DMARDs in Rheumatological Practice
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Direct answer
Methotrexate remains the anchor DMARD around which everything else is arranged: 7.5–25 mg once weekly with folic acid at least 5 mg weekly, monitored by blood counts and liver enzymes every two to four weeks initially, then every eight to twelve weeks. Sulfasalazine (2–3 g daily) is the pregnancy-safe and peripheral-spondyloarthritis option; hydroxychloroquine (never above 5 mg/kg/day) carries the ophthalmic rule of a baseline retinal examination and annual screening after five years; leflunomide is the teratogen that needs an eleven-day cholestyramine washout before conception is attempted. Biologics and the oral JAK inhibitors sit above these, chosen after conventional failure, with tuberculosis and hepatitis screening before every single one.
What you must remember
- Methotrexate is weekly, never daily — daily dosing is a fatal prescription error; add folic acid 5 mg weekly on a different day; avoid in pregnancy, eGFR below 30, active liver disease and significant alcohol use.
- Monitoring schedule: baseline full blood count, creatinine, transaminases and hepatitis serology; repeat every 2–4 weeks for the first three months, then every 8–12 weeks.
- Sulfasalazine 2–3 g daily: first choice in pregnancy planning and in peripheral spondyloarthritis; check G6PD before starting.
- Hydroxychloroquine ceiling of 5 mg/kg/day real body weight (2016 American Academy of Ophthalmology rule), with baseline fundus examination and annual screening only after five years of use unless risk factors exist.
- Leflunomide: half-life about two weeks; washout with cholestyramine 8 g three times daily for 11 days, confirmed by drug levels twice, before conception is attempted.
- Biologic map: etanercept (soluble receptor), infliximab (chimeric — must travel with methotrexate to prevent anti-drug antibodies), adalimumab, golimumab, certolizumab (minimal placental transfer — the pregnancy-allowed one), rituximab (B-cell depletion; hepatitis B reactivation and progressive multifocal leucoencephalopathy risk), abatacept (T-cell co-stimulation blockade), tocilizumab (IL-6).
- JAK inhibitors (tofacitinib, baricitinib, upadacitinib): oral small molecules carrying a class boxed warning for major cardiovascular events, venous thromboembolism and malignancy after the ORAL Surveillance trial in patients over 50 with cardiovascular risk — position them after a TNF inhibitor.
- Indian practice: quality biosimilars have made rituximab and anti-TNF therapy genuinely affordable; the discipline that has not changed is tuberculosis and hepatitis B screening before the first dose.
Numbers worth knowing before you prescribe
The prescriptions that hurt patients are almost always dosing and monitoring failures, so the numbers deserve to be carried concretely. Methotrexate goes from 7.5 to 25 mg once a week, orally or subcutaneously — write "once a week" in words and name the day, because a daily misread at the pharmacy counter is a documented catastrophe. Hold methotrexate for transaminases beyond two to three times the upper limit, for falling leucocyte or platelet counts, and perioperatively in high-risk surgery.
Hydroxychloroquine's 5 mg/kg ceiling uses real body weight, and the screening timetable is baseline plus annual after year five — earlier and yearly when the dose has been high, duration long, or renal impairment or tamoxifen coexists. Leflunomide needs eleven days of cholestyramine 8 g three times daily, with non-teratogenic levels then confirmed twice, a fortnight apart. Vaccinate with influenza and pneumococcal vaccines before rituximab, which blunts antibody responses for about six months; methotrexate is commonly held for two weeks after influenza vaccination to preserve the response, per current ACR guidance. These intervals — 2–4 weekly becoming 8–12 weekly, year five for the eyes, eleven days for the washout — are precisely the sort of number pairs vivas are built on.
The prescribing traps
Daily instead of weekly methotrexate is the classic fatal error, and the defence is writing "Sundays" on the prescription. Prescribing infliximab without methotrexate invites anti-drug antibodies and loss of response within a year. Certolizumab is the biologic of choice in pregnancy precisely because its pegylated Fab structure does not cross the placenta — examiners like that mechanism. Stopping hydroxychloroquine in a lupus pregnancy is the wrong answer in every paper, because the drug crosses safely and reduces flares. And a JAK inhibitor handed first-line to a 60-year-old smoker with prior stents ignores a boxed warning written for exactly that patient.
Frequently asked questions
What is the maximum safe daily dose of hydroxychloroquine?
5 mg per kg of real body weight per day, with a baseline ophthalmic examination and annual retinal screening after five years of use.
How is leflunomide cleared before pregnancy?
Cholestyramine 8 g three times daily for 11 days, then drug levels checked twice at least two weeks apart before conception is attempted.
Which biologic is preferred during pregnancy?
Certolizumab, because its structure minimises placental transfer; most whole monoclonals cross the placenta from the second trimester.
Why must methotrexate accompany infliximab?
Concurrent methotrexate suppresses anti-drug antibody formation against the chimeric antibody, preserving infusion responses.
What monitoring does methotrexate require?
Full blood count and liver enzymes every 2–4 weeks for the first three months, then every 8–12 weeks, alongside renal function.
Who should not receive a JAK inhibitor first?
Patients over 50 with cardiovascular or malignancy risk factors, per the ORAL Surveillance safety signal — use a TNF inhibitor first.