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P172 Incidence and risk factors of serious viral infections in inflammatory bowel disease

A. Wisniewski*1, 2, C. Landman1, J. Kirchgesner1, A. Bourrier1, I. Nion-Larmurier1, H. Sokol1, P. Seksik1, J. Cosnes1, L. Beaugerie1

1Hôpital Saint-Antoine AP-HP, Department of Gastroenterology and Nutrition, Paris, France, 2Hôpital Charles-Lemoyne, Université de Sherbrooke, Department of Gastroenterology et Hepatology, Montréal, Canada

Background

Use of immunosuppressants in inflammatory bowel disease (IBD) is associated with an increased risk of serious infections that varies considerably according to infection and immunosuppressant subtypes. This study aimed to determine the incidence rate and risk factors for serious viral infection (SVI) according to drug exposure and IBD activity in patients with IBD.

Methods

Using the MICISTA registry, a prospective observational cohort of IBD patients treated at our tertiary care hospital, we identified, between January 2005 and December 2014, patients who developed SVI as defined by need for hospitalisation, definite organ damage, or disabling sequelae. Cases of CMV colitis without systemic manifestations were excluded. We first estimated incidence rates of SVI, overall and according to maximal yearly treatment. Additionally, we performed a case-control study (4 controls for 1 case matched for age, gender, IBD subtype, and duration) assessing risk of SVI according to IBD drug use and IBD clinical activity in the 3 months preceding the SVI (data extracted from individual health records).

Results

We identified 31 patients with SVI amongst 2 645 patients, followed for a median period of 6.2 years and a total observational time of 16 922 patient-years. We identified 13 cases of CMV systemic infection (primary infection [n = 6], reactivation [n = 7]), 10 cases of EBV infection (primary infection [n = 6]) including 2 haemophagocytic syndromes, reactivation (n = 4), 5 cases of VZV infection (varicella [n = 3]), shingles (n = 2), and 3 cases of HSV infection (severe esophagitis, facial nerve paralysis, and severe refractory cutaneous manifestation). Most patients required hospitalisation (94%) and received IV anti-viral therapy (52%), and no death occurred. The incidence rate of SVI in patients with IBD was 1.83 per 1 000 patients-years. Table 1 shows the incidence rate of SVI according to the maximal treatment received during the year. In the case-control study, risk of SVI was associated with exposure to thiopurine (adjusted odds ratio (aOR), 5.1; 95% CI, 1.9–13.4; p = 0.001) and methotrexate (aOR, 4.1; 95% CI, 1.0–16.8; p = 0.05), and active clinical disease (aOR, 3.2; 95% CI, 1.3–8.1; p = 0.02). Odds ratios for corticosteroids and anti-tumour necrosis factor (TNF) did not reach statistical significance (1.1 and 1.2, respectively).

Conclusion

SVI are rare events in patients with IBD who do not receive immunosuppressants. Exposure to thiopurines or methotrexate, and IBD clinical activity increases substantially the risk. Amongst 100 patients treated with thiopurines for 10 years, 3 will develop SVI.

Table 1 Incidence rate of severe viral infection (SVI) in IBD according to treatment exposure