Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we evaluated the cardiovascular (CV) event rates and changes in blood pressure (BP) in the tofacitinib Phase 3 (P3) and long-term open-label extension (LTE) studies up to March 29, 2011. These data were presented previously.¹

Methods: Five P3 studies in patients (pts) with inadequate response to nonbiologic/biologic disease-modifying anti-rheumatic drugs (DMARDs) and 2 LTE studies were included. Tofacitinib was administered as monotherapy or with background nonbiologic DMARDs, predominantly methotrexate. One P3 study included adalimumab (ADA) as active control. An independent CV Safety Endpoint Adjudication Committee performed blinded adjudication of deaths, potential major adverse CV events (MACE), and events of congestive heart failure (CHF). MACE was defined as CV death and non-fatal CV events.

Results:

MACE IRs (per 100 pt-y) in placebo (PBO) and tofacitinib groups in P3 were low. IR in the LTE studies in the tofacitinib All Dose group (0.19) was lower than in P3 (0.57). IRs of CHF in tofacitinib groups were low. In P3, mean changes from baseline at Month 3 for systolic and diastolic BP, respectively, were 0.1 mmHg and -0.8 mmHg for PBO and -0.2 and 0.3 mmHg for tofacitinib. Mean BP changes at Months 6 and 12 and in the LTE studies remained stable.

Conclusion: Incidence rates of MACE were similar across groups in P3 with lower rates in LTE, suggesting no increased risk over 3 years of follow up. Tofacitinib was not associated with clinically meaningful increases in BP. Although the number of events has been few and longer observation periods are warranted, CV risk does not appear to be increased with tofacitinib treatment, and rates of CV events are consistent with those observed among patients with RA of similar disease severity.^2-4

References:

1. Charles-Schoeman et al. Ann Rheum Dis 2012; 71(Suppl. 3): 201.

2. Solomon DH et al. Circulation 2003; 107: 1303-1307.

3. Solomon DH et al. Ann Rheum Dis 2006; 65: 1608-1612.

4. Nicola PJ et al. Arthritis Rheum 2006; 54: 60-67.