JAK inhibitors and targeted synthetic DMARDs — Rapid

Synopsis

Use oral JAK inhibitors and other targeted synthetic DMARDs only after guideline-based risk stratification, with exact dosing, infection and laboratory screening, and active prevention of cardiovascular, thrombotic, malignant and reproductive harm.

JAK inhibitors are oral small molecules that block intracellular cytokine signalling; faster onset and oral convenience do not make them lower-risk than injectable biologics.
MHRA requires all JAK inhibitors for chronic inflammatory disorders to be used only when no suitable alternatives exist in people aged 65 or over, current or past long-term smokers, and those with cardiovascular or malignancy risk.
Use caution in anyone with venous-thromboembolism risk and use the lower authorised dose where the product recommends it for risk reduction.
Before treatment, screen active and latent tuberculosis, hepatitis B and C and HIV, review vaccines and zoster history, and obtain FBC, liver and renal profiles plus fasting lipids.
Tofacitinib for adult rheumatoid or psoriatic arthritis is 5 mg orally twice daily; the 10 mg twice-daily dose is not a rheumatoid-arthritis regimen and carries greater thrombotic risk.
Do not combine a JAK inhibitor with a biologic DMARD or another potent immunosuppressant such as ciclosporin because additive infection and immune suppression outweigh evidence of benefit.
Check lipids about eight weeks after starting and monitor counts, liver and renal function at the product-specific interval; cytopenia thresholds determine interruption.
Herpes zoster is a prominent class toxicity. Give recombinant zoster vaccine before treatment where eligible and investigate painful dermatomal or disseminated lesions promptly.
Apremilast is a PDE4 inhibitor rather than a JAK inhibitor and has less laboratory immunosuppression, but diarrhoea, weight loss, depression and severe renal impairment modify its use.
JAK inhibitors and apremilast are not compatible with pregnancy or breastfeeding; apply each product's contraception interval and switch to a proven compatible DMARD before conception.

Key red flags

Fever, hypotension, confusion, hypoxaemia, widespread vesicles or focal severe infection requires immediate JAK-inhibitor withholding and urgent antimicrobial assessment.

New unilateral leg swelling, pleuritic pain, haemoptysis, unexplained tachycardia or sudden dyspnoea requires emergency venous-thromboembolism assessment.

Chest pressure, diaphoresis, focal neurological loss, speech change or acute limb ischaemia requires the relevant myocardial-infarction or stroke pathway.

Severe abdominal pain, guarding or fever can indicate diverticulitis or gastrointestinal perforation and should not be treated as routine drug-related diarrhoea.

New lymphadenopathy, weight loss, persistent cough, skin lesion or unexplained anaemia requires malignancy and infection assessment rather than automatic continuation.

Pregnancy on a JAK inhibitor or apremilast requires immediate specialist review because these medicines are not compatible with pregnancy or breastfeeding.

Herpes zoster

Pain, dysaesthesia and grouped vesicles can be subtle; ophthalmic distribution, dissemination, neurological features or immunocompromised systemic illness is urgent.

Venous thromboembolism

Unilateral swelling or pain, sudden breathlessness, pleurisy, haemoptysis or unexplained tachycardia requires immediate DVT or pulmonary-embolism assessment.

Investigation priorities

First-line vascular and cancer risk inventoryFirst stepFirst line

Determine whether MHRA requires use only after suitable alternatives and whether VTE risk is acceptable.

Management branches

First selection gateCompare JAK risk with suitable alternatives

A targeted synthetic DMARD is being considered after the disease-specific prior-treatment sequence.

Confirm active inflammatory disease and NICE eligibility, then document age, smoking, cardiovascular, malignancy, VTE, infection and reproductive risk.
In MHRA high-risk groups, use a JAK inhibitor only if no suitable alternative can meet the same clinical need and record why.
Select the exact product and authorised lower dose where relevant, with an efficacy target and stop criteria agreed before initiation.

Apremilast routeTitrate and watch weight and mood

Psoriatic disease meets an apremilast pathway and a less immunosuppressive oral option is preferred.

Use the five-day starter titration to 30 mg twice daily, reducing maintenance to 30 mg once daily in severe renal impairment.
Record weight, gastrointestinal tolerance, sleep and depression or suicidal history and provide early contact for severe diarrhoea or mood change.
Assess joint and skin response at the NICE continuation interval and stop when the required improvement is not reached.

Key medicines

TofacitinibGive 5 mg orally twice daily for adult rheumatoid or psoriatic arthritis; reduce to 5 mg once daily in specified moderate or severe renal impairment, moderate hepatic impairment or potent interaction settings under the product table.Do not use 10 mg twice daily for rheumatoid arthritis. Avoid serious infection, combine with neither biologic nor potent immunosuppressant, and review MACE, VTE, cancer, zoster, cytopenia and pregnancy.

BaricitinibGive 4 mg orally once daily for adult rheumatoid arthritis; use 2 mg once daily in adults aged 65 or over and when product-defined infection, VTE, MACE, malignancy or renal factors favour the lower authorised dose.Check renal function and blood counts, avoid active TB or serious infection and review thrombosis, cardiovascular and malignancy risk; do not use during pregnancy or breastfeeding.

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