SAT0643\u2005FACIT-FATIGUE TO PROMIS-FATIGUE CROSS-WALKED DATA FROM MONARCH, MOBILITY AND TARGET RANDOMIZED CLINICAL TRIALS OF SARILUMAB FOR THE TREATMENT OF MODERATELY-TO-SEVERELY ACTIVE RHEUMATOID ARTHRITIS (RA)

Abstract

Background Fatigue is a common symptom in RA and increasingly recognized as an important therapeutic target in disease management. Phase 3 randomized clinical trials (RCTs) have shown significant improvements in fatigue for sarilumab, based on the 13-item Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue measure. In TARGET (n=546) and MOBILITY (n=1197), patients receiving sarilumab 150 or 200 mg subcutaneous (SC) every 2 weeks (Q2W) achieved clinically meaningful improvements in fatigue vs placebo. In MONARCH (n=369), there was a trend towards greater improvement in fatigue scores for sarilumab 200mg mg Q2W vs adalimumab 40 mg Q2W monotherapies. To facilitate comparability of fatigue outcomes across studies and measures, the National Institutes of Health (NIH)-funded Patient Reported Outcomes Measurement Information System® (PROMIS®) initiative developed a fatigue item bank of 95 items that includes the FACIT-Fatigue scale within it. This allows FACIT-F scores to be cross-walked to the PROMIS T-score metric, including the subset of 10 FACIT-F items deemed most relevant to RA patients. Objectives To describe patient-level, cross-walked PROMIS-fatigue and scoring service 13- and 10-item PROMIS-fatigue scores from TARGET, MOBILITY and MONARCH. Methods FACIT-Fatigue scores were cross-walked to PROMIS-Fatigue (using look up tables at the individual patient level), with PROMIS-Fatigue 10- and 13-item T-scores derived from individual patient level data via the publicly available scoring service (http://www.healthmeasures.net). Between-group comparisons of differences (Δ) on least-square mean (LSM) Week 24 change-from-baseline (CFB) scores were evaluated between sarilumab 150 or 200 mg SC Q2W vs placebo (+conventional disease modifying anti-rheumatic drugs in both arms) in TARGET and MOBILITY (including Week 52 CFB) and sarilumab 200 mg SC Q2W vs adalimumab 40mg Q2W monotherapies in MONARCH. Results In TARGET and MOBILITY, Week 24 LSM CFB for cross-walked PROMIS-Fatigue scores ranged from −6.10 to −7.22 for sarilumab 150mg and −6.76 to −7.05 for sarilumab 200mg (−6.72 and −6.94 Week 52 CFB in MOBILITY, respectively) and −4.08 to −4.90 for placebo (−4.34 Week 52 CFB). ΔLSM were significant (p < 0.05) for sarilumab vs placebo for both doses, in both RCTs. In MONARCH, Week 24 LSM was −5.80 for adalimumab and −7.24 for sarilumab, with non-significant ΔLSM. T-scores on 13- and 10-item PROMIS-fatigue obtained similar results across all studies (Table). Conclusion Consistent with trial results shown for FACIT-Fatigue, following cross-walk to PROMIS-Fatigue and on PROMIS-Fatigue 13 and 10 T-scores, patients treated with sarilumab demonstrated statistically greater and clinically meaningful improvement in fatigue vs placebo and a trend towards greater improvement vs adalimumab. Converting FACIT-fatigue data to PROMIS-fatigue using either the patient level cross-walk or via the patient level scoring service provides a common metric for comparisons of fatigue outcomes across treatments for RA and against US clinical population reference scores.Table Week 24 least-square mean differences of change from baseline from TARGET, MOBILITY (and 52) and MONARCH from FACIT-Fatigue raw scores, cross-walked patient-level PROMIS-Fatigue scores and PROMIS-Fatigue 13 and 10 T-score scoring service Green boxes P < 0.05; * P < 0.001 Acknowledgement Medical writing support was provided by Gauri Saal, MA Economics, Prime, Knutsford, UK and funded by Sanofi and Regeneron Pharmaceuticals, Inc. The study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interests Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Susan Boklage Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Toshio Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., David Cella Consultant for: Sanofi and Regeneron Pharmaceuticals, Inc.