AbbVie announced positive topline results from the Phase 3b/4 SELECT-SWITCH study, the first head-to-head trial comparing TNF inhibitor cycling with switching to the JAK inhibitor upadacitinib in adult patients with moderate to severe rheumatoid arthritis who had inadequate response or intolerance to a TNF inhibitor other than adalimumab. The study achieved its primary endpoint and majority of ranked secondary endpoints at week 12 with no new safety risks identified.
Study Design and Patient Population
SELECT-SWITCH enrolled 492 adult patients with moderate to severe rheumatoid arthritis on stable methotrexate background therapy who had inadequate response or intolerance to a single TNF inhibitor other than adalimumab. The multicenter, randomized, double-blind, double-dummy, active comparator-controlled study compared upadacitinib 15 mg once daily versus adalimumab 40 mg every other week, both administered with methotrexate.
The study comprised a 35-day screening period followed by a 12-week randomized controlled period and a 36-week blinded extension period. Participants were randomized 1:1 to receive either treatment combination, with the primary endpoint measuring the percentage of participants achieving low disease activity defined as Disease Activity Score 28 C-reactive protein (DAS28-CRP) ≤3.2 at week 12.
Efficacy Results
Upadacitinib demonstrated statistically significant superiority over adalimumab for both primary and key secondary endpoints. A significantly higher proportion of patients receiving upadacitinib achieved low disease activity compared to adalimumab: 43.3% versus 22.4% (p<0.001). For the ranked secondary endpoint of remission, defined as DAS28-CRP<2.6, upadacitinib again showed superior results with 28.4% of patients achieving remission compared to 14.5% on adalimumab (p<0.001).
"Upadacitinib demonstrated superiority in achieving low disease activity and remission at week 12 in nearly twice as many patients compared to adalimumab, providing clinicians with evidence-based guidance for those who need an alternative approach after failure or intolerance of initial TNF inhibitor therapy," said lead study investigator Eduardo Mysler, M.D., rheumatologist and executive medical director, Organización Medica de Investigación, Argentina.
Clinical Context and Treatment Landscape
Treatment guidelines establish remission as the optimal treatment goal in rheumatoid arthritis, yet more than half of patients fail to achieve remission even on advanced therapies. As longer disease duration is associated with reduced likelihood of achieving remission, optimizing treatment strategies early in the disease course is crucial. TNF inhibitors represent the most common first-line targeted therapy in rheumatoid arthritis, and switching to a second TNF inhibitor is highly prevalent in clinical practice, despite limited evidence on the efficacy of TNF inhibitor cycling compared to switching to a different mechanism of action after first TNF inhibitor failure.
"These positive results strengthen the growing body of evidence supporting the benefits of switching to a new mechanism of action after inadequate response or intolerance to a first TNF inhibitor," said Andrew Anisfeld, Ph.D., vice president, global medical affairs, immunology, AbbVie. "The recommended goals for treatment of people with RA are to achieve remission or low disease activity, and this study demonstrated upadacitinib can deliver these outcomes for many patients."
Safety Profile
The safety profile for both upadacitinib and adalimumab in this study was consistent with previously reported studies, with no new safety risks identified during the 12-week period. The most frequently reported treatment emergent adverse events (≥3%) in any treatment group were urinary tract infection, nasopharyngitis and rheumatoid arthritis worsening.
Rates of serious adverse events were generally balanced across treatment groups, occurring in 2.4% of patients treated with adalimumab and 2.0% of patients treated with upadacitinib. One malignancy was reported in each group. No adjudicated venous thromboembolism, major adverse cardiovascular events or deaths were observed during the study period.
Disease Burden and Unmet Need
Rheumatoid arthritis affects more than 17 million people worldwide and is a complex, systemic autoimmune disease that occurs when the immune system mistakenly attacks joints, creating inflammation that causes tissue inside joints to thicken, damaging bones and associated connective tissue. Pain, fatigue and stiffness are among the signs and symptoms that can impact daily living. If not properly treated, rheumatoid arthritis can lead to permanent, debilitating bone and cartilage damage.
SELECT Program Context
The robust SELECT Phase 3 rheumatoid arthritis program has evaluated more than 4,900 patients with moderate to severe rheumatoid arthritis across six studies. The studies include assessments of efficacy, safety and tolerability across multiple rheumatoid arthritis patient populations, including patients with prior non-response to advanced therapies. Key measures of efficacy evaluated include ACR responses, Disease Activity Score (DAS28-CRP), patient-reported outcomes and inhibition of radiographic progression.
Full results from SELECT-SWITCH will be published in an upcoming medical journal and shared at future medical congresses, providing additional detailed data to support clinical decision-making for rheumatoid arthritis patients who have failed initial TNF inhibitor therapy.
