Background TNF inhibitors may increase the risk of melanoma in patients with RA.1 In light of that possible association, we reviewed the clinical trial data for abatacept, a cytotoxic T lymphocyte-associated antigen-4–immunoglobulin G1 fusion protein that selectively modulates the CD80/CD86–CD28 co-stimulatory pathway required for T-cell activation.
Objectives To investigate the incidence rates (IRs) of skin cancer in IV and SC abatacept in pooled clinical trial data with 16,671 patient-years (pt-yrs) of exposure.
Methods Data were pooled from the cumulative (double-blind and open-label short-term [ST] and open-label long-term extension [LTE]) periods of 13 clinical studies, including one Phase II and four Phase III trials with SC abatacept,2 and two Phase II and six Phase III trials with IV abatacept.3 IRs and annualized IRs were calculated as events per 100 pt-yrs of exposure (Poisson 95% CI). IRs for the cumulative period were compared with IRs originally estimated from the pooled ST periods.
Results A total of 6028 patients received IV or SC abatacept during the cumulative period (IV: 4149; SC: 1879 patients), with abatacept exposure of 16,671 pt-yrs (IV: 12,132; SC: 4215 pt-yrs). Median (range) exposure was 31 (2–104) months; 1167 (19.4%) patients received abatacept for >5 yrs. In the pooled ST periods of the eight IV abatacept clinical studies, median (range) exposure was 11.7 (1.9–13.8) months.3 During the ST period, there were 19 cases of non-melanoma skin cancer (NMSC) (IR: 0.82/100 pt-yrs; 95% CI: 0.49, 1.28) in the IV abatacept group and 7 (IR: 0.82/100 pt-yrs; 95% CI: 0.33, 1.70) in the placebo group. In the ST period, there were zero cases of melanoma in the IV abatacept group, and one (IR: 0.12/100 pt-yrs; 95% CI: 0.00, 0.65) in the placebo group. During the cumulative (ST+LTE) period, 111 patients (IV+SC abatacept) experienced NMSC (IR: 0.69/100 pt-yrs; 95% CI: 0.57, 0.83) and 7 patients experienced melanomas (IR: 0.04/100 pt-yrs; 95% CI: 0.02, 0.09).The risk of NMSC and melanoma did not increase over time with increasing exposure to abatacept (Table).
Conclusions Based on cumulative IV and SC abatacept clinical trial data, including nearly 17,000 total pt-years and >30 months of average individual exposure, skin cancer IRs were similar to placebo rates in ST observations, and did not increase over time in abatacept-treated patients with RA. The incidence of melanoma continues to be within the expected range for an age- and sex-matched general population. The IRs of both melanoma and NMSC are within published ranges for an RA population. These data will continue to be updated as more abatacept exposure accrues.
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Disclosure of Interest T. A. Simon Employee of: Bristol-Myers Squibb, C. Poncet Consultant for: Bristol-Myers Squibb [full-time contractor], Employee of: DOCS, Nanterre, France, M. Hochberg Grant/research support from: NIH, Consultant for: Bristol-Myers Squibb, Eli Lilly Co., EMD Serono Inc., Genentech/Roche, Novartis Pharma AG, Pfizer Inc, UCB Inc., M. Boers Consultant for: Bristol-Myers Squibb Abatacept Safety Panel