Upadacitinib or Abatacept in Rheumatoid Arthritis

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Posted by Carla Rothaus

How did upadacitinib compare with abatacept in patients with rheumatoid arthritis in the SELECT-CHOICE trial?

Rubbert-Roth et al. conducted a phase 3, double-blind trial (SELECT-CHOICE) that compared the efficacy and safety of upadacitinib with those of abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs (DMARDs). Both upadacitinib and abatacept were administered in combination with stable synthetic DMARDs. Read the NEJM Original Article here

Clinical Pearls

Q: Describe the two drugs compared in the SELECT-CHOICE trial.

A: Upadacitinib is an oral, reversible Janus kinase (JAK) inhibitor with selectivity for JAK1 over JAK2, JAK3, and tyrosine kinase 2 that has been approved for the treatment of rheumatoid arthritis. Abatacept, a drug approved for the treatment of rheumatoid arthritis, modulates T-cell costimulation by binding to CD80 and CD86 receptors on antigen-presenting cells, thereby inhibiting T-cell proliferation and B-cell stimulation. The efficacy and safety of abatacept have been shown in phase 3 trials involving patients with active rheumatoid arthritis and an inadequate response to methotrexate or biologic DMARDs.

Q: What are the components of the Disease Activity Score for 28 joints (DAS28-CRP)?

A: The DAS28-CRP is a continuous but nonlinear composite measure ranging from 0 to 9.4, with higher scores indicating more active disease. The score is calculated on the basis of a continuous scale of combined measures of the tender-joint count (TJC) of 28 joints (TJC28); the swollen-joint count (SJC) of 28 joints (SJC28); the patient’s global assessment of disease activity (PtGA) on a visual-analogue scale ranging from 0 to 100, with higher scores indicating greater disease activity; and the high-sensitivity C-reactive protein (hs-CRP) level measured in milligrams per liter.


Morning Report Questions

Q: How did upadacitinib compare with abatacept in patients with rheumatoid arthritis in the SELECT-CHOICE trial?

A: The primary end point of the trial was the change from baseline in the DAS28-CRP at week 12, tested for the noninferiority of upadacitinib to abatacept. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and superiority in the percentage of patients having clinical remission based on the DAS28-CRP, defined as a score of less than 2.6. At baseline, the mean DAS28-CRP was 5.70 in the upadacitinib group and 5.88 in the abatacept group. At week 12, the mean change from baseline in the DAS28-CRP was −2.52 points and −2.00 points, respectively (difference, −0.52 points; 95% confidence interval [CI], −0.69 to −0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission according to a DAS28-CRP of less than 2.6 was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001).

Q: In the SELECT-CHOICE trial, how did the safety of upadacitinib compare with that of abatacept?

A: Throughout the 24-week trial period, the incidences of serious adverse events, adverse events leading to discontinuation of the trial drug, and severe adverse events were numerically higher with upadacitinib than with abatacept. Two adjudicated venous thromboembolic events, one major adverse cardiac event, and a higher percentage of patients with grade 3 or 4 elevations in hepatic enzyme and creatine kinase levels were reported with upadacitinib. One death during the treatment period was reported in a patient who received upadacitinib, and one death after the trial period was reported in each of the treatment groups.

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