27 January 2021 - - US-based pharmaceutical company Pfizer Inc. (NYSE: PFE) has released co-primary endpoint results from a recently completed post-marketing required safety study, ORAL Surveillance (A3921133; NCT02092467).

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 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 TNFi in regard to major adverse cardiovascular events and malignancies (excluding non-melanoma skin cancer).

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.

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.

Pfizer is working with the US Food and Drug Administration and other regulatory agencies to review the full results and analyses as they become available.

In contrast to previous tofacitinib studies, ORAL Surveillance was specifically designed to assess the risk of CV events and malignancies, and therefore subjects were required to be 50 years of age or older and have at least one additional CV risk factor at screening.

All subjects in this study were also required to be treated with background methotrexate to be eligible for enrollment.

Xeljanz (tofacitinib) is approved in the US 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).

Xeljanz has been studied in more than 50 clinical trials worldwide and prescribed to over 208,000 adult patients (the majority of whom were RA patients) worldwide in the last eight years.

As the developer of tofacitinib, Pfizer is committed to advancing the science of JAK inhibition and enhancing understanding of tofacitinib through robust clinical development programs in the treatment of immune-mediated inflammatory conditions.

Xeljanz/Xeljanz XR (tofacitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.

Limitations of Use: Use of Xeljanz/Xeljanz XR in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Xeljanz/Xeljanz XR (tofacitinib) is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).