Pre -security data (IMIDs) show a serious infection rate from a French registry on a French combination therapy and show the need for controlled research before the use of combination therapy, Eric M. Ruderman, MD, Chicago in the Rheumatology Department of the Department of Medicine, Chicico Department of Rheumatology in the CLICOGOGO It was told to the Department of Rheumatology. Symposium (RWCS) 2025.
Data Reported in a poster The American Rheumatology College was emphasized in the 2024 -year -old meeting and RWCS 2025 by Ruderman and Arthur Kavanaugh, and in the Review Seance, MD, Medical Professor, Rheumatology, Rheumatology, Otoimmunity and Rheumatology Department at the University of San Diego.
Kavanaugh, one of the hottest issues last year and forward -looking issues, said therapy therapy, ”he said. “I think the combination therapy is coming; which is just a question of combinations,” he added.
The French Combatt record is an academic, observational, country -wide record aimed at recording at least 1000 patients with IMIDs treated with combined treatment. In the summary, the researchers reported the first 79 patients treated with more than one combination and 97 therapy combination. Nine of 79 patients developed serious infection.
Although the researchers said that their pre -findings proposed a “acceptable short -term security profile ,, Ruderman called on to be careful. “I think we need to act really carefully. I’m looking at this [preliminary data] And I see more than 10% serious infection. ” That’s not what we’re used to seeing with these drugs. “
Combination therapy for a refractory IMID in 46 patients was initiated for two relevant IMIDs in 16 patients and two irrelevant IMID in 17 patients. Refractory imides were mainly rheumatoid arthritis (43.5%), spondyloarthritis (19.6%) and PSA (10.8%). According to summary, the median of six -target treatment was tried before a combination approach was started.
Severe infections occurred in four patients receiving tumor necrosis factor (TNF) + Janus kinase (JAK) inhibitors; TNF + interleökin (IL) -23 Inhibitor receiving two patients; one CTLA4-IG (abatacept) + jak inhibitor; one of the IL-23 + JAK inhibitors; And one CD20 inhibitor + B-Hujre activating factor inhibitor Alan Kavanaugh and Ruderman shared.
Ruderman, “A TNF inhibitor and JAK inhibitor, a combination I’m not really satisfied to try, because you hit a lot of places on the roads,” he said.
“On the other hand, some new agents, such as an IL-17 or an IL-23 inhibitor, are so specific that it can be combined with something else,” he said. “But we have to do this in a thoughtful way and see if we can do it in a way that we can target the complementary ways without increasing risk.”
The roots and future of the combination therapy
The roots of rheumatology’s interest in combination therapy are in gastroenterology JANSSEN Sponsored Phase 2 Vega Trial Kavanaugh found that the Golimumab, a IL-23 inhibitor of ulcerative colitis induction therapy, and a TNF inhibitor, which is a TNF inhibitor, found that only the drug could be more effective than both drugs for ulcerative colitis.
The results of the 2nd phase 2 attempt of the same combination in PSA – proximity – He’s waiting now. In an e-mail interview after the meeting, Ruderman is considered by the industry as “there are essays for some ongoing researchers on the therapy of combination for the PSA”.
Combatt registry data and other open observational data can provide useful information about security, “However, we need controlled data to verify the real safety and effectiveness of the combination therapy.” He said.
In the meantime, in practice, in the interview, “Considering the risk of infection with IL-23 inhibitors, some clinicians begin to think of combining them with other biology.” He said. Vedolizumab, a intestine -specific immune modulation agent for inflammatory bowel disease, is increasingly used with other biologicals for skin and joint disease.
Combination therapy reports in IMIDs usually contain apremilast, a phosphodiesterase 4 inhibitor, but “We think of Apremilast as a powerful anti-inflammatory and is not a trustees in a trustee, not the type of combination treatment that needs research. “Most people are comfortable to use in combination.”
At the meeting, Ruderman said that his warning on combination therapy was 20 years of early combinations of TNF inhibitors and other biologies in RA. [rheumatoid arthritis]. “Published studies showed that the risk of serious infection has doubled.
But still, “Considering the targeted nature of new biologies, I think we can start thinking about combinations after many years of avoiding them,” he said.
Preliminary activity
According to the researchers, the first findings from Combatt Registry suggest that combination treatments can reduce disease activity in some refractory patients. Primary failure (n = 20), loss of secondary activity (n = 9), remission (n = 6), intolerance (n = 5) or unreserved cause (n = 1) due to at least one follow -up visit to 41 of the 80 combinations were cut.
According to summary, 20 out of 36 combination treatment, which has a refractory IMID and at least one follow -up visit, were effective, six were partly effective and two were initially effective with the loss of activity.
In addition to nine serious infections, cytopenia developed in two patients and one had a thromboembolic event.
The study researchers reported financial relations with Abbvie, Gilead Sciences, Eli Lilly Company, Pfizer and other companies. At the RWCS meeting, Kavanaugh reported consultancy to Amgen, BMS, Eli Lilly Company, Janssen and other companies. Ruderman reported that it provides consultancy and/or service for data safety monitoring boards for Jansen, Eli Lilly Company, Merck and other companies.
