Abstract

The development of biomarkers to guide treatment decisions is a major research focus in rheumatoid arthritis (RA). Patients with RA have elevated interleukin-6 (IL-6) levels; however, the utility of IL-6 as a predictor of treatment response is unclear. The objective of this study was to investigate, by post hoc analysis, whether baseline IL-6 levels could predict sarilumab treatment responses in two phase III studies.Serum IL-6 concentrations were measured in patients with RA prior to receiving sarilumab 200 mg (n = 148) or adalimumab 40 mg (n = 152) every two weeks (Q2W) (MONARCH, NCT02332590) or sarilumab 150 or 200 mg+methotrexate (n = 401 and n = 396, respectively) or placebo+methotrexate (n = 397) Q2W (MOBILITY, NCT01061736). Efficacy and patient-reported outcomes were compared between and within groups according to IL-6 tertile using linear and logistic regression.In MONARCH, patients with high baseline IL-6 (n = 100; all =3×upper limit of normal) had higher disease activity at baseline than those with low IL-6 (n = 100). The magnitude of clinical improvement over 24 weeks with sarilumab versus adalimumab was greater in patients with high baseline IL-6 than patients with low baseline IL-6. In MOBILITY, patients with high IL-6 (n = 398) had higher disease activity and joint damage at baseline than those with low IL-6 (n = 397), were more likely to have joint progression, and had less clinical improvement over 52 weeks' treatment with placebo+methotrexate compared with sarilumab 150/200 mg+methotrexate. Baseline IL-6 and C-reactive protein were both predictive of outcomes. Safety profiles were similar between defined IL-6 tertiles.IL-6 may be a prognostic marker of disease progression and severity, and patients with high IL-6 may be likely to benefit from sarilumab compared with adalimumab or methotrexate. Prospective validation is warranted to confirm the results of these post hoc analyses.

View details for DOI 10.1002/art.41299

View details for PubMedID 32343882