Comparative Analysis of Upadacitinib and Abatacept for Rheumatoid Arthritis

Overview of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive and often debilitating disease that impacts approximately 19 million individuals globally. This condition leads to joint inflammation, resulting in pain, swelling, and mobility challenges. In recent years, advancements in biotechnology have facilitated the development of new RA treatments. Biological disease-modifying anti-rheumatic drugs (DMARDs) have emerged as key therapies, although they do not work for every patient.

Study Objective

A recent study published in the New England Journal of Medicine aims to explore the efficacy of two drugs, upadacitinib and abatacept, for patients whose RA has not responded to prior treatments. Both medications are approved for RA treatment but are typically prescribed after other therapies, such as methotrexate and/or biologic DMARDs, have failed.

Study Design

The study involved patients with moderate-to-severe RA who had previously been treated with biologic DMARDs. Participants were diagnosed at least three months prior to joining the trial. They were randomly assigned in a 1:1 ratio to receive either upadacitinib or abatacept, with both patients and doctors blinded to the treatment allocation. Background medications were continued throughout the trial, which lasted for 24 weeks, although primary outcomes were assessed at the 12-week mark.

Primary Outcome Measures

The primary endpoint of the trial was the Disease Activity Score for 28 joints (DAS28-CRP), which incorporates biological markers such as C-reactive protein along with patient-reported symptoms. The study evaluated upadacitinib for non-inferiority against abatacept, with a secondary endpoint assessing the superiority of upadacitinib.

Results of the Study

In total, 303 patients received upadacitinib, while 309 received abatacept. After 12 weeks, upadacitinib patients experienced a reduction in the DAS28-CRP score averaging 2.52, compared to a 2.00 reduction in the abatacept group. These results indicate that upadacitinib demonstrated both non-inferiority and superiority over abatacept. Additionally, 30% of patients on upadacitinib achieved remission by week 12, compared to only 13.3% of those on abatacept.

Considerations and Caveats

While the findings suggest that upadacitinib is more effective for DMARD-resistant RA, safety concerns must also be taken into account. Serious adverse events were reported more frequently in the upadacitinib group (3.3%) compared to the abatacept group (1.6%). Furthermore, 7.6% of patients taking upadacitinib experienced liver function issues, contrasting with 1.6% in the abatacept cohort.

Long-Term Efficacy

The study also examined changes in four core components of the DAS28-CRP over the full 24-week period. By week 24, the differences in improvement between the two drugs were less pronounced than at week 12. For instance, the reduction in the patient’s global assessment of disease severity at week 12 was 33.85 for upadacitinib versus 28.35 for abatacept, a notable difference of 5.5. However, this gap narrowed to 1.83 by week 24.

Funding and Future Research

It is important to note that the study was funded by AbbVie, the manufacturer of upadacitinib. Although the results indicate that both upadacitinib and abatacept are viable treatment options for RA, further independent studies with extended follow-up periods are necessary to conclusively determine the best choice for patients.

Conclusion

This study highlights the potential of upadacitinib as a superior option for treating RA in patients unresponsive to other therapies, while also emphasizing the importance of considering safety alongside efficacy in treatment decisions.

Written by Michael McCarthy
Reference: Rubbert-Roth A, Enejosa J, Pangan AL, Haraoui B, Rischmueller M, Khan N, et al. Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. New England Journal of Medicine. 2020;383(16):1511-21.