Expert Consensus Statement on the Treatment of Immune‑Mediated Inflammatory Diseases with Janus‑Kinase Inhibitors: 2024 UpdatePubMed

Annals of the Rheumatic Diseases, 2025; 84(5):664‑679；DOI: 10.1016/j.ard.2025.01.032 International multidisciplinary expert task‑force；updated from 2019 consensus；modified‑Delphi voting；two independent systematic‑literature‑reviews underpinned the recommendations；includes patient‑representative inputPubMed

Abstract

Objective This international expert‑consensus updates the prior 2019 JAK‑inhibitor consensus, responding to newly‑approved JAK‑inhibitor agents, expanded indications, real‑world post‑marketing safety‑data and regulatory‑updates for immune‑mediated inflammatory diseases (IMIDs)PubMed. The task‑force covers core‑principles, patient‑selection, baseline‑screening, dosing, comedication, safety‑risk‑stratification, monitoring, adverse‑event‑management, contraindications/precautions and gaps‑for‑future‑research. It does not decide whether to start JAK‑inhibitor therapy; it provides guidance after the clinical decision‑to‑treat has been madePubMed.

Methods Two systematic‑literature‑reviews evaluated efficacy and safety evidence across 51 immune‑mediated‑inflammatory‑diseases, incorporating phase 2‑3 RCTs, extension‑trials and large observational‑cohorts. Multidisciplinary voting by international experts across rheumatology, dermatology, gastroenterology, cardiology, pharmacology and patient‑advocates.

Conclusion JAK‑inhibitors are effective oral targeted‑synthetic DMARDs for multiple IMIDs. Mandatory pre‑treatment risk‑stratification for cardiovascular‑disease, thromboembolism, infection and malignancy is required. Age‑related and comorbidity‑driven safety‑profiles heavily inform prescribing decisions. Shared‑decision‑making with patients is essential throughout treatment.

Keywords: JAK‑inhibitor; Janus‑kinase; immune‑mediated inflammatory‑disease; IMID; risk‑stratification; tsDMARD; consensus‑statement

Overarching‑principles

1. JAK‑inhibitors are oral targeted‑synthetic‑DMARDs acting intracellularly upon JAK‑STAT cytokine‑signalling pathways; efficacy‑and‑safety differ across‑agents, cannot be fully generalised across‑the‑whole‑class.
2. Pre‑treatment comprehensive‑risk‑assessment is mandatory before first‑dose; risk‑re‑evaluation at every major clinical‑flare and before dose‑escalation.
3. Shared‑decision‑making: discuss expected‑benefits versus MACE, venous‑thromboembolism(VTE), serious‑infection and malignancy‑risks; document discussions in clinical‑notes.
4. Treatment‑target: achieve‑low‑disease‑activity / remission, minimise‑glucocorticoid‑exposure, preserve‑function‑and‑quality‑of‑life.
5. Drug‑labelling / regional‑regulatory‑requirements always take precedence over consensus‑advice.

1 Indications and patient‑selection

Approved disease‑areas covered in‑consensus

• Rheumatoid‑arthritis (RA), psoriatic‑arthritis (PsA), axial‑spondyloarthritis (axSpA)
• Moderate‑severe‑psoriasis, atopic‑dermatitis
• Inflammatory‑bowel‑disease (ulcerative‑colitis; selected‑for‑Crohn’s‑disease)
• Other off‑label / emerging‑IMIDs: juvenile‑inflammatory‑arthritis, myositis, Sjogren‑syndrome (only upon specialist‑expert‑review)

General‑eligibility prerequisites

1. Confirm diagnosis of IMID by specialist‑clinician.
2. Inadequate‑response / intolerance / contraindication to conventional‑synthetic‑DMARDs and/or biologic‑DMARDs according‑to‑licence.
3. Acceptable benefit‑risk‑balance after‑risk‑stratification.

Important‑statement: Age ≥ 65 years is a major combined‑risk‑marker for MACE,‑VTE‑and‑malignancy. In patients ≥ 65 years‑old,‑JAK‑inhibitors should‑preferably‑only‑be‑used‑when‑biologic‑alternatives‑have‑failed‑or‑are‑intolerable.

2 Baseline pre‑treatment work‑up checklist

1. Full‑medical‑history: prior‑MACE‑event,‑VTE‑history,‑malignancy‑(current‑/‑past),‑smoking‑history,‑diabetes‑mellitus,‑hypertension,‑obesity,‑autoimmune‑comorbidities‑(APS‑antiphospholipid‑syndrome).
2. Vaccination‑status‑review: update‑vaccines prior‑to‑initiation (influenza,‑zoster‑shingles‑vaccination strongly‑recommended).
3. Laboratory‑baseline: CBC,‑renal‑function,‑liver‑function‑tests,‑lipid‑profile,‑CRP/ESR‑inflammatory‑markers.
4. Screening‑for‑latent‑TB and‑hepatitis‑B /‑C viral‑screening.
5. Cardiovascular‑risk‑calculator‑assessment (e.g. ASCVD‑score).
6. Document‑patient‑reported‑outcomes:‑pain,‑global‑disease‑activity,‑functional‑status.

3 Dosing and comedication‑principles

1. Always start‑with licensed‑approved‑dose; use‑dose‑reduction‑for‑renal‑/‑hepatic‑impairment‑per‑product‑information.
2. Avoid‑simultaneous‑combination‑of‑two‑different‑JAK‑inhibitors (no‑benefit‑proven,‑higher‑safety‑risk).
3. Conventional‑synthetic‑DMARD‑co‑therapy (methotrexate‑etc.) may‑be‑continued‑if‑clinically‑indicated.
4. Minimise‑concurrent‑systemic‑glucocorticoid‑dose;‑taper‑steroids‑to‑lowest‑possible‑dose‑whenever‑feasible.
5. Drug‑drug‑interaction‑check:‑CYP‑enzyme‑modifying‑co‑medications‑require‑dose‑adjustment.

4 Risk‑stratification: key safety‑domains

4.1 Major adverse cardiovascular‑events (MACE:‑MI,‑ischaemic‑stroke,‑CV‑death)

Elevated‑MACE‑risk‑factors ‑ Age ≥ 65 y ‑ Prior‑ischaemic‑heart‑disease,‑peripheral‑arterial‑disease,‑prior‑stroke/TIA ‑ Current‑or‑past‑heavy‑tobacco‑smoking ‑ Uncontrolled‑hypertension,‑dyslipidaemia,‑diabetes‑mellitus,‑CKD‑stage ≥ 3b

Recommendation:‑Optimise‑BP‑and‑lipid‑profile‑before‑starting‑JAK‑inhibitor.‑Avoid‑JAK‑inhibitor‑if‑very‑high‑CV‑risk‑and‑biologic‑alternatives‑are‑available.

4.2 Venous‑thromboembolism‑risk (DVT / PE)

Risk‑factors:‑personal/family‑history‑of‑unprovoked‑VTE,‑thrombophilia‑(inherited‑or‑acquired‑e.g.‑APS),‑obesity‑BMI > 30,‑oestrogen‑containing‑hormonal‑therapy,‑recent‑major‑surgery‑or‑prolonged‑immobilisation.

Statement:‑Patients‑with‑prior‑unprovoked‑VTE‑should‑prefer‑biologic‑DMARD‑alternatives;‑if‑JAK‑inhibitor‑must‑be‑used‑haematology‑co‑management‑is‑required.

4.3 Infection‑risk‑screening

‑ Screen‑and‑treat‑latent‑TB‑before‑commencing‑therapy. ‑ Screen‑chronic‑viral‑hepatitis‑B/C. ‑ Patient‑education‑for‑early‑recognition‑of‑severe‑infection‑symptoms‑(fever,‑persistent‑cough,‑unexplained‑weight‑loss).‑Hold‑JAK‑inhibitor‑during‑severe‑active‑infection‑episodes.

4.4 Malignancy‑risk

‑ Avoid‑JAK‑inhibitors‑in‑active‑solid‑or‑haematological‑malignancy. ‑ Patients‑with‑prior‑successfully‑treated‑malignancy‑require‑oncology‑review‑prior‑to‑starting‑JAK‑inhibitor‑therapy. ‑ Smoking‑history‑is‑a‑combined‑risk‑factor‑for‑both‑CV‑and‑malignancy‑outcomes.

5 Monitoring‑during‑treatment

1. Early‑response‑assessment:‑Evaluate‑efficacy‑and‑safety‑8‑12 weeks‑after‑initiation.
2. Stable‑phase‑follow‑up:‑Every 3‑6 months‑review‑disease‑activity,‑lab‑parameters‑(CBC,‑LFT,‑renal‑function,‑lipids).
3. Patient‑safety‑education‑to‑prompt‑report‑warning‑signs:‑chest‑pain,‑dyspnoea,‑unilateral‑limb‑swelling‑pain,‑focal‑neurological‑symptoms,‑persistent‑fever,‑unexplained‑lymphadenopathy,‑unintentional‑weight‑loss.
4. If‑adequate‑clinical‑response‑is‑absent‑at‑12 weeks:‑Re‑assess‑adherence,‑exclude‑comorbid‑pain‑conditions‑(fibromyalgia‑overlap),‑consider‑switch‑therapy‑rather‑than‑dose‑escalation‑without‑evidence‑of‑partial‑response.

6 Discontinuation‑and‑switch‑criteria

Discontinue‑JAK‑inhibitor‑and‑switch‑to‑alternative‑therapy‑when‑any‑of‑following‑occur:

1. Confirmed‑MACE‑event‑(myocardial‑infarction,‑ischaemic‑stroke,‑CV‑death).
2. Confirmed‑VTE‑episode‑(DVT‑or‑pulmonary‑embolism).
3. New‑diagnosis‑of‑active‑malignancy‑or‑lymphoproliferative‑disorder.
4. Severe‑opportunistic‑or‑recurrent‑serious‑infection‑despite‑optimal‑anti‑infective‑treatment.
5. Clinically‑significant‑persistent‑drug‑related‑organ‑toxicity‑(hepatic‑/‑renal‑/‑haematological).

Tapering‑strategy:‑If‑sustained‑low‑disease‑activity‑is‑achieved‑over‑many‑months,‑dose‑reduction‑may‑be‑trialled‑with‑close‑surveillance;‑complete‑routine‑drug‑withdrawal‑is‑associated‑with‑high‑flare‑risk‑and‑not‑generally‑recommended.

7 Special‑populations

7.1 Pregnancy‑and‑lactation

‑ JAK‑inhibitors‑are‑not‑recommended‑during‑pregnancy‑and‑breast‑feeding.‑Discontinue‑JAK‑inhibitor‑prior‑to‑planned‑conception‑for‑both‑female‑and‑male‑patients‑where‑possible.‑If‑conception‑occurs‑on‑JAK‑inhibitor,‑prompt‑multidisciplinary‑obstetric‑rheumatology‑review‑is‑mandatory.

7.2 Chronic‑kidney‑and‑liver‑impairment

‑ Dose‑adjust‑according‑to‑renal‑and‑hepatic‑function‑per‑product‑labelling.‑Intensified‑safety‑monitoring‑because‑CKD‑itself‑raises‑MACE‑and‑thrombotic‑risk.

7.3 Antiphospholipid‑syndrome‑(APS)

‑ Higher‑intrinsic‑thrombotic‑risk.‑Biologic‑DMARD‑alternatives‑preferred‑first‑choice.‑If‑JAK‑inhibitor‑is‑required,‑haematology‑co‑management‑is‑mandatory.

8 Key‑updates compared‑with‑2019‑consensus

1. Full‑updated‑risk‑stratification‑framework‑for‑MACE,‑VTE‑and‑malignancy‑based‑upon‑ORAL‑Surveillance‑and‑real‑world‑cohorts.
2. Clear‑recommendation‑for‑patients ≥ 65 years‑old:‑JAK‑inhibitors‑second‑line‑only‑after‑biologic‑failure.
3. Standardised‑pre‑treatment‑check‑list‑and‑structured‑patient‑shared‑decision‑making‑documentation‑requirement.
4. Updated‑vaccination‑guidance‑including‑herpes‑zoster‑vaccination‑prior‑to‑JAK‑inhibitor‑start.
5. Explicit‑stop‑rules‑for‑cardiovascular‑thrombotic‑and‑malignant‑adverse‑events.
6. New‑research‑agenda‑identifying‑evidence‑gaps‑for‑selective‑JAK‑agents,‑long‑term‑real‑world‑safety‑and‑tapering‑strategies.