title: Increased risk of malignancy with adalimumab combination therapy, compared with monotherapy, for Crohn's disease.
abstract: OBJECTIVE
  Few studies have assessed the risk of malignancy from anti-tumor necrosis factor monotherapy or combination therapy for Crohn's disease (CD). We determined the relative risk of malignancy in patients with CD who received adalimumab monotherapy, compared with the general population. We also compared the risk of malignancy associated with combination adalimumab and immunomodulator therapy with that of adalimumab monotherapy.
  
  
  METHODS
  We performed a pooled analysis of data from 1594 patients with CD who participated in clinical trials of adalimumab (CLASSIC I and II, CHARM, GAIN, EXTEND, and ADHERE studies; 3050 patient-years of exposure). We calculated rates of malignancy among patients; the expected rates of malignancy, based on the general population, were derived from the Surveillance, Epidemiology, and End Results registry and National Cancer Institute survey.
  
  
  RESULTS
  Compared with the general population, patients receiving adalimumab monotherapy did not have a greater than expected incidence of nonmelanoma skin cancer (NMSC) or other cancers, whereas those receiving combination therapy had a greater than expected incidence of malignancies other than NMSC (standardized incidence ratio, 3.04; 95% confidence interval [CI], 1.66-5.10) and of NMSC (standardized incidence ratio, 4.59; 95% CI, 2.51-7.70). Compared with patients receiving adalimumab monotherapy, those patients receiving combination therapy had an increased risk of malignancy other than NMSC (relative risk, 2.82; 95% CI, 1.07-7.44) and of NMSC (relative risk, 3.46; 95% CI, 1.08-11.06).
  
  
  CONCLUSIONS
  In patients with CD, the incidence of malignancy with adalimumab monotherapy was not greater than that of the general population. Co-administration of immunomodulator therapy and adalimumab was associated with an increased risk of NMSC and other cancers.
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: mark.osterman@uphs.upenn.edu.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Osterman
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Mount Sinai Medical Center, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Robinson
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Winnie
authors.initials: W
authors.lastname: Lau
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Bidan
authors.initials: B
authors.lastname: Huang
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pollack
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Roopal B
authors.initials: RB
authors.lastname: Thakkar
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
mesh_terms: D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab
keywords: Anti–Tumor Necrosis Factor; Inflammatory Bowel Disease; SEER; Thiopurine