Background/Purpose : Sarilumab, a human monoclonal antibody directed against the IL-6 receptor, in combination with non-biologic DMARDs, demonstrated efficacy in the TARGET RCT (NCT01709578). TEAEs and SAEs were more frequent in the sarilumab-treated groups. Laboratory findings were consistent with IL-6 blockade and observations from the MOBILITY study. From an RA patient perspective, fatigue, morning stiffness, pain, ability to participate in family/leisure activities, and work are important outcomes to assess treatment effectiveness. These analyses present the effects of sarilumab+DMARD on the pre-defined secondary endpoints of fatigue, AM stiffness, pain, work within and outside the home and participation in family/leisure activities, and HRQoL at Week 24, as well as change in patient global assessment of disease activity (PtGA) and physical function by Health Assessment Questionnaire (HAQ).

Methods : The intent-to-treat population included 546 patients randomized 1:1:1 to placebo, sarilumab 150 mg every 2 weeks (q2w) or 200 mg q2w + background DMARDs. Patient-reported outcomes (PRO) included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), AM stiffness, Pain VAS, Work Productivity Survey (WPS),Rheumatoid Arthritis Impact of Disease (RAID), and Short Form-36 (SF-36) assessed at baseline, Weeks 2 (FACIT, RAID, Pain and AM stiffness only), 4, 12, and 24. PRO changes from baseline to week 24 were analyzed using mixed-model repeated measures using region, number of prior TNFis, visit, treatment, and treatment by visit interaction as fixed effects and baseline PRO scores as covariates.

Results: Baseline SF-36 Physical (PCS) and Mental Component Summary (MCS) scores were >2 and >1 standard deviation below normative values, respectively, indicating significant disease burden. Statistically significant (p<0.025, simple Bonferroni adjustment) improvements versus placebo+DMARD in FACIT-F, AM stiffness, pain, WPS and RAID were reported by patients receiving sarilumab 150 mg+DMARD and similarly for sarilumab 200 mg+DMARD. SF-36 PCS significantly improved for both doses with no worsening of SF-36 MCS. Significant improvements were seen for 5/8 SF-36 domain scores for sarilumab 150mg + DMARD and 7/8 domain scores for sarilumab 200mg + DMARD. PtGA and HAQ, included in the primary analysis, were statistically significantly improved with both doses of sarilumab.  With few exceptions, statistically significant improvements between sarilumab treatment groups and placebo exceeded the minimum clinically important difference (MCID) for those PROs with established MCIDs.

Conclusion: In this Phase 3 RCT, TNF-IR RA patients receiving either dose of sarilumab+DMARD reported statistically significant and clinically meaningful changes from baseline in fatigue, AM stiffness, pain, productivity and participation, RA impact scores and HRQoL at Week 24.

Table 1. HRQoL, Fatigue, WPS, and RAID at Baseline and Week 24

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-sarilumab-on-fatigue-pain-morning-stiffness-productivity-and-health-related-quality-of-life-hrqol-in-patients-with-active-rheumatoid-arthritis-who-were-inadequate-responders-or-intoler/