Upadacitinib improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying anti-rheumatic 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 2300 patients with psoriatic arthritis for an average of 6 to 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 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.
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," 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.
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 end point was an improvement of at least 20% (ACR20) at week 12.
Secondary end points 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 ACR 70 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 ARC20 (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, Magrey reported, "so 15 mg seems like it will be the dose to go toward FDA approval."
SELECT-PsA 2 compared upadacitinib —15 mg or 30 mg once daily — with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.
The primary end point was the achievement of ACR20 at week 12.
Among the many secondary end points were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.
Adverse events were reported for patients who received at least one dose of upadacitinib.
At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs 63.8% vs 24.1%; P < .0001), as was ACR50 (31.8% vs 37.6% vs 4.1%; P < .0001) and ACR70 (8.5% vs 16.5% vs 0.5%; P < .0001). In addition, all secondary end points were significantly better with upadacitinib than with placebo.
Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.
"I was pleasantly surprised by the overall safety profile," Mease said. "Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low."
"We didn't see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action," he added.
Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.
"I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis," he told Medscape Medical News. "I don't think it's going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients."
Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn't measured in these trials.
"I don't see this as a weakness" of the current research, he said, but "having some spinal measures would be helpful. It's something additional we'd like to know."
Both trials were funded by AbbVie. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Mease reports financial relationships with Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Ritchlin has disclosed no relevant financial relationships.
European League Against Rheumatism (EULAR) 2020 Congress: Abstract LB0001, presented June 3, 2020; abstract OP0223, presented June 5, 2020.
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Cite this: Upadacitinib Looks Effective for Psoriatic Arthritis - Medscape - Jun 09, 2020.