Upadacitinib Yields Positive Results in Phase 3 RA Trial

Upadacitinib (ABT-494) as monotherapy showed positive results in a phase 3 rheumatoid arthritis (RA) trial, AbbVie announced.

The ongoing SELECT-MONOTHERAPY clinical trial is a multicenter randomized double-blind parallel-group study evaluating upadacitinib, an investigational oral JAK1-selective inhibitor, as a monotherapy treatment for patients with moderate to severe RA who did not adequately respond to treatment with methotrexate. The evaluation yielded positive results, meeting all primary and key secondary endpoints.

“This trial addresses the clinical impact of switching from methotrexate to upadacitinib as monotherapy in patients with inadequate response to methotrexate,” said study investigator Josef S. Smolen, MD, Department of Medicine, Division of Rheumatology, Medical University of Vienna, Austria, in the statement from AbbVie. “Results suggested that both doses of upadacitinib can provide clinically meaningful responses."

After 14 weeks of treatment, both once-daily doses (15 mg and 30 mg) met the study’s primary endpoints of low disease activity (LDA) and ACR20 versus continuing methotrexate therapy. The American College of Rheumatology (ACR) 20%/50%/70% benchmarks reflect improvements in both tender and swollen joint counts, plus 3 of the following: patient assessments of pain, global disease activity and physical function, physical global assessment of disease activity, and acute phase reactant. Both doses also achieved all ranked and all key secondary endpoints.

At week 14, 68% of patients who switched to 15 mg once-daily upadacitinib achieved ACR20, 42% achieved ACR50, and 23% achieved ACR70; 71% of patients who switched to 30 mg once-daily upadacitinib achieved ACR20, 52% achieved ACR50, and 33% achieved ACR70. Meanwhile, 41% of patients continuing on methotrexate achieved ACR20, 15% achieved ACR50, and 3% achieved ACR70.

“The positive results from the SELECT-MONOTHERAPY study are encouraging, as they are the first evidence to support the potential of upadacitinib as a therapy without the need for background methotrexate,” said Michael Severino, MD, executive vice president of research and development and chief scientific officer of AbbVie, in the statement. “These findings add to the growing body of data showing the potential for upadacitinib as a meaningful treatment option for patients suffering from rheumatoid arthritis.”

The results from the phase 3 trial are consistent with findings of previously reported Phase 3 SELECT clinical trials and Phase 2 studies, according to AbbVie. Serious adverse events occurred in 5% of patients in the 15 mg group and 3% of patients in the 30 mg group, compared with 3% in the methotrexate group.