Tofacitinib Safety and Effectiveness in Canadian Patients with Rheumatoid Arthritis by Cardiovascular Risk...

Area of Science:

• Rheumatology
• Pharmacology
• Cardiovascular Medicine

Background:

• ORAL Surveillance indicated increased risks of major adverse cardiovascular events (MACE) and malignancies with tofacitinib versus TNF inhibitors in rheumatoid arthritis (RA).
• This study evaluated tofacitinib safety and effectiveness in a real-world Canadian cohort, stratified by cardiovascular (CV) risk criteria.

Purpose of the Study:

• To assess the safety and effectiveness of tofacitinib in RA patients with and without enriched cardiovascular risk.
• To compare tofacitinib's safety profile and treatment persistence across different CV risk strata.

Main Methods:

• A real-world observational study (CANTORAL) included 504 RA patients initiating tofacitinib.
• Patients were stratified into CV risk-enriched (CV+) and not CV risk-enriched (CV-) cohorts.
• Safety, persistence (up to 36 months), and effectiveness (up to 18 months) were evaluated using standard clinical endpoints.

Main Results:

• Adverse events were more frequent in the CV+ cohort (138.5/100 PY) compared to the CV- cohort (112.5/100 PY).
• Higher rates of serious AEs, deaths, serious infections, and malignancies were observed in the CV+ group.
• Tofacitinib demonstrated comparable effectiveness (CDAI LDA/remission, DAS28-CRP <3.2/<2.6) and persistence between the CV+ and CV- cohorts.

Conclusions:

• Adverse events, particularly in older patients (≥65 years), were more common in the CV risk-enriched RA population treated with tofacitinib.
• Tofacitinib's effectiveness and persistence were similar across CV risk strata.
• Individualized benefit-risk assessment, including CV risk management, is crucial for optimizing RA treatment outcomes.