The monotherapy resulted in LDA by week 14 in both the 15 mg (45%) and 30 mg (53%) groups.
Marek Honczarenko, MD, PhD
AbbVie has announced positive top-line results from the phase 3 SELECT-MONOTHERAPY clinical trial evaluating upadacitinib (ABT-494) as a monotherapy treatment in patients with moderate to severe rheumatoid arthritis (RA) who did not adequately respond with methotrexate.
The investigational oral JAK1-seclective inhibitor demonstrated positive phase 3 results. Findings indicated that after 14 weeks of treatment in both once-daily doses of upadacitinib (15 mg and 30 mg) the study’s primary endpoints were met.
“These positive results further our understanding of the potential benefit that upadacitinib monotherapy may provide to patients with rheumatoid arthritis,” Marek Honczarenko, MD, PhD, vice president immunology development, AbbVie, told MD Magazine. “The significant progress we’ve made across the upadacitinib development program builds on over 2 decades of expertise in immunology as we pursue a robust portfolio of innovative therapies to address unmet patient needs.”
The phase 3 study evaluated the safety and efficacy of upadacitinib monotherapy in adult patients with moderate to severe RA who did not respond to a stable dose of methotrexate. Methotrexate is commonly used as a first-line therapy in RA, however, several patients cannot tolerate the therapy.
In the study, patients were randomized to switch from methotrexate to upadacitinib monotherapy, 15 mg or 30 mg, or continue on the prior stable dose of methotrexate in a blinded manner.
Primary endpoints included the percentage of subjects who achieved an ACR20 response and low disease activity (LDA) versus continuing prior stable methotrexate therapy. Both doses achieved all ranked and all key secondary endpoints.
“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,” Michael Severino, MD, executive vice president, research and development, chief scientific officer, AbbVie, said. “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.”
Findings showed that at week 14, 68/42/23% of patients switched to 15 mg-once daily upadacitinib and 71/52/33% of patients switched to 30 mg once-daily upadacitinib, achieving an ACR 20/50/70 response, as opposed to 41/15/3% of patients treated with methotrexate.
The results were statistically significant compared to those who continued on the baseline methotrexate dose.
A high proportion of upadacitinib patients in both dose groups achieved LDA and clinical remission targets at week 14 compared to patients receiving methotrexate. Low disease activity was achieved by 45% and 53% of patients in the 15 mg and 30 mg upadacitinib arm versus 19% of those on methotrexate.
Clinical remission was achieved by 28% and 41% of patients in the 15 mg and 30 mg groups, versus 19% of patients on methotrexate.
The safety profile in this trial was consistent with previously reported phase 3 studies and no new safety signals were detected.
Serious adverse effects occurred in 5/3% of patients in the 15/30 mg groups compared to 3% in the methotrexate group.
Across the SELECT program, including the extension and placebo-controlled periods, the rate of deep vein thrombosis and PE remains consistent with the background rate for the patient population.
“This trial addresses the clinical impact of switching from methotrexate to upadacitinib as monotherapy in patients with an adequate response to methotrexate,” Josef S. Smolen, MD, investigator of the study, department of medicine, division of rheumatology, Medical University of Vienna, said in a statement. “These findings support the potential for upadacitinib monotherapy as a treatment option for patients with RA.”
The SELECT phase 3 RA program evaluates more than 4,000 patients with moderate to severe RA in 6 studies which include assessing efficacy, safety and tolerability across several patient populations. Efficacy measures include ACR responses, Disease Activity Score (DAS28-CRP) and inhibition of radiographic progression.
Phase 3 trials of upadacitinib in treatment for psoriatic arthritics are currently underway, and the therapy is also being investigated to treat Crohn’s disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis.