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Interleukin-6 level shows promise as predictor of disease progression in rheumatoid arthritis

Key clinical point: Higher serum IL-6 levels at baseline may predict RA severity, and these patients may reap greater benefit from sarilumab compared with adalimumab or methotrexate.

Major finding: Rheumatoid arthritis patients with higher serum levels of IL-6 at baseline showed greater clinical improvement when treated with sarilumab compared with adalimumab or with sarilumab plus methotrexate compared with a placebo plus methotrexate.

Study details: The data come from rheumatoid arthritis patients given sarilumab or adalimumab in the MONARCH study and patients given sarilumab plus methotrexate or placebo plus methotrexate in the MOBILITY study.

Disclosures: The research was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. Lead author Anita Boyapati, PhD, is an employee of Regeneron Pharmaceuticals and may hold stock and/or stock options in the company.

Commentary

“A prospective biomarker to help guide treatment of RA would be invaluable in helping patients achieve control of their disease as quickly as possible. This study aims to investigate whether baseline serum IL-6 levels can predict patient response to sarilumab, an IL-6 inhibitor, vs. adalimumab, a TNF-inhibitor, or methotrexate, a conventional DMARD. The study uses post-hoc data from the MONARCH and MOBILITY trials. In the MOBILITY trial (sarilumab vs. methtorexate), IL-6 was prespecified to be measured at baseline and multiple timepoints during the course of the trial, while in MONARCH, IL-6 levels were obtained from patients who gave consent after the trial began and had a baseline measurement. Efficacy parameters in MONARCH included DAS28 (ESR and CRP), CDAI, ACR response, HAQ DI improvement, TJC, and SJC.

Odds ratios for efficacy of sarilumab vs. adalimumab were higher in the high IL-6 tertiles, but these results must be interpreted with the understanding that intra-subject IL-6 variability is not accounted for, and that some of the measures that show response (for example CRP in DAS28-CRP) are also linked to IL-6 level. The MOBILITY post-hoc analysis data also show numerically greater improvement of these indices in patients treated with sarilumab in the high vs. low IL-6 tertiles, but both groups did tend to respond to sarilumab. Because this study uses post hoc analysis, these findings could provide the basis for future randomized controlled trials, but do not yet give us information that we can use to stratify RA patients prior to biologic therapy.”

Arundathi Jayatilleke, MD

Lewis Katz School of Medicine, Temple University

Citation:

Boyapati A et al. Arthritis Rheumatol. 2020 Apr 28. doi: 10.1002/art.41299.