Sarilumab scores over adalimumab in improving physical function in RA: Study
The study is published in the Journal of Arthritis and Research Therapy.
Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL).
Therefore, Vibeke Strand and colleagues from the Stanford University, Palo Alto, CA, US conducted the MONARCH phase III randomized controlled trial to evaluate the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab.
Sarilumab is a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor α (anti-IL-6Rα) whereas adalimumab is a tumor necrosis factor α inhibitor, both of which are approved for treatment of active Rheumatoid Arthritis.
The authors designed the study in the following manner-
a. Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6–7.1 pg/mL), medium (7.2–39.5 pg/mL), and high (39.6–692.3 pg/mL) tertiles.
b. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale
c. Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference.
The researchers found that at baseline, patients with high versus medium or low IL-6 levels reported worse SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores.
There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS PCS improvements ≥MCID were higher in high versus low tertiles with sarilumab versus adalimumab . Adverse events between IL-6 tertiles were similar, they further added.
So the authors finally concluded that "Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade."
For further reference, log on to-Strand, V., Boklage, S.H., Kimura, T. et al. High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab. Arthritis Res Ther 22, 250 (2020).