Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAK-pot’ collaboration

Abstract

BackgroundJAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers.MethodsIn this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk.ResultsWe included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA.ConclusionThe adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway

“…A causal link between inflammation and the development of RA is generally accepted (44). IL-2, IL-6, IL-10 and TNF-α serve important roles in RA pathogenesis, participating in Th1-mediated processes, and causing cartilage and bone destruction (45)(46)(47)(48). The present study confirmed that overexpression of UBD significantly induced the secretion of IL-2, IL-6, IL-10 and TNF-α in RA-FLSs.…”

After JAK inhibitor failure: to cycle or to switch, that is the question – data from the JAK-pot collaboration of registries

“…The aim of this collaboration is to carry out studies to evaluate the effectiveness and safety aspects of JAKi and bDMARDs. The first study resulting from this collaboration has recently been published 21. In this specific nested cohort, we included patients with RA with first JAKi treatment failure who were subsequently being treated with a second JAKi or with a bDMARD.…”

Perifolliculitis capitis abscedens et suffodiens treatment with tumor necrosis factor inhibitors and baricitinib: A case report and literature review

“…Given the potential for increased frequency of serious adverse events (including heart disease, blood clots, infections, and anemia) when combining targeted therapies, we are very cautious in setting the dosage of the two medications. According to a meta-analysis published in 2022, JAK inhibitor was discontinued more often among patients with RA for adverse events, and less often for inefficacy compared to TNF inhibitor ( 26 ). Treatment continues to be dominated by adalimumab, with baricitinib playing an adjuvant role.…”