The arrival of biosimilar adalimumab in European markets has been cause for enthusiasm among those seeking greater patient access and lower costs for the treatment of rheumatoid arthritis (RA). However, AbbVie (maker of the reference adalimumab, Humira) has revealed that its oral Janus kinase inhibitor, upadacitinib, outperformed both placebo and adalimumab in a phase 3 study.
The arrival of biosimilar adalimumab in European markets has been cause for enthusiasm among those seeking greater patient access and lower costs for the treatment of rheumatoid arthritis (RA). However, AbbVie (maker of the reference adalimumab, Humira) has revealed that its oral Janus kinase (JAK) inhibitor, upadacitinib, outperformed both placebo and adalimumab in a phase 3 study.
The results of the SELECT-COMPARE trial, which AbbVie first announced in topline in April 2018, were presented during the American College of Rheumatology (ACR)’s annual meeting, held in Chicago, Illinois, October 19-24, 2018.
In the trial, 1629 patients with active RA despite methotrexate treatment were randomized 2:2:1 to receive 15 mg of upadacitinib daily, placebo, or 40 mg of adalimumab every other week, all while continuing methotrexate. The study’s primary end points were noninferiority and superiority of upadacitinib versus adalimumab at week 12 and radiographic inhibition for upadacitinib versus placebo at week 26.
In total, 91% of patients completed the full 26 weeks. At week 12, 70.5% of those receiving upadacitinib and 36.4% of those receiving placebo achieved ACR criteria for 20% improvement (ACR20); 28.7% and 6.1%, respectively, had a disease activity score in a count of 28 joints plus C-reactive protein (DAS28-CRP) of under 2.6. At week 26, more patients receiving upadacitinib had no radiographic progression than patients receiving placebo (83.5% vs 76.0%).
Upadacitinib also demonstrated superiority versus adalimumab at week 12 for ACR50 (45.2% vs 29.1%) and for DAS28-CRP of 3.2 or less (45.0% vs 28.7%). Furthermore, upadacitinib was superior in terms of reduction of pain and improvement in quality of life as measured by the Health Assessment Questionnaire Disability Index.
The proportion of patients with adverse events (AEs) was higher for those given upadacitinib than those given placebo, but similar to those given adalimumab. Notably, thromboembolic events were similar across the 3 arms; 6 venous thromboembolic events occurred, 1 in the placebo arm, 2 in the upadacitinib arm, and 3 in the adalimumab arm. In a previous phase 3 study in the same clinical program, SELECT-MONOTHERAPY, some concerns arose about the safety of the drug; 1 patient taking the study drug died of a hemorrhagic stroke, caused by a ruptured aneurysm.
The positive data from this phase 3 trial may to support AbbVie in its effort to find a fresh foothold in the RA market as 4 EU competitors to Humira begin to sell their products, and as sales will begin for adalimumab biosimilars in the United States in 2023.
Fleischmann R, Pangan AL, Mysler E, et al. A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Presented at: American College of Rheumatology 2018 Meeting; October 19-24, 2018; Chicago, Illinois. Abstract 890. https://acrabstracts.org/abstract/a-phase-3-randomized-double-blind-study-comparing-upadacitinib-to-placebo-and-to-adalimumab-in-patients-with-active-rheumatoid-arthritis-with-inadequate-response-to-methotrexate/.