RINVOQ Demonstrates Superior Efficacy Over HUMIRA in First Head-to-Head Trial for TNF-Inhibitor Experienced Rheumatoid Arthritis Patients

AbbVie (search)Search company announced positive topline results from the Phase 3b/4 SELECT-SWITCH study, the first head-to-head trial comparing TNF (search)Search target inhibitor cycling with switching to the JAK (search)Search target inhibitor upadacitinibView drug details in adult patients with moderate to severe rheumatoid arthritis (search)Search disease who had inadequate response or intolerance to a TNF inhibitor other than adalimumabView drug details. 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 (search)Search disease on stable methotrexateView drug details background therapy who had inadequate response or intolerance to a single TNF (search)Search target inhibitor other than adalimumabView drug details. The multicenter, randomized, double-blind, double-dummy, active comparator-controlled study compared upadacitinibView drug details 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

UpadacitinibView drug details demonstrated statistically significant superiority over adalimumabView drug details 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).

"UpadacitinibView drug details demonstrated superiority in achieving low disease activity and remission at week 12 in nearly twice as many patients compared to adalimumabView drug details, providing clinicians with evidence-based guidance for those who need an alternative approach after failure or intolerance of initial TNF (search)Search target 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 (search)Search disease, 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 (search)Search target 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 (search)Search target inhibitor," said Andrew Anisfeld, Ph.D., vice president, global medical affairs, immunology, AbbVie (search)Search company. "The recommended goals for treatment of people with RA are to achieve remission or low disease activity, and this study demonstrated upadacitinibView drug details can deliver these outcomes for many patients."

Safety Profile

The safety profile for both upadacitinibView drug details and adalimumabView drug details 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 (search)Search disease worsening.

Rates of serious adverse events were generally balanced across treatment groups, occurring in 2.4% of patients treated with adalimumabView drug details and 2.0% of patients treated with upadacitinibView drug details. 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 (search)Search disease 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 (search)Search disease 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 (search)Search disease patients who have failed initial TNF (search)Search target inhibitor therapy.