Early Upadacitinib Response Predicts Long-Term Rheumatoid Arthritis Outcomes

Patients with rheumatoid arthritis (RA) with a poor early response to upadacitinib may not achieve disease activity targets with long-term therapy, according to research results presented at the American College of Rheumatology (ACR) Convergence 2022, held from November 10 to 14, in Philadelphia, Pennsylvania.

Researchers conducted a post-hoc analysis using data from 2 phase 3 trials (SELECT-BEYOND and SELECT-CHOICE) to identify early predictors of long-term upadacitinib treatment response. Patients who received upadacitinib 15 mg once daily with an inadequate response or intolerance to at least 1 tumor necrosis factor (TNF) inhibitor were included in the analysis.

Early predictors of interest included at least a 6-point improvement in Clinical Disease Activity Index (CDAI) and at least a 1.2-point improvement in Disease Activity Score 28-joint count with C-reactive protein (DAS28-CRP) at weeks 4 and 12. Positive and negative predictive values were used to assess whether these improvements reliably predicted achievement of CDAI low disease activity (LDA; ≤10) or remission (≤2.8), along with the percentage of patients achieving DAS28-CRP of 3.2 or lesser and less than 2.6, at weeks 24 and 48, respectively.

The analysis included 140 patients from the SELECT-BEYOND cohort and 258 patients from the SELECT-CHOICE cohort.

At weeks 4 and 12 in the SELECT-BEYOND study, 31 (22%) and 14 (10%) patients, respectively, did not achieve at least a 6-point improvement in CDAI from baseline. Of these individuals, 9 (29%) and 2 (14%), respectively, achieved LDA and 1 (3%) and none of them, respectively, achieved remission at week 24. At week 48, 12 (39%) and 1 (7%) patient (s) without at least 6 CDAI improvement at weeks 4 and 12, respectively, achieved LDA, and 2 (6%) and none of them, respectively, achieved remission.

Similar trends were observed in the SELECT-CHOICE cohort, with patients who did not demonstrate early CDAI improvement not achieving LDA or remission. In addition, early DAS28-CRP improvements from baseline were predictive of reaching DAS28-CRP targets at weeks 24 and 48.

The majority of patients receiving upadacitinib achieved early improvements in CDAI and DAS28-CRP scores; the remaining were unlikely to reach remission at weeks 24 and 48.

Study authors concluded, “…these patients may benefit from therapy adjustment, consistent with treat-to-target recommendations.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.