Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis

Abstract

We believe that the trial conducted by Rubbert-Roth et al. (Oct.15 issue) 1 may not show that upadacitinib was more efficacious than abatacept in patients with rheumatoid arthritis.Janus kinase (JAK) inhibitors such as upadacitinib target interleukin-6 signaling and thereby reduce the level of C-reactive protein (CRP), a dominant constituent of the primary end point of the trial -the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity).Consequently, the DAS28-CRP decreased dramatically only in patients who were receiving upadacitinib.Among non-CRP-related outcomes, upadacitinib was not clearly better than abatacept.The reductions in the counts of tender and swollen joints in the two groups were almost identical, and although the patients' global assessment of disease activity improved more with upadacitinib than with abatacept at 12 weeks, no differences were present thereafter.We do not endorse a DAS28-CRP of less than 2.6 as a threshold for remission.We led the joint American College of Rheumatology-European League against Rheumatism task force that rejected the use of the DAS28-CRP for defining remission. 2Because the swollen-joint count is underweighted in the calculation of the DAS28-CRP, patients with a DAS28-CRP of less than 2.6 can have 10 or more swollen joints, a level that is inconsistent with remission. 3Furthermore, many patients with a DAS28-CRP of less than 2.6 have progressive disease as assessed radiographically.Given the focus on a CRP-dependent end point and the selection of a nonstringent definition of remission, we conclude that this trial did not show clinically meaningful differences between upadacitinib and abatacept.

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