Adalimumab as a Promising Therapy for Pediatric Plaque Psoriasis

Introduction to Psoriasis

Psoriasis is a chronic skin condition marked by the presence of scales and red patches, often located on the scalp, elbows, and knees. This autoimmune inflammatory disease results from an excessive buildup of skin cells on the epidermis and currently lacks a cure. The condition is driven primarily by immune system T-cells and elevated levels of tumor necrosis factor-alpha (TNF-α). Among the various types of psoriasis, plaque psoriasis is the most prevalent, characterized by plaques forming on the skin’s surface. Symptoms can include itching, burning, soreness, and cracked skin, with severity classified as mild, moderate, or severe based on the percentage of skin affected.

Prevalence of Psoriasis in Pediatric Patients

Psoriasis impacts approximately 2% of the general population, with a significant portion of diagnoses occurring in individuals aged 20 years and younger. Effective management of pediatric psoriasis is crucial as it can reduce the risk of psychosocial issues and comorbidities such as hypertension and diabetes. Initial treatment options for limited disease generally include topical therapies, while severe pediatric psoriasis may require ultraviolet B phototherapy or systemic treatments, including methotrexate, ciclosporin, and retinoids.

Adalimumab’s Role in Treatment

While methotrexate, a TNF-α inhibitor, is commonly prescribed for treating children and adolescents with psoriasis, it has not received approval from the European Medicine Agency, making it a candidate for clinical research. The management of psoriasis through TNF-α blockage has been complicated by the absence of standardized guidelines and approved systemic therapies. In 2015, adalimumab was approved in the United States for treating severe psoriasis in patients aged four years and older who did not respond adequately to topical treatments or phototherapy. This necessitates a comparative analysis of the efficacy and safety of adalimumab and methotrexate in managing severe pediatric plaque psoriasis.

Study Overview

A double-blind randomized controlled study was conducted to assess the safety and efficacy of adalimumab versus methotrexate in children suffering from severe psoriasis. A total of 114 patients were randomly assigned to receive either 0.8 mg/kg or 0.4 mg/kg of adalimumab, or 0.1-0.4 mg/kg of methotrexate. Adalimumab was administered subcutaneously every other week, while methotrexate was taken orally once a week. The study comprised four phases: a 16-week primary treatment period, a withdrawal phase lasting up to 36 weeks, a 16-week re-treatment phase, and a 52-week long-term follow-up. The Psoriasis Area and Severity Index (PASI) was used to evaluate the percentage of affected skin, with a 75% improvement (PASI75) being a key endpoint. The Physician Global Assessment (PGA) measured psoriasis activity to determine clear or minimal areas.

Results and Findings

At the 16-week mark, PASI75 was achieved in 58% of patients receiving 0.8 mg/kg of adalimumab, 44% of those on 0.4 mg/kg adalimumab, and 32% of patients taking methotrexate. According to the PGA results, 61% of the adalimumab 0.8 mg/kg group, 41% of the 0.4 mg/kg group, and 41% of the methotrexate group demonstrated clear or minimal PGA scores. Adverse events, primarily infections, were reported in 45% of patients on 0.8 mg/kg of adalimumab, 56% on 0.4 mg/kg adalimumab, and 51% on methotrexate. Overall, treatment with adalimumab showed significant improvements over methotrexate in achieving PASI75, despite the increase in patients with clear or minimal PGA scores not reaching statistical significance.

Long-Term Implications

This study represents one of the few investigations into the long-term safety of treating severe psoriasis in children. A noted limitation was the absence of methotrexate control data for direct comparison with the investigated population. Nevertheless, the safety and efficacy profile of adalimumab was effectively evaluated against methotrexate.

Conclusion

In summary, a treatment regimen of 0.8 mg/kg of adalimumab for 16 weeks in children and adolescents with severe plaque psoriasis resulted in significant improvements in PASI75 scores and a non-significant increase in patients achieving clear or minimal PGA scores compared to methotrexate. These findings offer new insights and present an additional safe and effective treatment option for managing severe plaque psoriasis in younger patients.

Author Information

Written By: Viola Lanier, Ph. D., M. Sc.