Appendix
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Rheumatology/Dermatology/Gastroenterology

Upadacitinib

This activity offers an in-depth examination of upadacitinib, a second-generation selective Janus kinase (JAK) inhibitor targeting the JAK1 enzyme, approved by the FDA for treating various chronic inflammatory conditions such as moderate to severe rheumatoid arthritis (RA), psoriatic arthritis, atopic dermatitis, ankylosing spondylitis, Crohn disease, and ulcerative colitis. The session will cover the specific mechanism by which upadacitinib inhibits key intracellular cytoplasmic enzymes (Janus

v1 · Reviewed Nov 7, 2026 by Automated Clinical Reviewer (Strict Verbatim v1)
  • Infections, malignancy, thrombosis, tuberculosis, death, and major adverse cardiovascular events (MACE) are significant risks.
  • Recent updates in upadacitinib use have shown an increased rate of all-cause mortality and sudden cardiovascular-associated mortality when used concurrently with another JAK inhibitor agent versus tumor necrosis factor (TNF) inhibitors in subjects with RA.
  • MACE includes cardiovascular mortality, myocardial infarction (MI), and stroke.
  • The predominant serious infections associated with upadacitinib include pneumonia, cellulitis, tuberculosis, herpes zoster, oral and esophageal candidiasis, and cryptococcosis.
  • Upadacitinib was found to be teratogenic in animal studies, although no human studies during pregnancy have been reported.
  • Administration of a live attenuated vaccine shortly before or during treatment is also not advised.
  • Before initiating treatment with upadacitinib, it is necessary to ensure that immunizations are up-to-date and to assess for active or latent tuberculosis (TB).
  • Additional evaluations include liver function, viral hepatitis panel, and pregnancy status in females of childbearing age.
  • Before initiating treatment with upadacitinib, a negative tuberculosis (TB) test is required as it may reactivate latent TB infection.
  • A complete blood count (CBC) must be monitored before starting therapy and routinely after that; initiating upadacitinib is not recommended for subjects with an absolute lymphocyte count (ALC) below 500 cells/mm³ or an absolute neutrophil count (ANC) below 1,000 cells/mm³.
  • Liver function tests (LFTs) should be checked before beginning therapy and regularly after that, as patients with severe hepatic impairment are not advised to start treatment.
  • The lipid panel should also be monitored 12 weeks after starting treatment, as increases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol may occur.
  • Endoscopic evaluation is advised to confirm inflammation and rule out other causes.
  • Before initiating treatment with upadacitinib, it is necessary to ensure that immunizations are up-to-date and to assess for active or latent tuberculosis (TB).
  • Additional evaluations include liver function, viral hepatitis panel, and pregnancy status in females of childbearing age.
  • Concomitant administration of upadacitinib with other JAK inhibitors, biologic DMARD agents, or potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
  • The medication may be taken with or without food and should be consumed as a whole tablet without splitting or crushing it.
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
monotherapy
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
monotherapy
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
For pediatric patients aged 12 years and older and weighing at least 40 kg
Upadacitinib
oral
Adult
45 mg once daily
Renal
Not specified in source
Duration
for 8 weeks (induction phase)
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
For maintenance therapy
Upadacitinib
oral
Adult
45 mg once daily
Renal
Not specified in source
Duration
for 12 weeks (induction phase)
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
For maintenance therapy
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
Not specified in source
Upadacitinib
oral
Adult
15 mg once daily
Renal
Not specified in source
Duration
Not specified in source
  • Upadacitinib is a new FDA-approved second-line agent for treating moderate to severe active rheumatoid arthritis (RA) in patients who have not shown an adequate response or intolerance to the first-line agent, methotrexate.
  • Using upadacitinib with other JAK inhibitors (JAKinibs) or robust immunosuppressants like azathioprine and cyclosporine is not advised.
  • However, its use in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs) such as methotrexate is supported, while its use with biological DMARDs is not recommended
  • Upadacitinib or other immunosuppressive therapies may be considered for refractory cases.
  • Administration of a live attenuated vaccine shortly before or during treatment is also not advised.
  • Upadacitinib is not recommended for severe hepatic impairment.
  • Administration of upadacitinib during pregnancy is not recommended.
  • Upadacitinib was also present in breast milk during animal studies, and women are advised not to breastfeed while receiving therapy.
  • Before initiating treatment with upadacitinib, a negative tuberculosis (TB) test is required as it may reactivate latent TB infection.
  • During treatment with upadacitinib, patients should be routinely tested for TB.
  • A complete blood count (CBC) must be monitored before starting therapy and routinely after that; initiating upadacitinib is not recommended for subjects with an absolute lymphocyte count (ALC) below 500 cells/mm³ or an absolute neutrophil count (ANC) below 1,000 cells/mm³.
  • Liver function tests (LFTs) should be checked before beginning therapy and regularly after that, as patients with severe hepatic impairment are not advised to start treatment.
  • The lipid panel should also be monitored 12 weeks after starting treatment, as increases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol may occur.
  • Patients should be monitored for serious infections during therapy, as severe bacterial, viral, fungal, tuberculous, and opportunistic infections have occurred, leading to hospitalization and mortality in patients receiving upadacitinib.
  • Monitoring for reactivation of prior hepatitis B virus (HBV) or herpes zoster virus (HZV) infections is recommended, as these infections were reported during clinical studies.
  • Subjects at increased risk for skin cancers receiving treatment are advised to undergo routine skin examinations, as they have an increased risk of non-melanoma skin cancers (NMSCs).
  • review
    Upadacitinib. StatPearls [Internet] — Inderbir S. Padda, Rajat Bhatt, Preeti Patel, Mayur Parmar — StatPearls Publishing, 2024

Decision support only. Verify against local protocols and current labeling. Source: www.ncbi.nlm.nih.gov