Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).
Objectives An evaluation of malignancies in the tofacitinib RA programme from the Phase (P) 2, P3, and long-term extension (LTE) studies based on data up to April 2013.
Methods Data were pooled from 6 P2 and 6 P3 randomised studies and 2 open-label LTE studies (ongoing at time of analysis; databases not locked). Patients (pts) in P3 and LTE studies (LTE pts rolled over from the P2 and P3 studies) were treated with tofacitinib 5 or 10 mg twice daily (BID); P2 included additional doses.
Results A total of 5,671 pts (12,664 pt-yrs) received tofacitinib in the P2, P3 and LTE studies. 107 receiving tofacitinib (all doses) reported malignancies (excluding non-melanoma skin cancer [NMSC]); the most common types were lung and breast cancer. There were 10 lymphoma cases. The overall incidence rate (IR, events per 100 pt-yrs) for all malignancies (excluding NMSC) and lymphomas were 0.85 (95% CI: 0.70, 1.02) and 0.08 (0.04, 0.14), respectively. The IRs (95% CI) for all malignancies (excluding NMSC) for P3 were 0.55 (0.27, 1.09) for 5 mg BID and 0.87 (0.50, 1.49) for 10 mg BID. In the LTE the IRs were 1.02 (0.75, 1.39) for 5 mg BID and 0.81 (0.60, 1.10) for 10 mg BID. The IRs (95% CI) for all malignancies (excluding NMSC) broken down into 0–6, 6–12, 12–18, 18–24, 24–30, 30–36, 36–42, and >42 months based on exposure to study drug were 0.70 (0.44, 1.11), 0.66 (0.40, 1.10), 0.94 (0.59, 1.49), 1.04 (0.64, 1.67), 0.83 (0.47, 1.46), 1.00 (0.57, 1.76), 0.79 (0.36, 1.76), and 1.04 (0.54, 2.0), respectively. The standardised incidence ratios (SIRs) (95% CI) (as compared with the US Surveillance Epidemiology and End Result database) for all malignancies (excluding NMSC) and lymphomas were 1.08 (0.89, 1.31) and 2.58 (1.24, 4.74), respectively. The SIRs (95% CI) for lung and breast cancer were 1.91 (1.22, 2.84) and 0.77 (0.46, 1.20), respectively. Overall, 66 pts experienced NMSCs, for an IR of 0.53 (95% CI 0.41, 0.67). The IRs (95% CI) for NMSC in P3 were 0.41 (0.19, 0.92) for 5 mg BID and 0.53 (0.27, 1.07) for 10 mg BID. In the LTE studies the IRs were 0.35 (0.21, 0.59) for 5 mg BID and 0.84 (0.62, 1.13) for 10 mg BID. By comparison, the IR of NMSC in pts treated with anti-TNF was 0.47 in a meta-analysis of randomised controlled trials  and ranged from 0.23–0.35 in a meta-analysis of registries .
Conclusions The malignancies that occurred in the tofacitinib RA programme, including more than 12,000 pt-yrs of drug exposure, are consistent with the type and distribution of malignancies expected for pts with moderately to severely active RA. The IRs for all malignancies (excluding NMSC), lung cancer, breast cancer, and lymphomas are stable over time and consistent with published estimates in RA pts treated with biologic and non-biologic DMARDs [3–6].
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Acknowledgements This study was sponsored by Pfizer Inc. Pfizer personnel were involved in protocol development and data analysis. Editorial assistance was provided by Claire Cridland, of Complete Medical Communications and funded by Pfizer Inc.
Disclosure of Interest : X. Mariette Grant/research support: Pfizer Inc, J. Curtis Grant/research support: Pfizer Inc, Consultant for: Pfizer Inc, E. Lee Consultant for: Pfizer Inc, B. Benda Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, I. Kaplan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Riese Shareholder of: Pfizer Inc, Employee of: Pfizer Inc
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