Disclosures: McInnes reports consulting fees from AbbVie, Crescendo, Gilead Sciences, Janssen Biotech, Novartis, Pfizer and Sanofi Pasteur; grant support paid to the University of Glasgow and consulting fees from Amgen; grant support paid to his institution and consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, and UCB; stock options in Cabaletta Bio; and grant support paid to his institution, consulting fees and stock options from Compugen. Please see the study for all other authors’ relevant financial disclosures.
March 31, 2021
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Higher-dose upadacitinib outperforms adalimumab in DMARD-refractory PsA

Disclosures: McInnes reports consulting fees from AbbVie, Crescendo, Gilead Sciences, Janssen Biotech, Novartis, Pfizer and Sanofi Pasteur; grant support paid to the University of Glasgow and consulting fees from Amgen; grant support paid to his institution and consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, and UCB; stock options in Cabaletta Bio; and grant support paid to his institution, consulting fees and stock options from Compugen. Please see the study for all other authors’ relevant financial disclosures.
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A daily 30 mg dose of upadacitinib — but not the 15 mg dose — is superior to adalimumab at improving the signs and symptoms of psoriatic arthritis among patients with inadequate response to non-biologic disease-modifying antirheumatic drugs.

The researchers, who published their findings in The New England Journal of Medicine, also concluded that a significantly higher percentage of patients with PsA achieve an ACR20 response with either dose of upadacitinib (Rinvoq, AbbVie) than with placebo, albeit with a higher frequency of adverse events.

“Upadacitinib offers a satisfactory efficacy and safety option now for the management of PsA,” Iain B. McInnes, FRCP, told Healio Rheumatology. “The data suggest that it afforded benefits in the treatment of synovitis, enthesitis and in skin disease, as well as in quality-of-life metrics.” Data derived from McInnes IB, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2022516.

“We need new options in the management of PsA — a lifelong disease with onset often in younger age groups,” Iain B. McInnes, FRCP, of the University of Glasgow College of Medical Veterinary and Life Sciences, in the United Kingdom, told Healio Rheumatology. “Therefore, expanding our armamentarium is important.”

To compared upadacitinib to placebo and adalimumab (Humira, AbbVie) in patients with PsA who had an inadequate response, or unacceptable side effects, with non-biologic DMARDs, McInnes and colleagues conducted the double-blind, phase 3 SELECT-PsA 1 trial. A total of 1,704 patients from 281 sites across 45 counties were randomized 1:1:1:1 to receive either 15 mg of daily upadacitinib, 30 mg of daily upadacitinib, 40 mg of subcutaneous adalimumab every other week, or placebo. Overall, 1,548 participants — or 90.8% of the randomized population — completed the 24-week trial.

Iain B. McInnes

The primary endpoint was an ACR20 response — defined as a 20% or greater decrease in the number of tender and swollen joints, and a 20% or greater improvement in at least three of five other domains — at week 12 with upadacitinib, compared with placebo. Secondary endpoints included comparisons of upadacitinib with adalimumab.

According to the researchers, 70.6% of patients in the 15 mg upadacitinib group, 78.5% of those treated with 30 mg of upadacitinib, and 36.2% of those who received a placebo achieved an ACR20 response at week 12 (P < .001 for both compared with placebo). Meanwhile, 65% of patients in the adalimumab group achieved the same.

The difference between groups for the 15 mg upadacitinib cohort compared with those treated with adalimumab was 5.6 percentage points (95% CI, –0.6 to 11.8). For patients in the 30 mg upadacitinib group, compared with the adalimumab group, the difference was 13.5 percentage points (95% CI, 7.5-19.4). Both doses of upadacitinib were noninferior to adalimumab for ACR20 response at week 12, while the 30 mg dose of upadacitinib was superior to adalimumab.

Regarding safety, 66.9% of participants in the 15 mg upadacitinib group experienced adverse events through week 24, compared with 72.3% in the 30 mg upadacitinib group, 64.8% among those treated with adalimumab, and 59.6% of those who received a placebo. Serious infections occurred in 1.2%, 2.6%, 0.7% and 0.9% of participants, respectively. In addition, although 9.1% of patients in the 15-mg upadacitinib group, and 12.3% of those who received the 30 mg dose, experienced hepatic disorders, grade 3 increases in aminotransferase levels occurred in 2% or fewer across all groups.

“Upadacitinib offers a satisfactory efficacy and safety option now for the management of PsA,” McInnes said. “In this trial, the data suggest that it afforded benefits in the treatment of synovitis, enthesitis and in skin disease, as well as in quality-of-life metrics. The safety profile was satisfactory. Going forward, we see JAK inhibitors in that list of useful modalities in the management of PsA. Further studies are necessary to properly understand their optimal use in the wider management paradigm.”