RA Patients Gain New Hope as AbbVie’s Upadacitinib Meets All Primary and Secondary Endpoints in Pivotal Phase 3 SELECT-MONOTHERAPY Trial

Recently, AbbVie announced the positive results of the pivotal Phase III clinical trial SELECT-MONOTHERAPY for upadacitinib in patients with moderate to severe active rheumatoid arthritis (RA) in *The Lancet*: Compared with methotrexate, upadacitinib met both primary endpoints of drug evaluation at Week 14, namely a significantly higher ACR20 response rate and lower disease activity in the upadacitinib group. The data provided demonstrate the potential of upadacitinib as an important treatment option for patients with rheumatoid arthritis.

SELECT-MONOTHERAPY is a multicenter, randomized, double-blind, parallel-group study conducted in adult patients with moderate to severe rheumatoid arthritis (RA) who had an inadequate response to stable-dose methotrexate (MTX), aiming to evaluate the efficacy and safety of upadacitinib monotherapy. In the study, patients were randomly assigned in a double-blind manner to switch from methotrexate to upadacitinib (15 mg/day or 30 mg/day) or to continue receiving their prior stable dose of methotrexate.

The primary endpoint of Phase 1 was the proportion of patients achieving ACR20 response and low disease activity (LDA) after 14 weeks of treatment. Secondary endpoints included the proportion of patients achieving ACR50, ACR70, and clinical remission at Week 14. Phase 2 was a double-blind, long-term extension period designed to evaluate the long-term safety, tolerability, and efficacy of upadacitinib monotherapy (15 mg/day and 30 mg/day) in patients who had completed Phase 1 treatment.

The data released this time show that after 14 weeks of treatment, compared with the group continuing to receive a stable dose of methotrexate, both upadacitinib monotherapy groups (15 mg/day and 30 mg/day) achieved the primary endpoints of ACR20 and LDA, as well as all key secondary endpoints. At week 14, the proportions of patients achieving ACR20/50/70 in the 15 mg and 30 mg dose groups were 68%/42%/23% and 71%/52%/33%, respectively, while those in the group continuing methotrexate treatment were 41%/15%/3%. These results were all statistically significant (p < 0.001).

Furthermore, at Week 14 of treatment, a significantly higher proportion of patients in both upadacitinib dose groups achieved the targets of low disease activity (LDA) and clinical remission compared with the group continuing methotrexate therapy (p < 0.001). Specifically, the proportions of patients achieving LDA were 45% and 53% in the upadacitinib 15 mg and 30 mg dose groups, respectively, while the proportions achieving clinical remission were 28% and 41%, respectively. In the group continuing methotrexate therapy, the proportions of patients achieving LDA and clinical remission were 19% and 8%, respectively.

In this study, the safety profile of upadacitinib was consistent with that reported in previous Phase III SELECT trials and Phase II studies, with no new safety concerns identified. The incidence rates of serious adverse events were 5%, 3%, and 3% in the 15 mg dose group, 30 mg dose group, and methotrexate treatment group, respectively. Notably, one patient in the 15 mg dose group died from hemorrhagic stroke due to a ruptured aneurysm; this patient had pre-existing cardiovascular risk factors. Additionally, one patient experienced pulmonary embolism (PE); this patient had pre-existing risk factors for PE.

Upadacitinib is an experimental oral selective JAK1 inhibitor discovered and developed by AbbVie. Since its inception, the industry has held high expectations for its commercial prospects. A previous report by EvaluatePharma predicted that upadacitinib’s global sales would reach $2.57 billion in 2024, making it the fifth best-selling antirheumatic drug worldwide. Previously published clinical data have suggested that upadacitinib may be more effective than Humira in treating rheumatoid arthritis.

In February this year, the FDA accepted the new drug application for this medication to treat adult patients with moderate-to-severe rheumatoid arthritis (RA) and announced that it would undergo priority review. Currently, Phase III studies of upadacitinib for the treatment of psoriatic arthritis, Crohn's disease, atopic dermatitis, and ulcerative colitis are ongoing.

References:

[1]Results from Upadacitinib Phase 3 SELECT-MONOTHERAPY Study Published in The Lancet

[2]Positive late stage rheumatoid arthritis trial results for Abbvie