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Switch, Don’t Cycle: Upadacitinib Outperforms Adalimumab in RA Post-TNFi, With Eduardo Mysler, MD
Mysler emphasized the first definitive evidence informing sequencing after failing a first TNF inhibitor.
New evidence supporting the superiority of upadacitinib (Rinvoq) over adalimumab (Humira) in patients with rheumatoid arthritis (RA) after failure of a first TNF inhibitor (TNFi) may finally have answered the highly-speculated question of whether to cycle between TNFis or switch to a different mechanism of action.
The new data, from the SELECT-SWITCH phase 3b/4 trial, have provided for the first time, clear, comparative data on treatment sequencing that treatment guidelines could not answer.
"We had an idea that... it's better to change mechanism of function than actually to cycle between TNFis. We all thought that that was the right decision, but we couldn't prove it. And unless somebody put the money into a trial like that, we would never be able to find that answer, and probably, in the close future, to change the guidelines," study investigator Eduardo Mysler, MD, Executive Medical Director, Organizacion Medica de Investigacion, Argentina, told HCPLive. I think that's the crucial thing about this trial, that we designed a trial that actually [assessed] people who fail one TNFi."
At week 12, 43.3% of patients with moderate to severe RA who had a prior inadequate or intolerable response to TNFi receiving upadacitinib achieved low disease activity (DAS28-CRP ≤3.2), compared with 22.4% of those receiving adalimumab (P <.001). Similarly, 28.4% of patients in the upadacitinib arm reached remission (DAS28-CRP <2.6) versus 14.5% in the adalimumab group (P <.001). Upadacitinib also outperformed adalimumab across additional ranked secondary endpoints, reinforcing its efficacy advantage in this treatment setting.
"Why the primary endpoint was low disease activity and not remission? Well, if you want to do remission, your number of patients that you require, the power [needed is] so much greater. So it was great that we have a hierarchy system, which means that we have a primary endpoint, low disease activity that we reached, and then you have as a secondary ranking key endpoint, remission. So the validity of that is extremely high," Mysler noted.
The safety profile of upadacitinib was consistent with prior studies, with no new safety signals observed over the 12-week period. The most frequent treatment-emergent adverse events (AEs, ≥3%) were urinary tract infection, nasopharyngitis, and worsening RA. Serious AEs occurred in 2.0% of upadacitinib-treated patients and 2.4% of those on adalimumab, with no reports of venous thromboembolism, major cardiovascular events, or deaths.
The study’s implications extend beyond efficacy. As Mysler emphasized, head-to-head trials like SELECT-SWITCH are rare but essential for shaping evidence-based guidelines.
"Even when you combine primary and secondary failures, the results are the remission rate and the low disease activity rate is so much better when you switch compared to cycle," Mysler emphasized.
Full data from SELECT-SWITCH will be published in an upcoming medical journal and presented at future scientific meetings, but the topline findings already represent a turning point in RA management and, as Mysler stressed, will iform clinical decision-making and optimize treatment outcomes for patients worldwide.
Watch the interview with Mysler below.
Mysler's disclosures include AbbVie, Pfizer, AstraZeneca, Novartis, Roche, Sanofi, Amgen, Eli Lilly, GSK, and Janssen.
