The JAK inhibitor upadacitinib was more effective than placebo and as or more effective than adalimumab in a randomised controlled trial of patients with psoriatic arthritis who had failed to respond to nonbiologic disease-modifying antirheumatic drugs (DMARDs). The efficacy, however, did come with some increase in toxicity as well.
One previous trial in rheumatoid arthritis found that upadacitinib was superior to adalimumab for several outcomes. Researchers led by Prof Iain McInnes, of the University of Glasgow, conducted a double-blind phase III trial in psoriatic arthritis that randomised a total of 1,704 patients to receive one of two doses of upadacitinib (15 mg/day or 30 mg/day), placebo, or subcutaneous adalimumab. The results were published in The New England Journal of Medicine
The primary outcome was the percentage of patients in each group who had an American College of Rheumatology 20 (ACR20) response, defined as at least a 20% decrease in the number of tender and swollen joints and at least a 20% improvement in at least three of five other domains, at week 12.
Both the upadacitinib dose groups fared better than placebo on that measure, with 70.6% in the 15-mg group and 78.5% in the 30-mg group achieving an ACR20 response, compared with 36.2% with placebo (p < .001 for both doses vs placebo).
The rate was 65.0% with adalimumab; both the upadacitinib groups were found to be non-inferior to adalimumab, but only the higher dose was superior (p < .001).
Serious adverse events occurred in 3.3% of the 15-mg upadacitinib group, in 6.1% of the 30-mg dose group, 59.6% of the placebo group, and 64.8% of the adalimumab group.
The most common AE was infection, occurring in 39.4%, 43.3%, 33.1%, and 34.0% of the four groups, respectively. There were 11 serious infections in the higher dose upadacitinib group (2.6%), compared with only three in the adalimumab group (0.7%). Herpes zoster was diagnosed in 1.2% of the higher dose group, 0.9% of the lower dose upadacitinib group, and in none of the adalimumab group.
“Longer and larger trials are required to determine the effect and risks of upadacitinib and its effects as compared with other drugs used to treat psoriatic arthritis,” the authors concluded.
The trial was sponsored by AbbVie, which markets upadacitinib and adalimumab. Dr McInnes and other co-authors report receiving consulting fees, grant support, lecture fees, and other financial support from AbbVie and a variety of other pharmaceutical companies.