Rinvoq (upadacitinib) demonstrated superiority versus Humira (adalimumab) for primary endpoint in a head-to-head study in rheumatoid arthritis patients who have failed first TNF Inhibitor – AbbVie

AbbVie announced positive topline results from the Phase IIIb/IV head-to-head SELECT-SWITCH study evaluating the efficacy and safety of upadacitinib (Rinvoq) 15 mg, once daily, compared to adalimumab (Humira) 40 mg, every other week, in adult patients with moderate to severe rheumatoid arthritis (RA) on a stable background of methotrexate (MTX) who had an inadequate response or intolerance to a TNF inhibitor (TNFi) other than adalimumab. This study achieved the primary endpoint and the majority of ranked secondary endpoints at week 12 with no new safety risks identified.

A significantly higher proportion of patients who received upadacitinib achieved low disease activity (defined as Disease Activity Score 28 C-reactive Protein [DAS28-CRP]≤3.2; primary endpoint) and remission (defined as DAS28-CRP<2.6; ranked secondary endpoint) compared to adalimumab at week 12. Upadacitinib also demonstrated superiority versus adalimumab for additional ranked secondary endpoints measured at week 12.

• • 43.3% of patients receiving upadacitinib achieved DAS28-CRP≤3.2 compared to 22.4% of patients on adalimumab (p<0.001)
• • 28.4% of patients receiving upadacitinib achieved DAS28-CRP<2.6 compared to 14.5% of patients on adalimumab (p<0.001)

Full results will be published in an upcoming medical journal and shared at future medical congresses.

Treatment guidelines establish remission as the optimal treatment goal in RA, yet more than half of patients fail to achieve remission, even on advanced therapies. As longer disease duration is associated with a reduced likelihood of achieving remission, it is important to optimize treatment strategies as early as possible in the disease course. TNFis are the most common first-line targeted therapy in RA, and switching to a second TNFi is highly prevalent in clinical practice, despite limited evidence on the efficacy of TNFi cycling compared to switching to a different mode of action after the first TNFi failure.

The safety profile for upadacitinib and adalimumab in this study were consistent with previously reported studies; with no new safety risks identified in the 12-week period. The most frequently reported treatment emergent AEs (≥ 3%) in any treatment group were urinary tract infection, nasopharyngitis and RA (worsening). Rates of serious adverse events were generally balanced across the 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 event or deaths were observed.

“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 Dr. Andrew Anisfeld, 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.”

“SELECT-SWITCH is the first head-to-head trial comparing TNF inhibitor cycling with switching to the JAK inhibitor upadacitinib,” said lead study investigator Dr. Eduardo Mysler, rheumatologist and executive medical director, Organización Medica de Investigación, Argentina. “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.”