2015 Treatment Recommendations for Polymyalgia Rheumatica

Polymyalgia rheumatica (PMR) is the most common inflammatory musculoskeletal disease of older people, but there is little high-quality evidence to guide treatment, which varies widely in clinical practice. The European League Against Rheumatism and the American College of Rheumatology have published treatment recommendations for polymyalgia rheumatic. The recommendations appear in the October 2015 issue of Annals of the Rheumatic Diseases. The expert panel divided their recommendations into strong recommendations supported by strong evidence and conditional recommendations with weaker evidence.[[{"type":"media","view_mode":"media_crop","fid":"41851","attributes":{"alt":"©Artem/FurmanShutterstock.com","class":"media-image media-image-right","id":"media_crop_1575929166283","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4483","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] 

• Glucocorticoids should be tapered off and discontinued after a year or possibly two in most cases. 

• Non-steroidal anti-inflammatory drugs and tumor necrosis factor-α blocking agents are not effective and should not be used. 

Annals of the Rheumatic Diseases (Source)

Eight overarching principles and nine specific recommendations were developed covering several aspects of polymyalgia rheumatic, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and nonpharmacological interventions, wrote the authors of the report which was led by Bhaskar Dasgupta, MB BS MD FRCP of Southend University Hospital, Essex, U.K. “These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR,” the authors wrote. The classic symptoms of polymyalgia rheumatica are pain and morning stiffness of the neck, shoulders, hips, upper arms and thighs, but not the distal limbs. Polymyalgia rheumatica is difficult to distinguish from other inflammatory arthritides, such as spondyloarthritis and rheumatoid arthritis. It’s also difficult to diagnose as a separate entity in the presence of other diseases. It is largely a diagnosis of exclusion starting with non-specific symptoms.  There are wide variations in the treatment of polymyalgia rheumatica (PMR) with respect to glucocorticoid (GC) dosages, tapering strategies, use of disease modifying anti-rheumatic drugs (DMARDs) and duration of treatment, Dasgupta and colleagues wrote. “Up to 29–45% of patients with PMR do not adequately respond to GCs within 3–4 weeks. Relapses and long-term GC dependency are common. GC side effects are frequently observed, occurring in around 50% of patients, and present a further challenge. Well considered, international recommendations can serve to standardize practice and improve patient care,” the authors wrote. The target population for the guidelines include patients with PMR who have been diagnosed by a clinician based on established diagnostic or classification criteria.  

Recommendations

   Glucocorticoids are strongly recommended instead of non-steroidal anti-inflammatory drugs, with the possible exception of short-term NSAID use and/or analgesics in PMR patients with unrelated pain. The relative harm of long-term NSAID use outweighs the possible small benefits in PMR. Use the minimum effective individualized duration of glucocorticoids. “Our recommended GC tapering schedule assumes a minimum of 12 months of treatment." The panel conditionally recommended a minimum effective glucocorticoid initial dose of between 12.5 and 25 mg prednisone equivalent daily. They conditionally discourage an initial dose of  less than or equal to 7.5 mg daily, and strongly recommended against initial doses greater than 30 mg daily. The panel strongly recommends individualizing dose-tapering schedules: Initial tapering: Taper dose to an oral dose of 10 mg/day prednisone equivalent within 4–8 weeks. Relapse therapy: Increase oral prednisone to the pre-relapse dose and decrease it gradually (within 4–8 weeks) to the dose at which the relapse occurred. Tapering once remission is achieved (following initial and relapse therapies): Taper daily oral prednisone by 1 mg every 4 weeks (or by 1.25 mg decrements using schedules such as 10/7.5 mg on alternate days, etc) until discontinuation as long as remission is maintained. The panel conditionally recommended considering intramuscular methylprednisone as an alternative to oral glucocorticoids.

The panel conditionally recommended using a single rather than divided daily doses of oral glucocortocoids. There was concern that evening doses can cause circadian rhythm and sleep disturbances, and disturbance of the hypothalamic-pituitary-adrenal axis, but they acknowledged that it might be appropriate for dealing with night pain while tapering below 5 mg prednisone equivalent daily. 

The panel conditionally recommended considering early introduction of methotrexate in addition to glucocorticoids in patients at high risk of relapse, prolonged therapy or other risk factors, on an individual basis. This could include patients who are female, who have high erythrocyte sedimentation rate, peripheral inflammatory arthritis, or comorbidities that may be exacerbated by glucocorticoids.

The panel strongly recommended against the use of tumor necrosis factor-α blocking agents. There is no evidence of benefit, and considerable risk of harm and high resource use.

The panel conditionally recommended considering an individualized exercise program for the maintenance of muscle mass and function and reducing the risk of falls. 

The panel strongly recommended against the use of the Chinese herbs Yanghe and Biqi capsules in PMR, pending better evidence. 

The panel strongly recommended against the Chinese herbal preparations Yanghe and Biqi capsules in PMR. There were two studies on the herbs. For Yanghe, there was moderate quality evidence for a lower erythrocyte sedimentation rate (which is not a clinical outcome), and very low quality evidence for a lower rate of glucocorticoid-related adverse events and lower morning stiffness; there was low quality evidence for Biqi. The panel based their decision on the small effect size, the weak evidence, the lack of approval by the U.S. Food and Drug Administration or the European Medicines Agency and problems associated with quality control and adverse events common to herbal products.

In an 

accompanying review

, Dr. Dasgupta and colleagues wrote:  ““One of our most intriguing observations is that fundamental treatment principles of PMR such as initial GC doses, tapering schedules and duration of treatment have not been examined by high-quality trials thus far. In contrast, we found moderate to good evidence that MTX is of benefit for patients with a new diagnosis of PMR. Interestingly, it is clinical practice to prescribe MTX to patients with GC-resistant disease, although this approach is not supported by published evidence. The clinical value of other conventional disease-modifying antirheumatic drugs for treatment of PMR is still unclear.” 

Related articles on Rheumatology Network

• GCA and PR on NEJM
• ACR/EULAR Guidelines on PMR Management Finalized
• Best Practice in Polymyalgia Rheumatica

References:

Dejaco C, Singh YP, Perel P, et al.

Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/American College of Rheumatology recommendations for the management of polymyalgia rheumatica. Annals of the Rheumatic Diseases.

October 2015. 2015;74(10):1808–1817. http://dx.doi.org/10.1136/annrheumdis-2015-207578 Dejaco C, Singh Y Perel P, et al. 2015

Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Annals of the Rheumatic Diseases.

2015;74(10):1799–1807. October 2015. http://dx.doi.org/10.1136/annrheumdis-2015-207492 Kermani TA, Warrington KJ.

Seminar: Polymyalgia rheumatica. The Lancet.

Jan 5, 2013. 2013;381(9860):63-72. http://dx.doi.org/10.1016/S0140-6736(12)60680-1 Mackie SL, Mallen CD.

Clinical Review: Polymyalgia rheumatica. BMJ.

2013;347:f6937 December 3, 2013. doi: http://dx.doi.org/10.1136/bmj.f6937