Lymphoma risk in systemic lupus: Effects of disease activity versus treatment

Sasha Bernatsky, Rosalind Ramsey-Goldman, Lawrence Joseph, Jean Francois Boivin, Karen H. Costenbader, Murray B. Urowitz, Dafna D. Gladman, Paul R. Fortin, Ola Nived, Michelle A. Petri, Soren Jacobsen, Susan Manzi, Ellen M. Ginzler, David Isenberg, Anisur Rahman, Caroline Gordon, Guillermo Ruiz-Irastorza, Edward Yelin, Sang Cheol Bae, Daniel J. WallaceChristine A. Peschken, Mary Anne Dooley, Steven M. Edworthy, Cynthia Aranow, Diane L. Kamen, Juanita Romero-Diaz, Anca Askanase, Torsten Witte, Susan G. Barr, Lindsey A. Criswell, Gunnar K. Sturfelt, Irene Blanco, Candace H. Feldman, Lene Dreyer, Neha M. Patel, Yvan St Pierre, Ann E. Clarke

Research output: Contribution to journalArticle

Abstract

Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.

Original languageEnglish (US)
Pages (from-to)138-142
Number of pages5
JournalAnnals of the rheumatic diseases
Volume73
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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    Bernatsky, S., Ramsey-Goldman, R., Joseph, L., Boivin, J. F., Costenbader, K. H., Urowitz, M. B., Gladman, D. D., Fortin, P. R., Nived, O., Petri, M. A., Jacobsen, S., Manzi, S., Ginzler, E. M., Isenberg, D., Rahman, A., Gordon, C., Ruiz-Irastorza, G., Yelin, E., Bae, S. C., ... Clarke, A. E. (2014). Lymphoma risk in systemic lupus: Effects of disease activity versus treatment. Annals of the rheumatic diseases, 73(1), 138-142. https://doi.org/10.1136/annrheumdis-2012-202099