IBD Maintenance Therapy: Positioning Biologics in the Biologic Era

Perform latent tuberculosis screening with an interferon-gamma release assay (or tuberculin skin test if IGRA unavailable) and a chest radiograph before any biologic or JAK inhibitor.

Test for hepatitis B (HBsAg, anti-HBc, anti-HBs), hepatitis C antibody, and HIV before initiating maintenance therapy — reactivation of occult hepatitis B with anti-TNF and JAK inhibitors is well described.

Complete any indicated live attenuated vaccines (MMR, varicella, zoster live) at least four weeks before starting biologic or JAK therapy. Once therapy begins, live vaccines are generally avoided.

Administer inactivated vaccines (annual influenza, pneumococcal series, hepatitis B if non-immune, HPV if eligible, COVID-19 boosters, recombinant zoster vaccine) either before therapy or alongside it — do not delay urgent biologic initiation for routine inactivated vaccination.

Discuss pregnancy planning early, ideally at the time of agent selection. Most monoclonal antibody biologics (anti-TNF, vedolizumab, ustekinumab) are considered low risk in pregnancy; JAK inhibitors and methotrexate are contraindicated.

Counsel every patient on smoking cessation. The benefit is especially large in Crohn’s disease, where continued smoking accelerates disease progression and reduces response to maintenance therapy.

Obtain baseline labs including complete blood count, comprehensive metabolic panel, CRP, and fecal calprotectin to establish reference values for future monitoring of IBD maintenance therapy response.

Start vedolizumab 300 mg intravenous at weeks 0, 2, and 6, then every 8 weeks, as a preferred first-line option in biologic-naive adults with moderate-to-severe ulcerative colitis — supported by the VARSITY head-to-head trial demonstrating superiority over adalimumab for clinical remission at week 52.

Initiate infliximab 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks, as the preferred first-line maintenance after rescue therapy for acute severe ulcerative colitis. Higher induction doses (10 mg/kg) may be needed in patients with severe inflammation and rapid drug clearance.

Consider mirikizumab or risankizumab as IL-23 inhibitor options for moderate-to-severe ulcerative colitis, particularly in patients who prefer subcutaneous self-administration and a non-anti-TNF mechanism.

Prescribe adalimumab 160 mg week 0, 80 mg week 2, then 40 mg every other week, as an alternative subcutaneous first-line option in moderate ulcerative colitis when an anti-TNF is preferred and intravenous infusion is impractical.

Prescribe infliximab as the preferred first-line maintenance therapy in fistulizing or perianal Crohn’s disease. Anti-TNF agents are the only class with consistent randomised evidence for perianal fistula closure.

Start risankizumab 600 mg IV at weeks 0, 4, and 8, then 360 mg subcutaneous every 8 weeks, as a first-line option in moderate-to-severe luminal Crohn’s, including biologic-experienced patients — supported by ADVANCE, MOTIVATE, and FORTIFY.

Consider ustekinumab as a first-line option in biologic-naive moderate-to-severe Crohn’s disease — the SEAVUE head-to-head trial showed broadly comparable clinical remission at one year with adalimumab and a favourable safety profile.

Consider vedolizumab in patients with luminal Crohn’s at elevated infection or malignancy risk where a gut-selective mechanism is desirable. Onset of action is slower than anti-TNF, so it is less suited to patients needing rapid symptom control.

Prescribe adalimumab 40 mg subcutaneous every other week as an alternative first-line maintenance for moderate luminal Crohn’s when subcutaneous self-administration is preferred and immunogenicity risk is considered acceptable.

Consider combining infliximab with a thiopurine (azathioprine or 6-mercaptopurine) or methotrexate during the first 6–12 months to reduce immunogenicity and improve durable response — benefit demonstrated most clearly with infliximab in Crohn’s (SONIC trial).

Avoid long-term thiopurine plus anti-TNF combination therapy in young men because of the rare but reported risk of hepatosplenic T-cell lymphoma. Methotrexate is a reasonable alternative immunomodulator in this group.

Confirm active inflammation with objective markers (fecal calprotectin, CRP, endoscopy or cross-sectional imaging) before changing IBD maintenance therapy. Symptoms alone are insufficient because IBS-like symptoms, bile salt diarrhoea, and small bowel bacterial overgrowth can mimic flare.

Use therapeutic drug monitoring to measure trough drug levels and anti-drug antibodies in patients losing response to an anti-TNF. Most secondary failure has a pharmacokinetic explanation that can be addressed without switching class.

Optimise the dose (shorten the interval or increase the per-dose amount) when anti-TNF trough levels are subtherapeutic and anti-drug antibodies are absent or low-titre.

Switch within the anti-TNF class (e.g., infliximab to adalimumab) when failure is driven by high-titre anti-drug antibodies. Adding an immunomodulator at switch can reduce repeat immunogenicity.

Switch out-of-class for primary non-response (no response within an adequate induction interval despite adequate drug exposure). A different mechanism is more likely to succeed than another agent in the same class.

Evaluate for non-inflammatory contributors (C. difficile, CMV in steroid-refractory UC, strictures, abscess, NSAID use, undiagnosed bile salt diarrhoea) before assuming a true biologic failure.

Reserve tofacitinib for moderate-to-severe ulcerative colitis after failure or intolerance of at least one anti-TNF agent. Use 10 mg twice daily for induction, then step down to 5 mg twice daily for maintenance once response is achieved.

Consider upadacitinib 45 mg daily induction, then 15–30 mg daily maintenance, for moderate-to-severe ulcerative colitis or Crohn’s disease after anti-TNF failure — supported by U-ACHIEVE and U-EXCEL/U-EXCEED.

Counsel patients on the class-wide FDA boxed warnings before starting a JAK inhibitor — particularly major adverse cardiovascular events, venous thromboembolism, malignancy, and serious infection. Document the discussion.

Avoid JAK inhibitors as the first agent of choice in patients aged 65 or older with cardiovascular risk factors, current or past smokers, prior thromboembolism, or prior malignancy — particularly when an effective biologic alternative exists.

Step down to the lowest effective JAK inhibitor maintenance dose once remission is achieved. The dose-related signal for adverse events makes this especially relevant for tofacitinib at 10 mg twice daily.

Administer recombinant zoster vaccine before starting a JAK inhibitor whenever feasible — zoster reactivation rates are higher with JAK inhibitors than with anti-TNF or other biologic classes.

Target steroid-free clinical remission, normalisation of CRP and fecal calprotectin, and endoscopic remission as the composite goal of IBD maintenance therapy.

Reassess at 3 months, 6 months, and 12 months after initiating or switching therapy, then at least annually. Earlier reassessment is appropriate after any flare.

Measure fecal calprotectin every 3–6 months in patients on maintenance therapy. A persistent value above approximately 250 μg/g is suggestive of ongoing inflammation and warrants further evaluation.

Perform endoscopic reassessment 6–12 months after starting a new agent for moderate-severe disease, then per long-term surveillance schedule.

Check CBC, comprehensive metabolic panel, and CRP every 3–6 months on long-term maintenance therapy. Add lipid panel and herpes zoster status check periodically for patients on JAK inhibitors.