Commentary: Coronavirus disease 2019 (COVID‐19)‐associated hospitalization and mortality in patients with psoriasis: A population‐based study

COMMENTARY

The safety of treatment for immune-mediated diseases like psoriasis during the COVID-19 pandemic is a matter of concern. In an Israeli population-based nested case-control study using the Clalit Health Services database, 3,151 patients with psoriasis that tested positive for SARS-CoV-2 infection were identified. Of these, 332 (10.5%) were hospitalized due to COVID-19, with 51 (1.6%) dying of the disease. The adjusted odds ratio (OR) for hospitalization from COVID-19 in oral methotrexate users (n. 44) was 2.30 (95% CI, 1.11-4.78), while biologic drug users (n. 74) had an OR of 0.75 (95% CI, 0.32- 1.73). No association was documented for COVID-19 mortality. Older age, comorbid cardiovascular diseases, metabolic syndrome, chronic obstructive pulmonary disease, and chronic renal failure independently predicted COVID-19-associated hospitalization and mortality. These results are at variance with data from other studies, such as a population-based Danish study (Nørgård BM et al. Br J Clin Pharmacol. 2021;87:2111–2120) showing, in multivariate analysis, no increased risk of hospitalization for COVID-19 in patients treated with methotrexate (n = 17,977), anti-TNF-α agents (n = 17,857), and anti-interleukin therapeutic agents (n = 3744), compared to the rest of the Danish population.

It is unclear if methotrexate, by means different from oral intake, was considered in the Israeli study. Moreover, the restriction of the Israeli study to SARS-CoV-2 infected patients does not allow evaluation of the rate of infection in different treatment groups. Among SARS-CoV-2 infected patients, more patients were treated with biologics than by methotrexate. I wonder if these proportions reflect the proportion of drug use in the underlying psoriasis population at large. Finally, the exposure to drugs in clinical practice is not a random process, and variables affecting prescription may also be linked to specific outcomes of interest. For example, socioeconomic factors may be related to both methotrexate prescription and COVID-19 outcome.

Methotrexate is a popular and long-used drug in psoriasis treatment. In systematic reviews, methotrexate has not been previously shown to increase the risk of severe infections and viral infections in psoriasis (J Clin Med. 2019; 8:15). Interestingly, methotrexate induces the generation of adenosine, which has been shown to inhibit lung inflammation in experimental models and to mitigate the expression of angiotensin-converting enzyme 2 (ACE2) in epithelial cells. There are reports of patients treated with methotrexate who remained healthy despite prolonged, close contact to SARS-CoV-2- infected individuals (Schälter et al. Arthritis Res Ther 2021, 23:166). On the other hand, methotrexate may not inhibit the hyper-inflammatory response in infected patients.

All in all, the impact of methotrexate exposure during the COVID-19 pandemic remains to be precisely defined. At this stage, in my opinion, no modifications in the management strategies are advisable, while intensive surveillance and structured data collection are advocated.