title: Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis.
abstract: Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy for these patients. Published studies have been small with few events, precluding robust estimates of risk.
  
  
  
  We searched Medline, EMBASE, and conference proceedings for terms related to immune-mediated disease, immune-suppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of patients with inflammatory bowel disease, and 1 of patients with psoriasis) and stratified studies by type of immune-suppressive therapy (monoclonal antibodies to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no immune suppression). A random-effects meta-analysis was performed to calculate the pooled incidence rates as well as risk differences between the various treatments.
  
  
  
  Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow-up evaluation after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8 per 1000 p-y), immune-modulator therapy (36.2 per 1000 p-y), or no immunosuppression (37.5 per 1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5 per 1000 p-y) (P > .1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease showed similar results, with no increase in risk. We found similar pooled incidence values for new or primary cancers when immunosuppression was initiated within 6 years (33.6 per 1000 p-y for immune-modulatory agents and 43.7 per 1000 p-y for anti-TNF agents) vs more than 6 years after the index cancer (32.9 per 1000 p-y for immune-modulatory agents, P = .86; and 21.0 per 1000 p-y for anti-TNF agents, P = .43).
  
  
  
  In a meta-analysis of 16 studies, we observed similar rates of cancer recurrence among individuals with prior cancer who received no immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination treatments. Prospective studies are needed to ascertain optimal intervals for re-initiation of immune-suppressive therapies for individuals with specific cancers.
authors.affiliation: Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Edward
authors.initials: E
authors.lastname: Shelton
authors.affiliation: Service d'Hépato-Gastroentérologie, University Bordeaux, Laboratoire de Bactériologie, Bordeaux, Pessac, France.
authors.forename: David
authors.initials: D
authors.lastname: Laharie
authors.affiliation: Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Frank I
authors.initials: FI
authors.lastname: Scott
authors.affiliation: Division of Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ronac
authors.initials: R
authors.lastname: Mamtani
authors.affiliation: Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: aananthakrishnan@mgh.harvard.edu.
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Ananthakrishnan
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007165:Immunosuppression Therapy / Q000009:adverse effects* / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced* / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha
keywords: IBD; Immunosuppression; Lymphoma; Melanoma