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Lymphoma risk in systemic lupus: effects of disease activity versus treatment.
Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence; Boivin, Jean-Francois; Costenbader, Karen H; Urowitz, Murray B; Gladman, Dafna D; Fortin, Paul R; Nived, Ola; Petri, Michelle A; Jacobsen, Soren; Manzi, Susan; Ginzler, Ellen M; Isenberg, David; Rahman, Anisur; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Yelin, Edward; Bae, Sang-Cheol; Wallace, Daniel J; Peschken, Christine A; Dooley, Mary Anne; Edworthy, Steven M; Aranow, Cynthia; Kamen, Diane L; Romero-Diaz, Juanita; Askanase, Anca; Witte, Torsten; Barr, Susan G; Criswell, Lindsey A; Sturfelt, Gunnar K; Blanco, Irene; Feldman, Candace H; Dreyer, Lene; Patel, Neha M; St Pierre, Yvan; Clarke, Ann E
Journal Title
Annals of the rheumatic diseases
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2013-01-08
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73
Publication Issue
1
Publication Begin
138
Publication End
42
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nihms504451.pdf
Adobe PDF, 45.55 KB
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Abstract
To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
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.
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.
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.
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.
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.
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.
Citation
Bernatsky S, Ramsey-Goldman R, Joseph L, Boivin JF, Costenbader KH, Urowitz MB, Gladman DD, Fortin PR, Nived O, Petri MA, Jacobsen S, Manzi S, Ginzler EM, Isenberg D, Rahman A, Gordon C, Ruiz-Irastorza G, Yelin E, Bae SC, Wallace DJ, Peschken CA, Dooley MA, Edworthy SM, Aranow C, Kamen DL, Romero-Diaz J, Askanase A, Witte T, Barr SG, Criswell LA, Sturfelt GK, Blanco I, Feldman CH, Dreyer L, Patel NM, St Pierre Y, Clarke AE. Lymphoma risk in systemic lupus: effects of disease activity versus treatment. Ann Rheum Dis. 2014 Jan;73(1):138-42. doi: 10.1136/annrheumdis-2012-202099. Epub 2013 Jan 8. PMID: 23303389; PMCID: PMC3855611.