Psoriasis treatment: no elevation of MACE and VTE on deucravacitinib

In a special analysis of safety data from phase 3 trials on deucravacitinib, increased frequency of major cardiovascular events (MACE) or venous thromboembolism (VTE) was not found compared with apremilast therapy. Even though many participants had an elevated cardiovascular (CV) risk at baseline, event rates were low and constant over longer drug exposure.

As the diagnosis of psoriasis has been linked to an increased risk of MACE and thromboembolic events, knowledge about a potential further increase of risk through anti-inflammatory medication is important [1,2]. In this context, Prof. Mark Lebwohl (Icahn School of Medicine at Mount Sinai, NY, USA) and colleagues investigated exposure-adjusted incidence rates of MACE and VTE in the treatment of psoriasis with the TYK2 inhibitor deucravacitinib [1]. The analysis was performed on data from the phase 3 POETYK PSO-1 and PSO-2 studies (NCT03624127 and NCT03611751), evaluating deucravacitinib against placebo and apremilast. After week 16, >95% of the participants in both trials continued on deucravacitinib until week 52 in a long-term extension study (NCT04036435). MACE were defined as non-fatal myocardial infarction or stroke, as well as CV death, and VTE comprised pulmonary embolism and deep vein thrombosis. Pooled data of all 3 trials with analysis cut-off in June 2021 included 2,166.9 deucravacitinib person-years (PY) and a median exposure time of 588 days.

The baseline characteristics of PSO-1 and PSO-2 demonstrated 31.3% hypertensive, 11.3% obese, 10.4% hyperlipidemic, and 10.3% diabetic participants. Adverse events up to week 16 were mostly mild to moderate and comparable among the study arms. However, adverse events involving drug discontinuation varied: the exposure-adjusted incidence rates were 17.9/100 PY for apremilast, 13.2/100 PY for placebo, and 8.0/100 PY for deucravacitinib. The corresponding exposure-adjusted incidence rates for weeks 0–52 were 11.6/100 PY, 9.3/100 PY, and 4.4/100 PY, for apremilast, placebo, and deucravacitinib, respectively. Nasopharyngitis and upper respiratory infection were the most common adverse events on deucravacitinib, while headache and diarrhoea were the most frequent on apremilast. MACE by adjudication through an external CV committee also varied according to therapy. In the 1-year safety pool, the placebo arm’s incidence amounted to 1.2 exposure-adjusted incidence rates/100 PY, compared with 0.9 exposure-adjusted incidence rates/100 PY with apremilast and 0.3 exposure-adjusted incidence rates/100 PY on deucravacitinib. In terms of VTE from weeks 0–52, the rate among deucravacitinib-treated participants was 0.1 exposure-adjusted incidence rates/100 PY.

The investigators concluded that despite the high proportion of participants with baseline CV risk factors, MACE and VTE were low overall and did not increase with a longer duration of deucravacitinib treatment. Thus, in their opinion, deucravacitinib treatment has a favourable safety profile.

1. Lebwohl M, et al. Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor: major adverse cardiovascular events (MACE) and venous thromboembolic events (VTEs) in the phase 3 POETYK PSO-1, PSO‑2, and long-term extension (LTE) trials. P078, SPIN 2022 Congress, 06–08 July, Paris, France.
2. Chen TL, et al. JAMA Dermatol. 2022;158:59-67.

 

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Posted on 26 August, 202229 February, 2024