P213 High baseline serum IL-6 predicts increased sarilumab treatment response for patient reported symptoms and health-related quality of life among RA patients with inadequate response to MTX
Authors: Strand Vibeke , Msihid Jerome , Kimura Toshio , Boyapati Anita , John Gregory St , Wei Wenhui 
Published: April 2020

Abstract

Background
IL-6, a key cytokine in rheumatoid arthritis (RA) pathogenesis, is elevated in patient serum and synovial fluid. However, the impact of baseline IL-6 levels on patient-reported RA symptoms and health-related quality of life (HRQoL) following IL-6 blockade has not been explored. Sarilumab targets IL-6 receptor alpha, and sarilumab+methotrexate (MTX) significantly improved clinical and patient-reported outcomes vs MTX alone among MTX inadequate responders (IR) in MOBILITY/NCT01061736. This post-hoc analysis evaluated whether baseline IL-6 levels predict greater improvements in symptoms and HRQoL with sarilumab+MTX vs MTX.

Methods
1,193 patients with moderate-to-severely active RA received MTX or MTX plus subcutaneous sarilumab at 200 mg (recommended dose) or 150 mg (recommended for management of laboratory abnormalities) every 2 weeks (q2w) and were grouped into tertiles according to baseline IL-6 levels. Patient-reported RA symptoms and HRQoL were measured at baseline and post-treatment (Weeks [W] 24 and 52).

Results
Baseline IL-6 tertiles among 1193 patients were 1.6-9.6 (low), 9.8-30.7 (medium), and 31.2-648.7 pg/mL (high). At baseline, patients with high IL-6 had greater disease activity, more radiographic structural damage, elevated CRP levels, and worse HRQoL (pain visual analog scale [VAS], SF36-physical component scores [PCS], and sleep VAS) vs those with low IL-6 (nominal p &lt; 0.05) and generally reported greater improvements in symptoms and HRQoL with sarilumab+MTX vs placebo+MTX. Significant differences (nominal p &lt; 0.005) between high and low tertiles were evident in improvement of pain VAS (W52) and SF-36 PCS (W24/W52) with sarilumab 200 mg q2w vs placebo, SF-36 mental component scores (both doses; W52) and FACIT-fatigue scores (both doses; W24/W52) vs placebo. Treatment-emergent adverse events were similar across IL-6 tertiles.

Conclusion
Among MTX-IR RA patients, high baseline IL-6 may predict better improvements in symptoms and HRQoL with sarilumab vs placebo, which was consistent with previous analyses across clinical/radiographic endpoints in the same study population.

Disclosures
V. Strand: Consultancies; AbbVie, Amgen, AstraZeneca, Biogen, BMS, Celltrion, CORRONA, Crescendo, Genentech/Roche, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sandoz, Sanofi and U. J. Msihid: Corporate appointments; Employee of Sanofi. Shareholder/stock ownership; Sanofi. T. Kimura: Corporate appointments; Employee of Regeneron Pharmacueticals Inc. Shareholder/stock ownership; Regeneron Pharmacueticals Inc. A. Boyapati: Corporate appointments; Employee of Regeneron Pharmacueticals Inc. Shareholder/stock ownership; Regeneron Pharmacueticals Inc. G. St John: Corporate appointments; Employee of Regeneron Pharmacueticals Inc. Shareholder/stock ownership; Regeneron Pharmacueticals Inc. W. Wei: Corporate appointments; Employee of Regeneron Pharmacueticals Inc. Shareholder/stock ownership; Regeneron Pharmacueticals Inc.