ORAL Surveillance post-marketing safety study of Xeljanz fails to meet endpoints in rheumatoid arthritis.- Pfizer

Pfizer announced co-primary endpoint results from a recently completed post-marketing required safety study, ORAL Surveillance (A3921133; NCT02092467) of Xeljanz (tofacitinib) in rheumatoid arthritis (RA). The primary objective of this study was to evaluate the safety of tofacitinib at two doses (5 mg twice daily and 10 mg twice daily) versus a TNF inhibitor (TNFi) in subjects with rheumatoid arthritis who were 50 years of age or older and had at least one additional cardiovascular (CV) risk factor. The co-primary endpoints of this study were non-inferiority of tofacitinib compared to TNFi in regard to major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer (NMSC)). Results showed that for these co-primary endpoints, the prespecified non-inferiority criteria were not met for the primary comparison of the combined tofacitinib doses to TNFi. Based on the prespecified secondary comparisons, there was no evidence of a difference in the primary endpoints between the two tofacitinib treatment groups. The study included 4,362 subjects who received study treatments. The primary analyses included 135 subjects with MACE and 164 subjects with malignancies (excluding NMSC). For tofacitinib, the most frequently reported MACE was myocardial infarction and the most frequently reported malignancy (excluding NMSC) was lung cancer. In those subjects with a higher prevalence of known risk factors for MACE and malignancy (e.g., older age, smoking), a higher occurrence of events was seen across all treatment groups.