8 out of 10 Patients with RA Achieve Sustained Remission at Month 12 with Upadacitinib

Andrew Östör, MD

Credit: SSR-MSR Workshops

In real-world practice, >79% of patients with moderate to severe rheumatoid arthritis (RA)were able to achieve Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) remission by 6 months, which was maintained through month 12, according to data presented at the 2024 European Congress of Rheumatology (EULAR).¹ These data boast a favorable benefit-risk profile for the drug and is consistent with the findings from the previous phase 3 clinical trials.

“Upadacitinib, an oral reversible Janus kinase [JAK] inhibitor, has shown efficacy with an acceptable safety profile in patients with moderate-to-severe RA in the SELECT clinical trials,” wrote a team of investigators led by Andrew Östör, MD, associate professor in the Department of Medicine at Monash University. “However, data on the effectiveness and safety of upadacitinib in a real-world setting, which may differ from clinical trials, are limited.”

Investigators sought to evaluate the achievement of remission at month 6 as well as sustained remission after 12 months of treatment among this patient population in real-world practice. They used data from UPHOLD, an ongoing, international, observational cohort study of upadacitinib-naïve adult patients with moderate to severe RA who were treated with upadacitinib 15 mg. The analysis included data between October 2020 and August 2023 for all patients within the 12-month follow-up visit window.

The primary endpoints were the percentage of patients treated with upadacitinib who were able to achieve DAS28-CRP remission (< 2.6) at 6 months, and the percentage of patients who were able maintain remission at month 12. This was analyzed by modified non-responder imputation (mNRI) in the first modified full analysis set (mFAS1) and as observed (AO) in the second (mFAS2). The mFAS1 included all patients within the FAS who completed 6 months of treatment coupled with available DAS28-CRP data, including those who discontinued treatment before 6 months. The mFAS2 included patients who achieved remission in mFAS1, with DAS28-CRP data, who completed 12 months of treatment, including those who discontinued upadacitinib between 6 and 12 months.

Other endpoints included the percentage of patients who achieved DAS28-CRP low disease activity (LDA; ≤ 3.2) at month 6 who were able to maintain LDA at 12 months, and the percentage of patients who achieved clinical disease activity index (CDAI)/simplified disease activity index (SDAI) remission (≤ 2.8/< 3.3) at month 12. Information on treatment-emergent adverse events were also reported.

A total of 1701 patients were included in the FAS, of which 48.4% received upadacitinib monotherapy and 51.6% received concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Most (n = 1523) received prior therapy, of which 64.3% were treated with ≥ 1 biologic DMARD (bDMARD) and 18.1% received ≥ 1 targeted synthetic DMARD (tsDMARDs).

Among 1074 patients in mFAS1, 55.3% (AO) and 46.5% (mNRI) were in remission at month 6. Of the 340 patients in mFAS2, 79.1% (mNRI) and 84.9% (AO) were able to sustain remission at 12 months.

Regarding secondary efficacy endpoints, the percentages of patients who achieved LDA at month 6 who maintained LDA at month 12 were comparable. DAS28-CRP, CDAI, and SDAI at month 12 were achieved in 59.8%, 28.0%, and 28.3% of patients, respectively.

Most patients treated with upadacitinib as either monotherapy or combination therapy who achieved DAS28-CRP at 6 months and continued treatment at month 12 (or discontinued between 6 and 12 months) maintained remission at the end of the study (80.5% and 79.4%, respectively).

A total of 2436 TEAEs were reported, of which the exposure-adjusted event rates (EAERs) for major adverse cardiovascular events (MACE), thrombotic events, and malignancy were low and consistent with previous long-term clinical trials.

References

1. ^{Östör A, Feist E, Sidiropoulos P, Avouac J, et al. Achievement and Maintenance of Remission with Upadacitinib in Patients with Moderate-to-Severe Rheumatoid Arthritis in a Real-World Setting: 1-Year Outcomes From the UPHOLD Study. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.}