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Persuasive long-term results for JAK inhibition in rheumatoid arthritis

Presented by
Prof. Josef Smolen, Medical University of Vienna, Austria
Conference
ACR 2020
Trial
Phase 3, SELECT-MONOTHERAPY
Over 7 years, the oral JAK inhibitor upadacitinib showed convincing results for lasting efficacy in patients with rheumatoid arthritis within the SELECT-MONOTHERAPY trial.

Upadacitinib as monotherapy already demonstrated significant results after 14 weeks in patients with moderate-to-severe rheumatoid arthritis (RA) compared with methotrexate within the SELECT-MONOTHERAPY (NCT02706951) study [1]. The current analysis focused on drug performance over 84 weeks [2].

Within the long-term extension of SELECT-MONOTHERAPY, 598 patients continued their previous medication with upadacitinib 15 or 30 mg or were switched to one of the upadacitinib doses in case of preceding methotrexate therapy, as prespecified at baseline.

“By week 84, approximately 80% of patients in either treatment group, blinded upadacitinib 15 or 30 mg, remained in the study,” said Prof. Josef Smolen (Medical University of Vienna, Austria). Baseline characteristics were balanced over the different treatment groups. They comprised 81% females, a mean of 6.6 ± 7.58 years since RA diagnosis, mean Disease Activity Score (DAS)28 using C-reactive protein (CRP) was 5.6 ± 1.0, mean clinical disease activity index (CDAI) was 38.0. In total, exposure to upadacitinib 15 mg corresponded to 421.5 patient-years (PY) and upadacitinib 30 mg to 425.9 PY.

Treatment-emerging adverse events occurred in the upadacitinib groups at a rate of ≥5/100 PY and were most frequently seen as urinary tract infections, creatine phosphokinase (CPK) elevation, or upper respiratory tract infections. “Events of herpes zoster infections, hepatic disorders, and CPK elevation were higher among patients receiving upadacitinib 30 mg, while rates of serious infections and malignancy appeared comparable between the doses,” revealed Prof. Smolen regarding long-term safety. He pointed out that the most common serious adverse event was pneumonia, occurring at 1.7 events/100 PY in the upadacitinib 15 mg group and 0.7 events/100 PY in the upadacitinib 30 mg group.

Concerning efficacy, 71% (upadacitinib 15 mg) and 78% (upadacitinib 30 mg) reached American College of Rheumatology (ACR)50 responses at week 84. The respective rates for DAS28 <2.6 were 60% and 77%, respectively. CDAI ≤10 was attained by 55% (upadacitinib 15 mg) and 67% (upadacitinib 30 mg). “Approximately one-quarter to one-third of patients receiving upadacitinib achieved CDAI and ACR/EULAR-based Boolean definitions of remission at week 84,” said Prof. Smolen. Furthermore, reductions in pain and physical function were also maintained until week 84.

“In summary, upadacitinib monotherapy resulted in continued and sustained benefit through 84 weeks with no new safety signals identified,” concluded Prof. Smolen.

  1. Smolen JS, et al. 2019;393:2303-11.
  2. Smolen JS, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis and prior inadequate response to methotrexate: results at 84 weeks. P0209, ACR Convergence 2020, 5-9 Nov.




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