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What Is the ORAL Surveillance Study and How Can It Be Applied to Clinical Practice?
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Join Heather Mambretti, PA-C, a rheumatology specialist in Houston, Texas, as she breaks down the key findings of the Oral Surveillance Study and discusses what they mean for clinical practice. This critical safety trial compared JAK inhibitors to TNF inhibitors in rheumatoid arthritis (RA) patients with cardiovascular risk factors, leading to significant regulatory changes by the FDA.
The Oral Surveillance Study was a randomized, open-label, non-inferiority post-authorization safety trial evaluating the safety of JAK inhibitors compared to TNF inhibitors in patients with active rheumatoid arthritis (RA) who were 50 years or older with at least one additional cardiovascular risk factor.
Patients were randomized to receive tofacitinib (5 mg or 10 mg twice daily) or a TNF inhibitor, with the primary endpoints being major adverse cardiovascular events (MACE) and cancers (excluding non-melanoma skin cancer) over a median follow-up of four years.
The study found that patients receiving tofacitinib had a higher incidence of MACE (3.4%) compared to TNF inhibitors (2.5%), with a hazard ratio of 1.33. Similarly, cancer incidence was higher (4.2%) in the tofacitinib group compared to 2.9% in the TNF inhibitor group. These findings did not meet non-inferiority criteria, raising significant safety concerns regarding JAK inhibitors.
As a result, the FDA extended these findings to all JAK inhibitors and restricted their use in RA patients only after failure of a TNF inhibitor. However, some clinicians question the external validity of the study, as it only assessed one JAK inhibitor (tofacitinib). Given differences in JAK receptor selectivity, certain JAK1-selective agents, like upadacitinib, may offer a different safety profile, but further comparative studies are needed.
Until head-to-head studies are conducted, clinicians should follow FDA guidelines, weighing the risks and benefits of JAK inhibitors carefully, particularly in older patients and those with cardiovascular risk factors.
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