[10] Upadacitinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs).

[10][11] Upadacitinib was approved in January 2022, by the FDA for treating adults and children twelve years of age and older with moderate to severe treatment refractory atopic dermatitis.

[10][17] Upadacitinib was approved in March 2022, by the FDA for treating adults with moderately to severely active ulcerative colitis who did not respond to treatment with anti-TNF drugs (e.g.

[18] Upadacitinib was approved in February 2023, by the UK Medicines and Healthcare products Regulatory Agency (MHRA) to treat adults with moderately to severely active Crohn's disease.

[19][20] In April 2023, upadacitinib was approved in the EU for the treatment of moderately to severely active Crohn's disease in adults.

[21][22][23] In May 2023, the FDA approved upadacitinib for the treatment of adults with moderately to severely active Crohn's disease who have had an inadequate response or intolerance to one or more TNF blockers.

[10][24][25] The US Food and Drug Administration (FDA) requires a boxed warning for tofacitinib, baricitinib, and upadacitinib to include information about the risks of serious heart-related events, cancer, blood clots, and death.

[12][28] Substances that strongly inhibit the liver enzyme CYP3A4, such as ketoconazole, itraconazole, or clarithromycin, increase upadacitinib concentrations in the body.

The most important pathway consists of oxidation to a carboxylic acid and subsequent glucuronidation, yielding a metabolite called M4.

[14] Trials enrolled participants with moderate to severe active RA in whom disease-modifying antirheumatic drugs did not work well or could not be tolerated.

[14] All participants had at least six tender and six swollen joints, and increased levels of high sensitivity C-reactive protein (hsCRP).

[14] Participants were randomly assigned to receive one of two doses of upadacitinib or placebo daily by mouth in addition to disease-modifying antirheumatic drugs for 12 weeks.

[14] Participants were randomly assigned to receive upadacitinib or placebo daily by mouth in addition to methotrexate for 14 weeks.

[14] Participants were randomly assigned to receive one of two doses of upadacitinib or placebo treatment daily added to disease-modifying antirheumatic drugs for 12 weeks.

[19][20] In April 2023, upadacitinib was approved in the EU for the treatment of moderately to severely active Crohn's disease in adults.

[32][33] The efficacy and safety of upadacitinib were evaluated in two randomized induction trials of 857 participants with moderately to severely active Crohn's disease, CD-1 (NCT03345836) and CD-2 (NCT03345849).

[24] Similarly, a greater proportion of participants treated with 45 mg of upadacitinib demonstrated improvement in intestinal inflammation as assessed by colonoscopy.

An investigation into absorption and metabolism found that dosing after a high-fat meal had no effect on upadacitinib total drug exposure over time (area under the curve or AUC).

In the first study, 276 rheumatoid arthritis participants were recruited who had previously experienced inadequate response to anti–tumor necrosis factor (TNF) therapy and were currently on a stable dose of methotrexate.

One case of community-acquired pneumonia occurred at 12 mg. [needs update] In this 16-week study, 220 participants were recruited with moderately to severely active Crohn's disease.

Abbvie has planned a total of six phase III trials that will evaluate over 4,000 participants with moderate to severe rheumatoid arthritis.

The study was designed and powered to test for non-inferiority and superiority of upadacitinib versus adalimumab clinically and functionally.

Upadacitinib was superior to placebo and adalimumab for improving signs, symptoms and physical function in RA participants on background methotrexate, and significantly inhibited radiographic progression versus placebo, while the overall safety profile was generally similar to adalimumab, except for higher rates of herpes zoster and CPK elevations on upadacitinib.

[40] SELECT-CHOICE was a phase III trial comparing upadacitinib and abatacept in 612 people whose rheumatoid arthritis did not respond to biologic disease-modifying antirheumatic drugs.

The trial found that after 12 weeks of treatment, people treated with upadacitinib had lower DAS-28 CRP scores and a higher rate of remission.