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Rheumatoid arthritis patients getting little or no relief from conventional drugs and injections saw “substantial improvement” in their condition from daily use of the experimental compound.
The findings of the 24-week American study were published in the Journal of the American Medical Association (JAMA).
Principal investigator Professor Mark Genovese, of Stanford University School of Medicine, said: “For patients who haven’t done well on other therapies, these findings are cause for optimism, enthusiasm and hope.”
Rheumatoid arthritis is a progressive, autoimmune disease affecting at least one in every 100 people worldwide. For reasons that aren’t understood, three of every four people with the disorder are women.
While its most visible hallmarks are pain, stiffness, inflammation and eventual deterioration of joints, patients also are at heightened risk for heart disease and other inflammatory complications.
In clinical trials, around 70 per cent of rheumatoid arthritis patients have appeared to benefit initially from small-molecule therapies in a pill form, such as methotrexate,
But Prof Genovese said: “In the real world, adherence to any of them is more like 50 per cent.”
He said patients for whom 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.
But Prof Genovese said these drugs, too, fail among about half the rheumatoid arthritis patients who use them.
He explained that the experimental compound, filgotinib, is a selective ‘JAK-1’ inhibitor which works by preferentially blocking one of a set of four closely related enzymes required for certain inflammatory signaling processes within cells.
The trial was conducted in 114 centres in 15 countries. The 449 participants averaged 56 years of age, and about 80 per cent of them were female.
They were divied into three study groups which received daily doses of either 200 milligrams of filgotinib, 100 milligrams of filgotinib or a placebo for 24 weeks. All
the participants had moderately to severely active rheumatoid arthritis.
The primary goal of the study was to observe whether there was an improvement at 12 weeks into the trial of at least 20 per cent on a measure of joint swelling and tenderness.
Prof Genovese said that an important secondary outcome was a score indicating low disease activity in 28 predetermined joints on a test called the DAS28-CRP.
The findings showed that, compared with the placebo group, a “significantly greater proportion” of participants on both the high- and low-dose filgotinib regimens achieved the primary endpoint: a 20 per cent improvement in symptoms.
Two out of three participants on 200 milligrams of filgotinib (66 per cent), and 57.5 per cent of those on 100 milligrams, fulfilled the criterion, compared to only 31.1 per cent of those in the placebo group.
But Prof Genovese said that of equal or even greater importance was the participants’ improvement on the DAS28-CRP at both 12 and 24 weeks.
By 12 weeks, 40.8 per cent of those on the 200 milligram dose of filgotinib and 37.3 per cent 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 per cent of those in the placebo group.
And the outcomes continued or improved over the course of the trial. By 24 weeks, 48.3 per cent of the high-dose filgotinib recipients and 37.9 per cent of those on the low dose had reached low-disease-activity status.
By week 12 of the trial, 22.4 per cent of high-dose and 25.5 per cent of low-dose filgotinib recipients, but only 8.1 per cent of placebo recipients, had DAS28-CRP scores indicating outright remission.
By week 24, high-dose recipients had a remission rate of 30.6 per cent; low-dose recipients, 26.1 per cent; and placebo recipients, 12.2 per cent.
Prof Genovese said: “The drug’s benefits to participants became apparent soon after the trial’s onset.
“We could see improvements as early as two weeks into the trial.”
He also noted a substantial difference among the study groups in how many participants completed the 24-week trial was telling.
Of the 148 participants in the placebo group, 51 dropped out before completion. Only 20 of the 148 high-dose recipients and 34 of the 153 low-dose recipients dropped out.
The researchers’ early concerns about increased susceptibility to infections, or the re-emergence of active forms of prior infections, such as TB or shingles, were eased by the relative smattering of such adverse events, compared with placebo.
Prof Genovese explained that patients for whom at least three different biologic therapies provided insufficient relief did as well in this trial as those who’d derived insufficient relief from just one biologic therapy.
He said: “We found that those high levels of response were independent of how many drugs you’d failed, and independent of which drugs you’d failed.”
Prof Genovese said that overall response rates to filgotinib appear to surpass those of the other commercially available JAK inhibitors at doses approved for use in the United States.
He added: “This novel drug works exceptionally well in patients who’ve already failed traditional therapies for rheumatoid arthritis.”
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