AbbVie's JAK Inhibitor Upadacitinib Meets Primary Endpoints in Phase 3 Trial, Demonstrating Significant Improvement in Crohn's Disease Symptoms

On December 6, 2021, AbbVie announced positive topline results from a Phase 3 clinical trial of upadacitinib (brand name: Rinvoq), an oral JAK inhibitor. The trial met two primary endpoints, showing that in patients with moderate to severe Crohn's disease who had an inadequate response or were intolerant to biologic therapies, a significantly higher proportion of patients achieved clinical remission and endoscopic improvement after 12 weeks of induction therapy with 45 mg upadacitinib compared to placebo. More than 60% of the enrolled patients had previously experienced failure with two or more biologic treatments. The safety profile of the drug was consistent with previous studies, with no new safety risks observed.

Crohn's disease is a chronic systemic condition characterized by inflammation in the gastrointestinal or digestive tract, which, during flare-ups, causes persistent diarrhea, abdominal pain, and rectal bleeding. It is a progressive disease that worsens over time. Due to the unpredictable nature of Crohn’s symptoms, it imposes significant physical, emotional, and financial burdens on patients.

Upadacitinib, discovered and developed by AbbVie scientists, is a selective and reversible JAK inhibitor. In August 2019, it received approval from the U.S. FDA for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to or intolerance to methotrexate. The JAK family of proteins mediates signaling of various inflammatory cytokines. In addition to Crohn's disease, upadacitinib has yielded positive results in phase 3 clinical trials for the treatment of multiple inflammatory diseases including rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, ulcerative colitis, and axial spondyloarthritis.

This Phase 3 trial evaluated clinical remission through the Crohn's Disease Activity Index (CDAI) and patient-reported stool frequency/abdominal pain symptoms (SF/AP). The trial results showed that after 12 weeks of treatment with 45 mg upadacitinib once daily, a significantly higher proportion of patients achieved clinical remission based on CDAI (39% vs. 21%; p<0.0001) and SF/AP (40% vs. 14%; p<0.0001) compared to placebo. Additionally, endoscopic assessment at Week 12 demonstrated that the proportion of patients in the upadacitinib group achieving mucosal healing was statistically significant compared to the placebo group (35% vs. 4%; p<0.0001).

Moreover, in patients using corticosteroids, the proportion of patients in the upadacitinib group who achieved steroid-free clinical remission at week 12 was also significantly higher than that in the placebo group (according to CDAI and SF/AP assessments).

The specific results of the trial are shown in the table below:

Table Source: Reference [1]

In the trial, upadacitinib demonstrated a safety profile consistent with findings observed in other indications. The most common adverse event was nasopharyngitis. No adjudicated cardiovascular events, malignancies, thromboembolic events, or deaths were reported across the treatment groups.

References:

[1] Upadacitinib (RINVOQ®) Achieved Primary and Key Secondary Endpoints in First Phase 3 Induction Study in Patients with Crohn's Disease. Retrieved December 6, 2021, from https://news.abbvie.com/news/press-releases/upadacitinib-rinvoq-achieved-primary-and-key-secondary-endpoints-in-first-phase-3-induction-study-in-patients-with-crohns-disease.htm

(Original text has been abridged)

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