1. Effectiveness and Safety of Immunomodulators With Anti–Tumor Necrosis Factor Therapy in Crohn’s Disease Mark T. Osterman,Kevin Haynes, Elizabeth Delzell,k Jie Zhang,k Meenakshi Bewtra, Colleen M. Brensinger, Lang Chen, Fenglong Xie, Jeffrey R. Curtis,k, and James D. Lewis Clinical Gastroenterology and Hepatology 2015 R3 최윤영 /Prof. 이창균

2. Introduction Anti–tumor necrosis factor + thiopurine : Currently the most efficacious therapy for moderate-to-severe Crohn’s disease Continuing immunomodulators + Stepping up to anti-TNF : Less clear

3. Introduction Immunosuppressive agent is not without risk Thiopurine : Viral infection such as herpes zoster Anti-TNF : Susceptibility to infection Effectiveness and safety of immunomodulators when combined with anti-TNF therapy, compared with anti-TNF monotherapy

4. Methods Study Design Retrospective cohort study From February 1, 2007 to December 31, 2010 Infliximab or adalimumab Exposure Definitions Newly initiated treatment At least 1 diagnostic code for CD in the 12 month

5. Methods Mono therapy Combination Therapy No use of immunomodulators Use of immunomodulators

6. Methods Outcome Measures 3 effectiveness primary outcome - Surgery, hospitalization, discomtinuation 2 safety primary outcome - Serious infection, opportunistic infection

8. Primary outcome Median time : 1.4-1.7 years Infliximab : 16% Adalimumab : 13%

9. 34cases of the 50cases opportunistic infection

11. Conclusion We found that combination therapy did not improve outcomes but was associated with an increased risk of opportunistic infection The importance of herpes zoster vaccination and potentially other vaccinations before initiation of immunosuppressive therapy.