The FDA approved upadacitinib (Rinvoq) for treating Crohn's disease, representing the first Janus kinase (JAK) inhibitor for the condition, the agency announced on Thursday.
Specifically, the once-daily pill is indicated for adults with moderately to severely active disease who have failed or are intolerant of one or more tumor necrosis factor (TNF) inhibitors.
Approval was based on findings from the U-EXCEED and U-EXCEL induction studies, which involved 857 patients with moderately to severely active Crohn's disease, along with the U-ENDURE maintenance study, all of which met their primary endpoints and key secondary endpoints.
"Symptoms of moderately to severely active Crohn's disease can be disruptive and uncomfortable for patients, so relief as early as possible is key," said Edward Loftus Jr., MD, of the Mayo Clinic in Rochester, Minnesota, in a press release from drugmaker AbbVie. "Given the progressive nature of the disease, endoscopic response is just as important."
In the two induction trials, endoscopic response (a visible reduction of intestinal lining damage) was significantly improved with a 45-mg dose of upadacitinib (34-46% vs 3-13% with placebo at week 12), with responses seen as early as 2 weeks. Clinical remission at 12 weeks, meanwhile, was achieved in 36-46% of patients in the upadacitinib groups, as compared with 18-23% of those in the placebo group.
Response was defined as a decrease in Simplified Endoscopic Score for Crohn's Disease (SES-CD) of more than 50% from baseline (or a 2-point SES-CD reduction for patients with isolated ileal disease and a baseline SES-CD of 4). Remission was defined as a Crohn's Disease Activity Index score below 150.
During the U-ENDURE maintenance study, which enrolled responders from the induction trials, endoscopic response at week 52 was achieved in 28% of patients treated with a 15-mg dose of upadacitinib and in 41% of those on a 30-mg dose, versus only 7% of patients receiving placebo.
Additionally, 42% and 55% of patients treated with the two upadacitinib maintenance doses, respectively, achieved clinical remission at this time point, compared with 14% of placebo participants.
"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," said Loftus.
The recommended maintenance dose is 15 mg once daily, according to the FDA, while the 30-mg dose can be considered as an option for refractory or severe case, or for patients with extensive Crohn's disease.
Common adverse events in the trials included anemia, acne, fever, headache, shingles, and upper respiratory tract infections. The FDA noted that the drug should not be used in combination with other JAK inhibitors or biologics for Crohn's disease, or in combination with strong immunosuppressive agents including azathioprine and cyclosporine.
Due to safety concerns -- ranging from increased risks for cancer, blood clots, and death observed in prior trials -- use of JAK inhibitors in inflammatory conditions such as Crohn's disease are restricted to patients who fail on or cannot tolerate TNF blockers.
The new indication represents the seventh approval for upadacitinib; the drug has indications in ulcerative colitis, rheumatoid arthritis, and atopic dermatitis, among other conditions.