Boyapati is an employee of Regeneron Pharmaceuticals and may hold stock and/or stock options in the company. Please see the study for all other authors’ relevant financial disclosures.
Among patients with rheumatoid arthritis and an inadequate response to methotrexate, high baseline IL-6 may be a prognostic marker of disease progression and severity, and predict better response to sarilumab compared with adalimumab, according to data published in Arthritis & Rheumatology.
“Treatment decisions could be optimized if diagnostics were available to help identify patients most likely to benefit from a particular therapy,” Anita Boyapati, PhD, of Regeneron Pharmaceuticals, and colleagues wrote. “However, currently, there are no validated predictive markers of treatment response. Although biomarkers have been evaluated in clinical trials and real-world cohorts, the ability to predict outcomes before therapy initiation remains elusive.”
“Patients with RA have elevated levels of interleukin-6 (IL-6) in serum and synovial fluid,” they added. “IL-6 drives inflammation and promotes articular destruction, is involved in the development of extra-articular manifestations, and correlates with disease activity. Despite the key role of IL-6 in RA, there are limited and inconclusive data on the potential of serum IL-6 to predict treatment response. Two monoclonal antibodies that target IL-6 signaling (sarilumab and tocilizumab) are approved for the treatment of RA, and patients with elevated IL-6 levels may be more likely to derive benefit from these agents versus others.”
To determine whether baseline IL-6 can predict sarilumab (Kevzara, Regeneron Pharmaceuticals and Sanofi) treatment response, Boyapati and colleagues conducted a post hoc analysis of two phase 3 studies. In the MONARCH study, 300 patients with moderate-to-severe RA who were intolerant of, or had an inadequate response to, methotrexate were randomly assigned to receive either sarilumab 200 mg or adalimumab (Humira, AbbVie) 40 mg every 2 weeks.
In the other study, called MOBILITY, investigators randomly assigned 1,197 patients with moderate-to severe RA and an inadequate response to methotrexate to receive sarilumab 150 mg, sarilumab 200 mg or a placebo every 2 weeks, alongside weekly methotrexate, for 52 weeks. Boyapati and colleagues used linear and logistic regression to compare the efficacy and patient-reported outcomes between and within treatment groups based on IL-6 tertile.
According to the researchers, MONARCH participants with high baseline IL6 — 100 in total, all with three or more times the upper limit of normal — demonstrated higher disease activity at baseline compared with those with low IL6. Further, sarilumab had a greater magnitude of clinical improvement over a period of 24 weeks, compared with adalimumab, among those with high baseline IL-6 compared with those with lower levels.
Additionally, MOBILITY participants with high IL6 — a total of 398 — demonstrated higher disease activity and joint damage at baseline compared with those with low IL6. Patients with higher IL-6 were also more likely to have joint progression and less clinical improvement over 52 weeks with placebo alongside methotrexate, compared with sarilumab plus methotrexate. Moreover, baseline IL6 and Creactive protein were predictive of outcomes. Safety profiles were similar between the defined IL6 tertiles.
“In MTX-IR patients, high baseline IL-6 predicted more joint damage in patients who remain on MTX therapy over time,” Boyapati and colleagues wrote. “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/intolerant patients.”