Critical appraisal of cardiovascular risk assessment in psoriasis: A response to Varghese et al.

Dear Editor,

We read with great interest the article titled “Effect of apremilast on cardiovascular risk in psoriasis patients in comparison with methotrexate” by Varghese et al.^[1] We appreciate the authors’ effort in conducting this prospective cohort study that evaluates the cardiovascular risk and efficacy of apremilast and methotrexate (MTX) in psoriasis patients over a 12-week period. Given the increasing recognition of psoriasis as a systemic disease with cardiovascular implications, we commend the authors for addressing this important issue. However, after a comprehensive discussion in our journal club, we would like to seek clarification on several aspects of the study.

First, we observed an inconsistency in the reported percentage reduction in psoriasis area and severity index (PASI) scores. The results section states that apremilast showed a greater reduction in PASI scores than MTX, whereas the discussion section suggests the opposite. We kindly request the authors to clarify this discrepancy.

Second, given that cardiovascular risk is typically evaluated over a period of 5–10 years, could the authors provide a rationale for choosing a short follow-up period of only 12 weeks? Cardiovascular risk is a cumulative process influenced by long-term inflammatory control, making a short follow-up period less conclusive for assessing meaningful cardiovascular outcomes.^[2]

In addition, there appear to be confounding factors that were not stratified or adjusted for in the analysis, including age, hypertension, body mass index, waist-hip ratio, smoking, and alcohol use. These factors could significantly impact cardiovascular risk assessment. We would appreciate clarification on whether any adjustments were made to account for these variables to minimize bias.

Regarding inflammatory markers, we noted that thromboxane B2 and high-sensitivity C-reactive protein were chosen as primary markers for cardiovascular risk. However, the exclusion of other well-established markers such as lipoprotein-associated phospholipase A2, adiponectin, lectin, systemic immune-inflammation index, and systemic inflammation response index raises questions.^[3] Could the authors provide insight into the rationale for selecting these specific markers when excluding others?

Furthermore, dosing inconsistencies may have influenced the study outcomes. Neither MTX nor apremilast was administered at optimal weight-based doses, which could have affected both drug efficacy and cardiovascular outcomes. A clarification on how dosing was determined would be valuable.

Another ambiguity lies in the reporting of thromboxane B2 levels. The results section states that 5 out of 20 patients in the MTX group had elevated levels, while the discussion suggests that 5 patients from both groups had elevated levels. A clarification on this inconsistency would be appreciated.

Finally, there is no mention of the concomitant use of topical therapies or the washout period before initiating the study drugs. Given the potential impact of topical treatments on psoriasis severity and systemic inflammation, information on this aspect would be helpful in understanding the study’s validity.

Despite these concerns, we reiterate our appreciation for the authors’ valuable contribution to expanding our understanding of psoriasis as a systemic disease with cardiovascular implications. Given the high stature and outreach of this esteemed journal, we believe that these discrepancies warrant clarification to ensure the study’s conclusions remain robust and reliable. We look forward to the authors’ response and appreciate the opportunity to engage in this academic discussion.