medwireNews: Janus kinase (JAK) inhibitors show promise for the treatment of moderate-to-severe psoriasis and psoriatic arthritis (PsA), finds a systematic review and meta-analysis of more than 6000 patients.
A total of 15 “high quality” randomized controlled phase 2 and 3 clinical trials involving patients with moderate-to-severe plaque psoriasis or PsA were included, report the researchers. The participants were treated with JAK inhibitors (tofacitinib in seven trials) or placebo for a minimum of 4 weeks and a maximum of 24 weeks, with follow-up periods ranging from 8 to 52 weeks.
All the studies included PASI75 as an outcome and patients treated with JAK inhibitors were 9.9 times more likely to achieve this response than those taking placebo. The improvement was greatest for patients treated with tofacinib versus placebo, at 14.4-fold compared with 5.9-fold for those treated with other JAK inhibitors, namely upadacitinib, itacitinib, peficitinib, filogtinib, or baricitinib.
ACR20 was included as an outcome in PsA patients in five of the studies, including OPAL Broaden, EQUATOR, SELECT-PsA 1, and SELECT-PsA 2, and patients taking a JAK inhibitor had an overall 4.5-fold increased odds of achieving this response compared with those taking placebo.
The researchers note that “there seemed to be an overall trend towards better effect of non-tofacitinib JAK [inhibitors] compared to tofacitinib in PsA.” Specifically, the pooled odds of achieving ACR20 with tofacitinib (in two studies) was increased threefold compared with placebo and for other JAK inhibitors (primarily upadacitinib), there was a 5.4-fold increase.
They add, however, that “the effect sizes cross over, and the individual studies did not compare tofacitinib to other JAK [inhibitors],” and therefore “we cannot definitively conclude that non-tofacitinib JAK [inhibitors] are superior.”
Enthesitis and dactylitis as secondary outcomes were also reviewed. The data were only available in a few studies, but the team highlights the response rates from the SELECT PsA 2 study, which were a significant 27.9% and 40.1% higher, respectively, after 12 weeks of treatment with upadacitinib compared with placebo.
From a safety perspective, most of the serious adverse events reported occurred at “a very low frequency” of 1–7% in patients taking the maximum dose, and were most often infections, report Don Thiwanka Wijeratne (Queen’s University, Kingston, Ontario, Canada) and co-researchers.
They make reference to recent concerns over herpes zoster infections with JAK inhibitors, which occurred at the highest dose in eight of the studies, and the risk for venous thromboembolism, for which many of the studies had insufficient data.
“Based on these findings, for patients with PsA with significant joint disease, but milder skin disease, certainly a JAK inhibitor could be the drug of choice,” say the researchers.
“Therefore, JAK inhibitors could conceivably have a place in the treatment algorithm for psoriatic disease because they are oral treatments or if other considerations, such as arthritis, dactylitis or enthesitis are present in the context of milder psoriasis.”
However, they recognize the need for further research, most notably with regard to direct comparisons between the different JAK inhibitors as well as therapies with different mechanisms of action, their use alone versus alongside background conventional DMARD use, and their long-term safety.
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