Upadacitinib

What is upadacitinib?

Upadacitinib (RINVOQ®) is an oral, second-generation selective Janus kinase (JAK) inhibitor used for atopic dermatitis (eczema). It targets the JAK1 enzyme and modulates the immune response.

Upadacitinib was approved by the US Food and Drug Administration (FDA) in January 2022 for the treatment of moderate to severe atopic dermatitis. Upadacitinib has since received approval for this indication by other regulatory bodies, including the MHRA (UK), TGA (Australia), and Medsafe (NZ).

Severe atopic dermatitis unresponsive to topical therapies, phototherapy, and methotrexate - candidate for a JAK inhibitor 

More images of atopic dermatitis

What is upadacitinib used for?

In dermatology, upadacitinib is used for adults and adolescents (12 years and older) with moderate to severe atopic dermatitis who are candidates for systemic therapy.

• It can be used as monotherapy or in combination with topical steroids.
• Clinical trials showed ≥75% improvement in the Eczema Area and Severity Index (EASI) score from baseline to week 16.

Off-label dermatological uses include:

• Alopecia areata
• Hidradenitis suppurativa
• Psoriasis
• Vitiligo.

Dermatological uses described in small studies include:

• Dermatomyositis
• Discoid lupus erythematosus
• Epidermolysis bullosa pruriginosa
• Keratosis lichenoides chronica (Nekam disease).

Other licensed uses:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Non-radiographic axial spondyloarthritis
• Ulcerative colitis and Crohn disease
• Giant cell arteritis.

What are the contraindications and precautions with upadacitinib?

Contraindications

• Hypersensitivity to upadacitinib or its excipients
• Lymphopenia, neutropenia, or anaemia: absolute lymphocyte count <0.5 × 10⁹/L; absolute neutrophil count <1 × 10⁹/L; haemoglobin concentration <80 g/L
• Active and serious infections (eg, active tuberculosis, hepatitis B, hepatitis C)
• Concurrent use of other immunomodulating agents such as other Janus kinase (JAK) inhibitors, biologics (eg, adalimumab, etanercept, rituximab), or potent immunosuppressants (eg, azathioprine, cyclosporine, tacrolimus) — risk of additive immunosuppression; lack of safety data
• Pregnancy and breastfeeding — lack of safety data
• Severe hepatic impairment (Child-Pugh class C) — lack of safety data
• End stage renal disease (eGFR <15mL/min/1.73m²) - lack of safety data.

Precautions

• Patients with risk factors for arterial or venous thrombosis (eg, past history of thromboembolism, obesity, prolonged immobilisation)
• Elderly patients (age ≥65)
• Paediatric populations
• Severe renal impairment (eGFR 15-30mL/min/1.73m²)
• Mild to moderate hepatic impairment (Child-Pugh class A or B) — requires dose adjustment if used for ulcerative colitis or Crohn disease
• Co-administration with other CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin) or CYP3A4 inducers (eg, rifampicin, phenytoin)
• Past or current malignancy risk factors for gastrointestinal perforation eg, history of diverticulitis, concurrent use of NSAIDs or corticosteroids
• For females of reproductive potential, ensure effective contraception is used during treatment and for at least 4 weeks after cessation.

As with other JAK inhibitors, ensure vaccination status is updated prior to commencing upadacitinib, including vaccination for herpes zoster (recombinant zoster vaccine).

Live vaccinations should not be given during or just before starting treatment. Live vaccines include measles-mumps-rubella (MMR), typhoid, bacillus Calmette-Guerin (BCG), yellow fever, varicella zoster, rotavirus, and Japanese encephalitis.

See: Immunisation in immunosuppressed dermatology patients.

Dosing

Upadacitinib is available as 15 mg modified-release oral tablets. Tablets can be taken with or without food and should be swallowed whole.

In adults and adolescents (≥12 years old and weighing ≥40 kg), the dosing for the treatment of atopic dermatitis is 15 mg once daily. If response is inadequate, consider increasing the dose to 30 mg once daily.

If elderly (age ≥65), or with severe renal impairment (eGFR 15-30mL/min/1.73m²), or taking a potent CYP3A4 inhibitor (eg, ketoconazole, clarithromycin) the maximum dose is 15 mg once daily.

Pre-treatment screening

• Latent tuberculosis (tuberculosis infection) screening with interferon gamma release assay (IGRA) and/or tuberculin skin test (TST). If positive:
  • Treat prior to initiating upadacitinib
  • Test for active tuberculosis (chest x-ray and sputum samples, mycobacterium culture, and nucleic acid amplification tests).
• Hepatitis B and C screening
• HIV screening
• Complete/full blood count (CBC/FBC)
• Serum electrolytes, creatinine, urea, and eGFR to assess kidney function
• Liver function tests
• Lipid studies
• Pregnancy test if relevant

Monitoring

• Routine FBC, liver enzymes, and lipid studies (12 weeks after initiation)
• Routine skin examinations are recommended for patients with skin cancer risk factors due to an increased risk of non-melanoma skin cancers
• Signs and symptoms of infection during and after treatment.

Treatment should be ceased if:

• Haemoglobin <80 g/L
• Absolute neutrophil count (ANC) <1 x 10⁹ cells/L, lymphocytes <0.5 x 10⁹ cells/L
• Serious or opportunistic infection develops (eg, reactivation of herpes zoster, viral hepatitis, tuberculosis, cryptococcus). Upadacitinib may be resumed once the infection is controlled.

What are the benefits of upadacitinib?

• Oral formulation
• Once daily dosing
• Rapid onset of action
• High level of skin clearance, itch improvement, and improved quality of life in patients with moderate to severe atopic dermatitis

What are the disadvantages of upadacitinib?

• Need to consider multiple drug interactions
• Careful monitoring with routine blood tests required during treatment
• Risk of serious infections
• Not safe in pregnancy or breastfeeding
• Immunisations with live vaccines should not be given during or just before starting treatment

What are the side effects and risks of upadacitinib?

Upadacitinib is generally well tolerated with a favourable benefit-risk profile.

Common side effects:

• Mild to moderate acne — one of the most common side effects
• Upper respiratory tract infections (eg, sinusitis, pharyngitis, tonsillitis)
• Nausea
• Fever
• Cough
• Headache
• Abdominal pain
• Weight gain
• Hypercholesterolaemia
• Herpes simplex infection
• Folliculitis.

Uncommon side effects:

• Anaemia
• Neutropenia
• Lymphopenia
• Increased liver enzymes
• Increased creatinine kinase
• Viral reactivation (eg, herpes zoster, hepatitis)
• Serious and/or opportunistic infections.

Rare side effects:

• Gastrointestinal perforation
• Malignancy (data in clinical trials are limited; ongoing long-term studies):
• Increased risk of lymphoma in patients with rheumatoid arthritis
• Non-melanoma skin cancer observed in patients treated with upadacitinib.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).