FDA approves Rinvoq as first oral therapy for moderate to severe Crohn’s disease
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Key takeaways:
- Upadacitinib is the first approved oral product to treat moderately to severely active Crohn’s disease.
- Expanded upadacitinib use is approved for patients who are refractory to treatment with one or more TNF inhibitors.
The FDA has approved AbbVie’s Rinvoq as a once-day pill intended for the treatment of adult patients with moderate to severe Crohn’s disease who are intolerant, or have had an inadequate response, to one or more TNF inhibitors.
Upadacitinib (Rinvoq, AbbVie) is now indicated for both Crohn’s disease and ulcerative colitis. Additionally, this decision marks the drug’s seventh FDA approval across gastroenterology, dermatology and rheumatology.
“AbbVie recognizes the need for more treatment options for Crohn’s disease that can help address both rapid relief of symptoms along with the visible reduction of intestinal lining damage,” Thomas Hudson, MD, senior vice president of research and development, chief scientific officer, AbbVie, said in the release. “We’re pleased that Rinvoq may provide this relief and is now available to treat Crohn’s disease.”
The FDA based its approval on results from two induction studies, U-EXCEED and U-EXCEL, and the U-ENDURE maintenance study. In the induction studies, 34% and 46% achieved endoscopic response following treatment with upadacitinib 45 mg at week 12 compared with 3% and 13% of patients treated with placebo. At week 52, 28% and 41% of patients treated with upadacitinib 15 mg and 30 mg achieved endoscopic response compared with 7% of those who received placebo.
Further, in the induction studies, 36% and 46% of patients treated with upadacitinib 45 mg achieved clinical remission at 12 weeks compared with 18% and 23% of patients who received placebo. At 52 weeks, 42% and 55% of patients treated with upadacitinib 15 mg and 30 mg achieved clinical remission during the maintenance study vs. 14% of those who received placebo.
According to the release, corticosteroid-free clinical remission was achieved as early as 2 weeks during the induction trials.
“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key,” Edward V. Loftus, Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota, and an U-EXCEL study investigator, said in the release. “Given the progressive nature of the disease, endoscopic response is just as important. Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation.”
The company stated that the overall safety profile for upadacitinib among patients with Crohn’s disease was consistent with the drug’s other indications.
The most common adverse events reported for patients who received upadacitinib include serious infections, serious allergic reactions, increased risk for death or cardiovascular events among patients older than 50 years with at least one heart disease risk factor, cancer, immune system issues and tears in the stomach or intestines.
Perspective
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Shubha Bhat, PharmD, MS, FCCP, BCACP
Despite significant therapeutic advances for the management of inflammatory bowel disease over the past several years, the need for oral treatment options for moderate to severe Crohn’s disease was only recently met with FDA approval of upadacitinib in May 2022. Upadacitinib, a Janus kinase (JAK) inhibitor, is a once-daily orally administered medication that is already approved for atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, axial spondylarthritis and ulcerative colitis.
Based on clinical trial data, upadacitinib for the treatment of CD is positioned to be an exciting advance, given the inclusion of adult patients who have had inadequate response or were intolerant to conventional or biologic therapy, the co-primary endpoint of endoscopic response and clinical remission (consistent with STRIDE II guidelines) and rapid symptom relief (eg, less abdominal pain and fewer bowel movements) as early as week 2 for approximately 30% of participants.
One caveat that remains, particularly with this class of medication (JAK inhibitors), is that upadacitinib can only be used in adults with moderately to severely active CD who have had an inadequate response or intolerance to at least one tumor necrosis factor inhibitor. This guidance related to results from the ORAL Surveillance study, which found a higher risk of major adverse cardiovascular events and cancers in patients older than 50 years with active rheumatoid arthritis and at least one cardiovascular risk factor treated with tofacitinib vs. those treated with TNF inhibitors. Thus, upadacitinib will not be available as a first-line option.
Although clinical trials could not identify rare or long-term adverse effects and results of the long-term extension study of U-ENDURE evaluating upadacitnib safety in CD for up to 5 years are pending, current safety data are reassuring, with herpes zoster, hepatic disorders and neutropenia being some of the most observed adverse effects. Some considerations to help optimize the safe use of upadacitinib include vaccinating patients against herpes zoster prior to treatment initiation, dosing appropriately in the setting of renal and hepatic impairment, and assessing for potential drug interactions.
Overall, upadacitinib represents a major milestone as the first advanced oral treatment for moderate to severe CD. I am hopeful this will help pave the way for additional oral treatment options in the future.
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