AB1276 EFFICACY AND SAFETY OF CORTICOSTEROID-SPARING TREATMENTS IN PATIENTS WITH POLYMYALGIA RHEUMATICA: A SYSTEMATIC LITERATURE REVIEW
Authors: S. Cholasamudram, S. Fiore, K. Steele, J. Palekkara Joseph, R. T. Vepuri, S. Voruganti, J. G. Jasso-Mosqueda, L. Araujo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Polymyalgia rheumatica (PMR) is a debilitating, immune-mediated, chronic inflammatory condition of unknown etiology. It is characterized by symmetrical pain and morning stiffness of the shoulders, neck, and pelvic girdle [1-2]. Glucocorticoids (GC) stand as initial therapy for PMR, however, for many patients the complexities of flares during tapering and the burden of GC associated side effects underscore the necessity [3] of alternative treatment options. <h3>Objectives:</h3> This systematic literature review (SLR) aimed to identify, extract, and synthesize relevant information from randomized, non-randomized, and observational studies of approved or late-phase development treatments in PMR, focusing on efficacy, safety and GC sparing effect of studied interventions. <h3>Methods:</h3> MEDLINE, Embase, and Cochrane databases were searched on 29 September 2023, with additional hand-searches of grey literature and articles' bibliographies. Studies including patients with PMR, without comorbid giant cell arteritis, and receiving interventions alongside GCs were included. Outcomes of interest encompassed sustained and clinical remission, flare, cumulative GC dose, PMR activity score, quality of life and tolerability. The randomized controlled trials (RCTs) and non-RCTs quality appraisal was assessed using the relevant checklists. <h3>Results:</h3> From 1,499 citations, 27 unique studies met inclusion criteria. Eight of those were RCTs and the remaining 19 were observational and single-arm studies. RCTs compared sarilumab, tocilizumab, tofacitinib, methotrexate, and infliximab versus placebo and/or GCs (Table 1). Two RCTs assessing sarilumab (SAPHYR [3]) and tocilizumab (SEMAPHORE [4]) included patients with relapsing PMR during GC tapering/GC dependent PMR, whereas the remaining RCTs included patients with new-onset or untreated PMR. The age of patients ranged from 64.4 to 78.3 years in RCTs and 62.0 to 78.6 years in non-RCTs. In RCTs assessing clinical efficacy in GC dependent PMR, both sarilumab and tocilizumab were superior compared to placebo and GC arm [3, 4]. GC showed higher sustained remission rates compared to methotrexate [5]. The primary endpoint in the SAPHYR trial was sustained remission, defined as the resolution of signs and symptoms of PMR by week 12 and sustained normalization of the C-reactive protein (CRP) level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52. The primary endpoint of SEMAPHORE trial was a composite of low disease activity, defined as CRP PMR activity score (PMR-AS) &lt;10, and either prednisone dose ≤5 mg per day or prednisone dose decrease by ≥10 mg vs baseline at 24-week follow-up. Cumulative GC dose was reported in 13 studies (seven RCTs and six non-RCTs). In RCTs, (Figure 1) sarilumab exerts a GC-sparing effect by showing lower usage of median actual GC dose at the end of follow-up (52 weeks) versus placebo (0.78 g vs. 2.04 g; p&lt;0.001; interarm difference= 1.26 g). Cumulative GC dose in tocilizumab (24 weeks) and methotrexate studies (24 weeks to 76 weeks) ranged from 0.78 g to 1.38 g and 1.84 g to 2.1 g, respectively. Other frequently reported outcomes in the studies included proportion of patients free from GC, and mean CRP; less frequent reported outcomes included GC toxicity index and proportion of patients receiving rescue therapy. <h3>Conclusion:</h3> Interleukin-6 receptor inhibitors are found to be effective in patients with GC refractory PMR. This SLR shows the high level of study heterogeneity, including wide variability in the definitions of the outcomes across studies in PMR. More studies are needed assessing GC-sparing related outcomes such as the proportion of patients receiving rescue therapy and the GC toxicity index. <h3>REFERENCES:</h3> [1] Dasgupta B, et al. <i>Arthritis Rheum</i>. 2012;64:943-54. [2] González-Gay MA, et al. <i>Lancet</i>. 2017;390:1700-12. [3] Spiera RF, et al. <i>N Engl J Med</i>. 2023;389:1263-72. [4] Devauchelle-Pensec V, et al. <i>JAMA</i>. 2022;328:1053-62. [5] Van der Veen MJ, et al. <i>Ann Rheum Dis</i>. 1996;55:218-23. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Sirish Cholasamudram Sanofi, Stefano Fiore Sanofi, Sanofi, Kevin Steele Sanofi, Sanofi, Jofson Palekkara Joseph Sanofi, Ravi Teja Vepuri Sanofi, Srija Voruganti Sanofi, Juan-Guillermo Jasso-Mosqueda Sanofi, Lita Araujo Sanofi, Sanofi.