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MADRID, July 24 (EUROPE PRESS) –
Patients with rheumatoid arthritis who achieved little or no relief from conventional small molecule drugs and injectable biologic drugs found a substantial improvement in their condition with respect to the daily use of a compound experimental in the context of a large 24-week study led by a researcher. Stanford University School of Medicine (USA), as published Tuesday in the journal "JAMA".
"For patients who have not had good results with other treatments, these results are a source of optimism, enthusiasm and hope," says Dr. Mark. Genovese, Professor of Immunology and Rheumatology and Principal Investigator of the Randomized Phase 3 Clinical Trial. Stanford Health Care provides services to patients with rheumatoid arthritis through its Immunology Clinic and Clinical Trial. rheumatology. As head of clinic, Genovese spends 3.5 days a week at the clinic, where he regularly treats patients with this disease.
Rheumatoid arthritis is a systemic and progressive autoimmune disease that affects at least 1 in 100 people worldwide. For reasons still unknown, 3 out of 4 people are women. Although its most visible features are pain, stiffness, inflammation and, finally, deterioration of the joints, patients also run an increased risk of cardiovascular disease and other inflammatory complications.
In clinical trials, about 70% of patients with rheumatoid arthritis appear to have initially benefited from treatment with small molecules in the form of pills, such as methotrexate, Genovese notes. However, "in the real world, joining one of them amounts to 50%," he adds.
Patients who lack conventional small molecule drugs are switching to expensive, injectable and transgenic drugs, including three of the world's top 15 most sold drugs. But these medications also fail in half of the patients with rheumatoid arthritis who use them, says Genovese.
The experimental compound, filgotinib, is a selective inhibitor of JAK-1. It works by preferentially blocking a set of four closely related enzymes required for certain inflammatory signaling processes within cells. In the United States, it is allowed to patients with rheumatoid arthritis to use two other compounds whose mechanism of action is similar to that of filgotinib, but which prevent family members of JAK enzymes so less selective, but only at low doses or With warning labels because of side effects.
The trial was conducted in 114 centers in 15 countries, mainly in North America and Europe. The 449 participants were on average 56 years old and about 80% of them were women. They were randomized to one of three study groups, in which they received daily doses of 200 mg filgotinib, 100 mg filgotinib or placebo for 24 weeks. All participants had moderate to severe active rheumatoid arthritis despite treatment with one or more biologic therapies.
The primary objective of the study was to determine whether there was an improvement at 12 weeks of the test of at least 20% of the measurement of inflammation and joint sensitivity called ACR20 established by the American College of Rheumatology. An important secondary outcome was a score indicating low disease activity in 28 predetermined joints in a test called DAS28-CRP.
Compared with the placebo group, a significantly higher proportion of participants in the high and low dose regimens of filgotinib reached the endpoint: a 20% improvement in symptoms measured by ACR20. 66% of participants taking 200 milligrams of filgotinib and 57.5% of those taking 100 milligrams met this criterion, compared to only 31.1% of those who received a placebo.
The improvement in DAS28-CRP participants at both 12 and 24 weeks was also of equal or greater importance. At 12 weeks, 40.8% of those taking the 200 milligram dose of filgotinib and 37.3% of those taking 100 milligrams had reached the stage of low disease activity, measured by DAS28-CRP, compared to only 15.5% of those who took the placebo. These results continued or improved throughout the trial. At 24 weeks, 48.3% of the high-dose filgotinib recipients and 37.9% of those taking the low dose had achieved a low level of disease activity.
In week 12 of the trial, 22.4% of patients receiving high dose filgotinib and 25.5% of those receiving low dose filgotinib, but only 8.1% of those receiving received a placebo. , had DAS28-CRP scores that indicated absolute remission. At week 24, patients receiving the high dose had a remission rate of 30.6%; low dose recipients, 26.1%; and placebo-treated patients, 12.2%.
The benefits of the drug for the participants became evident shortly after the start of the trial. "We could see improvements as early as two weeks after the trial," Genovese said.
The number of participants completing the 24-week trial was also a substantial difference between the study groups. Of the 148 participants in the placebo group, 51 dropped out before completing. Only 20 of the 148 high dose recipients and 34 of the 153 low dose recipients were withdrawn.
Initial concerns of researchers regarding increased susceptibility to infections, or the reappearance of active forms of previous infections, such as tuberculosis or herpes zoster, have been mitigated by the relative dispersion of these adverse events, compared with placebo
In particular, patients for whom at least three different biological therapies provided insufficient relief also did so in this trial, such as those who achieved insufficient relief with a single biological therapy, notes Genovese. "We found that these high levels of response were independent of the number of failed and failed drugs," he adds.
The overall response rate to filgotinib appears to exceed that of other commercially available JAK inhibitors at approved doses in the US, he explained. "This new drug works exceptionally well in patients who have previously failed traditional therapies for rheumatoid arthritis," Genovese concludes.
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