Background The overall incidence of malignancies in patients with rheumatoid arthritis (RA) has been reported to be comparable or slightly higher than that in general population, whereas the increased incidence of malignant lymphoma has been reported to be consistent in most studies, including our previous report.1-3 However, the impact of expand use of methotrexate (MTX) and biological agents on the incidence of malignancies has not been thoroughly examined.
Objectives To examine the incidence of malignancies in a large observational cohort of Japanese patients with RA over a long-term period.
Methods The Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort is a large, single institute-based, observational cohort of RA patients established at our institute in 2000. All malignancies were extracted from the biannual self-reports of Japanese RA patients enrolled in the IORRA cohort from 2000 to 2013 and confirmed by their medical records. Patients with RA who dropped out of the IORRA were asked about comorbidities including malignancies by follow-up mail. For the overall malignancies and malignancies at each site, the standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated according to the data from the general Japanese population.
Results Data from 11,106 patients with RA (1,992 males; 9,114 females), including 122,706 person-years (19,597 males; 103,109 females), were analysed. Percentages of MTX and biologics user increased from 34.2% and 0% in 2000, respectively, to 77.5% and 19.8% in 2013, respectively, in the IORRA. A total of 830 overall malignancies were confirmed (676.4 malignancies/100,000 person-years, SIR 0.96, 95% CI 0.90-1.03). Malignant lymphoma and lung cancer were the most frequent types of malignancy (114 cases each). A significant increase in the SIR was identified for malignant lymphoma in both males (SIR 4.62, 95% CI 3.04-6.72) and females (SIR 5.27, 95% CI 4.22-6.50) and for lung cancer in males (SIR 1.36, 95% CI 1.03-1.75). A significant decrease in the SIR was identified for gastric cancer in both males (SIR 0.58, 95% CI 0.39-0.82) and females (SIR 0.77, 95% CI 0.60-0.99) and for colorectal cancer in both males (SIR 0.53, 95% CI 0.35-0.78) and females (SIR 0.56, 95% CI 0.43-0.71).
Conclusions No significant difference in the overall incidence of malignancies in Japanese patients with RA was noted compared with the general Japanese population regardless of the expand use of MTX and biological agents in this period. However, there was a significant difference in the sites of the malignancies. A marked significant increase in the incidence of malignant lymphoma in both males and females was observed.
Smitten AL, et al. Arthritis Res Ther 2008;10:R45.
Wolfe F, et al. Arthritis Rheum 2004;50:1740-51.
Yamada T, et al. Rheumatol Int 2011;31:1487-92.
Disclosure of Interest N. Sugimoto: None declared, E. Tanaka: None declared, E. Inoue: None declared, R. Yamaguchi: None declared, Y. Shimizu: None declared, A. Kobayashi: None declared, K. Shidara: None declared, D. Hoshi: None declared, A. Nakajima: None declared, A. Taniguchi Grant/research support from: Takeda, Consultant for: AbbVie, Eisai, Mitsubishi-Tanabe, and Teijin, S. Momohara Consultant for: AbbVie, Bristol-Myers-Squibb, Eisai, Mitsubishi-Tanabe, and Takeda, H. Yamanaka Grant/research support from: AbbVie, Asahikasei Pharma, Astellas, Bristol-Myers-Squibb, Chugai, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin Pharma, Consultant for: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Nihon-Kayaku, Mitsubishi-Tanabe, Pfizer, Takeda, UCB