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Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis

One-paragraph summary

ORAL Surveillance randomized 4,362 patients aged ≥50 with active RA and at least one additional cardiovascular risk factor to tofacitinib 5 mg twice daily, 10 mg twice daily, or a TNF inhibitor. Tofacitinib did not meet prespecified noninferiority criteria versus TNF inhibition for major adverse cardiovascular events or malignancy excluding nonmelanoma skin cancer (PMID 35081280; ClinicalTrials.gov NCT02092467, live-verified 2026-08-30).

Key findings

  • The comparator was active TNF inhibition, not placebo or untreated disease.
  • The population was deliberately enriched for cardiovascular risk.
  • Both relative and absolute risk depend on baseline risk.
  • Findings changed warnings and JAK-inhibitor positioning.

Limitations

  • Direct transport to young, never-smoking, low-risk patients is uncertain.
  • The trial establishes a tofacitinib comparison most directly; class extrapolation requires judgment.
  • Open-label treatment can affect non-objective outcomes, though endpoints were adjudicated.

Why it matters

This is the pivotal example of a postauthorization active-comparator safety trial overturning assumptions drawn from shorter registration programs.

Cited by wiki pages

  • overview
  • JAK inhibitors
  • extra-articular disease
  • guidelines
  • red flags and safety