Traditional Systemic Therapies in Pediatric Psoriasis: An International Real-World Study

While the prevalence of psoriasis is lower in children compared to adults, approximately one-third of patients report disease onset within the first two decades of life.³ The incidence and severity of pediatric psoriasis also increase with age, resulting in a growing number of children with clinical manifestations that may be inadequately controlled by topical therapies alone. Additionally, managing moderate to severe psoriasis in pediatric patients can be challenging due to the reduced number of available or approved systemic therapies, limited clinical trials compared to adults, and the need to incorporate caregivers into the shared decision-making process.

Compared to adults, pediatric patients with moderate to severe psoriasis are more commonly treated with phototherapy or traditional systemic therapies. In their ACMe (Acitretin, Cyclosporine, and Methotrexate) study, Miao et al. investigated the 2-year drug survival and comparative treatment profiles of three traditional systemic therapies widely available. They are referenced in treatment guidelines for pediatric psoriasis. Over 10 years (2014–2024), the authors retrospectively collected demographic and clinical data from > 500 pediatric psoriasis patients in 5 countries (France, Canada, Italy, the United Kingdom, and Portugal) who had received acitretin (n = 316), cyclosporine (n = 122), or methotrexate (n = 245). The authors also collected measures of disease severity (e.g., PGA and PASI scores). They obtained relevant clinical information about subsequent treatment-related events, such as dose modifications, concomitant treatments, efficacy, adverse events, and reasons for discontinuation. Efficacy was based on mean PGA and PASI scores at 3 and 6 months compared to baseline.

Patients included in this study had a mean age of 10, with more than two-thirds of patients between the ages of 2 and 12 years. The mean PGA and PASI scores at baseline were 3 and 11, respectively, which is generally consistent with those of psoriasis patients who are candidates for systemic treatment. There were no significant differences in the sex of the participants. One-third of patients were considered overweight or obese based on international definitions. Other psoriasis-associated comorbidities, such as psoriatic arthritis, neuropsychiatric disorders, diabetes, inflammatory bowel disease, and metabolic syndrome, occurred in < 5% of patients. However, the overall prevalence of these comorbid conditions is still significantly higher in similar patients without psoriatic disease.⁴ Lastly, a few study patients were noted to have been previously treated with phototherapy (6%) or biologics (1%).

The authors report that drug survival, or the duration that patients remain on a specific treatment, was significantly higher and comparable for methotrexate (10.92 months) and acitretin (10.79 months) compared to cyclosporine (3.95 months). The lower median drug survival of cyclosporine is likely best explained by its real-world use for limited durations due to concerns about adverse events for prolonged periods. However, it is curious that the primary reason for discontinuation was due to ineffectiveness, raising questions about medication dosing and/or medication adherence to a twice-daily oral regimen. Notably, treatment-related adverse events were relatively high for each medication: acitretin (42%), cyclosporine (25%), and methotrexate (37%). Methotrexate had a higher percentage of patients discontinuing therapy due to treatment-related adverse events. Cyclosporine, however, had the highest rate of skin clearance at 3 and 6 months, with PASI90 being achieved in 18% and 13% of patients, respectively.

Despite the differences in drug survival among the treatments, the authors found no significant difference in efficacy at 3 or 6 months of treatment, regardless of the patient’s baseline PGA and PASI scores. The authors report that only the country, sex of the patient, age, clinical type of psoriasis (i.e., plaque psoriasis versus non-plaque variants), presence of psoriatic arthritis, and PGA score at baseline influenced the clinician’s first-line choice of acitretin, cyclosporine, or methotrexate in their univariate analysis. Their data also suggests that methotrexate tends to be the preferred treatment choice when treating pediatric patients with psoriatic arthritis. While the multivariate analysis identified several interesting patterns between countries, the interpretation of these findings is limited by the unbalanced representation of centers from each country and two-thirds of patients from France alone.

The widespread use of acitretin, cyclosporine, and methotrexate globally is of particular interest and significance, given their relatively nonspecific mechanisms of action, potential risks, and off-label use for pediatric psoriasis. While acitretin is approved for disorders of keratinization with no age limitations, methotrexate is not approved for the treatment of pediatric plaque psoriasis in the United States, Europe, or Canada. Similarly, cyclosporine is considered off-label in those same countries for all patients who are less than 16 years of age. Thus, their use in pediatric patients may be supported by expert opinion, but not by regulatory agencies.

In summary, Miao et al. offer valuable insights into the prescriber preference and comparative treatment profiles of acitretin, cyclosporine, and methotrexate in a multicenter, international cohort of pediatric psoriasis patients. Their data suggest that these widely available systemic therapies have a comparable efficacy profile in the first 3-6 months after treatment initiation as well as a very low rate of serious adverse events. Such studies are crucial in informing international and consensus guidelines on treatment strategies for psoriatic disease, particularly in countries where biologic therapies are inaccessible or prohibitively expensive. Nevertheless, comparisons between these traditional systemic and biologic therapies are lacking, but necessary for comprehensive psoriasis treatment recommendations and to assess the relative safety and efficacy of these very different medication classes. Additional comparative drug survival studies for traditional systemic therapies and biologics are crucial for evaluating the long-term health benefits and potential disease-modifying effects of individual systemic treatments administered to pediatric patients with severe psoriasis.