Version July 2025
INTRODUCTION —
Traditionally, dermatomyositis (DM) and polymyositis (PM) are two classic forms of idiopathic inflammatory myopathies (IIM); however, the term "polymyositis" as a distinct myositis subclassification is falling out of favor, given that what was previously labeled as "polymyositis" is now better classified as either antisynthetase syndrome, immune-mediated necrotizing myopathy, myositis as part of overlap syndromes (including the antisynthetase syndrome in the absence of rash), or unrecognized inclusion body myositis (IBM). So patients who have true PM, that cannot be otherwise better classified, are now believed to be relatively rare.
Many patients with these diagnoses respond to initial therapy with methotrexate or azathioprine, and some achieve sustained disease remission either off all therapy or with low-dose maintenance therapy.
However, some patients will develop recurrent disease (ie, disease flare or relapse) after achieving disease control. Other patients may have resistant disease, which does not respond entirely to initial treatment with methotrexate or azathioprine.
Approaches to the treatment of recurrent and resistant muscle disease in adults with IIM will be reviewed here. This topic consists of practice suggestions based almost entirely on the expert experience of the authors. The initial therapy of these disorders in adults, the management of the cutaneous and pulmonary manifestations of myositis, and issues related to myositis in children are discussed separately.
●(See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Initial therapy'.)
●(See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Treatment'.)
●(See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment".)
MANAGEMENT OF RECURRENT MUSCLE DISEASE —
Recurrent disease commonly occurs in one of the following scenarios:
Recurrence following a drug-free remission — If relapse occurs in a patient not currently treated with immunosuppression, we use the same strategies employed for the initial treatment of dermatomyositis (DM) or polymyositis (PM). (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Initial therapy'.)
In general, this involves restarting the last effective immunosuppressive regimen along with glucocorticoids. The dose of glucocorticoids is determined by the severity of the recurrence. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Rationale for glucorticoids'.)
Recurrence while tapering prednisone — If relapse occurs in a patient while tapering prednisone, we increase the prednisone to the last effective dose.
We generally maintain that dose of prednisone for at least one month prior to attempting to taper prednisone again, at a rate no faster than the previous taper, to 5 mg daily.
We continue prednisone 5 mg daily for a year or longer prior to attempting to discontinue prednisone entirely.
Strategies used to taper glucocorticoids in patients with DM and PM are discussed elsewhere. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Glucocorticoid tapering'.)
Recurrence while taking immunosuppression — If relapse occurs in a patient already using immunosuppression, the dose of the immunosuppressive agent should be increased to the maximum tolerated dose.
If the patient is already taking the maximum tolerated dose, that patient should be treated as having resistant disease. (See 'Initial management of resistant muscle disease' below.)
INITIAL MANAGEMENT OF RESISTANT MUSCLE DISEASE —
Dermatomyositis (DM) and polymyositis (PM) often respond to initial treatment with glucocorticoids and either methotrexate or azathioprine. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Treatment approach'.)
Patients are said to have resistant DM or PM if they fail to respond to initial treatment with methotrexate or azathioprine for at least three months.
Selection of agents (including glucocorticoid dose) depends on the severity of the muscle disease. We avoid using agents that were previously ineffective at preventing disease relapse.
Pretreatment considerations — In some patients, DM or PM does not respond entirely to initial treatment with methotrexate or azathioprine, and other therapies must be considered.
Prior to initiating pharmacotherapy for resistant disease, we consider the following questions:
●Is the disease truly treatment resistant? – A patient should not be classified as having resistant disease without having been treated for at least three months. Typically, improvements in strength are observed only after four to six weeks of treatment, and normalization of creatine kinase (CK) may take even longer.
A persistent, mild elevation of muscle enzymes (eg, CK up to 750 units/L) should not be interpreted as evidence of resistant muscle disease if the muscle strength has normalized.
●Is the diagnosis of a treatment-responsive inflammatory myopathy correct? – Before initiating alternative therapies in patients with resistant disease, consideration should be given to an alternative diagnosis, particularly inclusion body myositis (IBM):
•Weakness of the quadriceps greater than weakness in the hip flexors, in combination with wrist and finger flexion weakness, is highly suggestive of IBM. (See "Clinical manifestations and diagnosis of sporadic inclusion body myositis", section on 'Determine distribution of weakness'.).
•If the initial biopsy is equivocal, a repeat biopsy may be necessary to confirm the diagnosis [1]. (See "Clinical manifestations and diagnosis of sporadic inclusion body myositis", section on 'Muscle biopsy findings'.)
Other myopathies may also be initially misdiagnosed as an idiopathic inflammatory myopathy (IIM). (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Differential diagnosis'.)
●Is muscle disease the most problematic manifestation? – In patients for whom the extramuscular manifestations of IIM (eg, pulmonary, cutaneous) are more severe than the muscular symptoms, treatment selection should be guided by these other disease manifestations. (See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment" and "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Selection of systemic therapy'.)
Categorizing disease severity
●Severe muscle disease – Severe muscle disease refers to patients with IIM who have evidence of active muscle inflammation (eg, muscle enzyme elevation, magnetic resonance imaging [MRI] demonstrating muscle edema) associated with dysphagia, diaphragmatic weakness, or weakness preventing self-care (eg, bathing, dressing, eating). (See 'Treatment of severe resistant muscle disease' below.)
●Mild to moderate muscle disease – Mild to moderate muscle disease refers to patients with IIM who have clinical weakness and evidence of active muscle inflammation but do not have dysphagia, diaphragmatic weakness, or weakness preventing self-care. (See 'Treatment of mild to moderate muscle disease' below.)
Treatment of severe resistant muscle disease — We generally treat severe muscle disease with high-dose glucocorticoids and a parenteral immunosuppressive or immunomodulatory agent, started simultaneously.
Glucocorticoids — For patients with severe muscle disease, we suggest initiating therapy with high-dose glucocorticoids. We use intravenous methylprednisolone (1 g daily for three days), followed by prednisone 1 mg/kg daily (to a maximum dose of 80 mg daily).
We continue prednisone at that dose for two to four weeks prior to initiating a glucocorticoid taper. (See 'Subsequent management of resistant muscle disease' below.)
We simultaneously start treatment with an parenteral immunosuppressive or immunomodulatory agent to prevent relapse following glucocorticoid taper. (See 'Plus a parenteral immunosuppressive/immunomodulatory agent' below.)
Plus a parenteral immunosuppressive/immunomodulatory agent — For patients with severe muscle disease, in addition to treatment with glucocorticoids, we suggest intravenous immunoglobulin (IVIG) over cyclophosphamide, rituximab, or other immunosuppressive agents.
We favor IVIG because it is immunomodulatory (rather than immunosuppressive). Additionally, in our experience, IVIG has a faster onset of action than rituximab. However, for patients who have previously failed to respond to IVIG, we recommend treatment with intravenous rituximab.
We consider intravenous cyclophosphamide only in patients with potentially life-threatening manifestations of myositis who have previously failed to respond to both IVIG and rituximab (or have other contraindications for the use of both agents).
Intravenous immunoglobulin (preferred) — We prefer IVIG for the treatment of DM and PM muscle disease resistant to initial therapy. IVIG is immunomodulatory rather than immunosuppressive, has a faster onset of action than rituximab, and is less toxic than cyclophosphamide.
●Administration – IVIG is administered monthly. The total monthly dose is 2 g/kg, which is divided over two to five days. For example, a 75 kg patient could receive 30 g of IVIG daily for five days.
We do not typically administer pooled immunoglobulin subcutaneously. Limited data support administering immunoglobulin through weekly subcutaneous injections. Subcutaneous administration is associated with a lower risk of thromboembolism than IVIG and avoids the need for an indwelling catheter. In a small case series of seven patients with DM or PM, the usual monthly dose was divided into weekly doses given subcutaneously through a programmable pump, and the treatment appeared to be safe and well tolerated [2].
However, we lack substantial experience using subcutaneous immunoglobulin for DM and PM. Furthermore, subcutaneous administration of immunoglobulin requires specialized equipment and training, due to the volume of drug.
●Precautions – Most common adverse reactions (eg, fatigue, abdominal pain, myalgias, headache, chills, flushing, hemolysis, neutropenia, acute kidney injury) resolve spontaneously. However, IVIG is also associated with anaphylaxis, especially with first exposure.
Thromboembolism is an important complication of IVIG. Thromboembolic events may occur during or after IVIG administration.
Although this is not yet standard, the risk of thromboembolism may be mitigated by reducing the rate of IVIG infusion. In one study of patients with DM, reduction of the maximum infusion rate from 0.12 mL/kg/minute to 0.04 mL/kg/minute led to a corresponding decline in thromboembolic events (1.54 per 100 patient-months versus 0.54 per 100 patient-months) [3]. However, larger and longer-term trials are needed to further clarify whether all patients with DM and PM should routinely use slower infusion rates.
The management of other risks associated with IVIG are discussed elsewhere. (See "Intravenous immune globulin: Adverse effects".)
●Rationale – The beneficial effects of IVIG for the treatment of DM have been supported by observational data and randomized trials [3-8]. The data supporting its use for the treatment of patients with PM are more limited [8,9].
The largest randomized trial of IVIG for DM included 95 patients. After 16 weeks of therapy, more patients achieved at least minimal improvement (based on a composite score of disease activity) if they received IVIG compared with placebo (79 versus 44 percent) [3]. After 16 weeks of therapy, more patients treated with IVIG also achieved a moderate or major improvement in the composite disease activity score (68 versus 23 percent).
In the open-label phase of this study, all patients received treatment with IVIG for a total of 40 weeks. The open-label phase demonstrated sustained benefit associated with IVIG treatment but also an increase in treatment-related adverse events, including the frequency of thromboembolic events [3].
Additional information regarding the dosing, administration, and other considerations regarding the use of intravenous immunoglobulin (IVIG) is discussed elsewhere. (See "Overview of intravenous immune globulin (IVIG) therapy".)
Rituximab — We use rituximab for the treatment of DM and PM muscle disease resistant to initial therapy when IVIG is not feasible. Rituximab has a slower onset than IVIG but is safer than cyclophosphamide therapy.
●Administration – Rituximab is administered as 1 g given twice separated by two weeks [10].
However, the optimal dose and administration of rituximab for DM and PM has not been well established. Other dosing regimens have been employed in a randomized trial and several small case series and case reports of patients with DM and PM [10-17].
Some data suggest that lower doses of rituximab may be sufficient. A study of 42 patients with refractory myositis indicated that two 500 mg doses two weeks apart were as effective as two 1 g doses at improving muscle strength, physician global assessment, and patient global assessment, after 6 and 12 months of follow-up [18].
●Precautions – Infections and infusion reactions are the main adverse effects of rituximab. In a randomized clinical trial of rituximab for idiopathic inflammatory myopathy, only one patient withdrew due to an adverse effect, although 26 serious adverse effects attributed to the rituximab were observed, most of which were infections (ie, pneumonia, cellulitis, urosepsis, herpes zoster) [11]. One patient died during the trial from a suspected malignancy and stroke. Infusion reactions were more common with the administration of rituximab compared with placebo (15.4 versus 5.3 percent).
Other complications are similar to those experienced when using rituximab for rheumatoid arthritis, which are discussed elsewhere. (See "Rituximab: Principles of use and adverse effects in rheumatologic disease", section on 'Adverse effects'.)
●Rationale – The Rituximab in Myositis (RIM) trial enrolled 76 patients with adult DM and 76 with PM and 48 patients with juvenile DM, all of whom had disease refractory to glucocorticoids and at least one other immunosuppressive or immunomodulatory agent [11]. Patients were randomly assigned to receive rituximab (750 mg/m2 up to 1 g, administered intravenously once weekly for two weeks) either on weeks 0 and 1 ("early arm") or on weeks 8 and 9 ("late arm"), and they were assigned to receive placebo at the timepoint during which they did not receive rituximab.
Overall, 88 percent of patients receiving rituximab demonstrated a reduction in disease activity and prednisone dose (from 20.8 to 14.4 mg daily). The treatment response was equivalent in the early versus late arms, suggesting that timing of therapy does not impact disease response.
Additional information regarding the dosing, administration, and other issues regarding the use of rituximab is discussed in detail elsewhere. (See "Rituximab: Principles of use and adverse effects in rheumatologic disease".)
Intravenous cyclophosphamide — We reserve cyclophosphamide for patients with potentially life-threatening manifestations of myositis who have previously failed to respond to both IVIG and rituximab (or have other contraindications for the use of both agents).
●Administration – Cyclophosphamide is typically administered at 0.5 to 1 g/m2 intravenous monthly for three to six months. While this approach is common, there are no studies demonstrating the optimal dose, frequency, and duration of cyclophosphamide therapy for DM or PM.
After three to six months of treatment with intravenous cyclophosphamide, patients are generally transitioned to a less toxic oral immunosuppressive agent, generally methotrexate, azathioprine, or mycophenolate mofetil. (See 'Subsequent management of resistant muscle disease' below.)
Cyclophosphamide can be administered orally. However, we avoid using oral cyclophosphamide because of its increased toxicity and lack of data demonstrating increased efficacy compared with intravenous cyclophosphamide for DM or PM.
●Precautions – Cyclophosphamide's utility is limited by its association with numerous complications, including cytopenias, hemorrhagic cystitis, infertility, and malignancy (including bladder cancer).
Mitigation of toxicities associated with cyclophosphamide are discussed elsewhere. (See "Cyclophosphamide in rheumatic diseases: General principles of use and toxicity", section on 'Adverse effects'.)
●Rationale – Most studies of cyclophosphamide examine its use as a treatment for interstitial lung disease associated with DM and PM [19,20]. However, cyclophosphamide has been used more broadly for other manifestations of these diseases, including muscle involvement [21].
For example, a systematic review identified 52 patients with IIM who received treatment with intravenous cyclophosphamide [22]. Treatment with cyclophosphamide for 6 to 12 months led to improvement in muscle strength in 81 percent of patients (42 of 52) and improvement in muscle function in 73 percent (38 of 52).
A more detailed discussion of cyclophosphamide dosing, dose adjustments, and adverse effects is presented separately. (See "Cyclophosphamide in rheumatic diseases: General principles of use and toxicity".)
Treatment of mild to moderate muscle disease — We treat mild to moderate muscle disease with glucocorticoids and an oral or parenteral immunosuppressive or immunomodulatory agent, started simultaneously, as discussed below.
Patients with mild to moderate muscle disease are treated with lower doses of glucocorticoids than those used to treat severe disease.
Oral immunosuppressive agents (such as mycophenolate mofetil) are potential options for patients with mild to moderate muscle disease, in contrast to patients with severe disease. (See 'Mycophenolate mofetil' below.)
Glucocorticoids — For patients with mild to moderate muscle disease, we suggest initiating therapy with prednisone 0.5 mg/kg daily (to a maximum dose of 40 mg daily), but there is no known evidence to substantiate a dose effect of prednisone at this level.
We simultaneously start treatment with an immunosuppressive agent to prevent relapse following glucocorticoid taper.
We continue prednisone at that dose for two to four weeks prior to initiating a glucocorticoid taper. (See 'Subsequent management of resistant muscle disease' below.)
Plus a parenteral or oral immunosuppressive/immunomodulatory agent
Selection of agents — For patients with mild to moderate muscle disease, in addition to treatment with glucocorticoids, we suggest instituting treatment with IVIG over rituximab or other immunosuppressive agents, given the considerations noted above. (See 'Intravenous immunoglobulin (preferred)' above.)
However, for patients who have previously failed to respond to IVIG, we use intravenous rituximab. (See 'Rituximab' above.)
For patients who prefer an oral agent, or have contraindications to both IVIG and rituximab, we use mycophenolate mofetil. (See 'Mycophenolate mofetil' below.)
For patients who have previously failed to respond to mycophenolate mofetil (or for whom mycophenolate mofetil is not feasible), calcineurin inhibitors are a reasonable option. (See 'Calcineurin inhibitors' below.)
We do not use cyclophosphamide for patients with mild to moderate muscle disease, given the substantial toxicity associated with this agent. (See 'Intravenous cyclophosphamide' above.)
Comparative studies among these agents have not been performed. Therefore, choosing among these agents is often guided by comorbidities and by patient, clinician, and payor preferences. We would also avoid agents that were previously ineffective at preventing disease relapse.
We prefer the approach outlined above because of the quality of evidence supporting the use of rituximab and IVIG for the treatment of DM and PM as well as the comparatively limited data supporting the use of oral agents for resistant muscle disease.
Oral agents for resistant muscle disease — We prefer parenteral immunosuppressive or immunomodulatory agents for resistant muscle disease. However, oral agents are a reasonable option for patients with mild to moderate muscle disease who have contraindications to parenteral agents and/or strongly prefer oral agents.
Mycophenolate mofetil — We use mycophenolate mofetil as a second-line agent in patients who have failed to respond to either methotrexate or azathioprine and prefer an oral agent.
Mycophenolate mofetil is administered orally at 1 to 1.5 g twice daily.
Mycophenolate mofetil is less expensive and easier to administer than other agents used to treat patients with resistant disease (ie, IVIG or rituximab). Trials comparing the relative efficacy of these agents for the treatment of refractory myositis are not available.
Mycophenolate mofetil has been used with some success in retrospective series of patients with inflammatory myopathy [23-26]. These case series suggest a role for mycophenolate mofetil in the treatment of resistant myositis:
●A retrospective series included 10 DM patients with a history of refractory disease [24]. After initiation of mycophenolate mofetil, manual muscle testing scores improved in five, and the glucocorticoid dose could be tapered in six. Serious opportunistic infections occurred in 3 of the 10 patients: a Mycobacterium xenopi abscess of the thigh; pulmonary blastomycosis; and Legionella pneumonia (fatal). However, it is likely that the patients' immunosuppressive regimens prior to the use of mycophenolate mofetil contributed to the development of opportunistic infections.
●In a second report, six patients with treatment-resistant myositis (two with DM, three with PM, one with overlap myositis) were treated for a mean of 22 months with mycophenolate mofetil (mean dose 1.6 g daily) [25]. Both muscle strength and serum CK levels improved in all patients, and the mean prednisone dose was tapered from 13.7 to 8.5 mg daily.
Additional information regarding the dosing, administration, and other issues regarding the use of mycophenolate mofetil, and the use of mycophenolate mofetil in patients with DM/PM-associated interstitial lung disease, is discussed in detail separately. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases" and "Interstitial lung disease in dermatomyositis and polymyositis: Treatment", section on 'Mycophenolate mofetil'.)
Calcineurin inhibitors — We use calcineurin inhibitors as a second-line agent in patients who have failed to respond to either methotrexate or azathioprine, prefer an oral agent, and cannot use mycophenolate mofetil (eg, due to cost, patient preference, or previous lack of efficacy).
Data on the use of calcineurin inhibitors, which include cyclosporine and tacrolimus, for DM and PM are limited to retrospective case series and to anecdotal reports. However, there are studies supporting both for the treatment of resistant DM and PM.
We generally select tacrolimus over cyclosporine because tacrolimus has fewer side effects than cyclosporine (eg, hypertension). Also, limited data suggest that tacrolimus may be more efficacious than cyclosporine for the treatment of DM and PM. However, larger studies are required before definitive conclusions are possible.
●Tacrolimus – Tacrolimus may be administered orally at 0.075 mg/kg daily, in two divided doses. The dose may be increased to 0.2 mg/kg daily. However, the optimal dose for this indication is not certain.
In one report, tacrolimus (0.075 mg/kg daily in two divided doses) was effective in a series of eight patients with refractory PM [27]. Strength normalized in 87 percent of patients (seven of eight) and the mean CK declined from 3114 to 87 international units/mL.
In a second series from the same authors (with some overlap), 13 patients with the antisynthetase syndrome (a form of IIM associated with interstitial lung disease) were treated with tacrolimus for a mean duration of 51 months [28]. The following benefits were noted:
•Serum CK levels improved by 75 percent
•Manual testing of muscle strength improved or remained stable in 10 of 13 patients
•The mean prednisone dose was tapered by 67 percent
In other small series of patients with DM or PM associated with interstitial lung disease, tacrolimus led to improvement in lung function among patients who had previously failed to respond to cyclosporine [29,30].
●Cyclosporine – Cyclosporine may be administered orally at 2.5 mg/kg daily in two divided doses. The total daily dose may be increased to a maximum of 4 mg/kg daily. However, the optimal dose for this indication is not certain.
Limited data support the use of cyclosporine both for primary therapy [31,32] and resistant disease, including DM- or PM-associated interstitial lung disease [33,34]. (See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment", section on 'Calcineurin inhibitors'.)
In one report, six patients previously resistant to methotrexate, azathioprine, cyclophosphamide, and/or IVIG underwent treatment with a mean daily cyclosporine dose of 3.5 mg/kg [33]. After a median of six months of treatment with cyclosporine, the mean daily prednisone dose was reduced by 75 percent. All six patients demonstrated improved strength in the shoulder girdle, and four had improved hip flexor strength.
Additional information regarding the dosing, administration, and other issues regarding the use of cyclosporine and tacrolimus (including calcineurin-associated nephrotoxicity) is discussed in detail elsewhere. (See "Pharmacology of calcineurin inhibitors" and "Cyclosporine and tacrolimus nephrotoxicity".)
Other oral agents
●Methotrexate and azathioprine combination therapy – We consider combination methotrexate and azathioprine therapy when mycophenolate mofetil (or other options) are unavailable or ineffective.
The only published study regarding combination treatment is a crossover study in which 30 patients with refractory myositis were randomly assigned to either a combination of weekly oral methotrexate (maximum dose 25 mg) and daily azathioprine (maximum dose 150 mg) or to intravenous methotrexate (500 mg/m2) with leucovorin rescue every two weeks for six months [35]. Twenty-five of the patients had had inadequate responses to previous cytotoxic therapies.
The results were as follows:
•Among the 15 patients initially assigned to oral methotrexate/azathioprine, eight improved with oral therapy, and one improved with intravenous methotrexate during the crossover period.
•Of the 15 patients initially assigned to intravenous methotrexate therapy, three improved with intravenous therapy, and four improved with oral combination therapy during the crossover period.
This study did not have sufficient power to compare the two treatment regimens. However, the data indicate that the combination of oral methotrexate and azathioprine may benefit some patients with refractory disease.
Additional information regarding the dosing, administration, and other issues regarding the use of methotrexate and azathioprine is discussed in detail elsewhere. (See "Use of methotrexate in the treatment of rheumatoid arthritis" and "Major adverse effects of low-dose methotrexate" and "Pharmacology and side effects of azathioprine when used in rheumatic diseases".)
●Janus kinase inhibitors – Janus kinase (JAK) inhibitors may have a role for the treatment of resistant DM or PM. The following reports are representative of the studies supporting JAK inhibitors for the treatment of DM:
•In a study of 10 patients with resistant, skin-predominant DM, treatment with tofacitinib improved muscle disease in all patients (ie, by 40 points on the 100-point Myositis Response Criteria Total Improvement Score) [36].
•A case report describes successful treatment of resistant DM with ruxolitinib, which was only partially responsive to glucocorticoids, azathioprine, IVIG, and mycophenolate mofetil [37]. The patient also had a JAK2 mutation-associated myeloproliferative neoplasm, and it is unclear whether treatment of the neoplasm resulted in improvement of the DM.
•Other reports have indicated that resistant pulmonary and cutaneous manifestations of DM (including calcinosis cutis) may respond to treatment with tofacitinib [38-40].
Additional information regarding the dosing, administration, and other issues regarding the use of JAK inhibitors is discussed in detail elsewhere. (See "Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders".)
●Cosyntropin gel – We rarely use corticotropin injection gel (a form of adrenocorticotropic hormone) for resistant DM or PM. Limited data support its use for patients with resistant disease.
A case series has suggested that cosyntropin gel may be beneficial in patients with exacerbations of DM or PM despite ongoing therapy with other immunosuppressive agents [41].
SUBSEQUENT MANAGEMENT OF RESISTANT MUSCLE DISEASE
Glucocorticoid tapering — We typically start a gradual glucocorticoid taper after two to four weeks of initial therapy. We gradually reduce the glucocorticoid dose over the next 9 to 12 months to the minimum dose required to maintain disease control. Most patients can eventually discontinue prednisone, but some will require chronic low dose prednisone (eg, 7.5 mg or less) to achieve disease control.
The decision to begin tapering glucocorticoids should be based on a combination of the improvement in muscle enzymes and recovery of muscle strength. Ideally, normalization of enzymes and complete recovery of muscle strength should occur before glucocorticoids are tapered. However, prolonged therapy with high-dose steroids may lead to a glucocorticoid-induced myopathy, which can be confused with refractory or recurrent muscle disease in patients with dermatomyositis (DM) or polymyositis (PM). (See "Glucocorticoid-induced myopathy", section on 'Clinical manifestations'.)
Glucocorticoid taper in patients with DM and PM is discussed in detail elsewhere. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Glucocorticoid tapering'.)
Maintaining remission — Most of the immunosuppressive agents discussed in this topic may be continued indefinitely to maintain disease remission, with the following exceptions:
●Rituximab – Rituximab does not result in permanent B-cell depletion. The duration of B-cell depletion is variable but generally lasts at least six months. However, some patients will remain in remission even after B-cell reconstitution.
Therefore, six months after initiating therapy with rituximab, the clinician and patient should decide whether to retreat with rituximab, initiate an oral immunosuppressive agent (eg, azathioprine, methotrexate, mycophenolate mofetil), or continue to observe without additional immunosuppression.
These issues are similar to the issues raised by the use of rituximab for rheumatoid arthritis, which are discussed elsewhere. (See 'Rituximab' above and "Rituximab: Principles of use and adverse effects in rheumatologic disease", section on 'Subsequent doses'.)
●Cyclophosphamide – Cyclophosphamide may be used for a maximum of six months, after which it should be replaced with an oral immunosuppressant. Typically, patients will transition to azathioprine, methotrexate, or mycophenolate mofetil. Because of lack of comparative studies, the choice of agent will generally depend on the patient's comorbid conditions, prior response to these agents, and the preferences of the clinician, patient, and payor. These issues are discussed elsewhere. (See 'Intravenous cyclophosphamide' above and "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Rationale and selection of DMARD'.)
Other considerations regarding the duration of therapy in patients with DM or PM are discussed elsewhere. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Duration of DMARD therapy'.)
Assessing disease response — The response to treatment should be assessed three months after the start of therapy for improvement in both muscle enzymes and strength. Failure to observe clinical or laboratory improvement after three to four months of therapy should prompt consideration of alternate treatment strategies. Patients who have failed to respond to multiple therapies should be reevaluated for alternate diagnoses that may mimic DM or PM (eg, adult-onset muscular dystrophies, inclusion body myositis [IBM]). (See 'Pretreatment considerations' above.)
Assessment of disease response in patients with DM and PM is discussed in detail elsewhere. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Assessing treatment response'.)
OTHER MANAGEMENT RECOMMENDATIONS —
Nonpharmacologic management, glucocorticoid complications, and considerations regarding pregnancy and lactation are discussed elsewhere:
●(See "Major adverse effects of systemic glucocorticoids".)
●(See "Safety of rheumatic disease medication use during pregnancy and lactation".)
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: Dermatomyositis and polymyositis".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Dermatomyositis (The Basics)" and "Patient education: Polymyositis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Recurrent dermatomyositis (DM) or polymyositis (PM) – Disease flare of PM or DM often occurs after tapering (or discontinuing) the drugs used to achieve remission.
Patients will generally respond to reinstitution of the last effective treatment regimen. Patients who experience disease flare while immunosuppressed should increase their immunosuppressive agent to the maximum tolerated dose, or they should be managed as having resistant disease. (See 'Management of recurrent muscle disease' above.)
●Pretreatment considerations
•Before initiating therapies for resistant disease, consideration should be given to an alternative diagnosis, particularly inclusion body myositis (IBM), which can mimic many of the characteristics of PM.
•In patients for whom the extramuscular manifestations of PM or DM are more severe than the muscular symptoms, treatment selection should be guided by these other disease manifestations. (See 'Pretreatment considerations' above.)
●Initial treatment of severe resistant muscle disease – Severe muscle disease refers to patients with DM or PM who have evidence of active muscle inflammation associated with dysphagia, diaphragmatic weakness, or weakness preventing self-care.
For patients with severe muscle disease, we suggest initiating combination therapy with high-dose glucocorticoids along with intravenous immunoglobulin (IVIG) (Grade 2C). We use intravenous methylprednisolone (1 g daily for three days) followed by prednisone 1 mg/kg daily (to a maximum dose of 80 mg daily). The dose of IVIG is 2 g/kg monthly; each monthly dose should be divided among two to five daily infusions.
For patients who are unable to use IVIG, we use rituximab. We use cyclophosphamide only for patients with potentially life-threatening manifestations of DM or PM who have previously failed both IVIG and rituximab, or for whom these agents are not otherwise feasible. (See 'Categorizing disease severity' above and 'Treatment of severe resistant muscle disease' above.)
●Initial treatment of mild/moderate resistant muscle disease – Mild to moderate muscle disease refers to patients with DM or PM who have clinical weakness and evidence of active muscle inflammation but do not have dysphagia, diaphragmatic weakness, or weakness preventing self-care.
For patients with mild to moderate muscle disease, we suggest initiating combination therapy with prednisone and IVIG (Grade 2C). We use prednisone 0.5 mg/kg daily (to a maximum dose of 40 mg daily). The dose of IVIG is 2 g/kg monthly; each monthly dose should be divided among two to five daily infusions.
For patients who are unable to use IVIG, we use rituximab. For patients who prefer an oral agent (or when rituximab and IVIG are not feasible), we use mycophenolate mofetil. We do not use cyclophosphamide for patients with mild or moderate DM or PM. (See 'Categorizing disease severity' above and 'Treatment of mild to moderate muscle disease' above.)
●Maintaining remission – IVIG and oral agents may be continued indefinitely to maintain disease remission, with the following exceptions (see 'Maintaining remission' above):
•Rituximab – Rituximab induces B-cell depletion that generally lasts at least six months. At that time, rituximab may need to be redosed or replaced with an oral immunosuppressive agent (eg, azathioprine, methotrexate, mycophenolate mofetil). Some patients will experience a durable remission after initial treatment with rituximab, even after B-cell repopulation.
•Cyclophosphamide – Cyclophosphamide should be used for a maximum of six months and then replaced with an oral immunosuppressive agent (eg, azathioprine, methotrexate, mycophenolate mofetil).
●Tapering glucocorticoids and assessing disease response – We typically start tapering glucocorticoids after four weeks of initial therapy, and we continue to taper over the next 9 to 12 months to the minimum dose required for disease control (typically no more than 7.5 mg of prednisone daily).
Patients should be assessed after three to four months of therapy for improvement in both muscle strength and creatine kinase (CK) levels.
Failure to improve should prompt consideration of alternate treatment strategies and/or reconsideration of the initial diagnosis. (See 'Glucocorticoid tapering' above and 'Assessing disease response' above.)
ACKNOWLEDGMENTS —
The UpToDate editorial staff acknowledges Stacy Rudnicki, MD and Marc L Miller, MD, who contributed to earlier versions of this topic review.
