Background: The background status and the current treatment options of patients with rheumatoid arthritis (RA) who develop malignant lymphoma (ML) and other malignancies are unclear. This study investigated the differences in background factors between ML and other malignancies that occur in RA patients and post-malignancy treatment.
Methods: We identified 935 RA patients with new-onset malignancies among 110,571 person-years registered in the National Database of Rheumatic Disease in Japan from 2012 to 2018. Analysis cohorts 1 and 2 included 597 and 490 patients with available data for 1 year before and after the development of malignancies, respectively. Factors associated with the development of ML were longitudinally evaluated by multiple logistic regression analyses.
Results: Of the 935 patients (mean age 70.5, standard deviation 9.9), 15.5% had ML; this was comparable to the rate of lung cancer (14.3%). In cohort 1, methotrexate (MTX), biological disease-modifying anti-rheumatic drugs (bDMARDs), and non-steroidal anti-inflammatory drugs (NSAIDs) were used in 74.4%, 23.4%, and 56.7% of ML and in 56.8%, 25.4%, and 35.3% of other malignancies 1 year before the occurrence of malignancies. Clinical disease activity index (CDAI) and C-reactive protein were similar between the two groups. Multivariable analysis showed that MTX use (odds ratio [OR]: 2.22, 95% CI [confidence interval]: 1.32-3.73, p=0.003) and NSAID use (OR: 2.51, 95% CI: 1.58-3.98, p <0.001) were significantly associated with the development of ML versus other malignancies. However, this association was not observed with bDMARDs. In cohort 2, one year after the development of malignancies, MTX was used in none of ML and 41.8% of patients who developed other malignancies. In both malignancy groups, approximately 15% of patients received bDMARDs and 50% received glucocorticoids. IL-6 inhibitors were preferentially prescribed in patients with ML versus those with other malignancies. At year 1, CDAI remission was achieved in 37.3% and 31.1% of patients in the ML and other malignancy groups, respectively.
Conclusion: Patients receiving long-term treatment with MTX and NSAIDs may be at a relatively high risk of developing ML. The treatment landscape after developing malignancies differed considerably between patients with ML and other malignancies, and different treatment strategies should be established.
Keywords: Biological disease-modifying anti-rheumatic drugs; Malignancy; Malignant lymphoma; Methotrexate; Rheumatoid arthritis.
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