JAKs Show Superior Efficacy in PsA With Upadacitinib Leading the Pack

A recent systematic review and meta-analysis of Janus kinase (JAK) inhibitors for the treatment of psoriatic arthritis (PsA) demonstrated that JAKs outperformed placebo, but also concluded that “long-term data, most notably safety data, are necessary before this can be incorporated into every day clinical practice” due to increased risk of infection.

This study also included the first subgroup analysis of individual JAKs in PsA, the authors noted in their report in the International Journal of Rheumatic Diseases. This analysis revealed that upadacitinib at both 15 mg and 30 mg once daily showed “statistically significant superiority” in efficacy across the domains of peripheral arthritis, enthesitis, dactylitis, and psoriasis in comparison to other JAK inhibitors. Upadacitinib 30 mg OD demonstrated the highest efficacy.

The investigators conducted a systematic literature search using EMBASE, PubMed and CENTRAL, identifying 5 randomized placebo-controlled clinical trials comprising 3292 unique patients. Of the 1820 patients who were treated with a JAK inhibitor, 474 were randomized to tofacitinib, 65 were treated with filgotinib, 1281 received upadacitinib, and 937 were randomized to placebo.

“JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo,” the authors stated, including American College of Rheumatology (ACR) 20, ACR 50, ACR 70, and  Psoriasis Area and Severity Index 75, as well as resolution of enthesitis and dactylitis.

JAK inhibitors were associated with an overall increased risk of adverse events, the authors noted. “The pooled analysis of these 3 trials showed a statistically significant increased relative risk of infection (RR 1.23, 95%CI [1.08–1.39], P = .001, I2 = 0%) associated with JAKi treatment vs placebo.” However, this analysis did not show a statistically significant increased relative risk of opportunistic infections (RR 2.15, 95%CI [0.46–10.07], P = .33, I2 = 0%) or venous thromboembolic events (RR 0.79, 95%CI [0.10–6.44], P = .83, I2 = 0%), the team stated.

“Furthermore, pooled analysis of all 5 trials did not reveal any statistically significant increased relative risk of herpes zoster (HZ) in those treated with a JAKi vs placebo,” the authors added.

“This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA,” the investigators concluded. “However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile.”

—Rebecca Mashaw

Reference:

Harkins P, Burke E, Swales C, Silman A, Conway R. Are Janus kinase inhibitors safe and effective in treating the key clinical domains of psoriatic arthritis? A systematic review and meta-analysis.

Int J Rheum Dis. 2023;26(1):31-42. https://doi.org/10.1111/1756-185X.14447