Biologic treatment of rheumatoid arthritis and the risk of malignancy: Analyses from a large US observational study

Frederick Wolfe, Kaleb D Michaud

Research output: Contribution to journalArticle

405 Citations (Scopus)

Abstract

Objective. Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database. Methods. We studied incident cases of cancer among 13,001 patients during ∼49,000 patient-years of observation in the years 1998-2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use. Results. Biologic exposure was 49%. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95% confidence intervals (95% CIs) compared with SEER data were as follows: all cancers 1.0 (1.0-1.1), breast 0.8 (0.6-0.9), colon 0.5 (0.4-0.6), lung 1.2 (1.0-1.4), lymphoma 1.7 (1.3-2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95% CI 1.2-1.8) and melanoma (OR 2.3, 95% CI 0.9-5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95% CI 0.8-1.2). Conclusion. Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.

Original languageEnglish (US)
Pages (from-to)2886-2895
Number of pages10
JournalArthritis and rheumatism
Volume56
Issue number9
DOIs
StatePublished - Sep 1 2007

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Observational Studies
Rheumatoid Arthritis
Biological Therapy
Neoplasms
Skin Neoplasms
Therapeutics
Confidence Intervals
Odds Ratio
Biological Products
Epidemiology
Databases
Sex Education
National Cancer Institute (U.S.)
Prednisone
Meta-Analysis
Melanoma
Lymphoma
Colon
Breast
Logistic Models

ASJC Scopus subject areas

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

Cite this

Biologic treatment of rheumatoid arthritis and the risk of malignancy : Analyses from a large US observational study. / Wolfe, Frederick; Michaud, Kaleb D.

In: Arthritis and rheumatism, Vol. 56, No. 9, 01.09.2007, p. 2886-2895.

Research output: Contribution to journalArticle

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abstract = "Objective. Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database. Methods. We studied incident cases of cancer among 13,001 patients during ∼49,000 patient-years of observation in the years 1998-2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use. Results. Biologic exposure was 49{\%}. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95{\%} confidence intervals (95{\%} CIs) compared with SEER data were as follows: all cancers 1.0 (1.0-1.1), breast 0.8 (0.6-0.9), colon 0.5 (0.4-0.6), lung 1.2 (1.0-1.4), lymphoma 1.7 (1.3-2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95{\%} CI 1.2-1.8) and melanoma (OR 2.3, 95{\%} CI 0.9-5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95{\%} CI 0.8-1.2). Conclusion. Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.",
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N2 - Objective. Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database. Methods. We studied incident cases of cancer among 13,001 patients during ∼49,000 patient-years of observation in the years 1998-2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use. Results. Biologic exposure was 49%. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95% confidence intervals (95% CIs) compared with SEER data were as follows: all cancers 1.0 (1.0-1.1), breast 0.8 (0.6-0.9), colon 0.5 (0.4-0.6), lung 1.2 (1.0-1.4), lymphoma 1.7 (1.3-2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95% CI 1.2-1.8) and melanoma (OR 2.3, 95% CI 0.9-5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95% CI 0.8-1.2). Conclusion. Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.

AB - Objective. Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database. Methods. We studied incident cases of cancer among 13,001 patients during ∼49,000 patient-years of observation in the years 1998-2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use. Results. Biologic exposure was 49%. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95% confidence intervals (95% CIs) compared with SEER data were as follows: all cancers 1.0 (1.0-1.1), breast 0.8 (0.6-0.9), colon 0.5 (0.4-0.6), lung 1.2 (1.0-1.4), lymphoma 1.7 (1.3-2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95% CI 1.2-1.8) and melanoma (OR 2.3, 95% CI 0.9-5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95% CI 0.8-1.2). Conclusion. Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.

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