Association of High Serum Interleukin-6 Levels With Severe Progression of Rheumatoid Arthritis and Increased Treatment Response Differentiating Sarilumab From Adalimumab or Methotrexate in a Post Hoc Analysis

Objective The development of biomarkers to guide treatment decisions is a major research focus in rheumatoid arthritis (RA). Patients withRAhave elevated interleukin-6 (IL-6) levels; however, the utility ofIL-6 as a predictor of treatment response is unclear. This study was undertaken to investigate, by post hoc analysis, whether baselineIL-6 levels are predictive of sarilumab treatment responses in 2 phaseIIIstudies. Methods SerumIL-6 concentrations were measured in patients withRAprior to receiving sarilumab 200 mg (n = 148) or adalimumab 40 mg (n = 152) every 2 weeks (in theMONARCHtrial; ClinicalTrials.gov identifier:NCT02332590) or sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks plus methotrexate (MTX) (n = 401, n = 396, and n = 397, respectively) (in theMOBILITYtrial; ClinicalTrials.gov identifier:NCT01061736). Efficacy and patient-reported outcomes were compared between and within groups according toIL-6 tertile using linear and logistic regression. Results InMONARCH, patients with high baselineIL-6 levels (all >= 3 times the upper limit of normal; n = 100) had higher disease activity at baseline than those with lowIL-6 levels (n = 100). The magnitude of clinical improvement over 24 weeks with sarilumab versus adalimumab was greater in patients with high compared to those with low baselineIL-6 levels. InMOBILITY, compared to patients with lowIL-6 levels (n = 397), patients with highIL-6 levels (n = 398) had higher disease activity and joint damage at baseline, were more likely to have joint progression, and had less clinical improvement over 52 weeks' treatment with placebo plusMTXcompared to sarilumab 150 mg or 200 mg plusMTX. BaselineIL-6 and C-reactive protein levels were both predictive of outcomes. Safety profiles were similar between definedIL-6 tertiles. Conclusion IL-6 may be a prognostic marker of disease progression and severity, and patients with highIL-6 levels may be likely to benefit from sarilumab compared to adalimumab orMTX. Prospective validation is warranted to confirm the results of these post hoc analyses.