Inflammatory bowel disease and demyelination: more than just a coincidence?

Abstract

Infliximab and other anti-TNF-α agents have been implicated for drug-induced demyelination in patients with inflammatory bowel diseases (IBDs). We evaluated existing data from MEDLINE and EMBASE and conducted a narrative review to investigate further the aforementioned association. Our literature search highlighted 34 case reports, 3 case-control studies, 1 prospective and 7 retrospective cohort studies published in English. Available data suggest that IBD patients can manifest demyelinating events in both central and peripheral nervous system, however, they are still insufficient to conclude whether anti-TNF-α therapies are an independent risk factor for demyelination. Prospective cohort studies with internal control groups are needed to estimate the true incidence of demyelinating disorders in patients with IBD and to elucidate if anti-TNF-α therapy increases further the risk of demyelination.

Keywords::

• anti-TNF-α
• biological agents
• Crohn's disease
• demyelination
• inflammatory bowel disease
• monoclonal antibodies
• multiple sclerosis
• ulcerative colitis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Infliximab and other anti-TNF-α agents have been implicated for drug-induced demyelination in patients with inflammatory bowel disease (IBD).

• Our literature search highlighted 34 case reports of IBD patients complicated with demyelination published between 2004 and 2013.

• The most frequent neurological findings were upper and/or lower limp paresthesia, weakness and gait impairment.

• We have also found one prospective and seven retrospective cohort studies investigating the association of IBD with demyelinating events. In four of them, IBD patients were treated with anti-TNF-α agents.

• The relationship between multiple sclerosis and IBD has been also addressed by three case–control studies, which attempted to estimate the prevalence of IBD comorbidity in patients with multiple sclerosis.

• There is evidence that IBD patients can manifest demyelinating events in both central and peripheral nervous system. However, literature data are still insufficient to conclude whether anti-TNF-α therapies enhance the risk of demyelination.

• The number of reported cases of demyelination in IBD patients treated with anti-TNF-α agents over the IBD cases of demyelination on treatment with other medications should be cautiously interpreted, as adverse events are more likely to be reported in novel treatments compared to conventional ones.

• Before receiving treatment with monoclonal antibodies, IBD patients should undergo complete neurological examination, ophthalmological examination and – if indicated – an imaging study of the CNS. Patients finally receiving anti-TNF-α should have a close neurological/ophthalmological monitoring and periodical reexaminations.

• If any patient develops signs suggestive of demyelination during or after anti-TNF therapy, the drug should be directly discontinued and therapy with monoclonal antibodies should never be re-administrated.