Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.
“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.
She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.
No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.
The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.
“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.
Mitchel L. Zoler/MDedge News
Dr. Philip J. Mease
The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.
“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.
Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
SELECT-PsA 1
In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.
The primary endpoint was an improvement of at least 20% (ACR20) at week 12.
Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.
Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.
Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).
More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.
The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”