Biologic Therapy in Inflammatory Bowel Disease

Biologic therapies are monoclonal antibodies that block defined inflammatory mediators or cell trafficking. They are used for moderate to severe ulcerative colitis and Crohn disease, steroid dependence, fistulating disease, and failure of conventional immunosuppression.

Classification. Anti-TNF (infliximab, adalimumab, golimumab); anti-integrin (vedolizumab, gut selective); anti-interleukin 12 and 23 (ustekinumab); anti-interleukin 23 (risankizumab, mirikizumab, guselkumab).

• Infliximab 5 mg/kg intravenously at weeks 0, 2 and 6, then every 8 weeks; dose escalation to 10 mg/kg or a shorter interval adjusted to drug levels. A subcutaneous form (120 mg every 2 weeks) is used for maintenance.
• Adalimumab 160 mg at week 0, 80 mg at week 2, then 40 mg every other week by subcutaneous injection.
• Golimumab (ulcerative colitis) 200 mg at week 0, 100 mg at week 2, then 50 mg or 100 mg every 4 weeks by weight.
• Vedolizumab 300 mg intravenously at weeks 0, 2 and 6, then every 8 weeks.
• Ustekinumab intravenous induction by weight (260 mg up to 55 kg, 390 mg over 55 to 85 kg, 520 mg over 85 kg), then 90 mg subcutaneously every 8 weeks.
• Risankizumab in Crohn disease 600 mg intravenously at weeks 0, 4 and 8, then 180 mg or 360 mg subcutaneously every 8 weeks.

Differences. Anti-TNF drugs act fastest and have the best evidence for fistulas. Vedolizumab has the best safety profile because it acts only in the gut. Anti-interleukin drugs have low immunogenicity.

• Ulcerative colitis: infliximab (also for rescue in acute severe disease), adalimumab, vedolizumab, ustekinumab, risankizumab.
• Crohn disease: early biologic therapy for high-risk disease (young age, perianal, stricturing, extensive, deep ulcers).
• Combination with a thiopurine: reduces antibody formation with infliximab; adds lymphoma risk.
• Loss of response: measure trough levels and antibodies, exclude infection (Clostridioides difficile, cytomegalovirus), then escalate the dose or switch drug within or outside the class.

Selection. Infliximab trough above 5 microgram/mL and adalimumab trough above 5 microgram/mL are the usual maintenance targets; levels vary by assay.

Contraindications. Active tuberculosis or other serious infection. Anti-TNF drugs in NYHA class III or IV heart failure and demyelinating disease. Recent malignancy.

Adverse effects. Infusion reactions, serious bacterial and opportunistic infection, tuberculosis and hepatitis B reactivation, drug-induced lupus, psoriasiform rash, heart failure, skin cancers and lymphoma (hepatosplenic T cell lymphoma in young men on a thiopurine with an anti-TNF drug). Anti-integrin and anti-interleukin drugs: headache, nasopharyngitis, arthralgia, hepatic enzyme rise (risankizumab).

Interactions. Live vaccines are contraindicated. Combination with other biologics or tofacitinib raises infection risk.

Special groups.

• Pregnancy: anti-TNF drugs are generally continued. Infants exposed to infliximab or adalimumab in the third trimester should have live vaccines, including BCG and rotavirus, delayed for 6 months where feasible; this needs a decision against the local birth immunisation schedule.
• Breastfeeding: acceptable.
• Children: specialist paediatric dosing.
• Older adults: higher infection and malignancy risk; favour vedolizumab.
• Regional: tuberculosis and hepatitis B are common in East Africa, so screening must be thorough.

Pre-treatment screening. Tuberculosis (symptoms, chest radiograph, interferon gamma release assay or tuberculin test), hepatitis B (HBsAg, anti-HBc, anti-HBs), HIV, hepatitis C, varicella status, and strongyloides in endemic areas.

Treat latent tuberculosis and delay anti-TNF therapy until at least 1 month of treatment is completed; practice varies. Give entecavir or tenofovir to people with positive HBsAg or anti-HBc throughout therapy and for 6 to 12 months after.

Update inactivated vaccines (pneumococcal, influenza, hepatitis B, recombinant zoster) before starting.

Monitoring. Full blood count, liver enzymes, CRP and faecal calprotectin; drug levels and antibodies at loss of response; skin checks yearly.

Referral and escalation. Infusion reaction (stop infusion, give hydrocortisone 100 mg intravenously and an antihistamine), serious infection, new neurological deficit, or no response to two biologics needs specialist review.