Paeds · clinical-pharmacology-and-therapeutics

Immunosuppressive and biologic therapies

Also known as Methotrexate in juvenile idiopathic arthritis · TNF inhibitors in children · Biologic therapies in paediatrics · DMARDs in children · Pre-biologic screening in children

A fellowship approach to immunosuppressive and biologic therapies in children covering low-dose weekly methotrexate as the anchor disease-modifying antirheumatic drug in juvenile idiopathic arthritis, the tumour necrosis factor inhibitors etanercept, adalimumab and infliximab across rheumatology and inflammatory bowel disease, the interleukin-1, interleukin-6 and B-cell-depleting biologics, the pre-biologic screen for tuberculosis, hepatitis B and varicella with dual tuberculin and IGRA testing, folic acid supplementation and full-blood-count and liver-enzyme monitoring on methotrexate, and live-vaccine timing before immunosuppression begins.

high11 referencesUpdated 17 July 202619 min readVerification in progress

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Target exams

RACP General PaediatricsRACP DWERACP DCERCPCH Progress+MRCPCH TheoryMRCPCH ClinicalABP General PediatricsACGME PediatricsRCPSC Pediatrics

Red flags

A biologic or methotrexate started without documented latent tuberculosis, hepatitis B and varicella screeningMethotrexate prescribed daily rather than once weekly — a cytotoxic overdose errorA live vaccine (measles-mumps-rubella, varicella, rotavirus) given to a child already on biologic therapyMethotrexate continued with a rising alanine aminotransferase, falling neutrophil count, or new mouth ulceration without rechecking bloodsAn anti-TNF agent started in a child with untreated latent tuberculosisFolic acid omitted from a methotrexate prescription

Life stages

infanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

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General and Community PaediatricsAllergy and ImmunologyCurrent 2026 PREP curriculum — Learning Objective: Safe prescribing and medication management in infants, children and young peopleCurrent 2026 PREP curriculum — Learning Objective 2.2.1: Recognise, prioritise and manage an acutely ill infant, child or young personRenewed curriculum for first-year trainees from 2027 — Learning goal 6: Clinical management – essential general paediatricsRenewed curriculum for first-year trainees from 2027 — Learning goal 9: Quality and safety, including medication safetyClinical ApplicationsMedical SciencesLong CasesShort Cases4. Professional skills and knowledge: Patient management7. Patient safety, including safe prescribing8. Quality improvement and patient safetyGeneral Paediatrics: Prescribes and monitors immunosuppressive and biologic medicines safely with appropriate pre-treatment screeningFoundation of Practice (FOP)Theory and Science (TAS)Applied Knowledge in Practice (AKP)ClinicalHistoryCommunicationGeneral Pediatrics Content Outline — Domain 10: Principles of Pharmacology and Medication ManagementGeneral Pediatrics Content Outline — Universal Task 4: Management and TreatmentGeneral Pediatrics Content Outline — Universal Task 2: Health MaintenanceSystems-Based Practice 2: Coordinated chronic disease carePatient Safety/Quality Improvement 1: Medication SafetyMedical Knowledge 2: Diagnostic and Therapeutic Decision MakingMedical ExpertCollaboratorPediatrics: Core EPA #5 — Recommending and Initiating Pharmacologic Interventions

Your progress

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Practise this topic

Target exams

RACP General PaediatricsRACP DWERACP DCERCPCH Progress+MRCPCH TheoryMRCPCH ClinicalABP General PediatricsACGME PediatricsRCPSC Pediatrics

Red flags

Life stages

infanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

Care settings

outpatientwardtelehealth

Clinical exam formats

written-only

Board mappings

The fellowship answer

Immunosuppressive and biologic therapies in children calm an overactive immune system with the right drug, given after the right screen, under the right monitoring. Methotrexate is the anchor: a low once-weekly dose that quiets inflammation in juvenile idiopathic arthritis through folate-pathway and adenosine-mediated mechanisms, not the high cytotoxic doses of cancer chemotherapy. The biologic agents go further, blocking a single cytokine at its source — etanercept, adalimumab and infliximab neutralise tumour necrosis factor, canakinumab blocks interleukin-1, tocilizumab blocks interleukin-6, and rituximab depletes B cells. Before any of them is started you must screen the child for the infections that immunosuppression will reactivate: latent tuberculosis with both a tuberculin skin test and an interferon-gamma release assay, hepatitis B, hepatitis C, HIV, and varicella. Live vaccines go in before the immunosuppression, never after. On methotrexate you give folic acid on the non-methotrexate days and you monitor the full blood count and liver enzymes at a structured interval. The single sentence the examiner wants is that the safe use of these drugs rests on three pillars — screen, treat, monitor — and that the classic failure is to prescribe the drug without completing the screen. [1] [5] [9]

Overview & Definition

Picture a six-year-old with polyarticular juvenile idiopathic arthritis whose morning stiffness will not settle, a twelve-year-old with Crohn's disease who is losing weight despite steroids, and a child with frequent-relapse nephrotic syndrome who has become steroid-dependent. Each of them will meet an immunosuppressive or a biologic drug. Methotrexate comes first in the rheumatic diseases, and the tumour necrosis factor inhibitors follow or run alongside it. [1] [6]

Two ideas carry the whole topic. The first is the screen-treat-monitor sequence: every biologic and every conventional immunosuppressant is started only after latent tuberculosis, hepatitis B, hepatitis C, HIV and varicella have been excluded or treated, and then kept safe by structured blood-count and liver-enzyme monitoring. The second is the anchor-and-target principle: methotrexate is the anchor disease-modifying drug in juvenile idiopathic arthritis, and the biologics are precision tools that block a single named cytokine when the anchor alone is not enough. [5] [6]

From the first referral to a child safely on therapy

1 · Confirm the diagnosis

Establish the immune-mediated disease with the specialist team before starting any immunosuppressive or biologic agent.

2 · Complete the pre-start screen

Screen for latent tuberculosis (tuberculin skin test and interferon-gamma release assay), hepatitis B, hepatitis C, HIV, varicella, and baseline bloods.

3 · Give live vaccines first

Complete measles-mumps-rubella and varicella vaccination, then wait before starting the immunosuppressant.

4 · Start the anchor or the biologic

Begin methotrexate once weekly with folic acid, or the chosen biologic at a weight-based or surface-area dose, under specialist guidance.

5 · Monitor and review

Check the full blood count and liver enzymes on a structured schedule, watch for infection, review growth and adherence, and plan the duration with the team.

[5] [11]

Paediatrics Fellowship Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References11Show ledger

[1]Giannini EH; Brewer EJ; Kuzmina N Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group The New England journal of medicine, 1992.PMID 1549149
[2]Lovell DJ; Giannini EH; Reiff A Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group The New England journal of medicine, 2000.PMID 10717011
[3]Lovell DJ; Ruperto N; Goodman S Adalimumab with or without methotrexate in juvenile rheumatoid arthritis The New England journal of medicine, 2008.PMID 18716298
[4]Foell D; Wulffraat N; Wedderburn LR Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial JAMA, 2010.PMID 20371785
[5]Ferrara G; Mastrangelo G; Barone P Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting Pediatric rheumatology online journal, 2018.PMID 29996864
[6]Shenoi S; Horneff G; Aggarwal A Treatment of non-systemic juvenile idiopathic arthritis Nature reviews. Rheumatology, 2024.PMID 38321298
[7]Hyams J; Crandall W; Kugathasan S Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children Gastroenterology, 2007.PMID 17324398
[8]Faubion WA; Dubinsky M; Ruemmele FM Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease Inflammatory bowel diseases, 2017.PMID 28129288
[9]Calzada-Hernández J; Anton J; Martín de Carpi J Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain European journal of pediatrics, 2023.PMID 36335186
[10]Parigi S; Licari A; Manti S Tuberculosis and TNF-α inhibitors in children: how to manage a fine balance Acta bio-medica : Atenei Parmensis, 2020.PMID 33004779
[11]Jansen MHA; Rondaan C; Legger GE EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: update 2021 Annals of the rheumatic diseases, 2023.PMID 35725297

Immunosuppressive and biologic therapies

Also known as Methotrexate in juvenile idiopathic arthritis · TNF inhibitors in children · Biologic therapies in paediatrics · DMARDs in children · Pre-biologic screening in children

high11 referencesUpdated 17 July 202619 min readVerification in progress

Practise this topic

Overview & Definition

From the first referral to a child safely on therapy

1 · Confirm the diagnosis

Establish the immune-mediated disease with the specialist team before starting any immunosuppressive or biologic agent.

2 · Complete the pre-start screen

Screen for latent tuberculosis (tuberculin skin test and interferon-gamma release assay), hepatitis B, hepatitis C, HIV, varicella, and baseline bloods.

3 · Give live vaccines first

Complete measles-mumps-rubella and varicella vaccination, then wait before starting the immunosuppressant.

4 · Start the anchor or the biologic

Begin methotrexate once weekly with folic acid, or the chosen biologic at a weight-based or surface-area dose, under specialist guidance.

5 · Monitor and review

Check the full blood count and liver enzymes on a structured schedule, watch for infection, review growth and adherence, and plan the duration with the team.

[5]

[11]

Paediatrics Fellowship Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References11Show ledger

[1]Giannini EH; Brewer EJ; Kuzmina N Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group The New England journal of medicine, 1992.PMID 1549149
[2]Lovell DJ; Giannini EH; Reiff A Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group The New England journal of medicine, 2000.PMID 10717011
[3]Lovell DJ; Ruperto N; Goodman S Adalimumab with or without methotrexate in juvenile rheumatoid arthritis The New England journal of medicine, 2008.PMID 18716298
[4]Foell D; Wulffraat N; Wedderburn LR Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial JAMA, 2010.PMID 20371785
[5]Ferrara G; Mastrangelo G; Barone P Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting Pediatric rheumatology online journal, 2018.PMID 29996864
[6]Shenoi S; Horneff G; Aggarwal A Treatment of non-systemic juvenile idiopathic arthritis Nature reviews. Rheumatology, 2024.PMID 38321298
[7]Hyams J; Crandall W; Kugathasan S Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children Gastroenterology, 2007.PMID 17324398
[8]Faubion WA; Dubinsky M; Ruemmele FM Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease Inflammatory bowel diseases, 2017.PMID 28129288
[9]Calzada-Hernández J; Anton J; Martín de Carpi J Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain European journal of pediatrics, 2023.PMID 36335186
[10]Parigi S; Licari A; Manti S Tuberculosis and TNF-α inhibitors in children: how to manage a fine balance Acta bio-medica : Atenei Parmensis, 2020.PMID 33004779
[11]Jansen MHA; Rondaan C; Legger GE EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: update 2021 Annals of the rheumatic diseases, 2023.PMID 35725297