The Food and Drug Administration has approved a new indication for upadacitinib (Rinvoq) for the treatment of moderately to severely active Crohn's disease in adults who have not had an adequate response or are intolerant to one or more tumor necrosis factor blockers. This is the first oral treatment for Crohn's disease.

Crohn's disease is a chronic inflammatory bowel disease producing inflammation in the gastrointestinal tract, most commonly in the small intestine and the beginning of the large intestine. According to the National Institutes of Health, more than half a million Americans have Crohn's disease.

Upadacitinib is a Janus kinase (JAK) inhibitor originally approved in 2019. It was previously approved for the treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, atopic dermatitis, and ulcerative colitis. Upadacitinib should not be used in combination with other JAK inhibitors, with biological therapies for Crohn's disease, or with potent immunosuppressants such as azathioprine and cyclosporine.

The efficacy and safety of upadacitinib was evaluated in two randomized, double-blind, placebo-controlled induction trials of 857 patients with moderately to severely active Crohn's disease. Patients were randomized 2:1 to receive upadacitinib 45 mg or placebo once a day for 12 weeks. A greater proportion of patients treated with upadacitinib than placebo achieved clinical remission at week 12, as determined by the Crohn's Disease Activity Index. Intestinal inflammation, as determined by colonoscopy, also improved in more patients treated with upadacitinib than placebo.

Another trial of 343 patients who had been responsive to 12 weeks of upadacitinib studied the effectiveness of the drug as a maintenance treatment. Patients were rerandomized to receive upadacitinib 15 or 30 mg or placebo for 52 weeks. A larger percentage of patients treated with upadacitinib achieved clinical remission and improved intestinal inflammation compared with placebo.

The most common adverse effects of upadacitinib when used for Crohn's disease were upper respiratory tract infections, anemia, fever, acne, herpes zoster, and headache. The boxed warnings for the product are the same whether it's used for Crohn's disease or for other indications and include serious infections, higher rate of all-cause mortality, malignancies, major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke), and thrombosis.

Nurses and NPs should assess patients for hypersensitivity and laboratory changes (low absolute neutrophil count, low absolute lymphocyte count, low hemoglobin, or elevated hepatic transaminases), evidence of gastrointestinal perforation symptoms (severe abdominal pain or cramping, bloated or swollen abdomen, fever and chills, nausea and vomiting, tenderness to palpation), and new onset of serious infections. If serious infections occur or laboratory values are significantly altered, therapy should be discontinued until the adverse effect is controlled. Because the drug can cause embryo-fetal toxicity, patients of childbearing age should be advised to test for pregnancy prior to starting therapy and to use effective contraception.

Nurses should utilize a drug database to determine if the patient is also being prescribed strong cytochrome P-450 (CYP) isoenzyme 3A4 inhibitors , which can increase exposure to the drug, or strong CYP3A4 inducers, which can reduce its therapeutic levels. Both drug types should be avoided if possible. Patients should be told not to eat grapefruit or drink grapefruit juice, both CYP3A4 inhibitors, to prevent adverse drug reactions. Patients should not receive live vaccines while receiving upadacitinib.

For full prescribing information for upadacitinib, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211675s015lbl.pdf.