Patients with rheumatoid arthritis who received sarilumab plus a DMARD who did not respond to anti-TNF medications showed statistically significant and clinically meaningful changes from baseline in fatigue, morning stiffness, pain, productivity, and participation at week 24.
In a Phase 3 trial, rheumatoid arthritis (RA) patients receiving sarilumab plus a DMARD who did not respond to anti-TNF medications showed statistically significant and clinically meaningful changes from baseline in fatigue, morning stiffness, pain, productivity and participation at week 24. The results were presented at the 2015 American College of Rheumatology Annual Meeting being held this week in San Francisco.
The findings are important, because fatigue, stiffness, and pain are important quality of life (QoL) indicators for RA patients and are key measures of treatment effectiveness.
Sarilumab, which is being co-developed by Regeneron and Sanofi, is a human monoclonal antibody directed against the Interleukin-6 (IL-6) receptor, in combination with non-biologic DMARDs. IL-6 is a key driver of inflammation, and is elevated in the serum and synovial fluid of patients with RA.
The findings are consistent with the 2014 Phase 2 MOBILITY study, which found that sarilumab improved signs and symptoms of RA over 12â€…weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. In that trial, sarilumab 150â€…mg and sarilumab 200â€…mg q2w had the most favorable efficacy, safety and dosing convenience, but lower doses of sarilumab were no more effective than placebo.
In the Phase 3 trail, 546 patients were randomized 1:1:1 to placebo, sarilumab 150 mg every 2 weeks (q2w) or 200 mg q2w + background DMARD. Patient-reported outcomes (PRO) included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), AM stiffness, Pain VAS, Work Productivity Survey (WPS), Rheumatoid Arthritis Impact of Disease (RAID), and Short Form-36 (SF-36) assessed at baseline and at regular intervals throughout the study period.
Statistically significant (p<0.025, simple Bonferroni adjustment) improvements versus placebo+DMARD in FACIT-F, AM stiffness, pain, WPS and RAID were reported by patients receiving sarilumab 150 mg+DMARD and similarly for sarilumab 200 mg+DMARD.
Significant improvements were seen for 5/8 SF-36 domain scores for sarilumab 150mg + DMARD and 7/8 domain scores for sarilumab 200mg + DMARD. With few exceptions, statistically significant improvements between sarilumab treatment groups and placebo exceeded the minimum clinically important differences.
Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)â€‘â€‘typically infectionsâ€‘â€‘were more frequent in the sarilumab-treated groups.