Characterization of IBD patients with Multiple Sclerosis at a large IBD unit

Background:

Targeting TNF-alpha is an important and effective therapeutic approach for patients with moderate to severe inflammatory bowel diseases (IBD). TNF-alpha antibodies have a favourable safety profile. However known side effects of this treatment are for example allergic reactions and infections. Rare adverse events like central nervous system (CNS) demyelinating disorders (eg multiple sclerosis, optic neuritis) in association with TNF-alpha antibody (AB) therapy have been reported. In summary of this complex and important therapeutic area, we reviewed our patient collective of 1200 patients for known CNS diagnosis, eg multiple sclerosis (MS) independent of their IBD treatment.

Methods:

All patients were recruited from our IBD outpatient clinic seen between Jun 2006 and Oct 2017. Only patient with MS and IBD diagnosis were included. The data was retrospectively collected by chart review and patients were split into 2 groups (CNS diagnosis without any TNF-alpha antibody treatment = cohort 1; and CNS diagnosis developed during TNF-alpha AB treatment = cohort 2). Data were analysed for age, age at diagnosis, sex, IBD diagnosis, Montreal Classification (Behaviour (B), Location (L)) and IBD family history with student t-test and chi – square test.

Results:

Overall, 13 patients with CNS diagnosis were included in this study. Six IBD patients were diagnosed with MS (cohort 1) without TNF-alpha AB treatment. Seven IBD patients were diagnosed during TNF-alpha AB treatment with MS (cohort 2). IBD diagnosis in cohort 1 was Crohns disease (CD) in 83.3%, Ulcerative colitis (UC) in 16.7%; and cohort 2 was CD in 57.1% and UC in 42.9%. Patients of cohort 2 were diagnosed significant early with IBD (p = 0.01; 16 – 53yrs; SD 9.7yrs) compared to cohort 1 (34 – 53yrs; SD 7.3yrs). The time between first Anti-TNF AB application and MS diagnosis differs about 12 – 109 months in cohort 2. Patients of this cohort reported more extraintestinal manifestations like arthralgia (p = 0.16; 85.7% vs. 50.0%) before MS diagnosis. Disease Behaviour (Montreal Classification) of cohort 2 patients was more severe (p = 0.19; B3 60.0%, B1 20.0%, B1 p 20.0%) compared to cohort 1 (B2 40.0%, B1 60.0%). In cohort 1 more patient had a family history of IBD than in cohort 2 (p = 0.20; 60.0% vs. 20.0%).

Conclusions:

In our cohort, patients with MS developed during TNF-alpha -AB treatment had a more severely IBD disease with a significant earlier onset of their symptoms including inflammation, stricturing and penetrating complications and extraintestinal manifestations than MS patients without TNF-AB treatment. Importantly, in IBD patients with neurological symptoms (e.g. paraesthesia, weakness at the extremities), CNS disorders should be considered, especially in TNF-alpha AB treated patients.