title: Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta-analysis of published randomized controlled studies.
abstract: The 2008 edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid tissues recognizes a new diagnostic entity termed "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" highlighting lymphomas arising in patients treated with immunosuppressive agents for autoimmune disorders. The role of antitumor necrosis factor alpha therapy (anti-TNFα) and lymphoma risk in rheumatoid arthritis (RA) patients remains unclear; therefore, the goal of our study was to determine whether anti-TNFα therapy is associated with iatrogenic lymphomas. A meta-analysis of all randomized controlled clinical trials published (2000-2009) in RA patients receiving anti-TNFα therapy was performed. Fourteen studies fulfilled all search criteria and included 2,306 control patients and 5,179 patients treated with anti-TNFα therapy, namely etanercept, adalumimab, and infliximab. Clinical information including the number of patients, age, gender, lymphoma rates, and follow-up time was recorded. The overall rate and rate differences were analyzed using the DerSimonian and Laird method. Of the control group, four (4/2,306, 0.17%) patients developed hematolymphoid neoplasms. Eleven (11/5,179, 0.21%) patients receiving anti-TNFα therapy developed lymphomas. The adjusted overall rates are 0.36 lymphomas per 1,000 person-years in patients who did not receive anti-TNFα therapy versus 1.65 lymphomas per 1,000 person-years in patients who received anti-TNFα therapy. The corresponding 95% confidence interval for this rate difference is (-0.214, 2.79). The adjusted rate difference is 1.29 lymphomas per 1,000 person-years (95% CI, -0.21, 2.8; p value = 0.093). The corresponding p value is p = 0.0928. There is a suggestion of increased lymphomas in the treated group, with the predominant subset being B-cell lymphomas. Since the outcome of lymphoma is rare, it does not reach statistical significance of p < 0.05.
authors.affiliation: Department of Pathology and Laboratory Medicine, UCSD School of Medicine, San Diego, CA, USA.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Wong
authors.forename: Susan
authors.initials: S
authors.lastname: Kerkoutian
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Hooman
authors.initials: H
authors.lastname: Rashidi
authors.forename: Sheeja T
authors.initials: ST
authors.lastname: Pullarkat
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects*; D000069285:Infliximab; D008223:Lymphoma / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept