The FDA approved upadacitinib (Rinvoq) to treat adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to at least one tumor necrosis factor (TNF) blocker.
The approval was based on findings from a pair of phase III trials, SELECT-PsA 1 and SELECT-PsA 2, the results of which were published earlier this year in The New England Journal of Medicine and The BMJ, respectively. While these two trials assessed upadacitinib at a dose of 15 mg and 30 mg, this latest indication only applies to the 15-mg dose.
In the SELECT-PsA 1 trial, as previously reported by BreakingMED, upadacitinib was pitted against placebo and a comparator drug, adalimumab, in adult patients with moderately to severely active PsA who had an inadequate response or unacceptable side effects with at least one nonbiologic disease-modifying antirheumatic drug (DMARD). At 12 weeks, the number of PsA patients with an ACR20 response—an improvement of at least 20% according to American College of Rheumatology criteria—was significantly higher than placebo at a dose of either 15 mg or 30 mg, as well as significantly higher than adalimumab at the 30-mg dose (70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo, 65.0% with adalimumab).
In the SELECT-PsA 2 trial, participants were randomized to receive 15 mg upadacitinib, 30 mg upadacitinib, or placebo followed by upadacitinib at either 15 mg or 30 mg at week 24; as with SELECT-PsA 1, the primary endpoint was proportion of patients with ACR20 response at week 12, and minimal disease activity was assessed at week 24. At week 12, more patients in the upadacitinib 15 mg and 20 mg groups achieved ACR20 (56.9% and 63,8%, respectively) compared to placebo (24.1%). At week 24, the upadacitinib 15 mg and 30 mg groups also saw more cases of minimal disease activity (25.1% and 28.9%, respectively, versus 2.8%).
Across both trials, the safety profile of 15-mg upadacitinib for PsA was comparable to the safety profile seen in patients with rheumatoid arthritis, the drug’s manufacturer explained in a company press release: the most common adverse events reported included upper respiratory tract infection and elevations of blood creatine phosphokinase.
While this new approval will grant patients with active PsA an additional therapeutic option, a safety update on JAK inhibitors published by the FDA may put a damper on use of the drug class.
In a drug safety communication released in September, the FDA required updated warning labels for tofacitinib, baricitinib, and upadacitinib due to evidence that the JAK inhibitors were linked to an increased risk for serious cardiovascular and other adverse events. The warning was triggered when a large randomized safety clinical trial of tofacitinib found that use of the drug led to increased risks for heart attack, stroke, cancer, blood clots, and cardiovascular mortality, the agency explained.
While the safety trial cited by the FDA specifically looked at tofacitinib, due to the shared mechanism of action between the three drugs, the agency concluded that upadacitinib and baricitinib may carry similar risks.
As a result, upadacitinib’s label was updated earlier this month to include warnings for a higher rate of all-cause and cardiovascular mortality, malignancies including lymphomas and lung cancers, major adverse cardiovascular events, and thrombosis, including pulmonary embolism and venous and arterial thrombosis.
Upadacitinib is manufactured by AbbVie.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 68
Topic ID: 90,68,730,192,725,68,925