Filgotinib well-tolerated, efficacious for up to 8 years in rheumatoid arthritis
Key takeaways:
- The 8-year long-term extension found no new safety signals with filgotinib for RA treatment.
- Disease response was sustained throughout, stabilizing after 12 weeks.
Filgotinib, a Janus Kinase 1 inhibitor, remains well-tolerated for up to 8 years with consistent efficacy in patients with rheumatoid arthritis, according to data published in RMD Open.
The findings come from DARWIN 3, an open-label, long-term extension of DARWIN 1 and DARWIN 2, a pair of phase 2b studies that assessed filgotinib (Gilead Sciences/Galapagos NV) in combination with methotrexate and as monotherapy, respectively.
“Janus kinase (JAK) inhibitors are the latest class of targeted, disease-modifying therapies used to treat patients with moderate-to-severe RA,” Rene Westhovens, MD, PhD, of the Skeletal Biology and Engineering Research Center at KU Leuven, in Belgium, and colleagues wrote. “An interim analysis of DARWIN 3 reported that the safety profile of filgotinib was consistent with that in the parent studies, and that filgotinib efficacy was sustained over the 4-year follow-up period.”
Following the subsequent phase-2 studies, the researchers continued their analysis of filgotinib for RA in a long-term extension trial with a maximum of 8 years’ follow-up. Patients in the long-term extension, including 47 from the DARWIN 1 placebo arm, received 200 mg of filgotinib daily, either all at once or 100 mg at a time — except for 15 U.S. men who received 100 mg daily due to an FDA requirement.
A total of 739 patients entered the long-term extension: 497 from the methotrexate trial and 242 from the monotherapy trial. The full study was completed by 242 patients (32.7%), with the top reasons for early discontinuation being treatment-emergent adverse events (n = 266), the patient’s decision (n = 119) and sponsor request (n = 53). The primary endpoint was the incidence of adverse events, indicating the tolerability of long-term treatment.
For treatment-emergent adverse events overall, the exposure-adjusted incidence rate was 67 (95% CI, 62-72.2) per 100 patient-years of exposure, dropping to 3.8 (95% CI, 3.2-4.5) when limited to serious treatment-emergent adverse events, according to the researchers. The most common serious treatment-emergent adverse events, reported in 10 patients each, were pneumonia and osteoarthritis.
Malignancies, most commonly lymphomas, were reported in 21 patients, a rate “comparable to the incidence rate in the general RA population,” the researchers wrote. According to an independent adjudication committee, the rates of major adverse cardiovascular events, venous thromboembolism and arterial systemic thromboembolism were low, with an overall exposure-adjusted incidence rates of 0.2 (95% CI, 0.1-0.4), 0.1 (95% CI, 0-0.3) and 0 (95% CI, 0-0.2), respectively.
In terms of efficacy, disease response was sustained throughout the long-term extension, increasing from baseline to week 12 and then stabilizing. With non-responder imputation, the overall ACR20/50/70 response rates were 26.9%, 20.2% and 14.7%, respectively, at week 396.
“This analysis through 8 years of filgotinib exposure demonstrated a safety profile consistent with previously published data for filgotinib in patients with RA,” Westhovens and colleagues wrote. “Patients who remained on continued filgotinib treatment, either alone or in combination with methotrexate, in the [long-term extension] experienced continued and durable responses through week 396. Together, these results show that long-term filgotinib treatment is both well-tolerated and associated with durable responses in patients with RA.”
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