Perception And Reality: Patterns Of Hospitalization, Surgery, Permanent Work Disability And Death In Crohn'S Disease Patients Requiring Anti-Tnf-Alpha Therapy

Purpose: Anti-TNF-α therapy has emerged as a mainstay for the treatment of moderate to severe Crohn's disease (CD) refractory to standard immunosuppressive agents. Perception regarding risk, specifically neoplastic and infectious complications may prompt clinicians to limit or cease use of biologic therapy. However, the natural history of moderate to severe CD and its associated complications including hospitalization, surgery, permanent work disability and death, in a routine clinical setting have not been well characterized in the biologic therapy eligible population. This information is essential to better understand risk-benefit assessment of the use of biologics in the treatment of CD. Methods: This was a retrospective observational cohort analysis at a single tertiary referral center. CD patients with any exposure to infliximab comprised the study population. Patients were grouped based on status of anti-TNF-α therapy, as either ONGOING MAINTENANCE (OM) or DISCONTINUED (DIS) therapy. Demographic information, location of disease, CD related hospitalization, surgery, permanent work disability or death were determined. Results: Out of 930 CD patients, 435 had been exposed to infliximab (47%) among who 205 were receiving ongoing maintenance (OM) therapy (22%) during the time period 1998 –2007. There was no difference regarding mean age (40.9 y vs. 42.3 y) or duration of disease (16.8 y vs. 13.5 y) between the OM and DIS groups. There was also no difference between hospitalizations and surgeries prior to infliximab initiation between the two groups. We identified strong trends towards higher mean per patient medical hospitalizations (1.80 vs. 1.23, P= 0.07) and surgery (2.30 vs. 1.73, P= 0.05) in the DIS group compared to those with those with ongoing maintenance. Rates of permanent work disability were also higher in the DIS (10.0%, N = 23) compared to the OM (3.4%, N = 7; P= 0.005). Deaths occurred in 1% of the OM group (N = 2) and 3.4% of the DIS group (N = 8) (P= 0.08) during the study period. Conclusion: CD patients who warrant anti-TNF-α biologic therapy have high rates of disease-related complications. Patients who discontinued maintenance biologic therapy had more adverse outcomes including higher health care utilization. Accurate risk-benefit assessment in the management of moderate-to-severe CD needs to take into account the high rate of complications associated with inadequately treated disease.