Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The incidence of non-melanoma skin cancer (NMSC) in the tofacitinib RA program was evaluated using data from randomized Phase (P) 1, 2, 3, and open-label long-term extension (LTE) studies (P1P2P3LTE studies).

Methods: NMSC data (cut-off date: August 30, 2013) were pooled from two P1, eight P2, six P3, and two LTE studies; LTE data collection and analyses are ongoing; study databases have not yet been locked. Patients in P1, P3 and LTE studies were treated with tofacitinib 5 mg or 10 mg twice daily (BID) either as monotherapy or with background disease-modifying antirheumatic drugs (DMARDs). LTE patients rolled over from qualifying P1, P2, and P3 studies; patients from P2 studies were treated with tofacitinib 1 to 30 mg BID or 20 mg once daily. Incidence rates per 100 patient-years (py) of exposure (IRs) for first new NMSC were calculated for combined doses (all doses) of tofacitinib in the P1P2P3LTE patient population. The overall NMSC IR was analyzed as well as IRs for subgroup analyses according to the following conditions: dose of tofacitinib (5 mg vs 10 mg); tofacitinib monotherapy vs tofacitinib + background DMARDs; previous treatment with tumor necrosis factor inhibitors (TNFi); age of patients (≥65 vs <65); ethnic background; and time period.

Results: A total of 6,092 tofacitinib-treated patients (representing 15,103 py of exposure) received tofacitinib (all doses) in the P1P2P3LTE studies. One or more events of NMSC occurred in 83 patients receiving tofacitinib (all doses). Of these 83, squamous cell carcinomas (SCC) occurred in 39 patients, and basal cell carcinomas (BCC) occurred in 52 patients. A total of five patients had a history of NMSC prior to tofacitinib exposure compared with 78 patients who did not. In the whole P1P2P3LTE population, the IR for NMSC overall was 0.55 (95% confidence interval [CI] 0.45, 0.69); the IRs for SCC and BCC were 0.26 (0.19, 0.35) and 0.35 (0.26, 0.45), respectively. The IRs for patients from the P1/2/3 and LTE cohorts receiving tofacitinib 5 mg BID were 0.61 (0.34, 1.10) and 0.41 (0.26, 0.66), respectively; for patients receiving tofacitinib 10 mg BID, the IRs were 0.47 (0.24, 0.90) and 0.79 (0.60, 1.05), respectively. Patients on background DMARDs had a numerically higher IR (IR 0.64, 95% CI 0.49, 0.84) than patients on tofacitinib monotherapy (IR 0.43, 95% CI 0.30, 0.64). There was a higher rate of NMSC in patients previously treated with TNFi (IR 1.01, 95% CI 0.67, 1.51) vs TNFi-naïve patients (IR 0.47, 95% CI 0.37, 0.61). Patients ≥65 years old had a higher rate of NMSC (IR 1.67, 95% CI 1.19, 2.35) vs patients <65 years old (IR 0.38, 95% CI 0.29, 0.51). Patients of White ethnicity had the highest IR of NMSC vs patients of Asian, Black, or Other ethnicity (0.86 vs 0.03, 0.00, or 0.14). The IRs for NMSC, analyzed in 6-month intervals (through >42 months), were stable over time.

Conclusion: The overall IR for NMSC in the tofacitinib clinical development program remained stable over time. The NMSC IRs appear to be consistent with published estimates in patients with RA treated with TNFi (IR 0.22-0.66).¹

   1.   Askling J et al.  Pharmacoepidemiol Drug Saf 2011; 20: 119-130.