Lymphoma risk in systemic lupus: effects of disease activity versus treatment.

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.

• Authors: 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 Wallace, Christine 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
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 73 Issue 1 Pg. 138-42 (Jan 2014) ISSN: 1468-2060 [Electronic] England
• PMID: 23303389 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Glucocorticoids
• Immunosuppressive Agents
• Cyclophosphamide
• Mycophenolic Acid
• Azathioprine
• Methotrexate

Topics

• Adult
• Antimalarials (therapeutic use)
• Azathioprine (therapeutic use)
• Case-Control Studies
• Cyclophosphamide (therapeutic use)
• Female
• Glucocorticoids (therapeutic use)
• Hodgkin Disease (epidemiology)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Lupus Erythematosus, Systemic (drug therapy, epidemiology)
• Lymphoma, Non-Hodgkin (epidemiology)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Mycophenolic Acid (analogs & derivatives, therapeutic use)
• Risk Factors
• Young Adult