title: Tumor necrosis factor inhibitors added to nonbiological immunosuppressants vs. nonbiological immunosuppressants alone: a different signal of cancer risk according to the condition. A disproportionality analysis in a nationwide pharmacovigilance database.
abstract: We aimed at detecting a signal of an increased risk of cancer in patients treated with TNF inhibitor (TNFi) and nonbiological immunosuppressant (NBIS), compared with NBIS alone for autoimmune diseases. Secondly, we aimed at comparing this risk between the different TNFis. We conducted a disproportionality analysis (case/noncase study) from the French National PharmacoVigilance Database. We selected all the reports of serious adverse drug reactions from 2000 to 2010 in patients treated with NBIS for labeled indications of TNFi. Cases were all the reports of cancer that occurred after a minimal 3-month exposure to NBIS. Noncases were all the other reports. We searched for exposure to TNFi and calculated reporting odds ratios (RORs), stratified by condition and type of cancer and adjusted by age, gender, history of cancer, type of NBIS and year of reporting. Of the 1918 reports included in the study population, 217 were cases (135 solid and 82 blood cancers). A safety signal was found in rheumatoid arthritis (RA) (ROR: 5.43, 95% CI[3.52-8.38]) particularly for nonmelanoma skin cancer (NMSC) (20.17[2.49-163.36]), and in psoriasis/psoriatic arthritis (3.45[1.09-10.92]). No signal was found in inflammatory bowel diseases (IBD) and ankylosing spondylitis, whatever the type of cancer. There was no difference between TNFis. This study puts the argument of an increased risk of cancer (particularly NMSC) in patients with rheumatoid arthritis exposed to TNFi and NBIS compared with NBIS alone, but not in IBD and ankylosing spondylitis patients. No signal was detected for melanoma potentially related to the lack of power. The signal seems similar whatever the TNFi.
authors.affiliation: Service de Pharmacologie Medicale et Clinique, Centre Midi-Pyrenees de PharmacoVigilance, de Pharmacoepidemiologie et d'Informations sur le Medicament, 37 allées Jules Guesde, 31000, Toulouse, France.|INSERM, UMR 1027, Université de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.
authors.forename: Layla
authors.initials: L
authors.lastname: Saliba
authors.affiliation: INSERM, UMR 1027, Université de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.|Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, Place du Docteur Baylac - TSA 40031 - 31059 Toulouse cedex 9, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moulis
authors.affiliation: Centre Régional de PharmacoVigilance, Centre Hospitalier Universitaire de Reims, Avenue du Général Koenig, 51092, Reims, France.
authors.forename: Malak
authors.initials: M
authors.lastname: Abou Taam
authors.affiliation: Service de Pharmacologie Medicale et Clinique, Centre Midi-Pyrenees de PharmacoVigilance, de Pharmacoepidemiologie et d'Informations sur le Medicament, 37 allées Jules Guesde, 31000, Toulouse, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rousseau
authors.affiliation: Service de Pharmacologie Medicale et Clinique, Centre Midi-Pyrenees de PharmacoVigilance, de Pharmacoepidemiologie et d'Informations sur le Medicament, 37 allées Jules Guesde, 31000, Toulouse, France.
authors.forename: Leila
authors.initials: L
authors.lastname: Chebane
authors.affiliation: Centre Régional de PharmacoVigilance, Centre Hospitalier Universitaire de Nancy, 29 avenue du Maréchal de Lattre de Tassigny, 54035, Nancy cedex, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Petitpain
authors.affiliation: Centre Régional de PharmacoVigilance, Hôpital de Cimiez BP 1179, 06003, Nice cedex 1, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Baldin
authors.affiliation: INSERM, UMR 1027, Université de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.|Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, Place du Docteur Baylac - TSA 40031 - 31059 Toulouse cedex 9, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Pugnet
authors.affiliation: Service de Pharmacologie Medicale et Clinique, Centre Midi-Pyrenees de PharmacoVigilance, de Pharmacoepidemiologie et d'Informations sur le Medicament, 37 allées Jules Guesde, 31000, Toulouse, France.|INSERM, UMR 1027, Université de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
authors.affiliation: Service de Pharmacologie Medicale et Clinique, Centre Midi-Pyrenees de PharmacoVigilance, de Pharmacoepidemiologie et d'Informations sur le Medicament, 37 allées Jules Guesde, 31000, Toulouse, France.|INSERM, UMR 1027, Université de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.
authors.forename: Haleh
authors.initials: H
authors.lastname: Bagheri
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000209:etiology*; D060735:Pharmacovigilance; D012306:Risk; D013167:Spondylitis, Ankylosing / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
keywords: cancer; immunosuppressant; safety signal; tumor necrosis factor inhibitor