AbbVie says upadacitinib monotherapy meets main goals of Phase III rheumatoid arthritis study

AbbVie announced Wednesday that both once-daily doses of its investigational oral JAK1-selective inhibitor upadacitinib tested in a Phase III trial met the primary endpoints of 20 percent improvement in symptoms of rheumatoid arthritis (ACR20) and low disease activity (LDA), versus continuing prior stable methotrexate therapy. Both doses also achieved all key secondary endpoints, the company added. Michael Severino, AbbVie's chief scientific officer and head of R&D, said the findings "are encouraging, as they are the first evidence to support the potential of upadacitinib as a therapy without the need for background methotrexate."

The ongoing SELECT-MONOTHERAPY study involved adults with moderate-to-severe rheumatoid arthritis and an inadequate response to a stable dose of methotrexate. Patients were randomised to either switch from methotrexate to one of two doses of upadacitinib monotherapy, or continue on their prior stable dose of methotrexate. In addition to the primary endpoints, secondary goals included the proportion of patients achieving ACR50, ACR70 and clinical remission at week 14.

Top-line results demonstrated that after 14 weeks of treatment, ADR20 responses were achieved in 68 percent and 71 percent of patients who had switched to low-dose and high-dose upadacitinib, respectively, versus 41 percent of those who continued on methotrexate. Additionally, LDA was achieved by patients in the low- and high-dose groups at respective rates of 45 percent and 53 percent, compared with 19 percent of patients continuing on methotrexate.

Meanwhile, the ACR50 rate was 42 percent in the low-dose upadacitinib arm and 52 percent in the high-dose arm, versus 15 percent for those on methotrexate, while the ACR70 rates in these groups were 23 percent, 33 percent and 3 percent, respectively. Moreover, AbbVie said clinical remission was achieved by 28 percent of patients on low-dose upadacitinib and 41 percent of those in the high-dose group, versus 8 percent of patients continuing on methotrexate.

FirstWord reports in this therapy area - KOL Insight Rheumatoid Arthritis: Find out how KOLs expect the market to evolve, which pipeline treatments are most promising, and which clinical trials will shape treatment decisions. Learn more. 

AbbVie noted that the safety profile of upadacitinib in SELECT-MONOTHERAPY was consistent with previously reported trials from the late-stage SELECT clinical development programme and from Phase II studies. Further results from the current trial will be presented at a future medical meeting and published in a peer-reviewed journal, the company added.

Earlier this year, AbbVie unveiled data from the SELECT-NEXT trial showing that upadacitinib, also known as ABT-494, met its primary endpoints of ACR20 and LDA among patients with moderate-to-severe rheumatoid arthritis who were on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs. The company also recently announced positive Phase IIb study results for the drug in the treatment of atopic dermatitis.

For related analysis on the JAK inhibitor class, see ViewPoints: ACR meeting rounds up some support for JAK safety.

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