FRI0151 Incidence Rates of Skin Cancers During Exposure to Intravenous and Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: Results from Pooled Clinical Trial Data
Authors: T.A. Simon, C. Poncet, M. Hochberg, M. Boers
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> TNF inhibitors may increase the risk of melanoma in patients with RA.<sup>1</sup> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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,<sup>2</sup> and two Phase II and six Phase III trials with IV abatacept.<sup>3</sup> 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. <h3>Results</h3> 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 &gt;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.<sup>3</sup> 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). <h3>Conclusions</h3> Based on cumulative IV and SC abatacept clinical trial data, including nearly 17,000 total pt-years and &gt;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. <h3>References</h3> Ramiro S et al. Ann Rheum Dis 2014;73:529–35. Alten R et al. Arthritis Rheumatol 2014;66:1987–97. Weinblatt M et al. J Rheumatol 2013;40:787–97. <h3>Disclosure of Interest</h3> 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