medwireNews: Study findings support a move to assess cardiovascular (CV) risk and monitor for malignancies in patients with psoriatic arthritis (PsA) and psoriasis taking the Janus kinase inhibitor tofacitinib.
This is based on a post-hoc analysis, presented at the EULAR 2022 Congress in Copenhagen, Denmark, showing a relationship between patients’ CV risk at the time they start taking tofacitinib and the incidence of major adverse cardiovascular events (MACE) and malignancies.
The analysis included data from trials of at least one dose of tofacitinib 5 or 10 mg twice daily in 783 patients with PsA (three trials; phase 3 plus one long-term safety extension study) and 3663 with psoriasis (seven trials; phase 2 or 3 plus one long-term safety extension study).
Reporting the findings, Lars Kristensen (Copenhagen University Hospital) pointed out that “despite having all these many trials, tofacitinib exposure was still limited.” The total exposure was 2038 patient–years for patients with PsA and 8950 patient–years for those with psoriasis, with median exposures of 3.0 and 2.4 years, respectively.
The incidence rates for MACE and malignancies were calculated based on whether the participants had metabolic syndrome (determined post-hoc) or a history of coronary artery disease at baseline and, if they had neither of these, their 10-year risk for atherosclerotic CV disease (ASCVD), which classified them as being high risk (at least 20%), intermediate risk (7.5 to 19.9%), borderline risk (5.0 to 7.4%), or low risk (below 5.0%).
Among the patients with PsA, 39 (5%) had a history of coronary artery disease and nearly half had metabolic syndrome. And the 10-year risk for ASCVD was high in 35, intermediate in 121, borderline in 91, and low in 467.
Kristensen commented that there was a “nice dose–response relationship,” between 10-year ASCVD risk and MACE (composite of myocardial infarction, stroke, and CV death) incidence rates, which rose from 0.1 per 100 person–years in those at low risk to 1.3 per 100 person–years in those at high risk. MACE incidence rates were also high (1.0) in people with a history of coronary artery disease..
The presence of metabolic syndrome was also associated with a slightly higher incidence of MACE, at an incidence of 0.6 versus 0.1 in patients without the syndrome.
The pattern of findings was the same for the patients with psoriasis, with an increasing incidence rate with greater background CV risk.
Moving on to the risk for malignancies, Kristensen commented that the picture is a “bit more blurry […] because we have very low numbers of malignancies, including nonmelanomic skin cancers – which is of course reassuring for this patient population.”
Incidence rates were highest in patients who had intermediate and high 10-year risks for ASCVD, at a corresponding 2.5 and 1.3 per 100 person–years in patients with PsA and 1.3 and 3.6 per 100 person–years in those with psoriasis, but there was no “clear dose–response relationship,” said Kristensen. Among patients with PsA, the incidence rates in those at high risk for ASCVD were numerically higher than rates for patients with psoriasis.
Kristensen reflected on some of the limitations of the trials, including the low numbers of MACE and malignancy events and the low total tofacitinib exposure, particularly in the PsA patients.
Nevertheless, he said the findings stress the need to “look beyond the disease targets – the skin and the joints. We should also care about comorbidities, and especially cardiovascular comorbidities.”
Kristensen continued: “These patients do actually get cardiovascular disease and it is a problem.”
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