Compared to bDMARDs, these drugs maintain continuity rates and efficacy after first-line therapy.
Continuation rates and efficacy were better among rheumatoid arthritis patients taking JAK inhibitors than comparator treatments, according to a new paper in Rheumatology.
“JAKi maintained continuation rates and efficacy in second-line treatment compared with first-line treatment, potentially advantageous over bDMARDs for patients with RA who require a change in initial therapy,” the authors wrote.
The researchers analysed data Japanese patients with RA across multiple centres, which covered almost 6000 treatment courses and almost 2000 second-line cases. More than 4000 cases were first-line, or naïve, cases.
The study, which was funded by multiple drug manufacturers, tracked the time until patients ceased treatment, as well as ineffectiveness, remission and adverse events.
Biological DMARDs had higher retention rates in first-line treatment, but then had a significant drop in second-line treatment. In contrast, treatment retention was stable across lines for the people taking JAK inhibitors.
Biological DMARDs also came with reduced efficacy in the second-line, whereas efficacy was similar across lines in the JAK inhibitor group.
“Among the TNF inhibitors, interleukin (IL)-6 inhibitors, CTLA4, and JAKi, only JAKi showed no significant difference in CIF [cumulative incidence function] of first- and second-line treatments,” they wrote.
“Competing risk analysis showed that consistent with the CIF analysis, second-line treatment influenced the drug continuation rates for all drugs except for JAKi.”
“Intriguingly, a divergence in trends between JAKi and bDMARDs has emerged in terms of efficacy, although the underlying reasons remain unclear.
“We speculate that JAKi’s broad mechanism of action may allow for efficacy across a wider range of cases. This suggests the potential of JAKi as a viable second-line treatment, namely Phase III treatment, for cases where initial treatment with either bDMARDs or JAKi has failed.”
Nevertheless, JAK inhibitors may not always be the most appropriate second-line therapy, the authors said.
“Owing to concerns about adverse effects—particularly infections, malignancies, thrombosis, and cardiovascular disorders—caution is recommended when using JAKi in Japan, the United States and Europe for patients aged ≥ 65 years, smokers (including those with a history of smoking), and individuals with cardiovascular risk factors, regardless of the indicated disease.
“To fully leverage the efficacy and convenience of JAKi as an oral medication, it is essential to understand their safety profile, carefully select suitable patients, and maintain close monitoring during treatment.”
