A Stanford University clinical investigator, Mark Genovese, led a trial of an experimental drug that produced clinically meaningful improvements for rheumatoid arthritis patients unresponsive to existing treatments.
The Study Summary
The double-blind, randomized Phase 3 clinical trial showed potential and according to investigator Mark Genovese, “for patients who haven’t done well on other therapies, these findings are cause for optimism, enthusiasm, and hope.”
About 70% of rheumatoid arthritis patients have appeared to benefit from small-molecule therapies in a pill form such as methotrexate, mentioned investigator Genovese. But he notes “In the real world, adherence to any of them is more like 50%. For those patients where the conventional small-molecule drugs fail are switched to pricey, injectable, bioengineered-protein drugs, including three of the world’s top-15 biggest selling drugs in dollar sales. But these drugs, too, fail among about half of the rheumatoid arthritis patients who use them.
The trial was conducted in 114 centers in 15 countries, mostly in North America and Europe. The 449 participants were an average of 56 and about 80% female. Randomized to 1 to 3 study arms, patients received daily doses of either 200 milligrams of filgotinib, 100 milligrams of filgotinib or a placebo for 24 weeks. Stanford Medicine News Center reported Bruce Goldman reported that all participants had moderately to severely active rheumatoid arthritis despite treatment with one or more biologic therapies.
The primary study goal was to observe whether there was an improvement at 12 weeks into the trial of at least 20% on a measure of joint swelling and tenderness called the ACR20 that was established by the American College of Rheumatology. An important secondary outcome was a score indicating low disease activity in 28 predetermined joints on a test called DAS28.
The primary goal of the study was to observe whether there was an improvement at 12 weeks into the trial of at least 20% on a measure of joint swelling and tenderness called the ACR20 that was established by the American College of Rheumatology. An important secondary outcome was a score indicating low disease activity in 28 predetermined joints on a test called the DAS28-CRP.
Compared with the placebo group, both the high- and low-dose filgotinib regimens achieved the primary endpoint: a 20% improvement in symptoms as measured by the ACR20. 66% of the participants on 200 milligrams of filotinib and 57% of those on 100 milligrams fulfilled this criterion, versus only 31.1% of those on the placebo.
Investigator Genovese reports that participants’ improvement on the DAS28-CRPn at both 12 and 24 weeks was key. By 12 weeks, 40.8% of those on the 200-milligram dose of filgotinib and 37.3% of those on 100 milligrams had reached the status of low disease activity as measured by the DAS28-CRP, as opposed to only 15.5% of those on the placebo. The outcomes continued or improved over the course of the trial. By 24 weeks, 48.3% of the high-dose filgotinib recipients and 37.9% of those on the low dose had reached low-disease-activity status reports Stanford’s Goldman.
A progressive, systemic autoimmune disease affecting at least 1 in every 100 people worldwide, the majority of patients are women—in fact up to 3 out of every 4 people. While its most visible attributes are a pain, stiffness and inflammation and eventual deterioration of joints, patients also are at heightened risk for cardiovascular disease and other complications.
The Investigational Compound: Filgotinib
Filgotinib, a selective JAK-1 inhibitor, it works by preferentially blocking 1 of the 4 closely related enzymes required for certain inflammatory signaling processes within cells. Two other compounds that are similar in the mechanism of action to filgotinib but that impede JAK enzyme family members less selectively are licensed in the United States for use by rheumatoid arthritis patients, but only at low doses or with warning labels due to side effects. Gilead is the maker of filgotinib.
Lead Research Investigator
This was a multinational study but Mark Genovese led the study on behalf of Stanford. Dr. Genovese is a consultant with Gilead based on self-disclosures.