Paeds SAQs · clinical-pharmacology-and-therapeutics
Immunosuppressive and biologic therapies — formative SAQs
Two MedVellum formative short-answer questions on immunosuppressive and biologic therapy in children: low-dose weekly methotrexate as the anchor disease-modifying drug in juvenile idiopathic arthritis with folic acid and full-blood-count and liver-enzyme monitoring, and the pre-biologic screen for tuberculosis, hepatitis B and varicella before a tumour necrosis factor inhibitor is started, with live-vaccine timing and the management of the febrile child on treatment. The marks and timing support transparent self-assessment. They are not an official board format or pass standard.
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Target exams
SAQ 1 — Starting methotrexate in juvenile idiopathic arthritis
Question 1 — 10 formative marks; suggested time 15 minutes [5]
A six-year-old girl with polyarticular juvenile idiopathic arthritis has ongoing morning stiffness and synovitis despite intra-articular corticosteroid and a non-steroidal agent. The paediatric rheumatology team decides to start methotrexate. [1] [5]
- State the methotrexate dose schedule you would expect, the route, and the folic acid plan. (3 marks)
- Outline the on-treatment monitoring and two clinical or laboratory reasons to hold the next dose. (3 marks)
- Explain why a daily methotrexate schedule would be a serious error, and how you would counsel the family about the weekly schedule. (2 marks)
- After twelve months of inactive disease, the family asks whether methotrexate can be stopped. Summarise the evidence and how you would frame the decision. (2 marks) [4]
Full-credit answer — SAQ 1
Reveal full-credit answer for SAQ 1
1. Dose schedule, route and folic acid
Methotrexate in juvenile idiopathic arthritis is given once weekly at about 10 to 15 mg/m², by mouth initially and by subcutaneous injection once the oral dose rises above about 12 to 15 mg/m² or when nausea limits tolerance. Folic acid is given on the non-methotrexate days to reduce mucosal and hepatic toxicity without abolishing the anti-inflammatory effect. The mechanism of the low weekly dose is anti-inflammatory — folate-pathway inhibition with accumulation of methotrexate polyglutamates and adenosine release — not the cytotoxic killing of high-dose chemotherapy. [1] [5]
2. Monitoring and reasons to hold
Baseline full blood count, liver enzymes and creatinine are checked, repeated soon after starting, and then roughly every four to twelve weeks depending on stability. I would hold the next dose and recheck for a falling neutrophil count, a rising alanine aminotransferase (transaminitis), and new clinical mouth ulceration or mucositis, involving the rheumatology team before restarting or adjusting the dose. [5]
3. The daily-dosing error
Giving the same total weekly dose daily is a cytotoxic overdose error: it causes severe bone-marrow suppression and mucositis because the anti-inflammatory effect depends on the once-weekly peak and the folate recovery between doses. I would teach the family to mark a single methotrexate day each week, store the drug safely, and never double up a missed dose on the next day; folic acid is clearly distinguished as the daily off-day tablet. [1] [5]
4. Duration and withdrawal
The Foell withdrawal trial showed that stopping methotrexate after twelve months of remission reduced the relapse rate compared with stopping at six months. I would frame the decision as a shared one with the rheumatology team, weighing the relapse risk against the burden of continued treatment and monitoring, and I would confirm that remission is sustained before any withdrawal. [4]
SAQ 2 — The pre-biologic screen before a TNF inhibitor
Question 2 — 10 formative marks; suggested time 15 minutes [9]
A twelve-year-old boy with steroid-dependent Crohn disease is to start infliximab. Before the first infusion the team must complete the pre-biologic screen. [9] [10]
- Describe the latent tuberculosis screen and why each component is used. (3 marks)
- List the remaining infection screen and the action for a child found to be non-immune to varicella. (3 marks)
- State the live-vaccine rule and how it applies to this child. (2 marks)
- Three months into treatment the boy presents with fever and cough. Give your differential priority, the immediate management, and the role of the next biologic dose. (2 marks) [10]
Full-credit answer — SAQ 2
Reveal full-credit answer for SAQ 2
1. The latent tuberculosis screen
Latent tuberculosis is screened with both a tuberculin skin test and an interferon-gamma release assay, because each method alone misses cases the other catches and the dual approach raises sensitivity. A chest X-ray is added when either test is positive or when tuberculosis risk is present (family or community exposure, endemic travel). Any latent tuberculosis is treated with chemoprophylaxis before the first biologic dose, because tumour necrosis factor blockade takes the brake off intracellular infection and can precipitate disseminated disease. [9] [10]
2. The viral and varicella panel
Hepatitis B is screened with surface antigen, core antibody and surface antibody (to distinguish chronic, resolved and susceptible states); hepatitis C and HIV are screened; and varicella immunity is confirmed with serology when the history is uncertain. A child found to be non-immune to varicella should receive the varicella vaccine before immunosuppression begins, with the recommended interval before the first biologic dose, because live vaccines are contraindicated once the child is on treatment. [9] [11]
3. The live-vaccine rule
Live vaccines — measles-mumps-rubella and varicella — are completed before immunosuppression begins and are then contraindicated on biologic therapy, because the dampened immune system may allow uncontrolled vaccine-strain infection. Inactivated vaccines, including annual influenza, can be given on treatment, although the immune response may be blunted. The EULAR and PRES paediatric vaccination recommendations make this explicit. [11]
4. The febrile child on a biologic
The priority is serious infection, including reactivated or disseminated tuberculosis that may present atypically, alongside bacteraemia and viral illness. I assess the child on the standard paediatric sepsis pathway, take cultures, begin empirical antibiotics early if sepsis is suspected, and hold the next biologic dose while I investigate. I involve the gastroenterology and infectious diseases teams and consider tuberculosis testing and imaging. [10]
References
- [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
- [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
- [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