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

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. Method(s): 1,193 patients with moderate-to-severely active RA received MTX or MTX plus subcutaneous sarilumab at 200mg (recommended dose) or 150mg (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). Result(s): 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<0.05) and generally reported greater improvements in symptoms and HRQoL with sarilumab+MTX vs placebo+MTX. Significant differences (nominal p<0.005) between high and low tertiles were evident in improvement of pain VAS (W52) and SF-36 PCS (W24/W52) with sarilumab 200mg 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(s): 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.