EP25 Impact of sarilumab on unacceptable pain and inflammation control in moderately-to-severely active rheumatoid arthritis (RA) patients in 3 Phase 3 studies

Abstract

Background/Purpose : Pain, a core-set domain and a troubling symptom to patients with RA, may be directly related to inflammation. Unacceptable pain (UP) levels may persist despite treatment-induced inflammation control, i.e. refractory pain (RP). Sarilumab is a subcutaneously-administered interleukin-6 receptor antagonist for treatment of adults with moderately to severely active RA with an inadequate response or intolerance to 1 or more diseasemodifying antirheumatic drugs (DMARD-IR). In 3 randomized controlled trials (RCTs) of sarilumab 150 mg or 200 mg every 2 weeks (q2w) vs comparators, we previously observed meaningful improvements in pain. This study assessed UP and RP for sarilumab vs comparators in these trials. Methods : Data were from RCTs of sarilumab 150 mg and 200 mg q2w vs placebo (+conventional DMARDs for all): MOBILITY [NCT01061736] (24/52 weeks) and TARGET [NCT01709578] (24-weeks); and MONARCH [NCT02332590] sarilumab 200 mg q2w vs adalimumab 40 mg q2w monotherapies. Post-hoc analyses were conducted on the odds ratios (ORs) of pain outcomes: UP (based on patient acceptable symptom state [PASS] on a threshold of visual analog scale pain >40 mm [0-100]), RP (UP+C reactive protein < 10 mg/L), and RP-strict (RP+ ≤1 swollen joint count [SJC]), and associations between pain and fatigue (FACIT-Fatigue) and disease activity (Health Assessment Questionnaire [HAQ], SJC and tender joint count [TJC]). Results : Across all 3 trials (with similar patient baseline characteristics per arm in each trial; Table ) sarilumab 150 mg and 200 mg had lower odds of UP vs comparators (nominal P < 0.05; Figure ). MOBILITY: both sarilumab doses had lower odds (nominal P < 0.05 ) of RP vs placebo at Week 24 (sarilumab 150 mg: 0.60 [0.38, 0.93]; sarilumab 200 mg: 0.57 [0.37, 0.87]) and Week 52 (sarilumab 150 mg: 0.64 [0.37, 1.02]; sarilumab 200 mg: 0.62 [0.37, 1.02]), and RP-strict at Week 52 (sarilumab 150 mg: 0.41 [0.19, 0.90]; sarilumab 200 mg: 0.35 [0.16, 0.76]); TARGET: sarilumab 150mg had lower odds (nominal P < 0.05 ) of RP-strict at Week 24 (0.05 [0.01; 0.39]) ( Figure ). Higher pain level was associated with worse levels of FACIT-fatigue, HAQ, SJC and TJC (all P < 0.001), and UP had mostly moderate agreements with the likelihood of achieving response (minimal clinically important differences) on all these outcomes ( Kappa coefficient values 0.41-0.60). Conclusion : In this post hoc analysis of 3 RCTs in DMARD-IR patients, sarilumab was associated with lower odds of unacceptable pain or refractory pain vs comparators. Further research is needed regarding the sources of persistant pain and the potential role of inflammation control in patients with RA.