Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program
Analysis of 19 studies involving the use of tofacitinib to treat RA showed that lymphoma incidence rate and type were consistent with expectations in the RA population as a whole, and did not increase with tofacitinib exposure time.
Previous research has suggested that there is a link between the likelihood of developing malignant tumours and RA. Previously, it has been unclear whether the increased rates seen are due to the use of immunomodulatory therapies, such as tofacitinib, which are used as a treatment, or whether a side effect of carrying the disease. Tofacitinib is a JAK inhibitor and a treatment for RA; it was, therefore, anticipated that there may be a difference in the number of cases of lymphoma in patients in the control and treatment groups.
This study analysed the data from 6194 patients from 19 studies (Phase 1, 2, 3 and long-term extension studies) that used tofacitinib as a treatment for RA. Incidence rates (IRs) and standardised incidence ratios (SIR) were calculated, and a descriptive case-matched control analysis (1:4) performed to identify potential risk factors for lymphoma. Nineteen lymphomas occurred with IR 0.10 (95% CI: 0.06, 0.15). EBV was tested in 13 cases; 3 were positive for EBV association.
Incidence rates were stable over time, and SIRs were within the range seen in clinical studies of biologic therapies. Baseline characteristics of patients with lymphoma were similar to those in the control groups.
Patients in clinical trials are normally receiving or have previously received some kind of immunomodulatory therapy for RA. Despite the difficulty this presents, it is important to continue to evaluate clinical trials and population-based observational research to try to determine the relative contribution of immunosuppressant therapies and underlying disease pathogeneisis to lymphoma risk.