SELECT-PsA-1 demos upadacitinib benefits in psoriatic arthritis
Upadacitinib may be a suitable treatment for patients with active psoriatic arthritis (PsA) who have insufficient response to non-biologic disease-modifying anti-rheumatic drugs (non-bDMARDs), according to results of the phase III SELECT-PsA-1* trial presented at EULAR 2020.
“In this … population, treatment with upadacitinib 15/30 mg demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, and fatigue, and inhibited radiographic progression,” noted first author Professor Iain McInnes from the University of Glasgow Institute of Infection, Immunity & Inflammation, Glasgow, UK, and co-authors.
Participants were 1,704 patients with active PsA (≥3 swollen and ≥3 tender joints; mean age 50.8 years, 53.2 percent female, mean duration of PsA 6.1 years) with inadequate response or intolerant to ≤2 non-bDMARDs. They were randomized 1:1:1:1 to receive upadacitinib (15 or 30 mg once daily), adalimumab (40 mg every other week), or placebo.
At week 12, more upadacitinib than placebo recipients achieved ACR20** response (70.6 and 78.5 percent for upadacitinib 15 and 30 mg, respectively, vs 36.2 percent for placebo; p<0.001 for both). Upadacitinib 30 mg also demonstrated superiority compared with adalimumab (65.0 percent; p<0.001). [EULAR 2020, abstract LB0001]
Reductions from baseline in HAQ-DI*** scores at week 12 were greater among upadacitinib 15/30 mg (-0.42/-0.47) compared with placebo (-0.14; p<0.001) or adalimumab (-0.34; p<0.05 and p<0.001 vs upadacitinib 15 or 30 mg, respectively). FACIT-F*** scores were also improved with upadacitinib 15/30 mg vs placebo (6.3/7.1 vs 2.8; p<0.001 for both), as were SF-36 PCS*** scores (7.9/8.9 vs 3.2; p<0.001 for both).
At week 12, greater reductions in patient assessed pain scores were observed with upadacitinib 15/30 mg (-2.3/-2.7) vs placebo (-0.9; p<0.001 for both) or adalimumab (-2.3; p<0.001 vs upadacitinib 30 mg).
More patients on upadacitinib 15 and 30 mg achieved PASI75# at week 16 (62.6 and 62.4 percent, respectively) vs placebo (21.3 percent; p<0.001 for both) and minimal disease activity (MDA) at week 24 (36.6 percent and 45.4 percent vs 12.3 percent [placebo]; p<0.001 for both or vs adalimumab [33.3 percent; p<0.001 vs upadacitinib 30 mg]).
At week 24, more patients on upadacitinib 15 or 30 mg experienced resolution of enthesitis (53.7 and 57.7 percent, respectively) compared with placebo (32.4 percent; p<0.001 for both) or adalimumab (47.2 percent; p<0.05 for both), or resolution of dactylitis (76.5 and 79.5 percent, respectively) vs placebo (39.7 percent; p<0.001 for both).
Serious adverse events (AEs) at week 24 were more frequent with upadacitinib 30 mg (6.1 percent), but comparable among upadacitinib 15 mg, adalimumab, and placebo recipients (3.3, 3.7, and 3.1 percent, respectively). This was mirrored with rates of serious infection (1.2, 2.6, 0.7, and 0.9 percent of upadacitinib 15 and 30 mg, adalimumab, and placebo recipients, respectively). Herpes zoster occurred in three, four, and five placebo, upadacitinib 15 mg, and upadacitinib 30 mg recipients, respectively.
No major adverse cardiovascular events were reported with upadacitinib. Malignancies occurred in one patient each on placebo and upadacitinib 15 mg, and three each on upadacitinib 30 mg and adalimumab. One patient each on placebo and upadacitinib 30 mg and two on adalimumab experienced venous thromboembolism. There was one death in the placebo group.
No new safety signals emerged compared with that of upadacitinib in RA treatment, noted the authors.
Approved for treatment of RA, SELECT-PsA-1 researchers aimed to examine the efficacy of upadacitinib in PsA. “These data are encouraging and add to the growing body of evidence that upadacitinib has the potential to improve outcomes for people living with PsA,” said McInnes. [https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-meets-primary-and-key-secondary-endpoints-in-phase-3-study-in-psoriatic-arthritis.htm, accessed 1 July 2020]