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Potential role of inflammation in cardiovascular comorbidity

Presented by
Dr Alexander Egeberg, Herlev and Gentofte Hospital, Denmark
Conference
WPPAC 2021
Trial
Phase 3, CANTOS, CIRT
Systemic inflammation appears to play a role in psoriasis comorbidities. However, the magnitude of this effect remains unclear. Bias and residual confounding are major limiting factors in many existing studies in patients with psoriasis. Dr Alexander Egeberg (Herlev and Gentofte Hospital, Denmark) discussed the association between psoriasis and cardiovascular comorbidities.

Systemic inflammation in psoriasis shows similarities with the inflammation observed in cardiovascular disease, specifically related to atherosclerosis; for example, the role of the IL-23/Th17 pathway [1,2]. “An interesting question is whether we can prevent this by treatment of psoriasis,” Prof. Egeberg suggested.
Negative studies

The CANTOS study (NCT01327846) evaluated whether the treatment of inflammation, independent of psoriatic disease, could lower the risk of cardiovascular disease [3]. Approximately 10,000 patients with a high cardiovascular risk were randomised to either canakinumab, a therapeutic monoclonal antibody targeting IL-1β, or placebo. After 5 years, a small effect was observed (HR 0.86; P=0.031).

The phase 3 CIRT trial (NCT01594333) was a similar study that randomised patients with high cardiovascular risk to either low-dose methotrexate or placebo [4]. This study was terminated early because no trend or effect was observed after 4 years (HR 1.01; P=0.91). “So, treatment with methotrexate in patients without inflammatory disease does not appear to reduce the cardiovascular risk,” Prof. Egeberg argued.

In patients with psoriasis, treatment with either placebo, the TNF inhibitor adalimumab, or phototherapy showed no difference in cardiovascular risk or reduction of cardiovascular inflammation [5].
True effect or bias?

Dr Egeberg subsequently emphasised that we should be aware of the question whether this is a true effect or bias. “Even if there is an effect, it may be insignificant.” Although statins were associated with reduced risk of all-cause mortality, the number needed to treat (NNT) was 250 after 1–6 years. “Now, assume that biologics are equally as cardioprotective as statins, what we need to know is not only the NNT but also the number needed to harm,” Prof. Egeberg stressed [6,7]. Data on the effect of established psoriasis therapies remains inconclusive. Even if there is a benefit of established psoriasis therapies, the NNT would be high, and the risk-benefit ratio favours established cardiovascular risk reduction strategies.

  1. Egeberg A. Potential for prevention of comorbidity. 6th World Psoriasis & Psoriatic Arthritis Conference, 30 June–3 July 2021.
  2. Egeberg A, et al. J Eur Acad Dermatol Venereol. 2020;34:1695–706.
  3. Ridker PM, et al. N Engl J Med. 2017;377:1119–31.
  4. Ridker PM, et al. N Engl J Med. 2019;380:752–62.
  5. Mehta NN, et al. Circ Cardiovasc Imaging. 2018;11:e007394.
  6. Bissonnette R, et al. Br J Dermatol. 2017 Oct;177(4):1033–42.
  7. Langley RG, et al. Br J Dermatol. 2015;172:1371–83.

 

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