Serum Interleukin-6 Levels Can Predict Response to Sarilumab in Rheumatoid Arthritis

In a study published in Arthritis & Rheumatology, interleukin (IL)-6 may be a prognostic marker of rheumatoid arthritis (RA) disease progression and severity, but may also be a potential predictor of a better response to sarilumab compared with adalimumab in patients intolerant or inadequately responding to methotrexate (MTX).

In this post-hoc analysis, Boyapati and colleagues aimed to determine whether serum baseline IL-6 levels can predict treatment response to sarilumab in RA patients intolerant or inadequately responding to MTX using data from the MONARCH and MOBILITY phase 3 studies.

Serum IL-6 levels were available in 1193 of 1197 patients in the MOBILITY population prior to receiving sarilumab or placebo and in 300 of 369 patients in the MONARCH population prior to receiving sarilumab or adalimumab.

At baseline, disease activity was moderately greater in patients in the high IL-6 tertile, compared with those in the low IL-6 tertile. Moreover, in patients with higher baseline serum IL-6 levels joint damage progression was faster and the clinical outcomes were worse.

High serum IL-6 levels at baseline predicted a greater response to sarilumab, compared with adalimumab or placebo+methotrexate. In patients with high serum IL-6 levels, treatment with sarilumab was associated with higher rates of Disease Activity Score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) or DAS28-C-reactive protein (DAS28-CRP) remission, and American College of Rheumatology (ACR) responses, compared with adalimumab. In both studies, baseline IL-6 and baseline CRP were predictive of outcomes.

There were no differences in safety events among patients in the low, medium, and high IL-6 tertiles in both studies. In addition, there was no difference in the rate of infections between sarilumab and adalimumab.

The study had several limitations, including those associated with post-hoc analyses, as the 2 studies were not designed to prospectively assess the predictive potential of serum IL-6 levels in RA, the limited number of patients in each IL-6 tertile, and no assessment of other potential markers associated with tumor necrosis factor-α signaling.

“These analyses suggest serum IL-6 could be a useful marker to guide treatment choices for patients with RA, if validated prospectively in an independent clinical study. High baseline IL-6 levels predicted a better response to sarilumab compared with adalimumab monotherapy in MTX-IR [inadequate response]/intolerant patients,” concluded the researchers.

Reference

Boyapati A, Schwartzman S, Msihid J, et al. High serum interleukin-6 is associated with severe progression of rheumatoid arthritis and increased treatment response differentiating sarilumab from adalimumab or methotrexate in a post hoc analysis [published online 28 Apr, 2020]. Arthritis Rheumatol. doi:10.1002/art.41299