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 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

doi:10.1136/annrheumdis-2012-202099

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

Department of Clinical Medicine

70 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 language	English
Journal	Annals of the Rheumatic Diseases
Volume	73
Issue number	1
Pages (from-to)	138-42
Number of pages	5
ISSN	0003-4967
DOIs	https://doi.org/10.1136/annrheumdis-2012-202099
Publication status	Published - Jan 2014

Keywords

Adult
Antimalarials
Azathioprine
Case-Control Studies
Cyclophosphamide
Female
Glucocorticoids
Hodgkin Disease
Humans
Immunosuppressive Agents
Lupus Erythematosus, Systemic
Lymphoma, Non-Hodgkin
Male
Methotrexate
Middle Aged
Mycophenolic Acid
Risk Factors
Young Adult

UN SDGs

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10.1136/annrheumdis-2012-202099

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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), 138-42. https://doi.org/10.1136/annrheumdis-2012-202099

Bernatsky, S, Ramsey-Goldman, R, Joseph, L, Boivin, J-F, 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, S-C, 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 2014, 'Lymphoma risk in systemic lupus: effects of disease activity versus treatment', Annals of the Rheumatic Diseases, vol. 73, no. 1, pp. 138-42. https://doi.org/10.1136/annrheumdis-2012-202099

@article{bc1f31192c8b4deaa7244d6c1d45215f,

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.",

keywords = "Adult, Antimalarials, Azathioprine, Case-Control Studies, Cyclophosphamide, Female, Glucocorticoids, Hodgkin Disease, Humans, Immunosuppressive Agents, Lupus Erythematosus, Systemic, Lymphoma, Non-Hodgkin, Male, Methotrexate, Middle Aged, Mycophenolic Acid, Risk Factors, Young Adult",

author = "Sasha Bernatsky and Rosalind Ramsey-Goldman and Lawrence Joseph and Jean-Francois Boivin 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 Sang-Cheol Bae 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 {St Pierre}, Yvan and Clarke, {Ann E}",

year = "2014",

month = jan,

doi = "10.1136/annrheumdis-2012-202099",

language = "English",

volume = "73",

pages = "138--42",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J 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 - St Pierre, Yvan

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.

KW - Adult

KW - Antimalarials

KW - Azathioprine

KW - Case-Control Studies

KW - Cyclophosphamide

KW - Female

KW - Glucocorticoids

KW - Hodgkin Disease

KW - Humans

KW - Immunosuppressive Agents

KW - Lupus Erythematosus, Systemic

KW - Lymphoma, Non-Hodgkin

KW - Male

KW - Methotrexate

KW - Middle Aged

KW - Mycophenolic Acid

KW - Risk Factors

KW - Young Adult

U2 - 10.1136/annrheumdis-2012-202099

DO - 10.1136/annrheumdis-2012-202099

M3 - Journal article

C2 - 23303389

SN - 0003-4967

VL - 73

SP - 138

EP - 142

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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