Biologic DMARD Initiation

Biologic disease-modifying drugs, including tumour necrosis factor inhibitors, interleukin-6 inhibitors, abatacept and rituximab, are started in inflammatory arthritis that remains active after adequate conventional therapy. Safe initiation depends on confirming indication, screening for latent infection, optimising vaccines and planning contraception.

Indication. Active rheumatoid arthritis (DAS28 over 5.1, or over 3.2 with active disease) after at least 6 months of 2 conventional drugs including methotrexate at an adequate dose, unless intolerance or contraindication; active axial spondyloarthritis after 2 NSAIDs; psoriatic arthritis after conventional drugs; severe juvenile idiopathic arthritis.

Biosimilars. Biosimilar adalimumab, etanercept, infliximab and rituximab are equivalent in efficacy and safety and are used where cost or supply requires.

Contraindications. Active tuberculosis or other serious infection, hepatitis B not on prophylaxis, demyelinating disease and NYHA class III to IV heart failure (tumour necrosis factor inhibitors), recent malignancy (within 5 years, case by case), live vaccines, and pregnancy for some agents.

Tumour necrosis factor inhibitors (first biologic in most patients).

• Adalimumab 40 mg subcutaneously every 2 weeks (weekly if partial response and no methotrexate).
• Etanercept 50 mg subcutaneously weekly (or 25 mg twice weekly).
• Certolizumab pegol 400 mg subcutaneously at weeks 0, 2 and 4, then 200 mg every 2 weeks (400 mg every 4 weeks).
• Golimumab 50 mg subcutaneously once monthly (100 mg if over 100 kg).
• Infliximab 3 mg/kg IV at 0, 2 and 6 weeks then every 8 weeks, increasing to 5 to 10 mg/kg or shortening the interval for partial response; must be given with methotrexate in rheumatoid arthritis.

Non-tumour necrosis factor biologics.

• Tocilizumab 162 mg subcutaneously weekly (or every 2 weeks), or 8 mg/kg IV every 4 weeks (maximum 800 mg).
• Abatacept 125 mg subcutaneously weekly, or IV 500 mg (under 60 kg), 750 mg (60 to 100 kg) or 1000 mg (over 100 kg) at weeks 0, 2, 4 then every 4 weeks.
• Rituximab 1000 mg IV on days 1 and 15, repeated every 6 months or when needed; premedicate with methylprednisolone 100 mg IV, paracetamol and an antihistamine.
• Secukinumab (psoriatic arthritis, axial disease) 150 mg subcutaneously weekly for 5 weeks, then every 4 weeks.

Choice. Use a tumour necrosis factor inhibitor first, except when recent lymphoma, demyelination or heart failure suggests another class; switch class or mechanism after a first failure.

Pre-treatment screening (mandatory).

• Tuberculosis: symptoms, chest radiograph and interferon-gamma release assay or tuberculin skin test (induration 5 mm or more in this setting). Treat latent infection first (isoniazid 300 mg with pyridoxine 10 mg daily for 6 months, or rifampicin 600 mg daily for 4 months) and start the biologic after at least 1 month of treatment.
• Hepatitis B: HBsAg, anti-HBc and anti-HBs. If HBsAg positive or anti-HBc positive, give entecavir 0.5 mg once daily or tenofovir (adjusted to kidney function) from before starting until 6 to 12 months after the last dose, with specialist input.
• Hepatitis C and HIV serology.
• Full blood count, creatinine, liver tests and baseline pregnancy test.

Vaccination. Give inactivated influenza, pneumococcal conjugate, hepatitis B and recombinant zoster vaccines at least 2 to 4 weeks before starting; avoid live vaccines during and for 3 months after treatment (6 to 12 months after rituximab for responses).

Kidney and liver impairment. Etanercept, adalimumab and rituximab need no dose change; tocilizumab needs liver tests and may need dose reduction for raised ALT; avoid in active liver disease.

Older adults. Higher infection risk; reduce concomitant steroid.

Pregnancy and breastfeeding. Certolizumab, etanercept and adalimumab may continue; stop others as discussed with an obstetric physician; delay live infant vaccines such as BCG and rotavirus by 6 months after most agents.

Regional. Tuberculosis is endemic in East Africa, and interferon-gamma release assays may be unavailable; use clinical history, chest radiograph and tuberculin test, and consider empirical latent tuberculosis treatment in high-risk patients. Hepatitis B prevalence is high; prophylaxis is often needed. Cost and supply favour biosimilars.

Response. Disease activity score at 12 weeks and every 3 to 6 months. Stop a tumour necrosis factor inhibitor that has not produced at least a moderate response by 3 to 6 months and switch.

Safety monitoring. Full blood count, creatinine and liver tests at 4 to 6 weeks then every 3 months. Tuberculosis symptom review at each visit and a repeat chest radiograph if risk changes. Skin check each year.

Infusion reactions. Slow or stop the infusion, give hydrocortisone 100 mg IV and an antihistamine, and restart at half rate once settled; stop for anaphylaxis (adrenaline 500 micrograms IM).

Stop and escalate. Stop for serious infection, active tuberculosis, new demyelinating symptoms, lupus-like syndrome, heart failure, lymphoma, severe hypersensitivity or pregnancy (for agents not compatible). Hold during febrile illness and before major surgery (usually omit 1 dosing interval).