Risk of Malignancies in Patients with Rheumatoid Arthritis Treated with Rituximab: Analyses of Global Postmarketing Safety Data and Long-Term Clinical Trial Data

Abstract

Introduction: Patients with rheumatoid arthritis (RA) are at an increased risk of developing malignancies, but it is unclear whether this increased risk is the result of disease pathobiology or immunosuppressant treatments for RA. This analysis evaluated the potential risk of malignancy in patients with RA treated with rituximab (MabThera Ò /Rituxan Ò) a CD20? B-cell depleting agent manufactured by F. Hoffmann-La Roche Ltd. Methods: Malignancy rates were obtained from the rituximab global company safety database for adverse event reporting and from the rituximab global clinical trial program for RA consisting of eight randomized clinical trials, two long-term open-label extensions, and one openlabel prospective study. Global company safety database searches were performed using the standard Medical Dictionary for Regulatory Activities (MedDRA) queries ''Malignant tumors wide'' and ''Skin malignant tumors wide'' up to April 30, 2017. Age-and sex-specific comparator values from the general population were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. Results: For the 409,706 patients with RA in the rituximab global company safety database since first market approval in 2006, 1739 cumulative malignant events were reported, with an overall malignancy reporting rate of approximately 4.2 events per 1000 patients. No evidence of increased risk of malignancy, of any organ-specific type, was found following rituximab treatment. The rate of malignancies from rituximab-treated patients in RA clinical trials was 7.4 per 1000 patient-years. This is within the expected range, with no evidence for increased risk over time or with additional rituximab courses.

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real‐life study

“…In other pathologies, such as neuromyelitis optica spectrum, monitoring of CD19+ and CD28+ was performed every 3 months, in order to perform infusion only if these lymphocytes were detectable [30]. This method could lead to more individualized administration of rituximab with similar efficacy and less risk of AEs.…”

“…There is no augmentation of risk of neoplasia with exposition to rituximab. The risk is estimated at 4.2 events per 1000 treated patients [29].…”

Risk of malignancy and biologic therapy in rheumatic inflammatory diseases: A single-center experience

“…[29] Other bDMARDs have been much less studied, but the data from meta-analyses and long-term extension studies showed no increased overall malignancy risk for rituximab, abatacept, and tocilizumab. [21,25,[30][31][32][33] Recently, other studies suggested that abatacept use is associated with a slight increase in skin cancer risk, both NMSC [34] and MSC. [6] In our cohort, the IR of malignancy was 3.47 per 1000 p-y, with a higher value was found in the RA subgroup (5.2 per 1000 p-y).…”

Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment

“…Meta-analysis of three clinical trials (DANCER, REFLEX and IMAGE) has demonstrated that RTX were comparable to placebo and MTX in terms of serious infections rate [ 96 , 133 ]. No increased risk of malignancies in patients treated for RA with rituximab was observed [ 134 ]. Yet, a major concern was raised on risk of reactivation of hepatitis B-virus (HBV) infection during RTX treatment compared to etanercept [ 133 ].…”