Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block TH2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.13
The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly TH2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.14
Advantages of Biologics and Laboratory Monitoring
By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.3,4,15,16
Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.2 No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.
Unanswered Questions: Vaccines and Antidrug Antibodies
Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.20 Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.
Cost Considerations
Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.25 This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.
On the Horizon
Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and TH17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.
