Sirukumab Improves Depression in Patients With Rheumatoid Arthritis
Results from this study may implicate IL-6 dysfunction in depression.
Peripheral anti-interleukin (IL)-6 cytokine treatment is associated with improvement in depressive symptoms in patients with rheumatoid arthritis (RA) and might also support a role for IL-6 dysfunction in depression, according to research presented at the European League Against Rheumatism (EULAR) Congress 2017, held June 14 to 17 in Madrid, Spain.1
A team of researchers from Janssen Research & Development, LLC, in Titusville, New Jersey, conducted post hoc analysis of 2 phase 3, randomized, double-blind, placebo-controlled trials to examine and validate the effects of sirukumab on relieving depressive symptoms in patients with RA.
They grouped patients according to presence and/or absence of prevalent depressed mood and anhedonia (PDMA), according to self-report frequencies of the 2 core depressive symptoms in the SF-36. They required that 1 symptom be present "most of the time" and the other be present "some of the time" in the previous 4 weeks.
They evaluated relief of depressive symptoms in PDMA by comparing changes in the depression score from baseline to week 8 and combined sirukumab groups directly, and with adjustment for RA activity as measured by the Disease Activity Score-28 with C-Reactive Protein.
"Changes in depression score were also analyzed in RA patients who did not have an [American College of Rheumatology 50] response to sirukumab," the researchers said. "The combined effect of anti-IL-6 treatment was estimated using meta-analysis of 2 Phase III, 1 Phase II studies of sirukumab and 1 Phase II study of the anti-IL-6 cytokine antibody siltuximab."
The researchers classified 19% and 22% of patients, respectively, as PDMA in the 2 studies at baseline. "Sirukumab treatment, compared to placebo, significantly improved depressive symptoms by week 8 among PDMA patients (p=0.022 and 0.046 for the 2 studies, respectively) before adjusting for changes in RA activity," the team from Janssen reported. "Within the sirukumab group, the reduction in depressive symptoms remained significant after adjusting for changes in RA activity (p<0.0001) and in ACR50 non-responders at week 8 (p<0.0001), while differences in improvements between the sirukumab and placebo group reduced to trends.
"Meta-analysis of 4 anti-IL-6 studies (1 siltuximab, 3 sirukumab) revealed that anti-IL-6 treatment helps alleviate depressive symptoms even after adjusting for changes in disease activity (Standardized Mean Difference = 0.25, p=0.03)," they added, confirming that, in keeping with results from a previous phase 2 RA study, peripheral anti-IL-6 cytokine treatment can assist with depressive symptoms in patients with RA.
- Sun Y, Hsu B, Wang D, et al. Improvement in Measures of Depressed Mood and Anhedonia in Two Randomized, Placebo-Controlled Phase III Studies of Sirukumab, a Human Anti-Interleukin-6 Antibody, in Patients with Rheumatoid Arthritis. Presented at: European League Against Rheumatism (EULAR) Congress 2017; June 14-17 2017; Madrid, Spain. doi:10.1136/annrheumdis-2017-eular.3263