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Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta-analysis of published randomized controlled studies

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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.

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Authors and Affiliations

  1. Department of Pathology and Lab Medicine, David Geffen School of Medicine at UCLA, 10833 Le conte Avenue, MC 173216, Los Angeles, CA, 90095, USA

    Susan Kerkoutian, Jonathan Said & Sheeja T. Pullarkat

  2. Department of Pathology and Laboratory Medicine, UCSD School of Medicine, San Diego, CA, USA

    Anna K. Wong & Hooman Rashidi

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  1. Anna K. Wong
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  2. Susan Kerkoutian
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Correspondence to Sheeja T. Pullarkat.

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Wong, A.K., Kerkoutian, S., Said, J. et al. Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta-analysis of published randomized controlled studies. Clin Rheumatol 31, 631–636 (2012). https://doi.org/10.1007/s10067-011-1895-y

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  • DOI: https://doi.org/10.1007/s10067-011-1895-y

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