MADRID — For patients with rheumatoid arthritis whose response to methotrexate is inadequate, filgotinib, an oral Janus kinase 1 (JAK1) inhibitor, leads to significant improvement, early data from the FINCH 1 trial (NCT02889796) suggest.
Filgotinib could become the third drug in its class to be approved for rheumatoid arthritis, and its effectiveness and ease of use makes it a potential monotherapy, said investigator Bernard Combe, MD, PhD, from Montpellier University in France.
“It’s a very important finding.” JAK inhibitors will probably be the leading treatment in rheumatoid arthritis in the near future, at the same level as TNF drugs, he said here at the European League Against Rheumatism (EULAR) 2019 Congress.
The data are in line with “what I’ve seen with previous JAK inhibitors,” Combe told Medscape Medical News. “What is maybe different here is filgotinib is specifically a JAK1 inhibitor, so the mechanism of action is slightly different than the two others.”
Those two JAK inhibitors — baricitinib (Olumiant, Eli Lilly) and tofacitinib (Xeljanz, Pfizer) — currently approved by the US Food and Drug Administration and the European Medicines Agency to treat rheumatoid arthritis both target the JAK pathway to ease inflammation.
Combe presented interim primary outcome results from the 52-week phase 3, double-blind, placebo-controlled international FINCH 1 trial.
FINCH 1 Trial
The study participants, 81.8% of whom were female, had moderate to severe rheumatoid arthritis for an average of 7 to 8 years, had an inadequate response to at least 12 weeks of methotrexate, and had been on a stable dose of methotrexate for at least 4 weeks immediately before randomization to one of four treatment groups.
Of the 1755 participants, 475 participants received filgotinib 200 mg daily, 480 received filgotinib 100 mg daily, 325 received the TNF inhibitor adalimumab (Humira, AbbVie) daily, and 475 received placebo.
Filgotinib acted quickly and sustained its effect through week 24, Combe reported. It appeared to help prevent radiographic progression of the disease and improved physical function, measured with the Health Assessment Questionnaire Disability Index at week 12.
Significantly more patients in the filgotinib groups than in the placebo group achieved an improvement of at least 20% in American College of Rheumatology criteria (ACR20) at 12 weeks.
|Interim Response Rates|
|Response||Filgotinib 200 mg, %||Filgotinib 100 mg, %||Placebo, %|
|*P < .001 vs placebo|
At week 24, ACR20, ACR50, and ACR70 response rates in the adalimumab group were similar to those in the filgotinib groups.
There were no significant safety differences between the study groups, and rates of serious infections, venous thrombosis, and other adverse events were low. Serious infections were slightly higher in the filgotinib groups than in the placebo group, and were higher in all those groups than in the adalimumab group.
The relatively high response rates in the placebo group were not a surprise, said Combe, who noted that the trial is ongoing, “so we’re looking for an explanation.” Participants from Eastern Europe had a much higher placebo responses than those in North America and Western Europe, he added.
Filgotinib could be an alternative JAK inhibitor for RA, if it’s approved.
Because participants had taken methotrexate before baseline, “there could still be a methotrexate effect during the trial,” despite the seeming inadequate response before data were collected, he pointed out.
This trial is “huge” compared with others testing JAK inhibitors in rheumatoid arthritis, said Thomas Dörner, MD, from Charité Universitätsmedizin Berlin, who is chair of the EULAR scientific program committee.
He said he agrees that the apparent effects of filgotinib in patients with rheumatoid arthritis are similar to the effects of other JAK inhibitors, and that it might be useful as a monotherapy.
“The safety profile also looks comparable to what we’ve seen for other compounds, so I think this represents what one would expect in this class of molecules in a phase 3 trial,” Dörner told Medscape Medical News.
“For me, this is a successful trial,” he added. “It’s convincing, and filgotinib could be an alternative JAK inhibitor for RA, if it’s approved.”
Additional data are needed, including safety data, said Combe, but filgotinib is “clearly promising” and “we can assume that the likelihood of it being on the market within 2 years is very good.”
Combe is a consultant for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, and UCB. Dörner receives grant/research support or is a consultant for Eli Lilly, Janssen, Roche, and UCB Pharma, and is a member of the speakers’ bureau for Eli Lilly and Janssen.
European League Against Rheumatism (EULAR) 2019 Congress: Abstract LB0001. Presented June 12, 2019.