Abstract Perspective: Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis


“In SELECT-COMPARE, a double blind study comparing upadacitinib to adalimumab or placebo, all on background MTX in patients with continued active RA, the primary endpoints were achieving a statistically significant difference in ACR20 responses and DAS28(CRP)<2.6 of upadacitinib vs placebo. Both primary endpoints were met. A key ranked multiplicity controlled secondary endpoint was comparing the ACR50 response and change from baseline in pain and Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 12 of upadacitinib and adalimumab. All three of these endpoints showed the superiority of upadacitinib compared to adalimumab. In patients who did not respond to upadacitinib or adalimumab as the first therapy, by not achieving a 20% decrease in tender and swollen joints at week 14, 18, and 22 or who did not achieve CDAI low disease activity by week 26 (even if they had a significant reduction in the CDAI over 26 weeks), they were switched to the alternative agent without washout. This is the first report of a patient not responding to a JAK inhibitor being switched to a TNF inhibitor. OF importance, what was found in this exploratory analysis, is that patients who do not respond to one agent, may well respond to the second agent (including a JAK failure responding to a TNF failure) without a safety signal with the immediate switch.  This was shown with ACR responses as well as CDAI responses, with a numerical difference favoring adalimumab to upadacitinib. Of equal importance was that in patients who were rescued to the alternative therapy because they did not achieve CDAI low disease activity, many were able to achieve CDAI low disease activity or remission, proving the treat-to-target strategy can be effective in this population of RA patients. This is also a unique finding which is very clinically relevant.”

Dr. Roy Fleischmann, study author