Steroid-Reducing Options for ReLapsING PMR (STERLING-PMR): a pragmatic, randomised trial to compare the clinical and cost-effectiveness of adding immunosuppression to steroid-tapering treatment for patients with relapsing PMR, versus steroid-tapering alone

Research question: In patients with relapsing polymyalgia rheumatica (PMR) receiving steroid taper, what is the clinical and cost-effectiveness of adding disease modifying antirheumatic drugs (DMARDs) to steroid tapering therapy? Background: 278,000 people in the UK have PMR; symptoms include pain, stiffness and restricted mobility. PMR is the commonest reason for long-term prednisolone therapy. The prednisolone dose is tapered over 12-18 months. 50% of patients relapse requiring dose escalations, prolonging therapy often far beyond 2 years. Cumulative prednisolone toxicity includes diabetes and fracture. Prednisolone dose may be reduced by adding the DMARD, methotrexate (MTX). Case series suggest a similar benefit from another DMARD, leflunomide (LEF). Aim: To determine clinical and cost-effectiveness of adding a DMARD to prednisolone-tapering treatment in people with PMR who have relapsed. Primary objective: To conduct a pragmatic, multicentre RCT to test whether adding DMARD to usual-care prednisolone-tapering reduces patient-reported cumulative steroid dose requirements over 18 months, compared with usual-care prednisolone tapering alone. Secondary objectives: To assess the impacts over 18 months of adding DMARD to steroids: PMR symptom severity and PMR disease activity; time to stopping steroids and to steroid-free remission; cumulative prescribed steroid dose; adverse events; health-related quality of life; work participation; diagnosis of adrenal insufficiency or of GCA; cost-effectiveness; and impact of increased referrals on capacity of rheumatology services. Methods: Multi-centre, Phase III, parallel-group, open-label, randomised controlled trial with internal pilot. Patients with PMR will be identified primarily from the community. Eligibility, including PMR diagnosis and history of relapse, will be confirmed in secondary care. 200 patients will be randomised and treated in 20 secondary care sites, providing 90% power to detect a 30% reduction in cumulative prednisolone dose at 18 months, assuming 20% attrition. 20 GP practices per secondary care study site will work with the NIHR Clinical Research Network to identify patients with PMR diagnostic Read codes. We will invite potential patients to contact their study site. Patients may also self-refer with GP assent or be recruited from rheumatology clinics. Central randomisation will be conducted on a 1:1 patient allocation basis between DMARD plus usual care or usual care alone. The primary DMARD prescribed will be MTX, starting at 15mg weekly, increasing to 20mg weekly at 4 weeks if tolerated. Folic acid will be co-prescribed with MTX to reduce toxicity. If MTX is not tolerated, contra-indicated, or fails to prevent further relapse despite 3 months therapy, MTX may be switched to LEF, starting at 10mg daily, increasing to 20mg daily if tolerated. All patients will continue a standardised prednisolone taper, based on current guidelines, under the care of their GP. Thus, care will be shared between GP and hospital. Timelines: 12 month set up; 24 month recruitment; 18 month follow-up; 6 month analysis. Anticipated impact and dissemination: This trial will quantify benefits and costs of adding DMARD to standard steroid treatment for patients with relapsing PMR. It will also standardise management of PMR across primary and secondary care. This will improve quality of care for PMR and build UK research capacity for further PMR clinical trials.