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Two Trials Show Efficacy of Upadacitinib for Rheumatoid Arthritis

The JAK1-selective inhibitor was found to have a solid safety profile.

A PPM Brief

AbbVie (North Chicago, IL), announced1 results from two Phase 3 clinical trials: SELECT-EARLY and SELECT-COMPARE, showing that patients receiving upadacitinib, an investigational, once-daily JAK1-selective inhibitor, demonstrated improved signs and symptoms of rheumatoid arthritis (RA) through 48 weeks.

In the SELECT-EARLY study, a 48-week double-blind active comparator-controlled trial, patients were randomized to monotherapy with upadacitinib (UPA 15 mg or 30 mg) or methotrexate (MTX).2 Approximately 945 patients were randomized and treated, with 747 (79%) completing treatment through 48 weeks. At week 26, UPA was added for 37 (12%) patients on MTX, and MTX was added for 19 (6%) and 9 (3%) patients on UPA 15 mg and UPA 30 mg, respectively.

  • Through 48 weeks, patients on UPA 15 mg and 30 mg vs MTX had significantly greater improvements in clinical, functional, and patient-reported outcomes.
  • At 48 weeks, Clinical Disease Activity Index (CDAI) Remission was achieved by 33% and 40% of patients on UPA 15 mg and 30 mg, respectively vs 17% on MTX; 28% and 33%, respectively, achieved Boolean Remission vs 13% on MTX.
  • At 48 weeks, ΔmTSS were significantly less on UPA 15 mg and 30 mg vs MTX.

The safety profile of UPA 15 mg and 30 mg monotherapy was generally similar to MTX; 62 patients (6.5%) discontinued due to adverse events and 20 patients (2.1%) discontinued due to lack of efficacy.

Upadacitinib is being studied as a once-daily therapy in moderately to severely active rheumatoid arthritis and across multiple other immune-mediated inflammatory diseases. (Source: 123RF)

In the SELECT-COMPARE study, a double-blind, 48-week study, patients were randomized to once-daily UPA 15 mg, placebo, or adalimumab 40 mg (a comparative RA drug) every other week, with patients continuing background MTX.3 Approximately 1,629 patients were randomized. Among 651 patients randomized to UPA, 38.7% were rescued between weeks 14 to 26, and 86% completed 48-week treatment; among 327 patients randomized to adalimumab, 48.6% were rescued between weeks 14 to 26, and 76% completed 48-week treatment.

  • At 26 weeks and 48 weeks, significantly more patients in the UPA vs adalimumab group achieved ACR20/50/70, low disease activity, and remission compared to placebo.
  • Improvements in pain and function were significantly greater in the UPA vs adalimumab group through 48 weeks compared to placebo.
  • At 26 weeks, there was significantly less radiographic progression for UPA vs placebo, maintained through 48 weeks.

“These data continue to support the potential of upadacitinib to help maintain consistent disease control for patients living with moderately to severely active rheumatoid arthritis,” said Ronald van Vollenhoven, MD, PhD, lead study researcher of the SELECT-EARLY study at the Amsterdam Rheumatology and Immunology Center, in the company press release. “While remission is the primary treatment goal, in accordance with the American College of Rheumatology and the European League Against Rheumatism recommendations, a majority of patients do not achieve clinical remission today, despite currently available treatment options.”

Upadacitinib has not yet been approved by regulatory authorities.

Last updated on: July 11, 2019
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Upadacitinib Shows Positive Top-Line Results for Rheumatoid Arthritis
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