A study published in Annals of the Rheumatic Diseases illustrated that immediate switching from upadacitinib to adalimumab, or vice versa appears to be safe and effective in rheumatoid arthritis individuals having nonresponse or incomplete response to initial treatment.

A study (SELECT-COMPARE) was conducted to investigate the safety and efficacy of switch from upadacitinib (tumor necrosis factor inhibitor) to adalimumab (Janus kinase inhibitor) or vice versa in individuals suffering from rheumatoid arthritis having non-response or incomplete-response to the initial therapeutic intervention.

Participants were randomly assigned to either 15 mg of upadacitinib once daily (n=651), placebo (n=651), or 40 mg adalimumab every other week (n=327). A treat-to-target strategy was executed, with blinded rescue occurring before week 26 for individuals who did not attain at least 20% improvement in both swollen and tender joint counts (non-responders) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (incomplete-responders) without washout.

Overall, 39 % (252/651) and 49 % (159/327) of participants initially randomized to upadacitinib and adalimumab were rescued to the alternate treatment. Remarkable improvements in disease activity at three and six months after rescue were observed in both the switch groups (adalimumab to upadacitinib and vice versa) and in incomplete and non-responders.

In both the incomplete and non-responder groups, more subjects were found to attain therapeutic goals of low disease activity and remission following a blinded switch in the mechanism of action. At six months following the switch, the percentage of non-responders and incomplete-responders attaining CDAI low disease activity and remission who switched to adalimumab and upadacitinib is depicted in the following figure:

ADA, Adalimumab; LDA, Low disease activity; UPA, Upadacitinib; CDAI, Clinical Disease Activity Index

About 5% of rescued subjects witnessed worsening in disease activity at six months’ post switch. The adverse events frequency illustrated similarity between the switch groups.

Thus, these findings advocate a treat-to-target approach, in which individuals who fail to respond at the initial stage (or do not attain sufficient response) are switched to treatment with an alternative mechanism of action and witness better outcomes. No novel safety findings were noted despite a prompt switch in the mechanism of action without washout.