Background As treatments for rheumatoid arthritis (RA) such as methotrexate (MTX) and biological agents have made dramatic progress in this decade, it is desirable to improve patient quality of life and prognosis, including management of various comorbidities. Malignancy is an important comorbidity in patients with RA1,2. No significant difference in the overall incidence of malignancies in Japanese patients with RA (standardized incidence ratio [SIR] 0.96, 95% confidence interval [CI] 0.90–1.03) was noted compared with the general Japanese population3. However, a markedly significant increase in the incidence of malignant lymphoma was observed (SIR 5.10, 95% CI 4.21–6.13), and the incidence of lung cancer in males was also increased significantly3. In contrast, the incidence of gastric cancer and colorectal cancer was decreased significantly3. It is important to investigate the risk factors for malignancies to examine the prognosis of patients with RA.
Objectives To investigate the risk factors for overall and site-specific malignancies in a large observational cohort of Japanese patients with RA over a long-term period.
Methods Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from April 2000 to September 2013, all malignancies were extracted from patients' self-reporting and confirmed by medical records. Patients who dropped out of the IORRA cohort were asked about comorbidities, including malignancies, by follow-up mail. With regard to overall malignancies and malignancies at frequently involved sites (lung cancer, malignant lymphoma, breast cancer, gastric cancer and colorectal cancer), risk factors were analysed with time-dependent Cox regression adjusted by age, gender, smoking history and BMI.
Results Among 11,106 Japanese patients with RA representing 122,706 person-years, a total of 830 overall malignancies, including 114 lung cancers, 114 malignant lymphomas, 105 breast cancers, 95 gastric cancers and 90 colorectal cancers, were confirmed. RA disease duration was a significant risk factor for lung cancer (hazard ratio [HR] 0.95, P =0.001) and malignant lymphoma (HR 0.95, P =0.004). RF positivity was a significant risk factor for lung cancer (HR 2.26, P =0.018). DAS28 score was a significant risk factor for overall malignancies (HR 1.10, P =0.008), lung cancer (HR 1.25, P =0.012) and malignant lymphoma (HR 1.22, P =0.049). Neither MTX nor biological agent use was a significant risk factor for overall malignancies or malignancies at specific sites.
Conclusions Higher disease activity was a risk factor for overall malignancies, lung cancer and malignant lymphoma in Japanese patients with RA. However, treatment with MTX and biological agents was not a risk factor for malignancy. These results suggest that tight control of RA disease activity would protect against the occurrence of malignancies in patients with RA.
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Disclosure of Interest N. Sugimoto: None declared, E. Tanaka Speakers bureau: ET has received speaker fees or consulting fees from Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Santen Pharmaceutical., E. Inoue: None declared, Y. Shimizu: None declared, K. Shidara: None declared, A. Nakajima: None declared, A. Taniguchi: None declared, S. Momohara Speakers bureau: SM has received speaker fees from Abbott, AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Mitsubishi Tanabe, Pfizer, Takeda, and Teijin., H. Yamanaka Speakers bureau: HY has received speaker fees from Abbott, AbbVie, Asahikasei, Astellas, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taishotoyama, Takeda, and Teijin.