The co-primary endpoint results from a recently completed post-marketing required safety study, ORAL Surveillance were presented.
The primary objective of this study was to evaluate the safety of Tofacitinib ( Xeljanz ) 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 risk factor.
The co-primary endpoints of this study were non-inferiority of Tofacitinib compared to TNF inhibitor in regard to major adverse cardiovascular events ( MACE ) and malignancies ( excluding non-melanoma skin cancer [ NMSC ] ).
Results have shown that for these co-primary endpoints, the prespecified non-inferiority criteria were not met for the primary comparison of the combined Tofacitinib doses to TNF inhibitor.
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 has included 4,362 patients.
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.
adjudicated MACE: hazard ratio for Tofacitinib versus TNFi: Tofacitinib 5 mg BID: HR=1.24; Tofacitinib 10 mg BID: HR=1.43;
adjudicated malignancies excluding NMSC: hazard ratio for Tofacitinib versus TNFi: Tofacitinib 5 mg BID: HR=1.47; Tofacitinib 10 mg BID: HR=1.48
Full study results, beyond the co-primary endpoints ( including, but not limited to, secondary endpoints such as pulmonary embolism and mortality as well as efficacy data ), are not yet available.
Xeljanz is approved in the U.S. in four indications: adults with moderately to severely active rheumatoid arthritis after Methotrexate failure, adults with active psoriatic arthritis after disease modifying antirheumatic drug ( DMARD ) failure, adults with moderately to severely active ulcerative colitis after tumor necrosis factor inhibitor failure, and patients 2 years of age or older with active polyarticular course juvenile idiopathic arthritis ( pcJIA ). ( Xagena )
Source: Pfizer, 2021