Upadacitinib

ATC code

L04AA44

Therapeutic class

Immunosuppressant, Janus Kinase (JAK) Inhibitor · Selective JAK1 inhibitor

Forms

extended-release tablet, oral solution

Brand names

Rinvoq (US) · Rinvoq (EU)

Overall confidence

high

Regulatory sources consulted

openfda-label-6c4bad0a-5930-4bb7-8509-6a8c6f279082
ema-epar-EMEA/H/C/004760
PubMed PMID:40174237 ↗
PubMed PMID:37224198 ↗
PubMed PMID:39572132 ↗
PubMed PMID:39018058 ↗
PubMed PMID:34347860 ↗
OpenFDA · L04AA44
RxNorm rxcui 2196092 ↗

Approved indications

Treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs).
Treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy.
Treatment of moderately to severely active ulcerative colitis (UC) in adult patients who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.
Treatment of moderately to severely active Crohn’s disease (CD) in adult patients who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.
Psoriatic arthritis, axial spondyloarthritis (non-radiographic and ankylosing spondylitis), and giant cell arteritis in adults with an inadequate response to previous therapies.

Contraindications

Absolute

Known hypersensitivity to upadacitinib or any of its excipients.
Active tuberculosis or active serious infections.
Pregnancy.

Clinical warnings

Boxed warning · RISK OF SERIOUS INFECTIONS, MORTALITY, MALIGNANCIES, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), AND THROMBOSIS. Patients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. A higher rate of all-cause mortality, including sudden cardiovascular death, has been observed with another JAK inhibitor compared to TNF blockers. Malignancies have been reported. Thrombosis events (deep vein thrombosis, pulmonary embolism) and MACE have occurred. — FDA

Drug interactions

HighKetoconazoleJ02AB02
Mechanism: Potent inhibition of CYP3A4, significantly increasing upadacitinib exposure.
Recommendation: Reduce upadacitinib dose. For UC/CD, reduce induction dose to 30 mg/day and maintenance to 15 mg/day. For AD, concomitant use with the 30 mg upadacitinib dose is not recommended.
FDA label
HighRifampinJ04AB02
Mechanism: Potent induction of CYP3A4, significantly decreasing upadacitinib exposure and its potential therapeutic effect.
Recommendation: Coadministration of upadacitinib with strong CYP3A4 inducers is not recommended.
FDA label

Adverse events

Common (≥1%)

upper respiratory tract infections · blood CPK increased · acne · herpes zoster · herpes simplex · headache · nausea · cough

Rare but serious

serious infections (tuberculosis, sepsis) · malignancies (lymphoma, non-melanoma skin cancer) · major adverse cardiovascular events (myocardial infarction, stroke) · venous thromboembolism (deep vein thrombosis, pulmonary embolism) · gastrointestinal perforation · serious hypersensitivity reactions

Pregnancy and lactation

Contraindicated during pregnancy due to potential for fetal harm based on animal studies. Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks after the final dose. Do not breastfeed during treatment and for 6 days after the last dose.

Recent literature (PubMed)

A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis.
Blockmans D, et al. · N Engl J Med · 2025 · Relevance 5/5
En pacientes con arteritis de células gigantes, upadacitinib 15 mg/día con un taper de glucocorticoides de 26 semanas fue superior al placebo con un taper de 52 semanas para lograr la remisión sostenida a la semana 52 (46.4% vs 29.0%). La dosis de 7.5 mg no fue superior. El perfil de seguridad fue similar entre los grupos.
Upadacitinib Induction and Maintenance Therapy for Crohn's Disease.
Loftus EV, et al. · N Engl J Med · 2023 · Relevance 5/5
En dos ensayos de fase 3, upadacitinib 45 mg/día fue superior al placebo para la inducción de remisión clínica y respuesta endoscópica en la enfermedad de Crohn. En el mantenimiento, las dosis de 15 mg y 30 mg fueron superiores al placebo a las 52 semanas. Se observó una mayor incidencia de herpes zóster con upadacitinib.
AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis.
Singh S, et al. · Gastroenterology · 2024 · Relevance 5/5
La guía de práctica clínica de la AGA recomienda upadacitinib para el tratamiento de la colitis ulcerosa de moderada a grave. En pacientes sin tratamiento previo con terapias avanzadas, se sugiere como una opción de alta eficacia. En pacientes con exposición previa a antagonistas del TNF-α, también se sugiere como una opción de alta eficacia.
Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.
Blauvelt A, et al. · JAMA Dermatol · 2021 · Relevance 5/5
En el ensayo clínico directo (head-to-head) Heads Up, upadacitinib 30 mg/día fue superior a dupilumab en el logro de EASI75 en la semana 16 (71% vs 61%) en adultos con dermatitis atópica de moderada a grave. Upadacitinib también mostró una mejora más rápida del prurito. Se observaron más eventos adversos como acné y herpes simple con upadacitinib.
Systemic Immunomodulatory Treatments for Atopic Dermatitis: Living Systematic Review and Network Meta-Analysis Update.
Drucker AM, et al. · JAMA Dermatol · 2024 · Relevance 4/5
Esta revisión sistemática y metaanálisis en red actualiza la evidencia sobre tratamientos sistémicos para la dermatitis atópica. Incluye datos de 97 ensayos clínicos, comparando la eficacia y seguridad de múltiples fármacos, incluyendo upadacitinib y el recién licenciado lebrikizumab, para informar la toma de decisiones clínicas.