Background Rheumatoid arthritis (RA) is associated with an increased incidence of malignancy compared to the general population. The long term safety of biologic therapies continues to be defined. Clinical trials of rituximab in the treatment of RA report an incident malignancy rate of 0.74 per 100 person years.1
Objectives To describe the frequency and characteristics of incident malignancies in a real-world, observational cohort of rheumatoid arthritis (RA) patients initiating rituximab in the United States.
Methods The Prospective Study of the Safety of Rituximab in Patients With Rheumatoid Arthritis After an Inadequate Response to Previous Anti-TNF Therapy (SUNSTONE) recruited patients from January 2007 to October 2008 from 173 private and academic practices across 38 states within the United States and Puerto Rico, with more than 350 rheumatologists contributing data. Included subjects were age 18 or greater with a diagnosis of RA and inadequate response to anti-tumor necrosis factor-α therapy (TNF-IR). Enrollment occurred at the time of treatment initiation with rituximab. Subjects were followed for 5 years or until death or loss to follow-up. Targeted safety events including malignancies were reported at follow up visits occurring at least every 6 months. Nonmelanoma skin cancers and non-malignant events were excluded. Standardized incidence rate (SIR) was calculated using the US National Cancer Institute Surveillance Epidemiology and End Results (SEER) reference population and matched for age and sex.
Results 989 subjects were followed for a mean of 3.9 years and contributed 3844 person-years in total. There were 17 incident malignancies yielding an event rate of 0.44 per 100 person years (95% C.I. 0.27–0.71) and age- and sex-adjusted standardized incidence ratio (SIR) of 0.36 (95% C.I. 0.21–0.57). Malignancy diagnosis occurred a median of 22 months after rituximab initiation (range 2.6–59.3) and following a median of 2 treatment cycles (range 1–6). Lung cancer was the most common malignancy reported (n=5) followed by melanoma (n=2). Subjects diagnosed with malignancy were older (67.7 vs. 57.1 years, P<0.001) and more likely to report current or prior tobacco use (94% vs. 57%, P=0.002) than those not diagnosed with malignancy.
Conclusions At five years' follow up, the observed rate of incident malignancies in this real-world cohort of RA patients treated with rituximab is not increased compared to the background population or clinical trials.
Van vollenhoven RF, et al. J Rheumatol. 2015;42(10):1761–6.
Disclosure of Interest M. Cascino Grant/research support from: Genentech/Roche, J. Pei Employee of: Genentech/Roche, T. Haselkorn Employee of: Genentech/Roche, A. John Employee of: Genentech/Roche, A. Jahreis Employee of: Genentech/Roche, D. Furst Grant/research support from: Actelion, BMS, Celgene, Genentech/Roche, Gilead, National Institutes of Health, Novartis, UCB, Consultant for: Abbott, Actelion, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor, Genentech/Roche, Gilead, GlaxoSmithKline, National Institutes of Health, Novartis, Pfizer, UCB, Speakers bureau: Abbott, Genentech/Roche