Mark T Osterman1, William J Sandborn2, Jean-Frederic Colombel3, Anne M Robinson4, Winnie Lau4, Bidan Huang4, Paul F Pollack4, Roopal B Thakkar4, James D Lewis5. 1. University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: mark.osterman@uphs.upenn.edu. 2. Division of Gastroenterology, University of California San Diego, La Jolla, California. 3. Mount Sinai Medical Center, New York, New York. 4. AbbVie, Inc, North Chicago, Illinois. 5. University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: Few studies have assessed the risk of malignancy from anti-tumornecrosis 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: Mark T Osterman; Kevin Haynes; Elizabeth Delzell; Jie Zhang; Meenakshi Bewtra; Colleen M Brensinger; Lang Chen; Fenglong Xie; Jeffrey R Curtis; James D Lewis Journal: Clin Gastroenterol Hepatol Date: 2015-02-24 Impact factor: 11.382
Authors: A N Ananthakrishnan; A Sakuraba; E L Barnes; J Pekow; L Raffals; M D Long; R S Sandler Journal: Aliment Pharmacol Ther Date: 2017-05-03 Impact factor: 8.171
Authors: Frank I Scott; Ravy K Vajravelu; Meenakshi Bewtra; Ronac Mamtani; Dale Lee; David S Goldberg; James D Lewis Journal: Clin Gastroenterol Hepatol Date: 2014-08-10 Impact factor: 11.382