Immunosuppressive and biologic therapies — formative SAQs

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]