Upadacitinib may benefit patients with PsA

The oral Janus kinase inhibitor upadacitinib – which has gained approval for the treatment of rheumatoid arthritis (RA) – showed potential for treating individuals with psoriatic arthritis (PsA) who have insufficient response to nonbiologic disease-modifying antirheumatic drugs, according to the phase III SELECT-PsA 1 trial.

“The percentage of PsA patients who achieved an ACR20* response at week 12 was significantly higher with upadacitinib 15 or 30 mg than placebo,” said the researchers. The percentages were twice as high with both upadacitinib doses compared with placebo (70.6 percent [15 mg] and 78.5 percent [30 mg] vs 36.2 percent), yielding significant between-group differences (34.5 and 42.3 percentage points, respectively; p<0.001 for both).

A third (65.0 percent) of participants on the tumour necrosis factor alpha inhibitor adalimumab achieved ACR20 response at week 12. Between-group comparisons revealed the noninferiority of both upadacitinib doses to adalimumab, while upadacitinib 30 mg achieved superiority over adalimumab (between-group difference, 13.5 percentage points; p<0.001). [N Engl J Med 2021;384:1227-1239]

Other efficacy endpoints, safety

“[Moreover, week-24] results for most [clinically important] musculoskeletal endpoints were significantly better with upadacitinib than placebo,” they added. These were seen in the greater fraction of upadacitinib vs placebo recipients achieving a PASI75** response (64.0 percent [15 mg] and 62.4 percent [30 mg] vs 26.5 percent), sIGA*** (45.3 percent and 52.5 percent vs 11.5 percent), minimal disease activity (36.6 percent and 45.4 percent vs 12.3 percent; p<0.001 for both), and resolution of enthesitis by LEI^# (53.7 percent and 57.7 percent vs 32.4 percent; p<0.001 for both).

Physical function, fatigue, quality of life, and inhibition of radiographic progression were also better with upadacitinib 15 and 30 mg vs placebo, as reflected by the changes from baseline HAQ-DI^## (–0.51 [both doses] vs –0.19 percent) and FACIT-F^## scores (7.9 percent and 8.0 percent vs 3.8 percent), as well as SF-36 PCS^## (9.8 percent and 9.9 percent vs 4.3 percent) and mTSS^## (–0.05 and 0.03 vs 0.24).

Adverse event (AE) rates with upadacitinib (66.9 percent [15 mg] and 72.3 [30 mg]) were higher compared with placebo (59.6 percent) and adalimumab (64.8 percent) through week 24. However, serious infection rates were low across all arms (ranging from 0.7 to 2.6 percent), as were treatment discontinuation rates owing to AEs (ranging from 3 to 5 percent).

The researchers noted that while the safety profile of upadacitinib mostly correlate with those observed in RA trials, comparing AEs between these two distinct diseases cannot be made. [Lancet 2018;391:2503-2512; Lancet 2018;391:2513-2524; Lancet 2019;393:2303-2311; Arthritis Rheumatol 2019;71:1788-1800]

SELECT-PsA 1 randomized 1,704 patients 1:1:1:1 to receive upadacitinib 15 or 30 mg QD, SC adalimumab 40 mg every other week, or placebo, for 24 weeks. Ninety-one percent of participants completed their regimen for 24 weeks.

“[Taken together,] the findings suggest that upadacitinib 15 or 30 mg QD was more effective than placebo in most measures of PsA activity and inhibited radiographic progression of disease,” said the researchers. Larger and longer trials are warranted to ascertain the efficacy and safety of upadacitinib in the long term and determine how it fares compared with other drugs used for treating PsA.