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Best practices and uncertainties in the management of PMR

Nature Reviews Rheumatology volume 12, pages 34 (2016) | Download Citation

Glucocorticoids are the mainstay of treatment for patients with polymyalgia rheumatica (PMR) and often produce substantial clinical improvements, but treatment can be complicated by relapse, adverse effects of therapies, and concomitant conditions. New recommendations aim to guide clinicians and improve the management of this disorder.

Refers to Dejaco, C. et al. 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann. Rheum. Dis. 74, 1799–1807 (2015)

A group of experts supported by the ACR and EULAR has published a series of recommendations intended to inform clinicians about best practice in the care of patients with polymyalgia rheumatica (PMR).1,2 Such attempts are welcome and the recommendations might be of interest to clinicians, given the current heterogeneity in the classification criteria for the diagnosis of PMR, the lack of agreement on the initial dose of prednisone required for the treatment of PMR, and the need to exclude conditions other than isolated PMR that can present with polymyalgia features. However, several considerations must be kept in mind when providing guidance for the management of these patients.

The target population of the recommendations by Dejaco et al.1,2 is individuals with PMR on the basis of clinician diagnosis supported by currently available diagnostic or classification criteria. The diagnosis of PMR is relatively straightforward when typical features—such as pain and early morning stiffness in the neck, shoulder and pelvic girdle in patients over the age of 50 years, associated with elevated levels of acute-phase reactants—are present.3 However, other conditions, mainly chronic inflammatory rheumatic diseases, such as elderly-onset rheumatoid arthritis, late-onset spondyloarthritis or late-onset systemic lupus erythematosus, and less commonly infections and endocrine, metabolic and malignant disorders, can present with PMR features or mimic PMR;3 the recommendations do not address the management of PMR with concomitant conditions. Atypical features such as diffuse pain, absence of morning stiffness or lack of response to corticosteroids should be considered red flags for the presence of a condition other than isolated PMR in a patient who presents with polymyalgia features (Box 1).3

Box 1: Take-home messages

• Corticosteroids constitute the cornerstone of therapy in the management of patients with isolated PMR

• An initial prednisone dose of 10–25 mg daily yields clinical improvement in most patients with PMR

• Consider a condition other than isolated PMR in patients who present with atypical features or in the absence of response to prednisone therapy

• Relapses are common in isolated PMR, predicted mainly by the rate of corticosteroid tapering

• Methotrexate can be used in patients with PMR who experience relapse

Abbreviation: PMR, polymyalgia rheumatica.

Of special concern is the association of PMR with giant cell arteritis (GCA). Both diseases are relatively common in elderly people from Western countries.4 PMR is the presenting manifestation in ≥10% of patients with GCA, and approximately 40–50% of patients with GCA have features of PMR.4 When comparing isolated PMR to GCA-associated PMR in a population from northwest Spain, we observed that patients with isolated PMR were slightly younger, less commonly had constitutional symptoms (asthenia, anorexia and weight loss) and had lower erythrocyte sedimentation rates and platelet counts than those with PMR associated with GCA.4 Conversely, haemoglobin levels were higher in patients with isolated PMR than in those with GCA-associated PMR.4 These subtle differences could have implications for prognosis as the prednisone dose required to treat PMR features, which is lower than the dose required to treat vascular complications of GCA, is not sufficient to prevent the development of blindness in the setting of GCA.4,5

Taking these considerations together, a detailed clinical history must be performed to exclude GCA as well as the presence of other conditions unrelated to isolated PMR, such as those associated with other rheumatic diseases, tumours or infections. Therefore, in accordance with the ACR–EULAR recommendations,1,2 additional testing might be required in cases of PMR with atypical features or without a good response to treatment with corticosteroids.5

Corticosteroids are the cornerstone of therapy for PMR.5,6 Dejaco et al.1,2 propose starting treatment with prednisone 12.5–25 mg daily or equivalent. In our experience, PMR is extremely predictable in its rapid and complete or nearly complete improvement after the onset of prednisone 10–20 mg daily.5 We and others support the claim that rapid response to this prednisone dose in less than a week is typical in patients with isolated PMR.4,5,6 It is also worth noting that patients with isolated PMR often experience a dramatic improvement in symptoms <72 h after the start of treatment.4,5,6 Consequently, we do not agree with Dejaco et al. when they say that up to 29–45% of patients with PMR do not respond adequately to corticosteroids within 3–4 weeks.1,2 This point of discrepancy might be due to the great variability in the initial doses of prednisone given to patients at the time of PMR diagnosis in different studies. In keeping with that statement, in the systematic literature review that formed the basis of the recommendations, the same group concluded that the initial doses of corticosteroids and tapering regimen have not, or only inadequately, been investigated.7

The panel of experts strongly recommended individualizing dose-tapering schedules, based on regular monitoring of disease activity, laboratory markers and adverse events.1,2 This consideration is prudent given the high frequency of relapse when the prednisone dose is tapered or discontinued.8,9 We found a relapse frequency of 23% in patients with isolated PMR from northwest Spain.8 Relapse generally occurred when the dose of prednisone was <5 mg daily (median dose 2.5 mg daily, range 0–10 mg daily at the time of first relapse).8

It is plausible that genetic factors predispose an individual to risk of relapse. We found a trend (not statistically significant) of increased relapse rates in patients with isolated PMR who carried HLA-DRB1*0401 and HLA-DRB1*0404 alleles.8 More importantly, the rate of tapering is known to be a major factor in the risk of relapse, as rapid tapering is an important predictor of future relapse.8,9 Kremers et al.9 reported that every 5 mg increase in the initial daily prednisone dose was associated with a 7% increase in the risk of relapse, although this finding was not confirmed in our series.8

The panel conditionally recommended that early introduction of methotrexate (along with corticosteroids) should be considered in patients at high risk of relapse and/or prolonged therapy, as well as in cases where adverse events related to corticosteroid use are more likely to occur owing to certain risk factors, comorbidities or concomitant medications. Methotrexate can also be considered for the treatment of patients who experience relapse, those with an inadequate response to corticosteroids or those who experience corticosteroid-related adverse events. However, the prospective studies conducted to address the efficacy of methotrexate were inadequately powered.1,2 Overall, the efficacy of methotrexate in the treatment of PMR is moderate. Nevertheless, we also support the use of methotrexate in the situations discussed above.

Finally, as discussed by Dejaco et al.,1,2 biologic therapies have been considered in the management of corticosteroid-resistant PMR. Use of anti-TNF therapy is not recommended, but preliminary data suggest that the anti-IL-6 receptor antibody tocilizumab might be useful in these cases.10 However, more information on the use of tocilizumab in isolated PMR is needed.

Although corticosteroids are the mainstay in the treatment of PMR, there is no consensus on the initial dose, as acknowledged in the aforementioned systematic review.7 Relapses are common and the use of other therapies needs further evaluation. In conclusion, the latest ACR–EULAR recommendations are an interesting step in standardizing the management of PMR, but additional efforts are needed in order to elucidate the most appropriate initial dose and rate of tapering of prednisone, as well as the best management of relapses.


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The work of M.A.G.-G. is supported by grants from Fondo de Investigaciones Sanitarias, Spain (PI06/0024, PS09/00748 and PI12/00060), and also partially supported by RETICS Program, RD08/0075 and RD12/0009/0013 (RIER) from Instituto de Salud Carlos III, Spain.

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  1. Instituto de Investigación Sanitaria de Santiago, Division of Rheumatology, Santiago University Clinical Hospital, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain.

    • Miguel A. González-Gay
  2. University of Cantabria School of Medicine–IDIVAL-CIBERESP, Avenida Herrera Oria s/n, 39011 Santander, Spain.

    • Javier Llorca


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Competing interests

The authors declare no competing financial interests.

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Correspondence to Miguel A. González-Gay.

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