Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.
OBJECTIVE
The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD.


METHODS
We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses.


RESULTS
Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy.


CONCLUSIONS
We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection.
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: mark.osterman@uphs.upenn.edu.
Mark T
MT
Osterman
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Teaching, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Kevin
K
Haynes
Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama.
Elizabeth
E
Delzell
Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama.
Jie
J
Zhang
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Meenakshi
M
Bewtra
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Colleen M
CM
Brensinger
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama.
Lang
L
Chen
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama.
Fenglong
F
Xie
Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama.
Jeffrey R
JR
Curtis
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Teaching, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
James D
JD
Lewis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003424:Crohn Disease / Q000188:drug therapy* / Q000601:surgery; D013505:Digestive System Surgical Procedures / Q000706:statistics & numerical data; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced / Q000453:epidemiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D028761:Withholding Treatment / Q000706:statistics & numerical data; D055815:Young Adult
D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha
Adalimumab; Hospitalization; Infection; Infliximab; Surgery; Thiopurines