Treatment of polymyalgia rheumatica

INTRODUCTION — Polymyalgia rheumatica (PMR) is an inflammatory rheumatic condition characterized clinically by aching and morning stiffness about the shoulders, hip girdle, and neck. It can be associated with giant cell arteritis (GCA, also known as Horton disease, Horton giant cell arteritis, and temporal arteritis); the two disorders may represent different manifestations of a shared disease process. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica".)

The treatment of PMR will be reviewed here. The clinical manifestations of PMR, as well as the clinical manifestations, diagnosis, and treatment of GCA, are discussed separately. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica" and "Clinical manifestations of giant cell arteritis" and "Diagnosis of giant cell arteritis" and "Treatment of giant cell arteritis".)

INITIAL MANAGEMENT

Overall approach — Initial treatment with low-dose glucocorticoids is recommended for all patients diagnosed with polymyalgia rheumatica (PMR) (algorithm 1). The primary goal of treatment is the relief of symptoms. The initial dose of prednisone needed to alleviate musculoskeletal symptoms in PMR is lower than that used to control the vascular inflammation associated with giant cell arteritis (GCA) (see "Treatment of giant cell arteritis"). Treatment has not been shown to improve prognosis or prevent progression to GCA.

The therapeutic response to low-dose prednisone or prednisolone is characteristically brisk and complete. Subsequently, the glucocorticoid dose is gradually reduced. The duration of treatment varies among patients. Many patients can be tapered off glucocorticoids in one to two years, though the need for longer courses of treatment is not uncommon.

Systemic glucocorticoids — Though there are no randomized trials comparing prednisone or prednisolone with placebo or other single agents, the efficacy of glucocorticoids for the management of PMR has been established by decades of clinical experience and observational studies. Patients are unlikely to respond to other therapies and do not spontaneously remit. Despite the general consensus around the approach to therapy, there is no universally accepted approach to initial glucocorticoid dosing, maintenance therapy, or dose reduction.

Initial dose — In most patients, an initial prednisone dose of 15 mg/day (or equivalent) given orally is suggested. The starting dose can be modified depending on the patient's weight, severity of symptoms, and comorbidities such as diabetes mellitus, severe hypertension, or heart failure. Lower doses of 7.5 to 10 mg/day may suffice in smaller patients with mild symptoms or brittle diabetes. By comparison, an initial dose of 20 or occasionally 25 mg/day may be appropriate in an otherwise healthy patient with severe aching and stiffness and constitutional symptoms. Patients typically respond quickly. Occasional patients report dramatic symptomatic relief after only a single glucocorticoid dose, and the majority of patients experience substantial improvement within days of starting treatment, even in the context of longstanding symptoms.

If symptoms are not significantly improved within one week of initiating therapy, the prednisone dose can be escalated to 20 mg/day. A divided dose of prednisone (twice daily) can be useful for securing symptomatic relief if a single morning dose is not fully effective. A salient feature of PMR is the intensity of the gel phenomenon, which refers to a worsening of pain and stiffness with inactivity. In consequence, some patients find that a single morning dose of prednisone will not prevent a significant recrudescence of aching and stiffness at night and the following morning; in such patients, split-dose glucocorticoid treatment can be an effective therapeutic maneuver. The administration of prednisone in divided doses for PMR has not been formally studied.

There are limited data regarding the optimal starting dose of glucocorticoids, and practice is largely based on experience by experts and conclusions drawn from systematic reviews. A systematic review of evidence comparing different starting doses of glucocorticoids identified one randomized trial and seven observational studies [1]. The randomized trial of 39 patients with PMR found that patients treated with starting doses of 20 mg/day were less likely to flare within two months compared with those who were started on prednisone 10 mg (11 versus 65 percent of patients, respectively) [2]. The observational studies included in the analysis, however, showed inconsistent results in terms of the effect of higher versus lower starting doses of prednisone on rates of relapse and remission [3-9]. Nonetheless, all patients experienced some degree of symptom improvement with glucocorticoids. Another study suggested that the optimal initial dose may depend on body weight [10].

Although the response to prednisone is typically described as brisk, two prospective studies have described slower responses to treatment with low-dose glucocorticoids. In one study, 26 percent of 129 patients reported continued proximal myalgias after three weeks of 15 mg/day of prednisolone [11], and in another study, 29 percent of 125 patients did not achieve a definition for a complete response to low-dose glucocorticoids at four weeks [12]. Nevertheless, the usually prompt and impressive therapeutic response to low-dose glucocorticoids remains a widely appreciated feature of PMR.

Alternate routes of administration of glucocorticoids have been studied but are generally not used in clinical practice. A double-blind randomized trial of intramuscular methylprednisolone, 120 mg every three weeks, versus oral prednisone showed comparable remission rates and lower cumulative glucocorticoid doses in the methylprednisolone-treated group [13]. In a subset of patients, bilateral shoulder injections with glucocorticoids given weekly for four weeks may alleviate symptoms of PMR for up to seven months [14]. Thus, in milder cases, or in patients with several comorbidities, intramuscular or intraarticular (shoulder) glucocorticoid injections may be a reasonable alternative.

Practically all patients with PMR alone will respond to 12.5 to 20 mg/day of prednisone or, at most, 25 mg/day. Persistent aching and stiffness mandate pursuit of an alternative diagnosis. If musculoskeletal symptoms subside but fevers and other constitutional symptoms continue, underlying GCA or another illness should be considered. (See "Diagnosis of giant cell arteritis", section on 'Differential diagnosis'.)

This approach is generally consistent with published guidelines [15-17] and expert reviews [1,18-21]. Guidelines proposed by a collaboration of the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) suggested the use of the lowest effective dose within a range of 12.5 to 25 mg of prednisone equivalent, administered once daily [15,16].

Monitoring response to therapy

Clinical assessment — The initial clinical response to therapy should be closely monitored. After one to two weeks, it is reasonable to seek some form of communication with the patient, either by phone or secure electronic communication, for the purpose of determining whether there has been the prompt symptomatic response to treatment characteristic of PMR, or whether adjustments in glucocorticoid dosing are needed. A formal return visit at four to eight weeks should be arranged in order to confirm resolution of symptoms and to outline a plan for glucocorticoid tapering, or, if symptoms persist, to initiate the workup for an alternative diagnosis. Subsequent follow-up visits can be scheduled at intervals between three to six months, depending on the clinical course of the individual patient. At each visit, patients should be questioned as to symptoms referable to PMR and GCA and should be assessed for glucocorticoid side effects (see 'Minimizing risks of glucocorticoid therapy' below). Patients must also be educated about the diagnosis of GCA once the initial diagnosis of PMR is confirmed and instructed to promptly report symptoms suggestive of this diagnosis. (See 'Assessment for GCA' below and "Clinical manifestations of giant cell arteritis".)

Laboratory testing — Elevations in the acute phase reactants (erythrocyte sedimentation rate [ESR] and serum C-reactive protein [CRP]) generally revert to normal with low doses of prednisone in association with symptomatic improvement. Some data [22] and clinical experience indicate that the CRP appears to be a more sensitive and reliable index of disease activity compared with the ESR, though controlled studies in this regard are lacking.

The acute phase reactants should be checked at the time of the patient's first return visit following the diagnosis of PMR. The ESR and CRP are then repeated as indicated every three to six months during glucocorticoid therapy, noting that patients with recurrent relapses often require more frequent laboratory monitoring. Repeat determinations are indicated for the assessment of recurring symptoms, but minor fluctuations in the ESR or CRP, in the absence of symptoms directly attributable to PMR, are not of themselves sufficient reason for increasing the glucocorticoid dose.

Continued or recurrent high levels of the acute phase reactants in the asymptomatic patient should raise concern about concurrent GCA (see 'Assessment for GCA' below). Other explanations for such elevations, such as coincidental malignancy or infection, should not be overlooked. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica", section on 'Differential diagnosis'.)

Interleukin (IL)-6 has also been shown to correlate with disease activity [23,24]. As assays are not available in most laboratories, however, a role for IL-6 measurement in routine clinical care has not been established. Fibrinogen levels have also been reported to track with disease activity in patients with PMR but, in most settings, are not used routinely for assessment of the disease course [25].

Glucocorticoid tapering — As is the case with the starting dose of glucocorticoids, there is no consensus regarding an optimal tapering regimen. In general, the glucocorticoid dose that controls symptoms is maintained for two to four weeks after aching and stiffness have resolved. The dose is then reduced by small decrements every two to four weeks thereafter as tolerated to the minimum amount needed to maintain suppression of symptoms. For example, in patients receiving over 10 mg of prednisone/day, the dose can be lowered by 2.5 mg/day decrements every two to four weeks. Below 10 mg/day, the use of 1 mg decrements is advised because of the characteristic and distinctive sensitivity of the symptoms of PMR to even minor changes in the glucocorticoid dose. Dose reductions by 1 mg per month are reasonable, provided there are no flares. With this regimen, patients without a relapse in symptoms will have been treated for approximately one year. (See 'Duration of therapy' below.)

Duration of therapy — In most patients, PMR runs a self-limited course, and glucocorticoids can eventually be discontinued. In about one-half of patients, treatment can be stopped after one to two years [26]. Other patients require continuation of prednisone for longer periods of time, commonly at stable doses of 5 mg/day or less. At one center, the median duration of some glucocorticoid therapy was 37 months [27]. Another study found that one-third of patients required management with glucocorticoids for more than six years [28]. Clinical inertia likely accounts for a protracted course of low-dose glucocorticoid treatment in some patients.

Practically, there appear to be two broad subgroups of PMR. In one, glucocorticoids can be rather uneventfully tapered off over a year or two, while in another, a relapsing course requires longer treatment.

Additional management considerations

Assessment for GCA — GCA can occur before, concurrent with, or after the diagnosis of PMR. All patients with PMR should be carefully assessed for symptoms and signs referable to GCA at initial diagnosis and then routinely screened for underlying GCA at subsequent visits. (See "Clinical manifestations of giant cell arteritis".)

Estimates of the overall occurrence of GCA in PMR patients vary; clinical practice suggests that about 10 percent of patients with PMR are at some point diagnosed with GCA. PMR can appear for the first time during the treatment of GCA as glucocorticoids are tapered to low doses. In about one-half of cases of GCA, the initial clinical presentation includes PMR. Late GCA, developing after an initial diagnosis of PMR, occurs in 7 to 10 percent of patients [29,30]; the duration between initial diagnosis of PMR and subsequent diagnosis of GCA ranges from months to years. GCA can occur despite prior or ongoing low-dose glucocorticoid treatment.

As risk factors for the occurrence of GCA have not been defined in patients with PMR, sustained and regular clinical vigilance for GCA is essential. In an otherwise asymptomatic PMR patient with unexplained elevations of the acute phase reactants, patients should be evaluated for the possibility of GCA, with regard to either cranial arteritis or large vessel vasculitis.

At any time during the disease course, patients with PMR who develop sudden vision loss, the most dreaded complication of GCA, should be immediately treated with adequate doses of glucocorticoids and evaluated for underlying GCA in order to prevent further cranial ischemic events [31]. (See "Treatment of giant cell arteritis".)

Minimizing risks of glucocorticoid therapy — Prevention of and monitoring for side effects, including osteoporosis, glucose intolerance, hypertension, glaucoma, and cataracts, are essential components of a comprehensive management program for PMR (see "Major adverse effects of systemic glucocorticoids"). Case series and disease cohorts have described and documented such side effects. In two studies, patients with PMR managed with glucocorticoids incurred at least one adverse event attributable to treatment in 81 of 124 patients (65 percent) and 95 of 222 patients (43 percent) [32,33].

In an inception cohort of 359 patients with PMR compared with population-based controls, however, only cataracts were found to be more common in PMR than comparators [34]. The rates of glucocorticoid-related diabetes mellitus, hypertension, hyperlipidemia, and fragility fractures were not significantly different between the two groups. It should be observed that this and other studies on adverse events from glucocorticoid treatment for PMR have not tracked side effects that are frequently more problematic in practice, such as facial hirsutism, Cushingoid facies, weight gain, and capillary fragility. Capillary fragility can result in widespread ecchymoses and slowly healing lacerations, especially in patients on concurrent treatment with aspirin or anticoagulants.

As most patients with PMR require glucocorticoid treatment for more than several months, standard guidelines for prevention of glucocorticoid-induced osteoporosis should be followed, including an assessment of bone mineral density at or near the time prednisone is begun, treatment with calcium and vitamin D supplementation, and, when indicated by treatment guidelines, prophylactic use of bisphosphonates. These issues are discussed in detail elsewhere. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Blood pressures should be monitored regularly, and, when indicated, glycosylated hemoglobin (hemoglobin A1c) levels should be obtained to monitor for the development of diabetes mellitus. (See "Screening for type 2 diabetes mellitus".)

Indications for referral to a rheumatologist — PMR is common and, depending on prevailing clinical practices, can often fall under the purview of a generalist. Referral to a rheumatologist should be considered if there are atypical features (eg, younger patients, presenting fever), prominent peripheral arthritis, an inadequate response to initial glucocorticoid treatment, or difficulties with glucocorticoid tapering.

MANAGEMENT OF RELAPSING OR RECURRENT DISEASE

Patients with recurrent symptoms — Relapses of aching and morning stiffness are frequent during the course of the glucocorticoid taper and have been reported in over 50 percent of patients [3,35,36]. In clinical practice, relapses during tapering are more the rule than the exception. Relapses are most common in the first one to two years of treatment and at prednisone doses under 10 mg/day [36]. As would be expected, a relapsing course is associated with a longer duration of glucocorticoid treatment [35]. Recurrences of polymyalgia rheumatica (PMR) after complete discontinuation of glucocorticoid treatment, months or even years later, also occur [37]. Why PMR is monophasic in some patients and polyphasic in others is unclear. (See 'Prognosis' below.)

Reports on prognostic factors for relapses in PMR are marred by inconsistencies [1]. Relapse has been variably associated with female sex, longer duration of morning stiffness, peripheral arthritis, higher erythrocyte sedimentation rate (ESR) at diagnosis, and persisting elevations of C-reactive protein (CRP), interleukin (IL)-6 levels, and soluble IL-6 receptor levels [4,35,36,38-40]. Increased relapses have also been described with larger initial doses of prednisone [3] and a faster rate of tapering [3,36]. In the absence of defined risk factors for relapses, treatment centers on finding the lowest glucocorticoid dose that controls stiffness and preserves function for the individual patient.

An approach to the treatment of patients with relapsing or recurrent symptoms is as follows:

●If recurrent symptoms develop following discontinuation of glucocorticoids and are accompanied by an elevation in the ESR and/or CRP, glucocorticoids can be resumed at the original dose that managed symptoms. Many patients will recognize the early symptoms of recurring PMR, allowing for a trial of lesser doses of prednisone than were used at their initial presentation.

●In patients who relapse while on treatment, the glucocorticoid dose is increased to the lowest dose that achieves symptomatic improvement. Elevations of the acute phase reactants can provide support for the diagnosis of a flare of PMR, but minor flares, requiring only a 1 or 2 mg increase in the prednisone dose, may not be accompanied by such increases.

●In patients who relapse several times, the interval between dose reductions can be lengthened to six to eight weeks.

Asymptomatic patients with abnormal testing — Elevations in the ESR and/or CRP can occur in the asymptomatic patient. In the absence of symptoms, minor increases do not warrant any change in the glucocorticoid dose. Asymptomatic patients with more significant elevations in the acute phase reactants should be carefully evaluated for symptoms and signs of giant cell arteritis (GCA).

Patients who appear glucocorticoid-dependent — Difficulties with tapering glucocorticoids in a patient with PMR can arise from a variety of causes.

●One common cause of such difficulty relates to the clinical course of PMR, which, as described above, is prone to relapse and recurrence.

●Another common cause of recurring achiness during the glucocorticoid taper is the symptomatic worsening of prevalent noninflammatory musculoskeletal problems, eg, rotator cuff tendonitis or osteoarthritis. It is important to distinguish recrudescent symptoms due to these local conditions from a bona fide relapse of PMR. This differentiation, however, is sometimes not easy, as patients often experience a degree of symptomatic relief from various degenerative causes of musculoskeletal pain with low-dose glucocorticoids that exceeds responses to previous treatment with nonsteroidal antiinflammatory drugs (NSAIDs) or other analgesia.

●Relapsing symptoms, especially if accompanied by distal synovitis, should direct attention to the possibility of a different diagnosis, ie, seronegative rheumatoid arthritis or "late-onset rheumatoid arthritis," and prompt a change in therapeutic paradigm from PMR to so-called late-onset rheumatoid arthritis.

●Fibromyalgia-like symptoms, in particular widespread muscle pain associated with stiffness and fatigue, have been reported during the glucocorticoid taper after longstanding therapy in PMR patients, but unlike a true PMR relapse, they are not associated with elevated serum acute phase reactants. Chronic low doses of glucocorticoids are sometimes required to control these manifestations.

●Rarely, diffuse pain can ensue from a rapid taper of prednisone in a patient who has been on long-term glucocorticoid therapy. (See "Glucocorticoid withdrawal", section on 'Recommended tapering regimen'.)

Limited role for glucocorticoid-sparing therapies — The routine use of adjunctive therapy is not recommended because definitive symptomatic control of PMR can usually be achieved with low doses of glucocorticoids and the adverse effects from treatment are often mild. Symptomatic relapses during the course of the glucocorticoid taper are common, and, if managed with only a minor change in the glucocorticoid dose, need not be construed as a failure of treatment.

Indications for considering the addition of an adjunctive medication to glucocorticoid therapy include preexisting comorbidities (eg, osteoporosis or insulin-requiring or decompensated diabetes mellitus), the development of serious glucocorticoid-related side effects, or multiple relapses of symptoms. In these situations, methotrexate (MTX) can be used, with the caveat that the use of this drug in contemporary doses used for management of rheumatoid arthritis (up to 25 mg/week) has not been formally studied in PMR. Results from preliminary studies on the use of IL-6 receptor blockade are encouraging, but more controlled studies are needed to assess the efficacy, toxicity, and economic viability of this approach. There are insufficient data to support the use of tumor necrosis factor (TNF) inhibitors or rituximab. Generally similar recommendations are included in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) guidelines [15,16] and in a systemic review [41].

●Methotrexate – Data from randomized controlled studies on the efficacy of MTX as a glucocorticoid-sparing agent are mixed, though generally favorable results have been reported with regard to cumulative glucocorticoid doses, relapse rates, and time to discontinuation of glucocorticoid treatment [42,43]. Interpretation of a negative controlled study on the use of concurrent MTX is limited by a high dropout rate [44]. These data, however, are limited by several factors including the small number of patients studied and by the relatively low doses of MTX used (in the range of 7.5 to 10 mg/week) compared with contemporary doses (in the range of 20 to 25 mg/week). Also, no study has demonstrated an actual reduction in glucocorticoid-related adverse events in MTX-treated patients compared with patients treated with glucocorticoids alone.

●IL-6 receptor blockade

•Sarilumab – Sarilumab has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with PMR who cannot tolerate glucocorticoid taper [45]. In a randomized trial of 118 patients with relapsing PMR, patients assigned to receive 52 weeks of sarilumab every two weeks (at a dose of 200 mg) plus a 14-week prednisone taper had a higher rate of sustained remission than patients assigned to placebo plus a 52-week prednisone taper (28 versus 10 percent), were less likely to relapse once remission was achieved (hazard ratio [HR] 0.56, 95% CI 0.35-0.90) and received a lower median cumulative glucocorticoid dose at 52 weeks (777 versus 2044 mg) [46]. The frequency of serious adverse events was lower among patients assigned to sarilumab (14 versus 21 percent), but more treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12 versus 7 percent).

•Tocilizumab – In a small, randomized trial of 36 patients with new-onset PMR, patients assigned to weekly subcutaneous tocilizumab had an increased rate of glucocorticoid-free remission compared with patients assigned to placebo (63 versus 12 percent) [47]. There was also a shorter time to relapse for patients in the placebo group. All patients received oral prednisone that was tapered from 20 mg down to 0 mg over 11 weeks. There were five serious adverse events in the placebo group compared with one in the tocilizumab group.

In a larger randomized trial of 100 patients with relapsing PMR, patients assigned to intravenous tocilizumab were more likely to achieve a reduction in disease activity and glucocorticoid dose at 24 weeks (67.3 versus 31.4 percent) [48]. Glucocorticoids were discontinued in more patients who had been assigned to tocilizumab (49 versus 19.6 percent). Infections were the most frequent adverse events for both treatment groups (46.9 versus 39.2 percent).

●Rituximab – Findings from a small proof-of-concept trial suggest that there may be role for B cell depletion in the treatment of PMR [49]. Among the 49 patients with PMR who participated in the study, patients who received a single infusion of rituximab in combination with a 17-week glucocorticoid tapering scheme were more likely to achieve glucocorticoid-free remission at 21 weeks compared with those who received the 17-week glucocorticoid tapering scheme alone (48 versus 21 percent; difference 27 percent [one-sided 95% CI 4]; relative risk 2.3 [1.1]) [49]. After one year of follow-up, patients who received a single infusion of rituximab were more likely to have achieved a drug-free remission than patients treated with placebo (47 versus 23 percent) [50]. There were more infusion-related adverse events in the rituximab group. More data with longer-term follow-up are needed to determine whether rituximab may be considered as a glucocorticoid-sparing agent for the treatment of PMR.

●Tofacitinib – Findings from a small proof-of-concept study suggest that tofacitinib may be effective for the treatment of PMR. In this study, 67 patients with newly diagnosed PMR were randomized to receive treatment with tofacitinib (5 mg twice daily) or to prednisone 15 mg daily (followed by a subsequent taper) [51]. At the end of 12 and 24 weeks, patients had an equivalent response to both therapies, as measured by acute phase reactants (ie, ESR, CRP) and the PMR Activity Score (PMR-AS). More data with longer-term follow-up are needed to determine whether tofacitinib is an effective substitute for glucocorticoids for patients with PMR.

●TNF inhibitors – Several studies have failed to demonstrate a significant benefit with TNF inhibitors compared with glucocorticoids. In a randomized trial of 51 patients with newly diagnosed PMR, the use of upfront infliximab dosed at 3 mg/kg on weeks 0, 2, 6, 14, and 22 was not more effective than prednisone plus placebo [52]. The proportion of patients in the two groups who were relapse- or recurrence-free was similar at 22 weeks (55 versus 54 percent with placebo) and at 52 weeks (30 versus 37 percent).

A randomized double-blind controlled study comparing etanercept to placebo in 20 patients with newly diagnosed PMR showed a modest reduction in the PMR activity score in etanercept-treated patients, but the study was only two weeks in duration [53].

Two small open-label studies, totaling 15 patients, described benefit from adjunctive treatment with etanercept in patients with relapsing PMR, with reduction or discontinuation of glucocorticoid treatment [54,55]. Other favorable anecdotes have been reported [56]. Given the limited size and quality of these studies, however, and the lack of additional randomized controlled trials, a role for etanercept (or other TNF inhibitors) cannot be endorsed for the management of PMR.

OTHER THERAPIES

●Physical therapy – Physical therapy has no role in the initial management of a patient with untreated polymyalgia rheumatica (PMR), as the extent of associated stiffness usually precludes meaningful participation in a program of therapeutic exercise. In an older adult who has become deconditioned, physical therapy can assist with the restoration of fitness once effective treatment for PMR has been implemented.

●Nonsteroidal antiinflammatory drugs – Nonsteroidal antiinflammatory drugs (NSAIDs) have no role in the initial management of PMR. Patients typically report no or minimal symptomatic improvement if these medications have been tried prior to initiation of glucocorticoid therapy.

PROGNOSIS — There is no evidence of increased mortality associated with polymyalgia rheumatica (PMR) [57]. PMR is not erosive and does not cause structural damage. Pain and functional limitations are eliminated with low doses of glucocorticoids. Morbidity in PMR most often relates to the longer-term impact of its treatment. Relapses of symptoms commonly respond to minor adjustments in the glucocorticoid dose, and treatment to prevent relapses must be weighed against the risks of drug-related toxicities.

The heterogeneity of the clinical course commits the clinician to the care of an older adult patient on glucocorticoids for what can be an extended period of time. Guidelines for initial management with glucocorticoids and for subsequent tapering can be outlined, but ultimately, treatment must be flexible and individualized.

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: Giant cell arteritis and polymyalgia rheumatica".)

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 5^th to 6^th 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 10^th to 12^th 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: Polymyalgia rheumatica and giant cell arteritis (The Basics)")

●Beyond the Basics topics (see "Patient education: Polymyalgia rheumatica and giant cell arteritis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Overall approach to therapy – Polymyalgia rheumatica (PMR) is characterized by a prompt response to glucocorticoids in low to moderate doses (algorithm 1). The primary goal of therapy is the relief of symptoms. Therapy has not been shown to improve prognosis or prevent progression to giant cell arteritis (GCA, also known as Horton disease, Horton giant cell arteritis, and temporal arteritis). (See 'Overall approach' above.)

●Systemic glucocorticoids – In all patients with PMR, we recommend initial treatment with prednisone (Grade 1B). Our practice is to start with a dose of prednisone 15 mg/day. The initial dose of prednisone can be modified depending upon the patient's weight, the severity of symptoms, and comorbidities such as diabetes mellitus, severe hypertension, or heart failure. (See 'Initial dose' above.)

•Initial dose – The symptomatic response to glucocorticoid treatment is typically rapid. If symptoms are not well controlled within one week of initiating therapy, the prednisone dose should be increased by 5 mg to a dose of 20 mg/day. Practically all patients with PMR alone will respond to 15 to 20 mg/day of prednisone. Split-dose prednisone can be effective in patients in whom the response to treatment is slow. Persistent aching and stiffness despite the administration of prednisone at these doses mandate pursuit of an alternative diagnosis. (See 'Systemic glucocorticoids' above and "Clinical manifestations and diagnosis of polymyalgia rheumatica", section on 'Differential diagnosis'.)

•Glucocorticoid tapering – The glucocorticoid dose that suppresses symptoms should be maintained for two to four weeks after aching and stiffness have resolved and can then be gradually reduced every two to four weeks to the lowest dose needed to maintain suppression of symptoms. (See 'Glucocorticoid tapering' above.)

-In patients receiving over 10 mg of prednisone/day, the dose can be lowered by 2.5 mg/day decrements every two to four weeks

-Once the dose of prednisone is 10 mg/day, further tapering can be done by 1 mg per month, provided the clinical course is stable

●Monitoring response to therapy – The clinical response to glucocorticoid therapy is closely monitored, which centers on screening for the presence and/or recurrence of symptoms of PMR or GCA. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be measured at baseline and then two months after initiating glucocorticoid therapy. The ESR and CRP are then repeated as indicated every three to six months during glucocorticoid therapy, noting that patients with recurrent relapses often require more frequent laboratory monitoring. (See 'Monitoring response to therapy' above.)

Minor fluctuations in the ESR and/or CRP can occur in the completely asymptomatic patient and alone are not necessarily grounds for intensification of glucocorticoid therapy. Patients with more significant elevations in ESR and/or CRP without an increase in PMR symptoms should be evaluated for other possible diagnoses, especially GCA. (See 'Asymptomatic patients with abnormal testing' above.)

●Management of relapsing or recurrent disease – Relapse is common, particularly when the glucocorticoid dose is tapered too rapidly. In patients in whom symptoms recur following discontinuation of glucocorticoids and are accompanied by an elevated ESR and/or CRP, glucocorticoids should be resumed at the dose that previously provided control of symptoms. In patients who relapse while on glucocorticoids, the strategy is similar, ie, resumption of the previous effective dose. (See 'Management of relapsing or recurrent disease' above.)

●Duration of therapy – In most patients, PMR runs a self-limited course, and glucocorticoid therapy can eventually be discontinued. Often, treatment can be stopped after one to two years, but the need for more protracted glucocorticoid therapy is not exceptional. (See 'Duration of therapy' above.)

●Minimizing risks of glucocorticoid therapy – Patients should also be monitored for adverse effects of glucocorticoids, including osteoporosis, glucose intolerance, and hypertension. (See 'Minimizing risks of glucocorticoid therapy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William P Docken, MD, who contributed to an earlier version of this topic review.