Lymphoma in rheumatoid arthritis: The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients

Frederick Wolfe, Kaleb Michaud

Research output: Contribution to journalArticle

523 Citations (Scopus)

Abstract

Objective. The risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTx) and anti-tumor necrosis factor (anti-TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA. Methods. We prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma eases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort. Results. The overall SIR for lymphoma was 1.9 (95% confidence interval [95% CI] 1.3-2.7). The SIR for biologic use was 2.9 (95% CI 1.7-4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95% CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI L9-7.5). The SIR for MTX was 1.7 (95% CI 0.9-3.2), and was 1.0 (95% CI 0.4-2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education. Conclusion. Lymphomas are increased in RA. Although the SIR is greatest for anti-TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti-TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.

Original languageEnglish (US)
Pages (from-to)1740-1751
Number of pages12
JournalArthritis and rheumatism
Volume50
Issue number6
DOIs
StatePublished - Jun 1 2004

Fingerprint

Methotrexate
Lymphoma
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Confidence Intervals
Incidence
Therapeutics
Sex Education
Rheumatic Diseases
Biological Products
Sample Size
Epidemiology
Clinical Trials
Databases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Lymphoma in rheumatoid arthritis : The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. / Wolfe, Frederick; Michaud, Kaleb.

In: Arthritis and rheumatism, Vol. 50, No. 6, 01.06.2004, p. 1740-1751.

Research output: Contribution to journalArticle

@article{a0f50a497e4f45bfab923d74e8495f5a,
title = "Lymphoma in rheumatoid arthritis: The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients",
abstract = "Objective. The risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTx) and anti-tumor necrosis factor (anti-TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA. Methods. We prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma eases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort. Results. The overall SIR for lymphoma was 1.9 (95{\%} confidence interval [95{\%} CI] 1.3-2.7). The SIR for biologic use was 2.9 (95{\%} CI 1.7-4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95{\%} CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95{\%} CI L9-7.5). The SIR for MTX was 1.7 (95{\%} CI 0.9-3.2), and was 1.0 (95{\%} CI 0.4-2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education. Conclusion. Lymphomas are increased in RA. Although the SIR is greatest for anti-TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti-TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.",
author = "Frederick Wolfe and Kaleb Michaud",
year = "2004",
month = "6",
day = "1",
doi = "10.1002/art.20311",
language = "English (US)",
volume = "50",
pages = "1740--1751",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Lymphoma in rheumatoid arthritis

T2 - The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients

AU - Wolfe, Frederick

AU - Michaud, Kaleb

PY - 2004/6/1

Y1 - 2004/6/1

N2 - Objective. The risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTx) and anti-tumor necrosis factor (anti-TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA. Methods. We prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma eases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort. Results. The overall SIR for lymphoma was 1.9 (95% confidence interval [95% CI] 1.3-2.7). The SIR for biologic use was 2.9 (95% CI 1.7-4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95% CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI L9-7.5). The SIR for MTX was 1.7 (95% CI 0.9-3.2), and was 1.0 (95% CI 0.4-2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education. Conclusion. Lymphomas are increased in RA. Although the SIR is greatest for anti-TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti-TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.

AB - Objective. The risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTx) and anti-tumor necrosis factor (anti-TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA. Methods. We prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma eases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort. Results. The overall SIR for lymphoma was 1.9 (95% confidence interval [95% CI] 1.3-2.7). The SIR for biologic use was 2.9 (95% CI 1.7-4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95% CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI L9-7.5). The SIR for MTX was 1.7 (95% CI 0.9-3.2), and was 1.0 (95% CI 0.4-2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education. Conclusion. Lymphomas are increased in RA. Although the SIR is greatest for anti-TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti-TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.

UR - http://www.scopus.com/inward/record.url?scp=2642554059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642554059&partnerID=8YFLogxK

U2 - 10.1002/art.20311

DO - 10.1002/art.20311

M3 - Article

C2 - 15188349

AN - SCOPUS:2642554059

VL - 50

SP - 1740

EP - 1751

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 6

ER -