Title : Neurological complications associated with infliximab therapy in inflammatory bowel disease: A systematic review of case reports
Abstract:
Introduction: Infliximab therapy in Inflammatory Bowel Disease is associated with rare but serious neurological complications including central and peripheral demyelination, neuropathy, optic neuritis, seizures and encephalomyelitis. These neurological events have not yet been systematically characterized despite an increasing use of this agent in IBD.
Aims & Methods: Our aim was to characterize the clinical spectrum, diagnostic findings, management and outcome of neurologic complications associated with infliximab treatment of inflammatory bowel disease (IBD) through systematic review of published case reports/series (PROSPERO CRD420261463893). The PubMed, Google Scholar, and ScienceDirect databases were queried from inception through 5 June 2026, identifying 972 records (PubMed n=124, ScienceDirect n=369, Google Scholar n=479). After removal of 132 duplicates, 840 records were screened and 693 excluded. Of the 147 reports sought for retrieval, 144 were assessed for eligibility (3 not retrieved); 95 were subsequently excluded (11 non-English, 3 wrong study design, 12 letters to the editor, 3 articles in press, 66 not meeting inclusion criteria), leaving 49 cases for inclusion. The quality of individual studies was assessed using the NIH Quality Assessment Tool. Relevant data were extracted by four reviewers independently with subsequent consensus achieved with two senior investigators. Statistical comparisons were made with chi-square or Fisher's exact tests for categorical variables and Mann-Whitney U or Kruskal-Wallis tests for continuous variables; statistical significance was set at p<0.05.
Results: Forty-nine cases were included (26 male, 23 female; median age 42.5 years, range 7–80), most with Crohn's disease (71.4%), followed by ulcerative colitis (26.5%) and indeterminate colitis (2.0%). Median time to onset was 32 days from the first infusion and 9.5 days from the most recent dose. Central events tended to occur earlier than peripheral or mixed events (median 28 vs 729 and 607 days; p=0.066). The neurological event occurred during active disease in 42.9% of cases and remission in 38.8%. Involvement was predominantly central (71.4%) rather than peripheral (20.4%) or mixed (8.2%), and non-infectious in 71.4%; among the 14 infectious cases, Listeria monocytogenes was the most common organism (8/14, 57.1%). Infliximab was discontinued in 77.6% of patients; full recovery occurred in 60.4%, partial recovery in 22.9%, persistent deficit in 10.4%, and death in 6.2% (median recovery time 37 days). Recurrence occurred in 12.2%. IBD type was not associated with site of involvement (p=0.089) or infectious aetiology overall (p=0.065), though ulcerative colitis was more often infectious than Crohn's disease on subgroup analysis (p=0.034). Neither IBD activity, sex nor age was associated with prognosis or onset timing.
Conclusion: This is the largest reported synthesis of infliximab-associated neurological complications in IBD. Central nervous system involvement predominates and tends to arise earlier than peripheral disease, with generally favourable outcomes after drug discontinuation. The short latency from the most recent dose (median 9.5 days) suggests clinicians should maintain heightened neurological surveillance in the days following every infusion, not solely during induction, given the unpredictable and recurrent nature of onset.
