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

56 Citations (Scopus)

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

Fingerprint

Systemic Lupus Erythematosus
Lymphoma
Cyclophosphamide
Therapeutics
Steroids
Azathioprine
Antimalarials
Immunologic Factors
Methotrexate
Glucocorticoids
Neoplasms
Sjogren's Syndrome
Cells
B-Cell Lymphoma
Hodgkin Disease
Non-Hodgkin's Lymphoma
Registries
Cohort Studies
Demography
Pharmaceutical Preparations

ASJC Scopus subject areas

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

Cite this

Bernatsky, S., Ramsey-Goldman, R., Joseph, L., Boivin, J. F., Costenbader, K. H., Urowitz, M. B., ... 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

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.; Pierre, Yvan St; Clarke, Ann E.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 1, 01.2014, p. 138-142.

Research output: Contribution to journalArticle

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, Pierre, YS & Clarke, AE 2014, 'Lymphoma risk in systemic lupus: Effects of disease activity versus treatment', Annals of the Rheumatic Diseases, vol. 73, no. 1, pp. 138-142. https://doi.org/10.1136/annrheumdis-2012-202099
Bernatsky S, Ramsey-Goldman R, Joseph L, Boivin JF, Costenbader KH, Urowitz MB et al. Lymphoma risk in systemic lupus: Effects of disease activity versus treatment. Annals of the Rheumatic Diseases. 2014 Jan;73(1):138-142. https://doi.org/10.1136/annrheumdis-2012-202099
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. ; Pierre, Yvan St ; Clarke, Ann E. / Lymphoma risk in systemic lupus : Effects of disease activity versus treatment. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 1. pp. 138-142.
@article{8368ac925c784ad68d051531a29e5062,
title = "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.",
author = "Sasha Bernatsky and Rosalind Ramsey-Goldman and Lawrence Joseph and Boivin, {Jean Francois} and Costenbader, {Karen H.} and Urowitz, {Murray B.} and Gladman, {Dafna D.} and Fortin, {Paul R.} and Ola Nived and Petri, {Michelle A.} and Soren Jacobsen and Susan Manzi and Ginzler, {Ellen M.} and David Isenberg and Anisur Rahman and Caroline Gordon and Guillermo Ruiz-Irastorza and Edward Yelin and Bae, {Sang Cheol} and Wallace, {Daniel J.} and Peschken, {Christine A.} and Dooley, {Mary Anne} and Edworthy, {Steven M.} and Cynthia Aranow and Kamen, {Diane L.} and Juanita Romero-Diaz and Anca Askanase and Torsten Witte and Barr, {Susan G.} and Criswell, {Lindsey A.} and Sturfelt, {Gunnar K.} and Irene Blanco and Feldman, {Candace H.} and Lene Dreyer and Patel, {Neha M.} and Pierre, {Yvan St} and Clarke, {Ann E.}",
year = "2014",
month = "1",
doi = "10.1136/annrheumdis-2012-202099",
language = "English (US)",
volume = "73",
pages = "138--142",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "1",

}

TY - JOUR

T1 - Lymphoma risk in systemic lupus

T2 - Effects of disease activity versus treatment

AU - Bernatsky, Sasha

AU - Ramsey-Goldman, Rosalind

AU - Joseph, Lawrence

AU - Boivin, Jean Francois

AU - Costenbader, Karen H.

AU - Urowitz, Murray B.

AU - Gladman, Dafna D.

AU - Fortin, Paul R.

AU - Nived, Ola

AU - Petri, Michelle A.

AU - Jacobsen, Soren

AU - Manzi, Susan

AU - Ginzler, Ellen M.

AU - Isenberg, David

AU - Rahman, Anisur

AU - Gordon, Caroline

AU - Ruiz-Irastorza, Guillermo

AU - Yelin, Edward

AU - Bae, Sang Cheol

AU - Wallace, Daniel J.

AU - Peschken, Christine A.

AU - Dooley, Mary Anne

AU - Edworthy, Steven M.

AU - Aranow, Cynthia

AU - Kamen, Diane L.

AU - Romero-Diaz, Juanita

AU - Askanase, Anca

AU - Witte, Torsten

AU - Barr, Susan G.

AU - Criswell, Lindsey A.

AU - Sturfelt, Gunnar K.

AU - Blanco, Irene

AU - Feldman, Candace H.

AU - Dreyer, Lene

AU - Patel, Neha M.

AU - Pierre, Yvan St

AU - Clarke, Ann E.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84889686638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84889686638&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2012-202099

DO - 10.1136/annrheumdis-2012-202099

M3 - Article

C2 - 23303389

AN - SCOPUS:84889686638

VL - 73

SP - 138

EP - 142

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 1

ER -