Tofacitinib

What is tofacitinib?

Tofacitinib (Xeljanz, Xeljanz XR ®, US) is an oral small-molecule inhibitor of Janus kinase (JAK) 1 and 3 that is used to treat psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, and ankylosing spondylitis.

JAK enzymes respond to extracellular growth factors, and cytokines which activate signal transduction and cell transcription activators (STATs). STATs regulate gene expression and intracellular processes. The JAK enzyme pathway is involved in haematopoiesis and immune cell signalling.

What is tofacitinib used for?

Tofacitinib is approved by the US Food and Drug Administration (FDA) for:

• Adults who have tried multiple tumour necrosis factor (TNF) blockers without improvement or with intolerable side effects for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and ankylosing spondylitis
• Children ≥2 years with active polyarticular course juvenile arthritis and who have tried multiple TNF blockers without improvement or with intolerable side effects.

Off-label uses include:

• Psoriasis
• Hospitalised COVID-19 patients.

Oral tofacitinib is also under investigation for treating:

• Alopecia areata
• Atopic dermatitis
• Vitiligo
• Lichen planus
• Dermatomyositis
• Granulomatous disorders such as sarcoidosis.

Topical tofacitinib is under investigation for treating:

• Atopic dermatitis
• Vitiligo.

Evidence

Alopecia areata: A meta-analysis of 30 studies including 289 patients with extensive alopecia areata showed that oral tofacitinib had a 72% response rate (partial in 21%) with a time to complete hair growth in 6 months. Cessation resulted in a high recurrence rate. Topical tofacitinib was much less effective.

Dermatomyositis: Oral tofacitinib showed significant improvement of skin lesions in amyopathic anti-MDA5 dermatomyositis and a benefit to the overall 6-month survival in patients with associated interstitial lung disease.

Vitiligo: Oral tofacitinib was used in a small study of 10 patients with vitiligo; concomitant light exposure was required to effect repigmentation.

What are the contraindications and precautions with tofacitinib?

Contraindications and precautions

• Avoid use during active serious infections. Carefully consider use in patients with a history of chronic, frequent, or serious infections, or tuberculosis exposure, as tofacitinib increases the risk of infections leading to hospitalisation and death.
• Carefully consider use in patients with risk of gastrointestinal perforations.
• Avoid live vaccines during use. Immunisations should be current before use. See also: Immunisation in immunosuppressed dermatology patients.
• Avoid in patients with severe hepatic impairment.
• Pregnancy Category C: foeticidal and teratogenic effects in rat and rabbit studies.
• Women are advised not to breastfeed during use.

Dosing and administration of tofacitinib

Dosing

Tofacitinib may be available as immediate-release (IR) tablets, extended-release tablets (ER), and as a 1mg/mL solution.

• Psoriasis (off-label): 5–10 mg IR tablet, twice daily.
• Psoriatic arthritis (alongside nonbiologic DMARDs): 5–10 mg IR tablet, twice daily or 11 mg ER tablet, once daily.
• Polyarticular-course juvenile arthritis: based on body mass.

Dose reductions are required for patients with moderate to severe renal impairment or moderate hepatic impairment. Avoid use with severe hepatic impairment.

Storage and administration

Store at room temperature in a closed container. Oral liquid should be administered within 60 days of opening the medication.

Oral tofacitinib may be taken with or without meals. Extended-release tablets should be swallowed whole. Oral solutions may be administered with a bottle adaptor to attach the oral syringe.

What are the benefits of tofacitinib?

• Reduces signs and symptoms of arthritic disease, ulcerative colitis, and ankylosing spondylitis.
• Improves health-related quality of life.
• Can be used by patients who do not respond to TNF inhibitors.

What are the disadvantages of tofacitinib?

• Monitoring requirements: need to monitor lymphocytes, neutrophils, haemoglobin, liver enzymes, and lipids during use.
• May lead to bone marrow suppression:
  • Discontinue if lymphocyte count <500 cells/mm³, absolute neutrophil count (ANC) <500 cells/mm³, or haemoglobin <8 g/dL
  • Interrupt therapy if ANC consistently between 500-1000 cells/mm³.
• Concomitant use of CYP3A4 inhibitors may decrease clinical response to tofacitinib.
• There is concern regarding the increased risk of cancers, thrombotic events and serious infections in oral JAK inhibitor use (see below).

What are the side effects and risks of tofacitinib?

Common side effects

• Increased frequency of infection eg, upper respiratory tract infection or urinary tract infection
• Gastrointestinal side effects eg, diarrhoea, dyspepsia, nausea
• Headaches
• Increased serum creatinine.

Uncommon side effects

• Cardiovascular side effects such as heart attack, stroke, or death (especially if >50 years with cardiovascular risk factors and smoking history)
• Thromboembolic side effects such as pulmonary embolism, deep vein thrombosis, or death (especially if >50 years with at least one cardiovascular risk factor)
• Malignancy and lymphoproliferative disorders reported
• Reactivation of hepatitis B and C.

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).