overlapping benefits for chronic plaque psoriasis. Concurrent treatment of psoriatic arthritis is important to prevent discomfort, joint damage, and disability. (See 'Patients with psoriatic arthritis' below.)

Patients with an inadequate response to topical therapy may benefit from phototherapy or systemic therapy. Topical therapy may still be used as an adjunctive treatment to accelerate or maximize improvement. (See "Chronic plaque psoriasis in adults: Treatment of disease amenable to topical therapy".)

TREATMENT SELECTION — 

Our approach to treatment selection for patients deemed candidates for phototherapy or systemic therapy begins with identifying an approach that is appropriate, feasible, and acceptable for the patient. (See 'Phototherapy versus systemic therapy' below and 'Selecting a systemic agent' below.)

The response of chronic plaque psoriasis to specific therapies varies. An inadequate response or treatment intolerance may require adjusting the approach to therapy. (See 'Response assessment' below and 'Treatment failure' below and 'Adjusting therapy' below.)

Phototherapy versus systemic therapy — Although the relative safety and efficacy of phototherapy support the consideration of phototherapy, factors that limit the feasibility of phototherapy are common. For most of our patients, the clinical scenario favors proceeding with systemic therapy rather than phototherapy.

Phototherapy takes longer to achieve a satisfactory response than some systemic therapies and requires either travel to a clinician office two to three times per week or a home phototherapy unit. Travel distance, work or other commitments, or a lack of accommodations suitable for a home unit can make phototherapy less feasible. Contraindications to phototherapy or disease that primarily affects sites where the potential adverse effects are of greater concern (eg, genitals, face) may also influence the appropriateness of phototherapy. (See 'Phototherapy' below and "UVB phototherapy (broadband and narrowband)", section on 'Contraindications' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Contraindications'.)

In addition, access to appropriate phototherapy equipment is important. Some disease sites may be challenging to treat with a standard phototherapy booth, such as intertriginous skin, hair-bearing scalp, palms, or soles. Targeted phototherapy equipment can facilitate treatment of these areas. (See "Targeted phototherapy", section on 'Targeted versus full-body phototherapy'.)

Phototherapy does not treat concomitant psoriatic arthritis. Therefore, we usually manage patients with concomitant psoriatic arthritis with systemic therapy. (See 'Patients with psoriatic arthritis' below.)

Selecting a systemic agent — For patients who will proceed to systemic therapy, review of the clinical presentation, drug characteristics, and patient preference is helpful for selecting a preferred systemic treatment (table 1B). Factors that often influence selection of a particular drug include:

●Patient comorbidities (eg, psoriatic arthritis, inflammatory bowel disease, other systemic disease)

●Drug efficacy

●Drug tolerability and adverse effects

●Patient preference regarding treatment goals

●Patient risk tolerance

●Patient preferences for route (oral versus injectable) and frequency of administration

●Drug availability or cost

Relative efficacy — Awareness of the relative efficacies of systemic treatments for psoriasis can aid with treatment selection.

Biologic agents include the most effective therapies for chronic plaque psoriasis that cannot be managed with topical therapy. However, network meta-analyses support varying degrees of efficacy for individual biologic agents [1-7].

●A network meta-analysis included randomized trials assessing any of 20 systemic therapies for moderate to severe plaque psoriasis (anti-interleukin [IL] 23 biologic agents [guselkumab, risankizumab, tildrakizumab], anti-IL-17 biologic agents [bimekizumab, brodalumab, ixekizumab, netakimab, secukinumab, sonelokimab], an IL-12/23 biologic agent [ustekinumab], and anti-tumor necrosis factor (TNF) biologic agents [adalimumab, certolizumab, etanercept, infliximab] and nonbiologic agents [apremilast, deucravacitinib, acitretin, ciclosporin, fumaric acid esters, methotrexate]) [2]. Some limitations of the network meta-analysis included restriction to relatively short-term outcome assessment (8 to 24 weeks of treatment), limited data for some nonbiologic therapies, and limited interpretation of adverse event outcomes due to inconsistent reporting and a low number of serious adverse events.

Key findings included:

•Biologic agents – As a group, biologic agents were more effective than older nonbiologic systemic agents (acitretin, cyclosporine, fumaric acid esters, methotrexate). The most effective therapies for achieving 90 percent improvement in the Psoriasis Area and Severity Index (PASI 90) were infliximab, bimekizumab, ixekizumab, and risankizumab, all of which demonstrated similar efficacy.

As a group, anti-IL-17 and anti-IL-23 drugs (excluding tildrakizumab) and anti-IL-17 biologic therapies were more effective than ustekinumab, three anti-TNF biologic agents (adalimumab, certolizumab pegol, etanercept), and deucravacitinib. All biologic agents and deucravacitinib were more effective than etanercept.

The meta-analysis also identified IL-17 inhibitors as the most effective therapies; however, the relatively short length of follow-up in the included trials (8 to 24 weeks) may be relevant. In studies, some IL-17 inhibitors have demonstrated faster response times than IL-23 inhibitors. (See 'Guselkumab' below and 'Risankizumab' below.)

•Comparisons of nonbiologic therapies – Relative efficacies among nonbiologic therapies for achieving PASI 90 are less clear. Trials of acitretin, cyclosporine, deucravacitinib, fumaric acid esters, and methotrexate were limited, contributing to lower confidence in the relative efficacy estimates for these agents.

Findings from the network meta-analysis support greater efficacy of deucravacitinib compared with apremilast. Although there was a trend toward greater efficacy of deucravacitinib compared with methotrexate, the difference was not statistically significant (risk ratio 1.43, 95% CI 0.99-2.19). Differences in efficacy for achieving PASI 90 were not detected between apremilast and either methotrexate or cyclosporine, although methotrexate was more effective than apremilast for achieving 75 percent improvement in the Psoriasis Area and Severity Index (PASI 75; risk ratio 1.29, 95% CI 1.0-1.67).

Efficacy data for PASI 90 for acitretin were lacking. For PASI 75, statistically significant differences between acitretin and the other small molecule and nonbiologic therapies were not detected, and study limitations prevent conclusions on relative efficacy. Drug ranking outcomes suggested that acitretin and fumaric acid esters were among the least effective agents.

Direct comparison trials of individual systemic therapies are reviewed below. (See 'Systemic therapies' below.)

Our general approach — Our preferred initial treatments for patients who place a high value on maximal skin clearance are the IL-23 inhibitors risankizumab and guselkumab and the IL-17 inhibitor ixekizumab because of the high efficacy and relative safety. When the speed of improvement is critical, we often select ixekizumab because of its rapid onset of effect, provided the patient does not have inflammatory bowel disease. (See 'Relative efficacy' above and 'Other factors influencing treatment selection' below.)

Bimekizumab and infliximab are highly effective, reasonable alternatives. However, bimekizumab appears to induce candidiasis more frequently than other IL-17 inhibitors (see 'Precautions' below). Disadvantages of infliximab include a broader risk profile compared with IL-23 and IL-17 inhibitors and an intravenous route of administration. (See 'Relative efficacy' above and 'IL-17 inhibitors' below and 'TNF-alpha inhibitors' below.)

Treatment with other biologic IL-17 inhibitors (brodalumab, secukinumab) or IL-23 inhibitors (tildrakizumab, ustekinumab) is an additional reasonable alternative when access to preferred therapies is limited.

Because of lesser efficacy or greater safety concerns, we tend to reserve treatment with TNF inhibitors and nonbiologic drugs for patients in whom comorbidities, patient preference, or other factors support selection of an alternative agent (table 1B). We typically avoid etanercept as a first-line TNF inhibitor for adults because of lower efficacy compared with other biologic TNF inhibitors [2]. (See 'Relative efficacy' above.)

Patient comorbidities and drug adverse profiles also impact treatment selection. (See 'Precautions, patient assessment, and monitoring' below.)

In the United States, payor (health insurance) drug preference often has a significant impact on treatment selection.

Patients with psoriatic arthritis — For patients with both chronic plaque psoriasis and psoriatic arthritis warranting systemic therapy, selection of a therapy with overlapping benefit is generally prudent. Consideration of the clinical presentation of psoriatic arthritis (eg, peripheral versus axial disease) is important because it influences the approach to treatment. (See "Treatment of psoriatic arthritis", section on 'Disease domains and treatment selection'.)

Examples of therapies with efficacy for both psoriatic arthritis and psoriasis include (table 1B):

●Multiple biologic agents (table 1B)

●Methotrexate

●Apremilast

●Oral tofacitinib (see 'Oral JAK inhibitors' below)

Biologic IL-17 inhibitors and IL-23 inhibitors are common initial treatments for patients with both diseases, with selection of a specific agent dependent on patient comorbidities, the specific manifestations of psoriatic arthritis, and the severity of skin disease. (See "Treatment of psoriatic arthritis" and "Treatment of peripheral psoriatic arthritis".)

We typically comanage patients with psoriasis and psoriatic arthritis with a rheumatologist. However, because of the potential for permanent joint damage due to psoriatic arthritis, we aim to avoid a delay in treatment. When patients with psoriasis present with signs or symptoms suggestive of psoriatic arthritis (eg, joint pain, joint swelling, morning stiffness, or "sausage digits" [dactylitis]), we perform a diagnostic evaluation, particularly if access to rheumatology will be delayed. If the findings are consistent with psoriatic arthritis, we begin a treatment regimen appropriate for both conditions and arrange for subsequent consultation with a rheumatologist. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Diagnosis'.)

The Psoriasis Epidemiology Screening Tool (PEST) is a helpful resource for psoriatic arthritis screening questions.

Patients who prefer oral therapy — The major options for oral therapy for psoriasis include apremilast, deucravacitinib, methotrexate, acitretin, and cyclosporine (table 1B). Because limited high-quality data inhibit definitive conclusions on the relative efficacy of most oral therapies, consideration of comorbidities, drug safety, and tolerability play key roles in treatment selection.

We most often treat with apremilast, deucravacitinib, or methotrexate because of data that suggest lower efficacy of acitretin and the potential serious adverse effects associated with long-term cyclosporine therapy [2]. Selection of the preferred initial therapy is heavily influenced by patient morbidities, risk tolerance, and preference.

For patients who place a high value on maximal skin clearance but who strongly prefer oral treatment, a randomized trial that supports greater efficacy of deucravacitinib over apremilast may prompt selection of deucravacitinib over apremilast. Long-term safety data for deucravacitinib are limited. (See 'Deucravacitinib' below and 'Apremilast' below.)

The wide availability and low cost of methotrexate may favor its use when access or cost inhibit use of other therapies. However, methotrexate is a less favorable option, particularly for patients at increased risk for methotrexate toxicity. (See 'Methotrexate' below.)

Although a rapid onset of action is an advantage of cyclosporine therapy, the adverse effects of long-term treatment with cyclosporine are a major concern and limit our use of this agent. (See 'Cyclosporine' below.)

Oral Janus kinase (JAK) inhibitors can be effective for chronic plaque psoriasis, but because of safety concerns, we primarily reserve these therapies for patients in whom oral JAK inhibitor therapy is indicated for psoriatic arthritis and patients with disease refractory to routine systemic therapies. (See 'Oral JAK inhibitors' below.)

Other factors influencing treatment selection — Examples of clinical presentations and preferences that influence our approach to treatment include:

●Patients requiring rapid improvement – When rapid and maximal skin clearance of psoriasis is a high priority due to disabling symptoms or effects of the disease on psychosocial functioning or quality of life, treatments with rapid onset of action and high efficacy are preferred. We tend to utilize IL-17 inhibitors in this scenario. For patients without access to biologic therapy, a short course of cyclosporine (eg, four to six weeks) with the plan to transition to another therapy for long-term treatment is an alternative. (See 'Cyclosporine' below.)

●Patients with disease in certain sites (eg, palmoplantar, scalp disease) – For palmoplantar psoriasis, the findings of a systematic review and meta-analysis of trials that assessed Physician Global Assessment outcomes after 12 to 16 weeks of adalimumab, apremilast, guselkumab, infliximab, or secukinumab support guselkumab, adalimumab, and secukinumab as the most effective of these five treatments [8]. For scalp psoriasis, the systematic review and network meta-analysis included trials assessing efficacy of adalimumab, apremilast, bimekizumab, deucravacitinib, etanercept, guselkumab, secukinumab, and ustekinumab. Guselkumab, bimekizumab, and secukinumab appeared to be the most effective of the eight treatments [8]. Other antipsoriatic biologic agents, such as ixekizumab and risankizumab, can also be effective [9,10].

●Patients who prefer infrequent dosing – The dose frequency of systemic therapies varies widely. The most convenient dosing intervals range from once monthly to every 12 weeks (table 1B).

Small molecule and other nonbiologic therapies are generally taken daily, with the exception of methotrexate, which is taken once weekly. (See 'Nonbiologic therapies' below.)

●Pregnant patients and patients of childbearing potential – Because of fetal safety concerns with some treatments, it is important to ask patients of childbearing potential about pregnancy and family planning when making decisions about treatment. Treatment of psoriasis in pregnant individuals is reviewed separately. (See "Management of psoriasis in pregnancy".)

●Scenarios requiring low-cost therapy – The high cost associated with many newer therapies (eg, biologic therapies, deucravacitinib, apremilast) for chronic plaque psoriasis can limit access to these therapies. When access to other therapies is not feasible, methotrexate is a low-cost option for systemic treatment. Phototherapy, particularly home phototherapy, may be less costly than some systemic treatments.

Response assessment — The response to phototherapy and systemic therapies is generally assessed through the physical examination, symptom assessment, and review of the impact of the disease on quality of life. Although the time to onset of action differs for individual therapies, three to six months of treatment is generally considered a reasonable period for assessing the response to phototherapy or systemic treatments. (See "Chronic plaque psoriasis in adults: Overview of management", section on 'Response assessment and follow-up' and 'Systemic therapies' below.)

Treatment failure — An inadequate response to phototherapy or systemic therapy should first prompt an assessment for reasons for treatment failure. Examples include an incorrect diagnosis, suboptimal treatment selection, inadequate administration of therapy, and disease resistant to therapy. We also perform a review of symptoms to identify potential exacerbating factors, such as infections and emotional or physical stressors. (See "Chronic plaque psoriasis in adults: Overview of management", section on 'Reasons for treatment failure' and "Psoriasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Other factors'.)

Adjusting therapy — Adjustment of the therapeutic regimen is indicated for disease resistant to appropriate therapy. Options include adding topical therapy or altering the approach to phototherapy or systemic therapy.

●Patients with limited residual disease – For patients receiving phototherapy or systemic therapy who have limited residual disease, optimizing adjunctive topical therapy may be sufficient for achieving satisfactory levels of improvement. (See "Chronic plaque psoriasis in adults: Treatment of disease amenable to topical therapy".)

●Patients with an inadequate response to phototherapy – When there is an inadequate response to phototherapy and adding topical therapy would be insufficient, we generally stop phototherapy and proceed to systemic therapy.

Alternatively, adding acitretin to phototherapy can augment the response. However, the availability of other effective therapies for psoriasis has reduced use of this regimen. (See 'Acitretin' below.)

●Patients with an inadequate response to biologic therapy – Inadequate responses to biologic therapy can occur when a biologic therapy is ineffective (primary failure) or loses efficacy following an initial satisfactory response to treatment (secondary failure). The approach to subsequent treatment selection is not standardized. Our approach is reviewed here; other approaches may be reasonable.

•For patients with primary failure (no response) to an IL-23 inhibitor, we typically switch to an IL-17 inhibitor. Similarly, for patients with primary failure to an IL-17 inhibitor, we typically switch to an IL-23 inhibitor.

•For patients who develop secondary failure to an IL-23 or IL-17 inhibitor, we most often switch to a drug in the same biologic class (eg, IL-17 inhibitor to IL-17 inhibitor).

•For patients with primary failure (no response) or secondary failure to either a TNF-alpha inhibitor or ustekinumab, we typically switch to an IL-23 inhibitor or IL-17 inhibitor unless the clinical scenario requires treatment with a different biologic agent.

•For patients who respond partially to a biologic drug and who have unacceptable levels of residual disease that cannot be managed with topical therapy, we switch to a different biologic drug. The new drug is typically an IL-23 inhibitor or IL-17 inhibitor unless the clinical scenario requires a different approach. The new drug can be in the same biologic class or a different biologic class (eg, IL-17 inhibitor to either an IL-23 inhibitor or IL-17 inhibitor). Dose escalation or increasing the frequency of dosing is an alternative for some therapies [11]. (See 'Biologic agents' below and 'Dose escalation' below.)

Data are insufficient to confirm optimal "wash-out" intervals for switching from one biologic therapy to another. Because of the relative safety of biologic therapy, we generally start the new biologic as soon as feasible, without a drug wash-out period.

Assessment for other reasons for treatment failure (eg, incorrect diagnosis) is important when there is a lack of response to both IL-17 inhibitor and IL-23 inhibitor treatment. (See 'Treatment failure' above.)

●Patients with an inadequate response to nonbiologic systemic therapy – Options for patients who experience an inadequate response to optimally dosed nonbiologic therapy include switching to an alternative nonbiologic agent or proceeding to biologic therapy.

PHOTOTHERAPY — 

Phototherapy involves use of ultraviolet (UV) irradiation to improve psoriasis. The major mechanisms of action may include antiproliferative effects (slowing keratinization) and anti-inflammatory effects (inducing apoptosis of pathogenic T cells in psoriatic plaques).

Modalities — Narrowband ultraviolet B (NBUVB) phototherapy, which involves treatment with 311 to 313 nm UV light, is the primary mode of phototherapy used for chronic plaque psoriasis. (See "UVB phototherapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

Less frequently used modalities include psoralen plus ultraviolet A (PUVA) photochemotherapy and broadband ultraviolet B (UVB) phototherapy. PUVA photochemotherapy involves treatment with a photosensitizer (either oral or bath psoralen) followed by exposure to ultraviolet A (UVA) light (320 to 400 nm). Broadband UVB involves exposure to 280 to 320 nm UV light. (See "UVB phototherapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

Compared with PUVA photochemotherapy, NBUVB is easier to administer (administration of psoralens is not required) and has a less severe side effect profile. Although greater efficacy of NBUVB over broadband UVB has not been confirmed with high-quality randomized trials, NBUVB is generally considered more effective [12-15].

Targeted phototherapy is an alternative approach that focuses on the treatment of limited skin areas. Targeted phototherapy is also the preferred route of phototherapy for sites that can be challenging to treat with booth phototherapy, such as the hair-bearing scalp, palms, and soles. (See "Chronic plaque psoriasis in adults: Treatment of disease amenable to topical therapy", section on 'Targeted phototherapy' and "Targeted phototherapy".)

Administration — The administration of phototherapy involves selection of appropriate candidates for phototherapy, access to phototherapy equipment, and implementation of an appropriate treatment protocol. Our approach is generally consistent with the American Academy of Dermatology and the National Psoriasis Foundation joint guidelines for the treatment of psoriasis with phototherapy [12].

●Patient selection – Candidates for phototherapy should be screened for absolute and relative contraindications to phototherapy. Major considerations include photosensitive disorders, prior cutaneous malignancy, and genetic disorders and other conditions that increase risk for cutaneous malignancies. We typically avoid phototherapy in patients with a history of melanoma or extensive nonmelanoma skin cancer. (See "UVB phototherapy (broadband and narrowband)", section on 'Contraindications' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Contraindications'.)

The feasibility and safety of treating the affected sites should also be considered. The feasibility of achieving adequate exposure of occluded sites (eg, hair-bearing scalp, skin folds) with the equipment available should be assessed. In addition, treatment of genital skin is generally avoided because of concern for increasing risk for genital squamous cell carcinoma [16]. Risk for accelerating skin photoaging can be a concern for the treatment of facial areas.

●Administration – Phototherapy and photochemotherapy require the supervision of a dermatologist trained in these treatments.

Phototherapy is typically administered three times per week during the treatment phase. Upon achievement of a satisfactory response, the frequency of treatment may be tapered to the lowest frequency required to maintain improvement. Treatment protocols for phototherapy are reviewed separately. (See "UVB phototherapy (broadband and narrowband)", section on 'Dosimetry and treatment protocols' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Treatment protocols'.)

Clinically significant improvement from phototherapy is generally expected within two to three months [17]. Combination treatment with phototherapy and acitretin may augment the response to phototherapy [12]. (See 'Acitretin' below.)

●Office-based versus home-based phototherapy – Phototherapy can be administered in an office setting or with a home-based phototherapy unit [18].

A clinician-prescribed home UVB phototherapy unit is a reasonable alternative to office-based phototherapy [18]. Home-based therapy may help to reduce the burden of treatment by eliminating the need to travel to a clinic site for treatment.

Randomized trial data support the efficacy and safety of home-based phototherapy [19,20]:

•In a multicenter randomized pragmatic trial (LITE trial), 783 adolescents and adults with plaque or guttate psoriasis deemed appropriate for phototherapy were randomly assigned to either home-based NBUVB phototherapy (n = 393) or office-based NBUVB phototherapy (n = 390) [20]. Concomitant psoriasis therapies were not prohibited. At week 12, more patients in the home phototherapy group had clear or almost clear skin compared with patients in the office-based phototherapy group (33 versus 26 percent, adjusted risk difference 7.2, 95% CI 0.8-13.5). Patients treated with home-based phototherapy were more likely to have a week 12 Dermatology Life Quality Index score of 5 or lower (equivalent to no effect to a small effect on quality of life); rates for this outcome were 52 and 34 percent, respectively (adjusted risk difference 18.6 percent, 95% CI 11.8-25.3).

Although both treatments were generally effective and well tolerated across all skin phototypes, episodes of the adverse event of mild to moderate persistent erythema (sunburn) were more frequent with home-based treatment (6 versus 1 percent). Limitations of the trial included regimen differences for office-based phototherapy, missing data, and limited cost difference analysis.

Home phototherapy units equipped with controllers that limit the number of treatments and symptom-based dosing controllers are available, ensuring follow-up with the provider and patient-friendly unit operation.

●Commercial tanning beds – Commercial tanning beds can improve psoriasis and are occasionally used for patients without access to medical phototherapy [21,22]. However, data are limited on this mode of treatment, and clinicians and patients should be cognizant that there is significant variability in the UV output of tanning beds [23].

●Efficacy – The efficacy of NBUVB phototherapy, the most common form of phototherapy used for chronic plaque psoriasis, is supported by randomized trials. In a systematic review that identified nine randomized trials that assessed the efficacy of 4 to 12 weeks of NBUVB monotherapy for achieving 75 percent improvement in the Psoriasis Area and Severity Index (PASI 75) score in plaque psoriasis, the mean percentage of patients achieving this endpoint was 62 percent (95% CI 45-79 percent) [24]. An analysis of the 10 randomized trials that assessed clearance rates revealed a mean complete clearance rate of 68 percent (95% CI 57-78 percent) [24].

Randomized trials comparing the efficacy of NBUVB with PUVA photochemotherapy have yielded inconsistent findings, though it appears that oral PUVA may provide a faster and more sustained response [15]. (See "UVB phototherapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

●Adverse effects and precautions – Potential short-term adverse effects of phototherapy include skin erythema, dryness, pruritus, blistering, and herpes simplex reactivation (table 2). PUVA photochemotherapy can have additional adverse effects related to the administration of psoralens. (See "UVB phototherapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Potential long-term effects of phototherapy include photoaging and skin cancer. PUVA photochemotherapy has been associated with increased risk for skin cancer. Although UVB phototherapy carries the theoretical risk for photocarcinogenesis, studies suggest that NBUVB and broadband UVB do not increase risk for skin cancer [25]. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Skin cancer' and "UVB phototherapy (broadband and narrowband)", section on 'Short- and long-term adverse effects'.)

UVB may be associated with folate degradation and decreased serum levels of folate [26]. Some authors have suggested ensuring supplementation with folic acid (at 0.8 mg per day) for all patients of childbearing potential who are receiving UVB phototherapy due to potential detrimental effects of folate deficiency in pregnancy [26].

SYSTEMIC THERAPIES — 

Multiple systemic medications are effective for chronic plaque psoriasis (table 1B). Immunosuppressive and immunomodulatory therapies are the mainstays of treatment. Acitretin, an oral retinoid, improves psoriasis through effects on epidermal proliferation and differentiation as well as immunomodulation. Fumaric acid ester drugs are additional immunomodulatory forms of psoriasis therapy primarily used in Europe.

Biologic agents — The major classes of biologic therapy for psoriasis include interleukin (IL) 23 inhibitors, IL-17 inhibitors, and tumor necrosis factor (TNF)-alpha inhibitors (table 1B). Consideration of the efficacy and safety profiles of individual biologic therapies, patient comorbidities, and patient preferences regarding dosing frequency and route of administration aid with selection of a specific biologic therapy. (See 'Selecting a systemic agent' above.)

Our approach to biologic therapy is generally consistent with the American Academy of Dermatology and the National Psoriasis Foundation joint guidelines for the treatment of psoriasis with biologic agents [27].

Biosimilar drugs are biologic agents that are similar in quality, pharmacokinetics, safety, and efficacy to an existing reference biologic agent [28,29]. Available biosimilars for specific agents are reviewed in the drug information content of UpToDate.

Precautions, patient assessment, and monitoring

●Patient history – The patient assessment may reveal comorbidities or risk factors that influence the safety of biologic therapy:

•Active or latent infection (a concern for all biologic therapies, though risk may differ based on the specific infection and biologic agent)

•Inflammatory bowel disease (a concern for IL-17 inhibitors)

•Congestive heart failure (a concern for TNF inhibitors)

•Demyelinating disease such as multiple sclerosis (a concern for TNF inhibitors)

•Vaccination status (because of uncertain safety, certain live vaccinations are avoided or approached with caution during biologic therapy) (see 'Vaccination during therapy' below)

•Pregnancy status and plans for pregnancy

Therapeutic approaches for patients with tuberculosis, HIV, viral hepatitis, and malignancy are reviewed separately. (See "Treatment selection for moderate to severe plaque psoriasis in special populations".)

Due to concern for an association with exacerbation of inflammatory bowel disease, we typically avoid IL-17 inhibitor therapy in patients with inflammatory bowel disease [30,31]. In addition, we generally avoid TNF-alpha inhibitor therapy in patients with congestive heart failure and patients with a history of multiple sclerosis [27]. (See 'IL-17 inhibitors' below and 'TNF-alpha inhibitors' below and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure' and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Demyelinating disease'.)

Additional considerations include malignancy, viral hepatitis, HIV infection, tuberculosis, and malignancy. (See "Treatment selection for moderate to severe plaque psoriasis in special populations".)

●Baseline laboratory tests – Routine baseline laboratory assessment for biologic therapy includes [27]:

•Tuberculosis screening (eg, interferon-gamma release assay [IGRA] or purified protein derivative [PPD])

•Hepatitis B and C screening (hepatitis B surface antigen, anti-hepatitis B surface antibody, anti-hepatitis B core antibody, hepatitis C antibody)

Hepatitis screening is considered most relevant for TNF inhibitor therapy. Because of limited data, the clinical relevancy of routine hepatitis testing for other biologic agents is unclear. (See "Treatment selection for moderate to severe plaque psoriasis in special populations", section on 'Chronic hepatitis B virus infection' and "Treatment selection for moderate to severe plaque psoriasis in special populations", section on 'Chronic hepatitis C virus infection'.)

For bimekizumab, obtaining liver function tests at baseline and according to routine patient management is advised in the US Food and Drug Administration (FDA) package insert for the drug [32]. However, further study is necessary to clarify whether bimekizumab has a clinically relevant impact on liver function [33].

Performance of additional studies for comorbidity or routine health screening may be appropriate but is not required specifically for biologic therapy. (See "Comorbid disease in psoriasis".)

●Subsequent monitoring – Our general approach to subsequent monitoring for patients on biologic therapy includes [27]:

•Clinical follow-up at three months to assess efficacy and then at least yearly

•Yearly tuberculosis screening for patients receiving TNF inhibitors (for other biologics, annual testing when there are symptoms of cough, night sweats, unexplained weight loss, or risk factors for exposure) (see "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)")

Vigilance for tuberculosis infection is considered most relevant for patients receiving TNF inhibitors. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)" and "Treatment selection for moderate to severe plaque psoriasis in special populations", section on 'Latent tuberculosis'.)

For patients on infliximab, we obtain a complete blood count and comprehensive metabolic panel after 3 months and then, provided the results are normal, every 6 to 12 months [27].

For patients on bimekizumab, we obtain liver function tests after three to six months of treatment and then either once yearly or based on symptoms. We also inquire about signs or symptoms of Candida infection during follow-up visits. (See 'Precautions' below.)

Performance of additional studies related to comorbidity screening may be appropriate but is not required specifically for biologic therapy. (See "Comorbid disease in psoriasis".)

Dose escalation — For some biologic therapies, dose escalation (ie, more frequent or higher dosing) is an alternative to switching to a different biologic therapy when an insufficient response seems related to insufficient drug exposure (eg, patient with obesity, patients who experience disease relapse toward the end of the treatment cycle) [11].

However, most often, we switch to a different biologic therapy. For patients with insufficient responses to ustekinumab, certolizumab pegol, adalimumab, or etanercept, we typically switch to a more effective biologic drug. In the infrequent event of an unsatisfactory response to a highly effective biologic IL-17 or IL-23 inhibitor, we often have difficulty obtaining payor approval for more frequent or higher doses. (See 'Adjusting therapy' above.)

IL-23 inhibitors — Interleukin (IL) 23 inhibitors for the treatment of chronic plaque psoriasis include guselkumab, tildrakizumab, and risankizumab.

Ustekinumab, an inhibitor of both IL-12 and IL-23, is reviewed separately. (See 'IL-12/23 inhibitor' below.)

Precautions — Examples of potential adverse effects of IL-23 inhibitors include increased risk for infection, particularly upper respiratory infection, injection site reactions, and hypersensitivity reactions. In trials, rates of serious infection were comparable (or less) than with placebo [34].

Pretreatment assessment and monitoring for biologic therapy is reviewed above. (See 'Precautions, patient assessment, and monitoring' above.)

Guselkumab — Guselkumab is a human immunoglobulin G1 (IgG1) lambda monoclonal antibody that binds to the p19 subunit of IL-23. IL-39 also contains this p19 subunit. The mechanism of action in psoriasis is thought to involve inhibition of IL-23 signaling.

●Administration – Standard adult dosing for guselkumab is:

•100 mg given subcutaneously at weeks 0, 4, and then every 8 weeks

Guselkumab can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis" and "Treatment of psoriatic arthritis".)

Extending the treatment interval may be a reasonable alternative for some patients who achieve a complete response. In a phase 3 trial, 297 patients receiving guselkumab for moderate to severe plaque psoriasis who had complete skin clearance (Psoriasis Area and Severity Index [PASI] score of 0) at weeks 20 and 28 were randomly assigned to continue guselkumab 100 mg either every 16 weeks or every 8 weeks [35]. Although most patients in both groups maintained complete skin clearance at week 68, clearance rates were lower for the 16-week interval than for the 8-week interval (69.1 percent, 90% CI 62.3-87.4 versus 81.1 percent, 90% CI 75.0-86.2, respectively). Week 68 response rates were similar for the less stringent outcome of a PASI score less than three (91.9 percent [90% CI 87.3-95.3 percent] for the 16-week interval compared with 92.6 percent [90% CI 88.0-95.8 percent] for the 8-week interval). Adverse event rates were similar between the groups.

●Efficacy – Randomized trials support greater efficacy of guselkumab compared with adalimumab and placebo. Outcomes from some trials suggest that guselkumab has a slower onset of action compared with secukinumab and ixekizumab but may have greater long-term efficacy compared with secukinumab. (See 'Relative efficacy' above.)

•Versus placebo and adalimumab – Guselkumab was effective for psoriasis and more effective than adalimumab in phase 3 randomized trials [36,37].

-In the 48-week VOYAGE 1 trial, 837 adults with moderate to severe plaque psoriasis were randomly assigned in a 2:1:2 ratio to guselkumab (at 100 mg at weeks 0, 4, then every 8 weeks), placebo (given at weeks 0, 4, and 12) followed by guselkumab (at 100 mg at weeks 16 and 20, then every 8 weeks), or adalimumab (at 80 mg at week 0, 40 mg at week 1, then 40 mg every 2 weeks) [36]. At week 16, more patients treated with guselkumab achieved 90 percent improvement in the Psoriasis Area and Severity Index (PASI 90) than patients in the adalimumab or placebo groups (73, 50, and 3 percent, respectively). Guselkumab remained more effective than adalimumab after 48 weeks. Adverse effects were comparable among the treatment groups.

-The initial 24 weeks of the 48-week phase 3 VOYAGE 2 trial (n = 992) involved random assignment of adults with moderate to severe plaque psoriasis in a 2:1:1 ratio to guselkumab, placebo followed by guselkumab, or adalimumab groups, with dosing regimens similar to those in VOYAGE 1 [37]. As in VOYAGE 1, guselkumab was more effective than adalimumab and placebo at week 16. At week 28, patients either continued (or started) guselkumab or transitioned to placebo followed by guselkumab upon loss of response. Guselkumab-treated patients who had achieved at least PASI 90 were rerandomized to one of these groups. Among the rerandomized patients, continued therapy was associated with greater maintenance of response than withdrawal; 89 versus 37 percent maintained PASI 90 through week 48 in the continued therapy and withdrawal groups, respectively.

•Versus other biologic agents – Guselkumab showed greater long-term (one year) efficacy than secukinumab in a phase 3 trial (ECLIPSE trial) in which 1048 adults with moderate to severe plaque psoriasis were randomly assigned to either guselkumab (at 100 mg at weeks 0 and 4, then every 8 weeks) or secukinumab (at 300 mg at weeks 0, 1, 2, 3, and 4, then every 4 weeks) [38]. In the trial, 84 percent of patients in the guselkumab group achieved the primary trial endpoint of a PASI 90 response at week 48 compared with 70 percent of patients in the secukinumab group, despite a more rapid initial response in the secukinumab group.

In a 24-week trial (IXORA-R trial) in which 1027 adults with moderate to severe plaque psoriasis were randomly assigned to treatment with either ixekizumab (at 160 mg at week 0, then 80 mg every 2 weeks until week 12, then 80 mg every 4 weeks) or guselkumab (at 100 mg at weeks 0 and 4 and then every 8 weeks), ixekizumab was associated with faster improvement [39,40]. At week 12, 215 of 529 patients (41 percent) treated with ixekizumab achieved 100 percent improvement in the Psoriasis Area and Severity Index (PASI 100) compared with 126 of 507 patients (25 percent) treated with guselkumab [39]. At week 24, responses to ixekizumab and guselkumab were comparable for achieving PASI 100 (50 versus 52 percent) [40]. Longer-term efficacy was not assessed.

Risankizumab — Risankizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and IL-39 [41].

●Administration and precautions – Standard adult dosing for risankizumab is:

•150 mg given subcutaneously at week 0 and week 4, then every 12 weeks

Risankizumab can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis".)

●Efficacy – Randomized trials support greater efficacy of risankizumab compared with placebo, ustekinumab, and adalimumab as well as greater long-term efficacy but a slower onset of action of risankizumab compared with an IL-17 inhibitor (secukinumab). (See 'Relative efficacy' above.)

•Versus placebo – Risankizumab had greater efficacy than ustekinumab and placebo in phase 3 trials.

-In the 16-week blinded phase of the 52-week UltIMMA-1 (n = 506) and UltIMMa-2 (n = 491) trials, patients with moderate to severe plaque psoriasis were randomly assigned to risankizumab (at 150 mg), ustekinumab (at 45 or 90 mg based upon weight), or placebo in a 3:1:1 ratio [42]. Doses in this phase were given at zero and four weeks. In UltIMMa-1, 75, 42, and 5 percent of patients, respectively, achieved PASI 90 at 16 weeks. In UltIMMa-2, 75, 48, and 2 percent achieved this endpoint, respectively. Overall, the proportion of adverse effects was similar among the three groups; however, minor infections were more frequent in the risankizumab and ustekinumab groups than in the placebo group.

•Versus other therapies – Risankizumab was more effective for plaque psoriasis than adalimumab in a randomized trial.

-In a phase 3 trial (IMMvent trial) in which 605 adults with moderate to severe chronic plaque psoriasis were randomly assigned to either risankizumab (at 150 mg at weeks 0 and 4, then every 12 weeks) or adalimumab (at 80 mg at week 0, then 40 mg at week 1 and every other subsequent week), 72 percent of patients in the risankizumab group achieved PASI 90 by week 16 compared with 47 percent of patients given adalimumab [43]. Risankizumab was also more effective than adalimumab in a second phase in which 109 intermediate responders to adalimumab were rerandomized to either risankizumab or continuation of adalimumab (66 versus 21 percent achievement of PASI 90 at week 44, respectively). Adverse effect rates were similar between risankizumab and adalimumab groups.

An open-label efficacy-assessor blinded trial (IMMerge trial) that compared risankizumab (at 150 mg at weeks 0 and 4, then every 12 weeks) versus secukinumab (at 300 mg at weeks 0, 1, 2, 3, and 4, then every 4 weeks) in 327 adults with moderate to severe plaque psoriasis suggests greater long-term efficacy for risankizumab [44]. While secukinumab appeared to improve psoriasis more quickly, risankizumab was noninferior to secukinumab at 16 weeks (PASI 90 in 74 versus 66 percent; noninferiority margin of 12 percent) and more effective than secukinumab at week 52 (PASI 90 in 87 versus 57 percent).

Tildrakizumab — Tildrakizumab is a human IgG1 kappa monoclonal antibody that binds to the p19 subunit of IL-23.

●Administration – Standard adult dosing for tildrakizumab is:

•100 mg given subcutaneously at weeks 0 and 4 and then every 12 weeks

●Efficacy – Randomized trials support greater efficacy of tildrakizumab compared with placebo and etanercept. Data from a network meta-analysis suggest lesser efficacy of tildrakizumab compared with other IL-23 inhibitors [27]. (See 'Relative efficacy' above.)

•Versus placebo and other therapies – Phase 3 trials (reSURFACE 1, reSURFACE 2) support superiority of tildrakizumab compared with placebo and etanercept [45].

In reSURFACE 1, 772 adults with moderate to severe plaque psoriasis were randomly assigned to receive tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo at weeks 0 and 4 and then every 12 weeks. After 12 weeks, 62, 64, and 6 percent of patients in the 200 mg, 100 mg, and placebo groups, respectively, achieved 75 percent improvement in the Psoriasis Area and Severity Index (PASI 75).

The reSURFACE 2 trial randomly assigned 1090 patients to similar groups plus an etanercept group. After 12 weeks, 66, 61, 6, and 48 percent of patients in the tildrakizumab 200 mg, tildrakizumab 100 mg, placebo, and etanercept groups, respectively, achieved PASI 75. Rates of serious adverse effects were similar among the groups in both reSURFACE 1 and reSURFACE 2. One patient in the tildrakizumab 100 mg group died of an unclear cause during reSURFACE 2.

IL-17 inhibitors — Inhibitors of the interleukin (IL) 17 pathway utilized for the treatment of psoriasis include bimekizumab, brodalumab, ixekizumab, and secukinumab.

Precautions — Pretreatment assessment and monitoring for biologic therapy is reviewed above. (See 'Precautions, patient assessment, and monitoring' above.)

●Infection – The most common adverse effect of biologic IL-17 inhibitor therapy is increased risk for infection. In particular, these drugs have been associated with an increase in risk for mild candidal infections; the risk of mild candidiasis is greatest with bimekizumab [46,47].

●Inflammatory bowel disease – We typically avoid IL-17 inhibitor therapy in patients with inflammatory bowel disease because of concern that anti-IL-17 biologic therapy may increase risk for the exacerbation or development of inflammatory bowel disease [48]. However, absolute rates of new-onset inflammatory bowel disease in patients treated with IL-17 inhibitors are low (<1 percent) [49-51].

•In a French population-based study that included 16,793 adults with psoriasis, psoriatic arthritis, or ankylosing spondylitis who started treatment with an IL-17 inhibitor between 2016 and 2019, new-onset inflammatory bowel disease occurred in 72 patients (0.43 percent). Although this rate was higher than the rate seen among 20,556 adults with the same diagnoses who started treatment with apremilast (0.05 percent) and similar to the rate among 10,294 adults who started treatment with etanercept (0.48 percent), potential differences in patient characteristics prevent definitive conclusions on relative treatment effects [49,52].

●Other precautions – In the United States, brodalumab therapy requires participation in a Risk Evaluation and Mitigation Strategy program for suicidal ideation and behavior. However, a causative relationship has not been confirmed [53]. (See 'Brodalumab' below.)

Bimekizumab — Bimekizumab is a monoclonal IgG1 antibody that inhibits IL-17A and IL-17F [47,54-56].

●Administration – Standard adult dosing for bimekizumab is:

•320 mg given subcutaneously every 4 weeks for the first 16 weeks, followed by 320 mg given every 8 weeks

Discontinuation of bimekizumab is reasonable if patients have no response within 16 weeks. Patients weighing ≥120 kg who have an inadequate response after 16 weeks may benefit from maintaining the four-week treatment interval [57-59].

Bimekizumab can also be effective for psoriatic arthritis [60]. (See "Treatment of peripheral psoriatic arthritis", section on 'Bimekizumab'.)

●Efficacy – Randomized trials support greater efficacy of bimekizumab compared with placebo, ustekinumab, adalimumab, and secukinumab. (See 'Relative efficacy' above.)

•Versus placebo – In the BE READY trial (n = 435), adults with moderate to severe plaque psoriasis were randomly assigned to receive either bimekizumab (at 320 mg every four weeks) or placebo in a 4:1 ratio [55]. At week 16, 317 of 349 patients (91 percent) in the bimekizumab group achieved PASI 90 compared with only 1 of 86 patients (1 percent) in the placebo group. Patients in the bimekizumab group who achieved PASI 90 were reallocated (1:1:1) to receive bimekizumab 320 mg every four weeks, bimekizumab 320 mg every eight weeks, or placebo over the subsequent 40 weeks. Patients who continued bimekizumab every four or eight weeks were more likely to achieve PASI 90 at week 56 than patients in the placebo group (87, 91, and 16 percent, respectively). The most common treatment-emergent adverse events for bimekizumab were nasopharyngitis, oral candidiasis, and upper respiratory tract infections.

•Versus other therapies – The BE VIVID trial (n = 567) compared the efficacy and safety of bimekizumab, ustekinumab, and placebo. Adults with moderate to severe plaque psoriasis were randomly assigned (4:2:1) to receive bimekizumab (at 320 mg every four weeks), ustekinumab (weight-based dosing of 45 or 90 mg at weeks 0 and 4, then every 12 weeks), or placebo (every four weeks) for 16 weeks [54]. At week 16, patients in the placebo group transitioned to bimekizumab, and patients in the active treatment groups continued treatment until week 52.

Patients in the bimekizumab group (n = 321) were more likely to achieve PASI 90 at week 16 than patients in the ustekinumab (n = 163) and placebo (n = 83) groups (PASI 90 achieved in 85, 50, and 5 percent of patients, respectively). The most common treatment-emergent adverse events for bimekizumab were nasopharyngitis, oral candidiasis, and upper respiratory tract infection, with candidiasis occurring more frequently in the bimekizumab group than in the ustekinumab group. Over 52 weeks, five major cardiac adverse events occurred in patients with pre-existing cardiovascular risk factors in the bimekizumab group, and none occurred in the ustekinumab group. Oral candidiasis rates were higher than for other drugs blocking the IL-17 pathway, and one case of inflammatory bowel disease was recorded. Additional study may be useful for clarifying safety.

Trials comparing bimekizumab with adalimumab or secukinumab also support greater efficacy of bimekizumab. In a 56-week phase 3 trial (BE SURE trial), adults with moderate to severe plaque psoriasis were randomly assigned to bimekizumab (at 320 mg every 4 weeks for 56 weeks), bimekizumab (at 320 mg every 4 weeks for 16 weeks and then every 8 weeks until week 56), or adalimumab (at 80 mg followed by 40 mg one week later and then 40 mg every two weeks until week 24) [56]. Patients in the adalimumab group were subsequently given bimekizumab (at 320 mg every 4 weeks from week 24 to 56). At week 16, 275 of 319 patients (86 percent) receiving bimekizumab achieved PASI 90 compared with 75 of 159 patients (47 percent) receiving adalimumab (adjusted risk difference 28.2 percentage points, 95% CI 19.7-36.7). Responses were maintained through week 56 with both dosing regimens for bimekizumab.

In a 48-week phase 3 trial (BE RADIANT trial), adults with moderate to severe plaque psoriasis were randomly assigned to bimekizumab (at 320 mg every four weeks) or secukinumab (at 300 mg weekly to week 4 and then once every 4 weeks) [47]. At week 16, patients receiving bimekizumab were rerandomized to receive bimekizumab once every four or eight weeks. At week 16, 230 of 373 patients (62 percent) in the bimekizumab group achieved PASI 100 compared with 181 of 370 patients (49 percent) in the secukinumab group (adjusted risk difference 12.7 percentage points, 95% CI 5.8-19.6). Bimekizumab maintained superior efficacy at 48 weeks (PASI 100 in 67 versus 46 percent of patients). The study was not adequately powered to detect differences between the two bimekizumab maintenance treatment groups.

Brodalumab — Brodalumab is an anti-IL-17 receptor A monoclonal antibody.

●Administration – Standard adult dosing for brodalumab is:

•210 mg given subcutaneously at weeks 0, 1, and 2 and then every 2 weeks

In the United States, use of brodalumab requires participation in a Risk Evaluation and Mitigation Strategy program due to concerns regarding risk for suicidal ideation and completed suicides in treated patients. However, a causal relationship between brodalumab treatment and suicidal ideation and behavior has not been confirmed. An analysis of data from five clinical trials did not find evidence of causality [61].

●Efficacy – Randomized trials support greater efficacy of brodalumab compared with placebo and ustekinumab [62,63]. (See 'Relative efficacy' above.)

•Versus placebo and other therapies – In two identically designed trials (AMAGINE-2 [n = 1831] and AMAGINE-3 [n = 1881]), patients were assigned in a 2:2:1:1 ratio to receive brodalumab 210 mg every two weeks; brodalumab 140 mg every two weeks; standard dosing of ustekinumab on day 1, week 4, and then every 12 weeks (a 45 mg dose if body weight ≤100 kg and a 90 mg dose if body weight >100 kg); or placebo [62]. At week 12, more patients receiving 210 mg of brodalumab or 140 mg of brodalumab achieved PASI 75 compared with patients in the placebo group (86, 67, and 8 percent, respectively [AMAGINE-2], and 85, 69, and 6 percent, respectively [AMAGINE-3]). In addition, the rate of complete clearance of skin disease (PASI 100) at week 12 was higher among patients given 210 mg of brodalumab compared with patients receiving ustekinumab (44 versus 22 percent, respectively [AMAGINE-2], and 37 versus 19 percent, respectively [AMAGINE-3]). A statistically significant benefit of the 140 mg dose of brodalumab over ustekinumab for achieving PASI 100 was evident in AMAGINE-3 at week 12 but not in AMAGINE-2.

Mild to moderate Candida infections were more frequent in the brodalumab groups than in the ustekinumab and placebo groups, and neutropenia occurred more frequently in the brodalumab and ustekinumab groups than in the placebo group. In addition, two suicides occurred in patients receiving brodalumab in crossover and open-label phases of AMAGINE-2.

Ixekizumab — Ixekizumab is a humanized monoclonal antibody against IL-17A.

●Administration – Standard adult dosing for ixekizumab is:

•160 mg given subcutaneously at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12. Subsequently, 80 mg are given every four weeks.

The proposed dose escalation regimen for ixekizumab is 80 mg given every two weeks rather than every four weeks [11,64]. (See 'Dose escalation' above.)

Ixekizumab can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'Ixekizumab'.)

●Efficacy – Randomized trials support greater efficacy of ixekizumab compared with placebo and etanercept [9,64-68]. A randomized trial suggests ixekizumab may induce faster improvement compared with guselkumab. This trial is discussed separately. (See 'Guselkumab' above and 'Relative efficacy' above.)

•Versus placebo and other therapies – In the UNCOVER-2 (n = 1224) and UNCOVER-3 (n = 1346) trials, patients with moderate to severe plaque psoriasis were randomly assigned to receive 80 mg of ixekizumab every two weeks after a 160 mg starting dose, 80 mg of ixekizumab every four weeks after a 160 mg starting dose, etanercept (at 50 mg twice weekly), or placebo in a 2:2:2:1 ratio [64]. At week 12, more patients treated with ixekizumab every two weeks or ixekizumab every four weeks achieved PASI 75 than patients treated with etanercept or placebo. In UNCOVER-2, PASI 75 rates were 90, 78, 42, and 2 percent, respectively. PASI 75 rates in UNCOVER-3 were 87, 84, 53, and 7 percent, respectively.

In a third phase 3 trial (UNCOVER-1, n = 1296) that compared the same two- and four-week dose regimens for ixekizumab with placebo, PASI 75 rates at week 12 were 89, 83, and 4 percent, respectively [65].

The 12-week induction periods in the UNCOVER trials were followed by 48-week extension periods. In UNCOVER-1 and UNCOVER-2, patients who responded to ixekizumab at week 12 (clear or minimal psoriasis on static Physician Global Assessment) were randomly reassigned to receive 80 mg of ixekizumab every four weeks, 80 mg of ixekizumab every 12 weeks, or placebo. At the week 60 time point, 74, 39, and 7 percent of patients, respectively, still had clear or minimal psoriasis. Patients in UNCOVER-3 continued ixekizumab at a dose of 80 mg every four weeks after the induction period at the discretion of the investigator and patient. At week 60, clear or minimal psoriasis rates among patients initially treated with ixekizumab every two weeks and every four weeks were 75 and 73 percent, respectively. The rates of serious adverse effects were similar in the ixekizumab and placebo groups. Overall, neutropenia, candidal infection, and inflammatory bowel disease occurred in 12, 3, and less than 1 percent of all patients exposed to ixekizumab during weeks 0 to 60, respectively. Neutropenia was generally transient and did not result in cessation of ixekizumab.

Secukinumab — Secukinumab is an anti-IL-17A monoclonal antibody.

●Administration – Standard adult dosing for secukinumab is:

•300 mg given subcutaneously once weekly at weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Doses of 150 mg are sufficient for some patients.

Secukinumab can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'Secukinumab'.)

•Dose frequency adjustments – Whether the dose frequency of secukinumab should be increased following insufficient responses to standard dosing is unclear. (See 'Dose escalation' above.)

-A randomized trial that included 325 patients with suboptimal responses to secukinumab (achievement of PASI 75 but not PASI 90 after 16 weeks of standard dosing) did not find a statistically significant difference in the proportion of patients who achieved PASI 90 at week 32 between patients who switched to secukinumab every two weeks and patients who continued secukinumab every four weeks (64 versus 57 percent, respectively; odds ratio 0.64, 95% CI 0.39-1.07) [69]. However, patients in the every-two-week secukinumab group had a lower absolute PASI score at week 32 and were more likely to achieve minimal disease activity on the Investigator's Global Assessment [69].

-In a randomized trial, 331 adults who weighed ≥90 kg and had moderate to severe psoriasis were assigned to receive 300 mg of secukinumab either every two or four weeks. Patients who did not achieve PASI 90 at week 16 were reallocated to continue secukinumab every four weeks or switch to secukinumab every two weeks [70]. At week 16, patients treated with secukinumab every two weeks were more likely to achieve PASI 90 than patients treated every four weeks (73 versus 56 percent, respectively, odds ratio estimate 2.3, 95% CI 1.4-3.8). The two-week dose interval remained more effective than the four-week dose interval at week 52 (PASI 90 achieved in 76 versus 52 percent of patients, respectively). Adverse events were comparable in the two groups.

●Efficacy – Randomized trials support greater efficacy of secukinumab compared with placebo, etanercept, ustekinumab, and fumaric acid esters [70-79]. Secukinumab improved psoriasis faster but had less long-term efficacy than guselkumab and risankizumab in randomized trials. These trials are discussed separately. (See 'Guselkumab' above and 'Risankizumab' above and 'Relative efficacy' above.)

•Versus placebo and other therapies – Two 52-week phase 3 placebo-controlled trials (ERASURE trial and FIXTURE trial) support the efficacy of secukinumab for moderate to severe plaque psoriasis [71]. In both trials, secukinumab was given as a 300 or 150 mg dose once weekly for five weeks, then once every four weeks.

-In the ERASURE trial (n = 738), PASI 75 at week 12 was achieved by 82 percent of patients in the 300 mg secukinumab group and 72 percent of patients in the 150 mg secukinumab group compared with only 5 percent of patients in the placebo group.

-In the FIXTURE trial (n = 1306), which incorporated similar doses of secukinumab, secukinumab was superior to both etanercept (at 50 mg twice weekly for 12 weeks, then once weekly) and placebo. After 12 weeks, PASI 75 was achieved by 77 percent of patients in the 300 mg secukinumab group, 67 percent of patients in the 150 mg secukinumab group, 44 percent of patients in the etanercept group, and 5 percent of patients in the placebo group.

Secukinumab has greater efficacy than ustekinumab with a similar degree of safety.

-In a prospective trial (CLEAR trial), 676 adults with moderate to severe plaque psoriasis were randomly assigned to secukinumab (at 300 mg given at baseline, week 1, week 2, and week 3, then every 4 weeks) and ustekinumab (at 45 or 90 mg given at baseline, week 4, and then every 12 weeks) [74]. After 16 weeks, PASI 90 occurred in 79 percent of patients in the secukinumab group compared with 58 percent of patients in the ustekinumab group. The rates of adverse effects were similar in the two groups. An analysis of additional data from the CLEAR trial revealed that with continued treatment, the efficacy of secukinumab was greater than that of ustekinumab for at least 52 weeks [75]. At week 52, 76 percent of patients in the secukinumab group achieved PASI 90 compared with 61 percent of patients in the ustekinumab group. Safety was comparable between the two groups.

IL-12/23 inhibitor — Ustekinumab is an interleukin (IL) 12 and IL-23 inhibitor indicated for the treatment of chronic plaque psoriasis. However, the development of more effective biologic IL-23 and IL-17 inhibitors has reduced our use of ustekinumab for psoriasis. (See 'Relative efficacy' above.)

Precautions — Pretreatment assessment and monitoring for biologic therapy is reviewed above. (See 'Precautions, patient assessment, and monitoring' above.)

●Infection and malignancy – Five-year safety data and registry data for ustekinumab show no increased risk of severe infection or malignancy [80-82].

●Cardiovascular events – Reports of major adverse cardiovascular events (MACE) during phase 2 and 3 studies for ustekinumab and briakinumab, another anti-IL-12/23 agent, led to the performance of a meta-analysis of placebo-controlled randomized trials evaluating the relationship between anti-IL-12/23 therapy and MACE in patients with chronic plaque psoriasis [83]. More MACE were reported in patients who received active treatment with ustekinumab or briakinumab than in those who received placebo (10 out of 3179 patients versus 0 out of 1474 patients). Although the difference in events was not statistically significant, the trial lengths were short (12 to 20 weeks), and the meta-analysis may have been underpowered to detect a significant difference. Other authors have suggested that the same data may indicate lower risk of MACE with IL-12/23 blockade compared with placebo [84].

A review of pooled data from phase 2 and 3 trials with up to five years follow-up did not reveal an increased risk for MACE [80]. In addition, analysis of data from a large observational study of patients receiving or eligible to receive systemic therapy for psoriasis (PSOLAR) did not find an association between ustekinumab therapy and MACE [81].

●Other – Uncommon adverse effects that may or may not be drug related, such as reversible posterior leukoencephalopathy syndrome and a lymphomatoid drug eruption, have occurred in individual patients [85,86].

The development of noninfectious pneumonia (eg, interstitial pneumonia, eosinophilic pneumonia, organizing pneumonia, hypersensitivity pneumonitis) has also been infrequently reported in the setting of ustekinumab therapy [87].

Ustekinumab — Ustekinumab is a human monoclonal antibody that targets IL-12 and IL-23.

Ustekinumab can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'Ustekinumab'.)

●Administration – Standard adult dosing for ustekinumab is weight based.

•For adults ≤100 kg – 45 mg given subcutaneously at weeks 0, 4, and every 12 weeks thereafter

•For adults >100 kg – 90 mg dose given in the same regimen

Dose escalation options for ustekinumab include escalating to 45 mg every 8 weeks or to 90 mg every 8 or 12 weeks for patients weighing ≤100 kg or escalating to 90 mg every 8 weeks for patients who lose response before the next 12-week treatment cycle.

Although serum ustekinumab levels may correlate with response to treatment, drug monitoring of ustekinumab levels is not a standard component of treatment [88,89].

●Efficacy – Phase 3 trials support greater efficacy of ustekinumab compared with placebo and etanercept [90-94]. (See 'Relative efficacy' above.)

•Versus placebo – In a randomized trial where 766 patients had moderate to severe plaque psoriasis, more patients treated with ustekinumab 45 or 90 mg achieved at least PASI 75 at week 12 than those treated with placebo (67 and 66 versus 3 percent) [90]. Ustekinumab was administered monthly by subcutaneous injection for the first two doses and then every 12 weeks. Responders who were kept on therapy generally maintained improvements in psoriasis out to at least 76 weeks. Serious adverse events were seen at similar rates in the ustekinumab and placebo arms.

In a second similarly designed trial where 1230 patients had moderate to severe plaque psoriasis, more patients treated with ustekinumab 45 or 90 mg achieved PASI 75 at week 12 than those treated with placebo (67 and 76 versus 4 percent) [91]. Patients who achieved a partial response at week 28 were randomly assigned to continue every-12-week dosing or escalate to every-8-week dosing. More frequent dosing did not enhance response rates at one year in patients receiving 45 mg but did enhance PASI 75 rates in those receiving 90 mg (69 versus 33 percent with continued 12-week dosing). Serious adverse events were again seen at similar rates in the ustekinumab and placebo arms.

The efficacy of ustekinumab appears to persist over time. In one of the phase 3 randomized trials above [90], ustekinumab maintained a high level of efficacy over three years [95]. In addition, treatment appears to be well tolerated [80,96].

•Versus other therapies – A randomized trial supports superior efficacy of ustekinumab over etanercept [97]. In the trial, 903 patients with moderate to severe psoriasis received 90 mg of ustekinumab at weeks 0 and 4, 45 mg of ustekinumab at weeks 0 and 4, or 50 mg of etanercept twice weekly. After 12 weeks, PASI 75 was observed in 73.8, 67.5, and 56.8 percent of patients in the 90 mg ustekinumab, 45 mg ustekinumab, and etanercept groups, respectively. In addition, some patients who did not respond to etanercept benefited from treatment with ustekinumab. Twelve weeks after crossover to 90 mg of ustekinumab (administered at weeks 16 and 20), 48.9 percent achieved PASI 75. The incidence of serious adverse effects was similar among treatment groups.

TNF-alpha inhibitors — Biologic tumor necrosis factor (TNF)-alpha inhibitors utilized for psoriasis include adalimumab, certolizumab pegol, etanercept, and infliximab.

Biologic TNF-alpha inhibitors can also be effective for psoriatic arthritis. (See "Treatment of psoriatic arthritis".)

Precautions — TNF-alpha inhibitors revolutionized the management of psoriasis. However, IL-17 and IL-23 inhibitors have better efficacy and safety profiles and have largely supplanted TNF-alpha inhibitors in the management of psoriasis.

Examples of potential adverse effects of TNF-alpha inhibitors include injection site reactions, infusion reactions, neutropenia, infections, and other skin reactions. Additional concerns include the potential impact of TNF-alpha inhibitor therapy on skin cancer, heart failure, hepatotoxicity, and demyelinating disease. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)

Formation of antibodies against adalimumab is estimated to occur in 6 to 50 percent of patients treated with adalimumab for psoriasis and may reduce the response to therapy [98-100]. Anti-infliximab antibodies may occur in 5 to 44 percent of patients who receive infliximab for psoriasis and may also reduce the response to treatment [98,100]. Although addition of methotrexate to biologic therapy to reduce antidrug antibodies and improve clinical response is sometimes used in clinical practice, some uncertainty remains about the clinical impact of this intervention in patients with psoriasis [101,102]. (See "Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases", section on 'Anti-drug antibodies'.)

Pretreatment assessment and monitoring for biologic therapy is reviewed separately. (See 'Precautions, patient assessment, and monitoring' above.)

Adalimumab — Adalimumab is a humanized monoclonal antibody with activity against TNF-alpha.

●Administration – Standard adult dosing for adalimumab is:

•An initial 80 mg dose given subcutaneously, followed by 40 mg given every other week, beginning one week after the initial dose (see "Treatment of peripheral psoriatic arthritis", section on 'TNF inhibitors for most patients')

The proposed dose escalation regimen for adalimumab is 40 mg given once weekly, rather than every other week [11]. (See 'Dose escalation' above.)

Adalimumab can also be effective for psoriatic arthritis. (See "Treatment of psoriatic arthritis" and "Treatment of peripheral psoriatic arthritis", section on 'TNF inhibitors for most patients'.)

●Efficacy – Randomized trials support greater efficacy of adalimumab compared with placebo. Trials comparing adalimumab with newer therapies, such as guselkumab, risankizumab, and bimekizumab, have found adalimumab less effective than these therapies. Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above and 'Guselkumab' above and 'Risankizumab' above and 'Bimekizumab' above.)

•Versus placebo – A randomized trial in 147 patients with moderate to severe plaque psoriasis compared adalimumab by subcutaneous injection 40 mg every other week, 40 mg weekly, and placebo [103]. After 12 weeks, more patients treated with adalimumab every other week or weekly achieved PASI 75 (53 and 80 percent, respectively) versus 4 percent with placebo. In an open-label extension of the study, improvements were sustained for 60 weeks.

•Versus other therapies – Adalimumab was more effective than methotrexate in a randomized trial involving 271 patients with moderate to severe psoriasis [104] (see 'Methotrexate' below). Other studies have demonstrated responses to adalimumab in some patients with poor responses to etanercept [105-107].

Certolizumab pegol — Certolizumab pegol is a pegylated humanized antibody Fab fragment with specificity for TNF-alpha. A potential advantage of certolizumab pegol is minimal transfer across the placenta; unlike other anti-TNF biologics, certolizumab pegol does not bind the neonatal Fc receptor because it lacks the immunoglobulin G (IgG) Fc [108].

●Administration – Standard adult dosing for certolizumab is:

•400 mg given subcutaneously every other week.

An optional regimen for patients who weigh ≤90 kg is 400 mg at weeks 0, 2, and 4, followed by 200 mg every other week.

The proposed dose escalation regimen for certolizumab pegol is 400 mg given every other week [11]. (See 'Dose escalation' above.)

The drug can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'TNF inhibitors for most patients'.)

●Efficacy – Randomized trials support greater efficacy of certolizumab compared with placebo and etanercept [109,110]. Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

•Versus placebo – In the CIMPASI-1 and CIMPASI-2 trials, adults with moderate to severe chronic plaque psoriasis (234 adults in CIMPASI-1 and 227 adults in CIMPASI-2) were randomly assigned to 400 mg of certolizumab pegol every two weeks, 200 mg of certolizumab pegol every two weeks (after loading dose of 400 mg at weeks 0, 2, and 4), or placebo every two weeks [109]. Patients who achieved at least 50 percent improvement in the Psoriasis Area and Severity Index (PASI 50) continued treatment through 48 weeks. At week 16, more patients in the certolizumab pegol 400 mg and certolizumab pegol 200 mg groups achieved PASI 75 than in the placebo group. PASI 75 response rates in CIMPASI-1 were 76, 67, and 7 percent, respectively. In CIMPASI-2, response rates were 83, 81, and 12 percent, respectively. The difference in effect for the 400 and 200 mg doses was statistically significant in CIMPASI-1 and pooled data from both trials but not in CIMPASI-2. Responses to certolizumab pegol were maintained over 48 weeks.

The most common adverse effects among patients receiving certolizumab were nasopharyngitis and upper respiratory infection. In total, serious treatment-emergent adverse effects occurred in 18 patients who received certolizumab pegol 400 mg, 11 patients who received certolizumab pegol 200 mg, and 1 patient who received placebo.

•Versus other therapies – A separate phase 3 trial (CIMPACT) randomly assigned 559 adults with moderate to severe chronic plaque psoriasis to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks for 16 weeks or etanercept 50 mg twice weekly for 12 weeks [110]. The trial found both the 400 and 200 mg dose regimens more effective than placebo, with greater response to the 400 mg dose. At 12 weeks, certolizumab 400 mg was more effective than etanercept, and certolizumab 200 mg was noninferior to etanercept for achieving PASI 75. As in the CIMPASI trials, nasopharyngitis and upper respiratory infections were the most common adverse effects.

Etanercept — Etanercept is a soluble TNF receptor fusion protein bound to the Fc portion of human IgG1. The drug binds to TNF and blocks its interaction with cell surface receptors. Given the availability of more effective biologic agents, we generally avoid use of etanercept for adults with plaque psoriasis.

●Administration – Standard adult dosing for etanercept is:

•50 mg given subcutaneously twice weekly for the initial three months of therapy, followed by a 50 mg injection once weekly for maintenance therapy

The proposed dose escalation regimen for etanercept is 50 mg twice weekly [11]. (See 'Dose escalation' above.)

Etanercept can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'TNF inhibitors for most patients'.)

●Efficacy – Randomized trials support efficacy of etanercept [111-113]. However, etanercept is less effective than other antipsoriatic biologic agents. Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

•Versus placebo – A randomized trial of etanercept in 652 adult patients with active but stable plaque psoriasis involving at least 10 percent of the body surface area found three doses of subcutaneous etanercept (at 25 mg weekly, 25 mg twice weekly, 50 mg twice weekly) superior to placebo [111]. After 12 weeks, 14, 34, 49, and 4 percent of patients, respectively, achieved PASI 75. After 24 weeks, such an improvement was seen in 25, 44, and 59 percent of patients, respectively (no patients received placebo for more than 12 weeks). Etanercept was well tolerated with adverse events and infections occurring at similar rates in all four groups.

The long-term safety of etanercept for psoriasis is supported by a 96-week study of etanercept 50 mg twice weekly [114].

Infliximab — Infliximab is a chimeric monoclonal antibody directed against TNF. The TNF-alpha inhibitor infliximab is of benefit in patients with moderate to severe plaque psoriasis and appears to generally be well tolerated.

●Dosing – Standard adult dosing for infliximab is:

•5 mg/kg given via intravenous infusion at weeks 0, 2, and 6, followed by every 8 weeks thereafter

The proposed dose escalation regimen for infliximab is 5 mg/kg given every six weeks rather than every eight weeks [11]. Higher doses (eg, 7.5 to 10 mg/kg) or more frequent doses (eg, four-week dose intervals) have also been utilized in clinical practice. (See 'Dose escalation' above.)

Infliximab can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'TNF inhibitors for most patients' and "Treatment of psoriatic arthritis".)

●Efficacy – Randomized trials support greater efficacy of infliximab compared with placebo and methotrexate [115-118]. Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

•Versus placebo – Infliximab was efficacious for psoriasis in a multicenter randomized trial in 249 patients with severe plaque psoriasis. Compared with placebo, more patients treated with infliximab 3 mg/kg or 5 mg/kg (given intravenously at weeks 0, 2, and 6) achieved PASI 75 at week 10 (6 percent versus 72 and 88 percent, respectively) [116]. The duration of response appeared to be longer with the higher dose. More patients treated with infliximab had serious adverse events (12 versus 0), including four cases that the authors felt were reasonably related to treatment: squamous cell carcinoma, cholecystitis, diverticulitis, and pyelonephritis with sepsis.

•Versus other therapies – The efficacy of infliximab (at 5 mg/kg given at weeks 0, 2, 6, 14, and 22) was compared with methotrexate (at 15 to 20 mg per week) in a 26-week open-label randomized trial in patients with moderate to severe psoriasis (RESTORE1 trial) [118]. At week 16, patients who did not achieve at least 50 percent improvement were able to switch to the alternative therapy. The trial found that patients treated with infliximab (n = 653) exhibited greater improvement (78 versus 42 percent achieved PASI 75 by week 16) and were much less likely than patients in the methotrexate group (n = 215) to require switching to the alternative therapy (1 versus 29 percent) [118]. In addition, patients who were transitioned from methotrexate to infliximab fared better than those who switched to methotrexate from infliximab; 73 versus 11 percent achieved PASI 75.

Other biologic therapy — Itolizumab, a monoclonal antibody against CD6, is a biologic agent that is available for the treatment of psoriasis in India. Itolizumab is not available in the United States.

The findings of a phase 3 trial support the superiority of itolizumab compared with placebo for the treatment of moderate to severe plaque psoriasis [119]. However, response rates in the phase 3 trial were lower than those reported in phase 3 trials of infliximab, adalimumab, and ustekinumab therapy [90,91,117,120]. The efficacy of itolizumab has not been directly compared with other biologic agents.

Nonbiologic therapies — The major nonbiologic systemic therapies for chronic plaque psoriasis include apremilast, deucravacitinib, acitretin, cyclosporine, and methotrexate (table 1B).

Acitretin — Systemic retinoids are derivatives of vitamin A. Acitretin is the retinoid of choice for chronic plaque psoriasis.

Acitretin is not effective for psoriatic arthritis.

●Administration – The usual adult dose range of acitretin is:

•25 mg every other day to 50 mg taken orally daily. When acitretin is the primary treatment, we often treat adults with doses of 25 to 50 mg per day. However, in our experience, cutaneous adverse effects (eg, dry skin, chapped lips) often limit tolerance of the 50 mg dose. Lower doses can be sufficient when acitretin is used to augment the response to phototherapy.

The onset of effect is relatively slow; the full benefit of acitretin may not be evident for three to six months [121]. If there is no response to acitretin within three months, treatment is typically changed (switching to or adding another agent).

Acitretin can be used in combination with ultraviolet B (UVB) or psoralen plus ultraviolet A (PUVA) therapy to achieve higher response rates with less ultraviolet (UV) exposure [122-124]. When adding acitretin to an ongoing phototherapy regimen, we typically reduce the phototherapy dose (usually by 30 to 50 percent) to avoid phototoxicity. Acitretin makes both normal skin and psoriasis plaques more sensitive to UV light.

●Precautions – Monitoring for hypertriglyceridemia and hepatotoxicity is indicated for oral retinoid therapy; we typically obtain laboratory studies four weeks after initiating treatment then every six months. Common side effects include cheilitis and alopecia. Acitretin is teratogenic; use is generally reserved for patients who cannot become pregnant. Pregnancy is contraindicated for three years after discontinuing the drug [125].

●Efficacy – Although available data support efficacy of acitretin, high-quality trials assessing acitretin monotherapy are lacking [126,127]. One randomized trial that compared acitretin therapy (n = 127) with etretinate therapy (n = 41) in patients with severe psoriasis found 76 and 71 percent improvement in the PASI score at week 12, respectively [126]. Patients were treated with 40 mg per day for four weeks, followed by dose adjustments. Etretinate is an older oral retinoid that is not available in the United States due to a longer period of potential teratogenicity.

Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

Apremilast — Oral apremilast is a phosphodiesterase 4 inhibitor. Phosphodiesterase 4 inhibition reduces production of multiple cytokines involved in the pathogenesis of psoriasis.

Apremilast can also be effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'Apremilast'.)

●Administration – Apremilast is associated with a short-term risk of diarrhea, especially when treatment is started, occurring in roughly 15 to 20 percent of patients. Tolerability of apremilast is improved by slowly ramping up the dose when treatment is initiated. The standard dose titration schedule for adults is:

•Day 1 – 10 mg in morning

•Day 2 – 10 mg in morning and 10 mg in evening

•Day 3 – 10 mg in morning and 20 mg in evening

•Day 4 – 20 mg in morning and 20 mg in evening

•Day 5 – 20 mg in morning and 30 mg in evening

•Day 6 and thereafter – 30 mg twice daily

In adult patients with severe renal impairment, the recommended final dose is 30 mg once daily. At the start of therapy, only the morning dose of the above titration schedule is given.

If there is no sign of response to apremilast within three to four months, we typically switch to a different treatment.

●Precautions – Examples of side effects of apremilast include diarrhea, nausea, upper respiratory infection, headache, drug interactions, and weight loss. Advising patients, their caregivers, and families to be alert for worsening depression, suicidal thoughts, or other mood changes during treatment is also prudent based upon the possibility of a slight increase in risk for depression [128].

Hypersensitivity reactions, such as angioedema and anaphylaxis, have rarely been reported during postmarketing surveillance [129].

●Efficacy – While apremilast represents an alternative systemic agent for the treatment of psoriasis, reported treatment success rates with apremilast are lower than those reported for biologic agents [130].

•Two 16-week multicenter randomized trials in which 1257 adults with moderate to severe psoriasis were randomly assigned to receive 30 mg of apremilast twice daily or placebo supported the efficacy of apremilast for moderate to severe plaque psoriasis [128]. In the first trial, 33 percent of 562 patients treated with apremilast achieved PASI 75 compared with only 5 percent of 282 patients in the placebo group. Results of the second trial were similar; 29 percent of 274 adults treated with apremilast achieved PASI 75 compared with 6 percent of 137 patients in the placebo group.

Randomized trial data also support apremilast therapy for patients with mild to moderate psoriasis.

•In the ADVANCE trial, 595 adults with mild to moderate chronic plaque psoriasis that could not be controlled with one or more topical therapies were randomly assigned to either apremilast (at 30 mg twice daily) or placebo [131]. At week 16, 22 percent of patients in the apremilast group achieved the primary endpoint (a static Physician Global Assessment score of 0 or 1 [clear or almost clear skin] and at least a two-point reduction from baseline) compared with only 4 percent of patients in the placebo group. Moreover, a higher proportion of patients achieved PASI 75 at week 16 in the apremilast group than in the placebo group (33 versus 7 percent, respectively).

Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

Cyclosporine — Cyclosporine is an immunosuppressive drug that induces T cell suppression. Cyclosporine is effective in patients with severe psoriasis [132,133]. Rapid onset of effect is the major advantage of cyclosporine therapy. However, because of drug safety concerns, cyclosporine is generally reserved for short-term therapy while awaiting access to other therapies or the onset of effect of slower-acting therapies.

Cyclosporine is not indicated for psoriatic arthritis.

●Administration – Usual adult doses for cyclosporine vary based on the formulation prescribed. A dose of 2.5 to 5 mg/kg per day is appropriate for modified cyclosporine (a microemulsion formulation). Modified cyclosporine is more steadily absorbed than nonmodified formulations. (See "Pharmacology of calcineurin inhibitors", section on 'Formulations'.)

Improvement is generally observed within four weeks.

●Precautions – Contraindications to cyclosporine therapy include prior PUVA treatment, abnormal renal function, uncontrolled hypertension, malignancy, and hypersensitivity to cyclosporine [121]. Caution is indicated in the setting of major infections or poorly controlled diabetes. Cyclosporine also has multiple drug interactions.

The major adverse effects of cyclosporine include nephrotoxicity, hypertension, neurotoxicity, metabolic abnormalities, infections, and risk for malignancy. Patients treated with cyclosporine require close blood pressure and laboratory monitoring (eg, complete blood count, liver function tests, lipids, magnesium, uric acid, potassium) for adverse effects. The need for pregnancy and tuberculosis screening should be assessed prior to treatment [121]. Live vaccinations should be avoided during cyclosporine treatment. (See "Pharmacology of calcineurin inhibitors", section on 'Side effects' and "Cyclosporine and tacrolimus nephrotoxicity".)

●Efficacy – The use of cyclosporine in psoriasis is based upon multiple studies supporting its status as a highly and rapidly effective treatment [134-137]. In a placebo-controlled randomized trial, after eight weeks of treatment with 3, 5, or 7.5 mg/kg of cyclosporine per day, 36, 65, and 80 percent of patients, respectively, were rated as clear or almost clear of psoriasis [135]. All three regimens were superior to placebo, and patients who received the 5 mg dose were least likely to require dose alterations due to side effects or lack of efficacy.

A few randomized trials have compared the efficacy of cyclosporine and methotrexate, utilizing varying treatment regimens and providing different results. Although a 16-week randomized trial in 88 patients failed to find a significant difference in the effects of cyclosporine (at 3 to 5 mg/kg per day) and methotrexate (at 15 to 22.5 mg per week) on moderate to severe plaque psoriasis [138], a subsequent 12-week randomized trial of 84 patients with moderate to severe plaque psoriasis found greater efficacy with cyclosporine (at 3 to 5 mg/kg per day) over methotrexate (at 7.5 to 15 mg per week) [139]. A smaller trial of patients with severe psoriasis found superior efficacy of methotrexate over cyclosporine (at 3 to 4 mg/kg per day) but utilized much higher doses of methotrexate than are typically prescribed in clinical practice (at 0.5 mg/kg per week) [140].

Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

Deucravacitinib — Deucravacitinib is an oral selective inhibitor of tyrosine kinase 2 (TYK2), a kinase that mediates signaling of cytokines involved in the pathogenesis of psoriasis, such as IL-23.

Efficacy of deucravacitinib in psoriatic arthritis appears promising and is under investigation. (See "Treatment of peripheral psoriatic arthritis".)

●Administration – Standard adult dosing for deucravacitinib is [141]:

•6 mg taken orally once daily

If there is no sign of response within three months, we typically switch therapies.

●Precautions – Deucravacitinib is generally well tolerated but may increase risk for viral infections (including herpes virus reactivation), acne, and folliculitis. Liver function test abnormalities, elevation in serum triglycerides, and malignancy have been reported, but rates were similar to the placebo and apremilast comparator groups in clinical trials [142,143]. Rhabdomyolysis has also been rarely reported [144].

Routine laboratory monitoring includes periodic assessment of serum lipids. Periodic evaluation of liver enzymes is indicated for patients with known or suspected liver disease. Patients should be screened for tuberculosis prior to treatment. Live vaccines should be avoided during deucravacitinib treatment.

●Efficacy – Two 52-week phase 3 trials (POETYK PSO-1 and POETYK PSO-2) support efficacy of deucravacitinib [142,143].

In POETYK PSO-1 (n = 666) and POETYK PSO-2 (n = 1020), adults with moderate to severe plaque psoriasis were randomly assigned (in a 2:1:1 ratio) to deucravacitinib (at 6 mg once daily), placebo, or apremilast (at 30 mg twice daily after completion of a five-day dose titration). In both trials, patients in the deucravacitinib groups were more likely to achieve PASI 75 at week 16 than patients in the placebo or apremilast groups. In POETYK PSO-1, week 16 PASI 75 rates in the deucravacitinib, placebo, and apremilast groups were 58, 13, and 35 percent, respectively [142]. In POETYK PSO-2, this endpoint was achieved by 53, 9, and 40 percent of patients, respectively [143]. Sustained efficacy was also demonstrated through 52 weeks among patients who received deucravacitinib continuously.

Overall rates of adverse events were similar among the three treatment groups in both trials, with nasopharyngitis and upper respiratory tract infection the most common adverse effects in patients treated with deucravacitinib. Serious adverse events were infrequent. In POETYK PSO-1, pericarditis and cholecystitis were the only severe adverse effects that occurred in more than one patient, with each occurring in two patients treated with deucravacitinib. In POETYK PSO-2, rates of herpes zoster, serious infections, acne, and folliculitis were slightly higher in the deucravacitinib group compared with the other groups.

Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

Methotrexate — Methotrexate is a folic acid antagonist. Although efficacy of methotrexate was originally thought to result from antiproliferative effects of methotrexate on deoxyribonucleic acid (DNA) synthesis in epidermal cells, subsequent evidence supported immunosuppressive effects on activated T cells as the major modes of action [145]. (See "Treatment of peripheral psoriatic arthritis", section on 'Methotrexate'.)

Methotrexate is also effective for psoriatic arthritis. (See "Treatment of peripheral psoriatic arthritis", section on 'Methotrexate'.)

●Administration

•Dose regimens – Methotrexate is usually administered in an intermittent low-dose regimen such as once weekly (not daily) dosing. Administration can be oral, subcutaneous, or intramuscular. In patients with chronic plaque psoriasis, methotrexate is usually given orally or, less commonly, subcutaneously.

The usual adult dose range is between 7.5 and 25 mg per week, although our experience suggests that most patients respond to doses less than 25 mg per week. Assessment of the efficacy response to a particular dose of methotrexate usually requires at least one month of treatment [121].

Treatment is usually started at 10 to 15 mg weekly. Alternatively, a more cautious approach can be taken, particularly for patients at increased risk for hematologic toxicity (eg, older patients and other patients with decreased renal function). With this approach, a single test dose of 5 mg can be followed by a complete blood count obtained one week later. If tolerated, the dose is then titrated upward (eg, by 2.5 to 5 mg per week) until a therapeutic dose is reached while patients are closely monitored for tolerance and toxicity.

Subcutaneous methotrexate may be helpful when doses higher than 15 mg/week are required, as hepatic metabolism may limit the bioavailability of higher oral methotrexate doses. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Absorption and route of administration'.)

If there is no sign of response within three months, we typically stop treatment. Signs of improved response after dose increases usually are not evident until at least one month after the dose increase [121].

•Coadministration of folic acid – Folic acid supplementation can be given during methotrexate therapy, as it may reduce risk for some of the common side effects seen with low-dose methotrexate [146]. Folate does not appear to protect against pulmonary toxicity, and it is uncertain whether it protects against hepatic toxicity. Dose regimens vary. A common regimen is 1 mg given five to seven days per week. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Folic acid supplementation'.)

●Precautions – The major adverse effects of methotrexate include hepatotoxicity, pulmonary toxicity, and bone marrow suppression. Methotrexate is also an abortifacient and teratogenic. Concomitant treatment with certain drugs (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], certain antibiotics, etc) can increase risk for methotrexate toxicity. (See "Major adverse effects of low-dose methotrexate".)

Methotrexate has multiple contraindications [121]. Absolute contraindications include pregnancy, nursing, alcoholism, alcoholic liver disease or other chronic liver disease, immunodeficiency syndromes, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia, or hypersensitivity to methotrexate. Relative contraindications include liver and renal function abnormalities and active infection. (See "Methotrexate: Drug information".)

For patients with one or more risk factors for hepatotoxicity from methotrexate, use of a different systemic drug should be considered. Risk factors for hepatotoxicity from methotrexate include [121]:

•History of more than moderate alcohol consumption

•Persistent abnormal liver function test findings

•History of liver disease, including chronic hepatitis B or C

•Family history of inherited liver disease (eg, hemochromatosis)

•Diabetes mellitus

•Obesity

•History of exposure to hepatotoxic drugs or chemicals

•Hyperlipidemia

Monitoring for bone marrow suppression and hepatotoxicity are necessary during therapy. Our routine laboratory monitoring generally consists of a complete blood count and liver function tests obtained at baseline, every week to every few weeks while increasing the dose, and every three to six months once a stable dose is achieved.

Because methotrexate is cleared by the kidney, close monitoring (or use of a different agent) is indicated for patients with poor renal function or risk factors for worsening renal function.

Screening for pregnancy, tuberculosis, and hepatitis B and C are also indicated prior to treatment. Administration of live vaccines is not advised during methotrexate treatment.

Previously, the American Academy of Dermatology and the National Psoriasis Foundation advised obtaining liver function tests every one to three months as well as consideration of a liver biopsy after a cumulative methotrexate dose of 3.5 to 4 g in the absence of risk factors for hepatotoxicity and after every 1 to 1.5 g in the presence of risk factors for hepatotoxicity [134,147]. The 2020 American Academy of Dermatology and National Psoriasis Foundation joint guidelines for the management of psoriasis with nonbiologic therapies support less frequent blood liver function tests and incorporate use of newer noninvasive monitoring techniques, including serologic panels of markers of fibrosis and transient elastography [121]. (See "Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations" and "Noninvasive assessment of hepatic fibrosis: Ultrasound-based elastography".)

●Efficacy – Methotrexate is effective for psoriasis but appears less effective than many biologic agents and deucravacitinib. (See 'Relative efficacy' above and 'Biologic agents' above.)

In one trial, 271 patients with moderate to severe plaque psoriasis were randomized to receive oral methotrexate (at 7.5 to 25 mg per week), adalimumab (at 40 mg every other week), or placebo [104]. After 16 weeks, the proportion of patients achieving PASI 75 with methotrexate was more than that with placebo but less than with adalimumab (36, 19, and 80 percent, respectively).

A placebo-controlled randomized trial evaluating subcutaneous methotrexate (at 17.5 to 22.5 mg per week) in patients with moderate to severe plaque psoriasis found a similar efficacy rate. After 16 weeks, 37 of 91 patients (41 percent) in the methotrexate group achieved PASI 75 compared with 3 of 29 patients (10 percent) in the placebo group [148].

Other systemic therapies

Fumaric acid esters — Fumaric acid esters (fumarates) have been used to treat psoriasis in Northern Europe [149]. Fumaric acid esters are not used for the treatment of psoriasis in the United States.

A systematic review of randomized trials found evidence to support superior efficacy of fumaric acid esters compared with placebo for psoriasis; however, the quality of the evidence was low overall [2]. In a randomized trial of 60 patients with moderate to severe psoriasis, reductions in disease severity after treatment with fumaric acid esters were similar to those observed with methotrexate therapy [150]. In other randomized trials, biologic agents such as risankizumab, guselkumab, ixekizumab, secukinumab, and brodalumab have demonstrated greater efficacy than fumaric acid esters [77,151-154]. Additional evidence on relative efficacy is reviewed separately. (See 'Relative efficacy' above.)

Lymphopenia is an occasional side effect of treatment with fumaric acid esters. In 2013, two cases of progressive multifocal leukoencephalopathy (PML) were reported in patients who continued to receive long-term fumaric acid ester therapy despite the development of severe lymphopenia [155,156]. These patients did not have other known causes of immunodeficiency. PML in the setting of fumaric acid therapy for psoriasis has also been reported in patients without severe lymphocytopenia [157,158].

Oral JAK inhibitors — Oral Janus kinase (JAK) inhibitors can improve psoriatic arthritis and psoriasis but are not routinely used for psoriasis alone because safety concerns are greater than with biologic treatments. In a 2023 systematic review and meta-analysis that included 11 randomized trials that assessed the response of moderate to severe psoriasis to an oral JAK inhibitor (tofacitinib [six trials], peficitinib, solcitinib, baricitinib, abrocitinib, or deucravacitinib), all drugs were more effective than placebo [159]. In addition, trials assessing the efficacy of upadacitinib for psoriatic arthritis have shown concomitant improvement in psoriasis [160,161]. (See "Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders", section on 'Adverse effects'.)

Precautions and adverse effects of JAK inhibitors are reviewed in detail separately. (See "Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders".)

Other therapies — Rarely, other systemic agents are used in select cases of chronic plaque psoriasis [133]. These drugs include hydroxyurea, thioguanine, and azathioprine, which have a place in the treatment of psoriasis when other systemic modalities cannot be used, and tacrolimus, which is similar to cyclosporine.

Limited data suggest benefit of oral roflumilast, a phosphodiesterase 4 inhibitor, for chronic plaque psoriasis [162,163]. Abatacept, a biologic drug used for psoriatic arthritis, appears to have modest benefit in psoriasis [164].

Tonsillectomy — An association between psoriasis (especially guttate psoriasis) and streptococcal infection has contributed to investigations of the role of tonsillectomy for the treatment of psoriasis. (See "Guttate psoriasis", section on 'Pathogenesis'.)

A systematic review that evaluated data on tonsillectomy for guttate or plaque psoriasis from controlled and observational studies (including case reports and case series) found that the majority of reported patients experienced improvement in psoriasis after tonsillectomy (290 of 410 patients) [165]. Lengthening of psoriasis remissions and improvement in response to treatments for psoriasis were also documented. However, data were insufficient to recommend the routine use of tonsillectomy for psoriasis because most of the patient data were derived from case reports and case series and publication bias may have contributed to the favorable results. Further study is necessary to confirm the effects of tonsillectomy on psoriasis.

Given the limitations of the available data, tonsillectomy should be reserved for select patients with recalcitrant psoriasis that clearly exhibits exacerbations related to episodes of tonsillitis [165]. Tonsillectomy is not a benign procedure; infection, hemorrhage, laryngospasm, bronchospasm, temporomandibular joint dysfunction, vocal changes, and rarely airway compromise are potential adverse effects [165]. Relapse after tonsillectomy is also possible.

Additional study is necessary to determine whether HLA-Cw6*0602 carriage is a reliable predictor of the response to tonsillectomy [166].

Vaccination during therapy — Because systemic immunomodulatory therapy may impact the safety or efficacy of some vaccines, consideration of vaccination status is prudent prior to beginning systemic psoriasis therapy. In addition, treatment interruption is sometimes indicated for vaccination during systemic psoriasis therapy. (See "Immunizations in autoimmune inflammatory rheumatic disease in adults", section on 'Live vaccines'.)

●A Delphi consensus from the medical board of the National Psoriasis Foundation provides guidance on the approach to vaccination for adults receiving systemic psoriasis therapies [167]. The drugs reviewed in the study included deucravacitinib; apremilast; methotrexate; cyclosporine; acitretin; tofacitinib; abatacept; and biologic TNF, IL-23, and IL-17 inhibitors. The consensus supported:

•Continuation of most systemic therapies without interruption or dose modification for nonlive vaccines, with the exception of methotrexate. For methotrexate, therapy should be delayed for two weeks after vaccination.

•Preferred administration of live vaccines prior to starting systemic therapy when feasible and the general avoidance of live vaccination during treatment with JAK inhibitors, deucravacitinib, methotrexate, cyclosporine, and biologic drugs. When the benefits of a live vaccine during systemic therapy outweigh the risks, most treatments should be stopped before vaccination (with the timing of cessation based on the drug) and for two to four weeks after vaccination. Apremilast and acitretin can be continued without modification. Cyclosporine may only require stopping treatment for two to four weeks after vaccination.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriasis".)

SUMMARY AND RECOMMENDATIONS

●Overview – Chronic plaque psoriasis is a common inflammatory disorder characterized by inflamed, well-demarcated plaques on the skin (picture 1A-H). Treatments for chronic plaque psoriasis include topical therapies, phototherapy, and systemic therapies (table 1A-B and algorithm 1). Topical therapy is often used as an adjunct to phototherapy and systemic therapy. (See 'Introduction' above.)

●Identifying disease appropriate for phototherapy or systemic therapy – Phototherapy and systemic therapy are typically selected when topical therapy is likely to be impractical or insufficiently effective. An extent of skin disease that would make topical therapy challenging (eg, involving more than 3 to 5 percent of the total body surface area) is a common indication. Other considerations include the location(s) of skin involvement, complications, comorbidities, treatment availability, and patient ability and preferences. (See 'Identifying disease appropriate for phototherapy or systemic therapy' above and "Chronic plaque psoriasis in adults: Overview of management", section on 'Selecting the primary mode of therapy'.)

●Phototherapy versus systemic therapy – Selection between phototherapy and systemic therapy is based on identifying the most appropriate, feasible, and acceptable mode of therapy. Favorable features of phototherapy include a high level of safety and relatively low cost. However, factors limiting the practicality, desirability, or appropriateness of phototherapy are common, and most patients proceed to systemic therapy. (See 'Phototherapy versus systemic therapy' above.)

●Selection of systemic therapy – Systemic therapies for chronic plaque psoriasis include biologic and nonbiologic therapies (table 1B). Patient comorbidities, drug accessibility, patient preference about treatment goals, risks, and the mode and frequency of drug administration influence treatment selection. (See 'Systemic therapies' above and 'Selecting a systemic agent' above.)

•General approach – For adults who require systemic therapy for chronic plaque psoriasis, we suggest treatment with risankizumab, guselkumab, or ixekizumab rather than other systemic therapies (Grade 2C). Data support high efficacy and relatively favorable safety profiles for these biologic therapies. (See 'Relative efficacy' above.)

The clinical scenario impacts selection among these treatments. We prefer risankizumab or guselkumab (both interleukin [IL] 23 inhibitors) for patients with inflammatory bowel disease due to a potential association between IL-17 inhibition and exacerbation of inflammatory bowel disease. Because of its rapid onset of effect, we tend to select ixekizumab (an IL-17 inhibitor) when rapid improvement is needed.

Bimekizumab and infliximab are alternative, highly effective biologic therapies. However, we tend to use other biologic agents for initial treatment because of the relatively frequent occurrence of Candida infection with bimekizumab and the broader adverse effect profile of infliximab. Other reasonable alternatives include tildrakizumab, ustekinumab, secukinumab, and brodalumab. (See 'Our general approach' above.)

For patients who prefer or require oral therapy, apremilast, deucravacitinib, and methotrexate are appropriate alternatives. (See 'Patients who prefer oral therapy' above.)

•Patients with psoriatic arthritis – The treatment of patients with both psoriatic arthritis and chronic plaque psoriasis requires careful consideration of the approach to therapy. Selection of a systemic agent with overlapping benefit is often preferred. The specific manifestations of psoriatic arthritis influence the approach to treatment. (See 'Patients with psoriatic arthritis' above.)

•Other factors – Other factors, such as pregnancy status and treatment cost, may also impact the treatment approach. (See 'Other factors influencing treatment selection' above and "Management of psoriasis in pregnancy".)

●Selection of phototherapy – For adults with chronic plaque psoriasis who will receive phototherapy as the primary mode of treatment, we suggest narrowband ultraviolet B (NBUVB) phototherapy rather than psoralen plus ultraviolet A (PUVA) photochemotherapy or broadband ultraviolet B (UVB) phototherapy (Grade 2C).

NBUVB phototherapy is easier to administer than PUVA photochemotherapy, is more widely available, and has a more favorable adverse effect profile. Limited data suggest that NBUVB is more effective than broadband UVB. (See 'Phototherapy' above.)