In patients with rheumatoid arthritis (RA) with nonresponse or incomplete response to initial therapy, switching from upadacitinib to adalimumab, or vice versa, may be safe and effective, according to study results published in Annals of the Rheumatic Diseases.
Previous studies have recommended a treat-to-target strategy for RA in which therapy is optimized every 3 to 6 months until clinical remission or at least low disease activity is achieved. The objective of the current study was to determine the safety and efficacy of an immediate switch from upadacitinib, a tumor necrosis factor (TNF) inhibitor, to adalimumab, a Janus kinase (JAK) inhibitor, and vice versa, in patients with nonresponse or incomplete response to initial therapy.
In the SELECT-COMPARE study (ClinicalTrials.gov Identifier: NCT02629159), patients were randomly assigned to receive upadacitinib, adalimumab, or placebo. Patients who did not achieve at least 20% improvement in both tender and swollen joint count from baseline to week 26 were considered “nonresponders.” Patients who did not achieve low disease activity, based on Clinical Disease Activity Index (CDAI) less than 10, at week 26 were considered “incomplete responders.” The total cohort included 651 patients who received upadacitinib 15 mg once daily, 327 patients who received adalimumab 40 mg every other week, and 651 participants who received placebo.
In the current study, among the patients who received either upadacitinib or adalimumab, 252 (38.7%) and 159 (48.6%) had no response or incomplete response, respectively, to initial therapy.
Among the nonresponders, a switch in mechanism of action had a beneficial effect on clinical response in both groups. At 6 months after switching to adalimumab, CDAI low disease activity and remission rates were 36.0% (n=41/114) and 5.3% (n=6/114), respectively, and 47.1% (n=33/70) and 14.3% (10/70), respectively, after switching to upadacitinib.
Among incomplete responders, 6 months after the switch to adalimumab, CDAI low disease activity and remission rates were 45.0% (n=54/120) and 5.0% (6/120), respectively. Among patients who were switched to upadacitinib, CDAI low disease activity and remission rates were 57.9% (n=44/76) and 15.8% (n=12/76), respectively.
Overall, 4.5% of patients who were switched to alternate therapy experienced a clinically relevant worsening of disease activity at 6 months. The frequency of adverse events was similar between both groups, regardless of whether patients were switched to adalimumab or upadacitinib.
The study had several limitations, including the observational design, the limited number of patients who met the rescue criteria, and that the results may not be applicable to all patients in clinical practice.
“These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes,” the researchers concluded.
Disclosure: This clinical trial was supported by AbbVie Inc. Please see the original reference for a full list of authors’ disclosures.
Fleischmann RM, Blanco R, Hall S, et al. Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis. Ann Rheum Dis. Published online November 4, 2020. doi:10.1136/annrheumdis-2020-218412