SAN FRANCISCO, CA—Long-term administration of mavrilimumab is safe and offers sustained clinical efficacy against moderate-to-severe rheumatoid arthritis (RA), according to an open-label extension study reported at the 2015 ACR/ARHP Annual Meeting.
These benefits were observed over the 74-week treatment duration, with the agent demonstrating “an acceptable sustained safety and tolerability profile, with no significant pulmonary signals,” said Gerd Burmester, MD, of the Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
Mavrilimumab is a “first-in-class” fully human monoclonal antibody that targets the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-α in patients with RA. Using GM-CSF to modulate macrophage function is “a novel therapeutic approach for RA,” he noted. To date, the agent has demonstrated efficacy and safety in 12- and 24‑week studies.
The open-label extension study evaluated long-term safety and efficacy of mavrilimumab through week 74 among patients diagnosed with RA who had completed the Phase 2b EARTH EXPLORER 1 and 2 studies, or who “were rescued as inadequate responders at a predefined time point.”
Study participants were administered subcutaneous mavrilimumab 100mg every other week, the highest dosage in the Phase 2a study, to assess its long-term risk-to-benefit ratio using treatment-emergent adverse events (TEAEs), TE serious AEs (TESAEs), and pulmonary function tests (PFTs).
Exploratory long-term efficacy end points, DAS28-CRP/ACR responses, were also measured. “Change from baseline in modified Total Sharp Score (mTSS) was used to explore radiographic progression in patients previously included in EARTH EXPLORER 1,” he noted.
At Week 74 (including treatment on the original study), 391 patients were enrolled in the open-label extension study. Of these, 329 (84.1%) continued on treatment and 62 (15.9%) discontinued. Reasons for treatment discontinuation included withdrawal of consent, 2.3%; death due to cardiopulmonary failure, 0.3%; adverse event, 1.8%; a non study-related site closure, 5.1%; “other,” 6.1%; and lost-to-follow-up, 0.3%.
“The most common TEAEs of special interest were documented as bronchitis and respiratory tract infection,” Dr. Burmester said; the most common TESAEs were osteoarthritis and bronchitis.
At Week 74, mavrilimumab “demonstrated sustained efficacy”: DAS28-CRP low disease activity (<3.2) was observed in 57.3% of patients and remission (<2.6) in 38.5%. “After 74 weeks of treatment, 68% of patients showed no radiographic progression (<0.5 change in mTSS vs. baseline).”
The study “further demonstrates the potential sustained benefit of inhibiting macrophage activity via the GM-CSFR-α pathway on RA disease activity,” he said.
“Further studies are warranted to investigate the sustained response of mavrilimumab 150mg every other week, previously identified as a well tolerated and the most efficacious dosage in patients with moderate-to-severe RA,” Dr. Burmester concluded.