FRI0475 STEROID SPARING AGENTS IN POLYMYALGIA RHEUMATICA: A SYSTEMATIC REVIEW
Authors: S. Banerjee, K. Chaudhuri, A. Desai, M. Krishna, N. Gullick
Journal: Annals of the Rheumatic Diseases (2020)

Background: Polymyalgia rheumatica (PMR) is the commonest chronic inflammatory musculoskeletal disease of the elderly. The mainstay of treatment for PMR is long term systemic glucocorticoid (GC), which is associated with significant systemic toxicity. There is a need for steroid sparing drugs in PMR to reduce GC cumulative dose and GC induced adverse effects.(1) Objectives: To evaluate the role of steroid sparing agents in PMR. Primary outcomes: 1. Steroid sparing effect of the intervention, measured by difference in cumulative glucocorticoid dose 2. Percentage of patients in remission. Secondary outcomes: 1. Mean reduction of CRP/ESR 2. Adverse event/toxicity the drugs being compared—measured as number of patients with adverse events in the compared groups 3. Percentage of patients with relapse during study period 4. Mortality Methods: Electronic databases including Medline, Embase and Cochrane databases (CENTRAL) were searched since inception for prospective randomized control trials comparing disease modifying anti rheumatic drugs (DMARDs) and biologics with systemic GC in PMR, published in English with more than 20 patients and a minimum study duration of 24 weeks. As different classification criteria for PMR exist, studies were included if they used any accepted classification criteria for PMR. Case series, case reports, retrospective, non-randomized trials, abstracts, systematic reviews and non English language trials were not included. Patients with Giant cell arteritis (GCA) were excluded. Risk of bias and quality was assessed using the Cochrane tool. The studies were assessed for cumulative GC dose, proportion of patients in remission, proportion of patients with relapse, reduction in inflammatory markers, adverse events and mortality. Results: 5 studies were selected for final review-- 3 studies involving Methotrexate, one study on azathioprine, one on Infliximab. The study on Azathioprine had high risk of bias, small sample size and low quality (Level 2 evidence) with high attrition rate but it revealed reduction of daily prednisolone with Azathioprine. A high quality RCT (Level 1) did not confirm a steroid sparing effect with Infliximab vs placebo, and there was no significant difference between relapse or remission rate. Methotrexate studies showed conflicting results: one high quality RCT (Level 1) and one low quality RCT (Level 2) on Methotrexate revealed statistically significant steroid sparing effect, however the remaining study did not demonstrate between Methotrexate and placebo. Two methotrexate studies assessed the risk of relapse, with conflicting results (relapses 73% placebo vs 47% methotrexate; or no difference). Methotrexate was not associated with increased adverse effects in any of the studies. Azathioprine was associated with significant adverse events resulting in high attrition. A meta analysis was not performed for methotrexate as the studies were heterogenous. Conclusion: There is a lack of evidence regarding DMARDs and biologics in PMR. Methotrexate is an effective steroid sparing agent, and is not associated with increased adverse events. Azathioprine may be effective but is associated with significant adverse events. Infliximab is not an effective steroid sparing agent in PMR. More high quality RCTs are needed to study the efficacy of steroid sparing agents. References: [1]Bhaskar Dasgupta, Frances A. Borg, Nada Hassan, Kevin Barraclough, Brian Bourke, Joan Fulcher, Jane Hollywood, Andrew Hutchings, Valerie Kyle, Jennifer Nott, Michael Power, Ash Samanta, on behalf of the BSR and BHPR Standards, Guidelines and Audit Working Group, BSR and BHPR guidelines for the management of polymyalgia rheumatica, Rheumatology , Volume 49, Issue 1, January 2010, Pages 186–190 Disclosure of Interests: None declared