Pharmacists Play Crucial Role in Dupilumab Treatment for Infants, Young Children With Atopic Dermatitis

Dupilumab (Dupixent; Sanofi and Regeneron Pharmaceuticals) is a fully human monoclonal antibody that has multiple FDA-approved indications. For atopic dermatitis (AD), it is indicated for the treatment of both adult and pediatric patients as young as 6 months with moderate to severe disease that is not adequately controlled with topical prescription therapies, or when those therapies are not advisable by providers. Approved by the FDA in 2022, dupilumab is the first biologic medicine to be approved for the treatment of moderate to severe AD from infancy through adulthood.^1,2

Image credit: Марина Терехова | stock.adobe.com

Dupilumab fully inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways, which are key and central drivers of the type 2 inflammation that has a major role in AD, asthma, and chronic rhinosinusitis. It is not an immunosuppressant drug and does not require lab monitoring.¹

“When a child is diagnosed with moderate-to-severe AD in the first few months of life, many aspects of their childhood can be significantly impacted. Parents and caregivers are challenged to find safe and effective treatment options,” said John Reed, MD, PhD, global head of Research and Development at Sanofi, in a news release.¹

The approval for this indication came after results from Part B of the LIBERTY AD PRESCHOOL study, a 2-part, phase 2/3 clinical trial (NCT03346434). The randomized, double-blind, placebo-controlled phase 3 part of the trial evaluated the safety and efficacy of dupilumab in combination with standard-of-care low-potency topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe AD. A total of 162 patients were randomly assigned to receive either dupilumab (200 mg for children weighing 5 to 15 kg, 300 mg for children weighing 15 to 30 kg) with low-potency TCS (n = 83) or low-potency TCS alone (placebo, n = 79).^1,3,4

The primary end point for Part B of this trial was to demonstrate the efficacy of multiple subcutaneous doses of dupilumab plus TCS administered every 4 weeks over a 16-week treatment period, which was assessed by the proportion of patients with an Investigator’s Global Assessment (IGA) score of 0 or 1. The key secondary end point was the safety and immunogenicity of the treatment, which was measured by the proportion of patients who achieved at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75).^1,3,4

“Moderate-to-severe AD in infants and young children is incredibly distressing for patients and their caregivers, who manage painful and persistent itch, intensive daily skincare routines such as chlorine baths and wet wraps, as well as sleepless nights for children and their families,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, in the news release.¹

The trial findings demonstrate the well-established efficacy and safety profile of dupilumab in younger age groups. During the 16-week treatment period, patients treated with dupilumab and TCS were approximately 50% less likely to experience a skin infection (dupilumab: 12%; placebo: 24%), with the total number of infections being approximately 70% lower (dupilumab: 11; placebo: 34). Additionally, more patients in the dupilumab group than in the placebo group had an IGA score of 0 or 1 (n = 23, 28% vs n = 3, 4%, respectively; difference: 24% [95% CI 13-34]; p < .0001) and EASI-75 (n = 44, 53% vs n = 8, 11%, respectively; difference: 42% [95% CI 29-55]; p < .0001).^1,4

Further, the overall prevalence of adverse events (AEs) was similar between the 2 groups (dupilumab: 64%, 53 of 83 patients; placebo: 74%, 58 of 78 patients). The investigators observed a higher conjunctivitis incidence in the dupilumab group (n = 4; 5%) than in the placebo group (none). The investigators did not observe any serious AEs related to dupilumab, or any AEs that led to treatment discontinuation. In addition to conjunctivitis, the most common AEs and AEs of special interest reported by both groups included nasopharyngitis (dupilumab: 8%; placebo: 9%), upper respiratory tract infection (dupilumab: 6%; placebo: 8%), herpes viral infections (dupilumab: 6%; placebo 5%), and injection site reactions (dupilumab: 2%, placebo 3%).⁴

“[In August 2021], the standard of care for this patient population is topical steroids and other immunosuppressive medicines may be used which can damage delicate skin and, if used long-term, potentially impact growth. Knowing that safety is of the utmost importance for physicians and parents when considering treatment options for children and infants, we are encouraged by the results of this trial showing [dupilumab] addressed the signs and symptoms of AD without broadly suppressing the immune system, demonstrating the potential it could have for these very young patients,” noted Reed in the news release.¹

In a Pharmacy Times interview, AD expert Monica Dougherty, PharmD, BCACP, clinical pharmacy specialist, dermatology and asthma, University of Rochester, discussed different treatments for AD. In particular, she highlighted the use of dupilumab in younger patients. She explained that although some providers prefer to use topical therapies in younger children as first-line treatment, dupilumab remains an effective treatment method for this patient group. Dougherty noted favoring dupilumab as a treatment when possible due to its ability to span a vast age group.⁵

Further, Dougherty also explained that caregivers or parents sometimes have concerns with their children receiving injections, but she emphasized that there are valuable resources available for patients. Oftentimes, dupilumab injections can be administered in pharmacies, and if that cannot be done or if caregivers and their children live far away from a pharmacy, they can often receive treatments in pediatric offices instead.⁵

“…when starting this trial, the disease covered more than half of children’s bodies and nearly a third had previously resorted to using immunosuppressive medicines. These data show that [dupilumab] dramatically reduced the impact of AD on the lives of these young children and their families, by rapidly clearing skin, improving itch, and improving observed patient outcomes including sleep and skin pain. In fact, [dupilumab]-treated patients experienced nearly 70% fewer skin infections compared to placebo patients,” said Yancopoulos in the news release.¹

References

1. Sanofi. Dupixent® (dupilumab) pivotal trial meets all primary and secondary endpoints becoming first biologic medicine to significantly reduce signs and symptoms of moderate-to-severe atopic dermatitis in children as young as 6 months. News release. August 30, 2021. Accessed June 10, 2024. https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-30-05-00-00-2288011

2. FDA Approves Dupilumab for Children 6 Months to 5 Years of Age With Atopic Dermatitis. Pharmacy Times. June 8, 2022. Accessed June 10, 2024. https://www.pharmacytimes.com/view/fda-approves-dupilumab-for-children-6-months-to-5-years-of-age-with-atopic-dermatitis

3. Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis (Liberty AD PRESCHOOL) (Liberty AD). ClinicalTrials.gov identifier: NCT03346434. Updated July 28, 2022. Accessed June 10, 2024. https://clinicaltrials.gov/study/NCT03346434

4. Paller, AS, Simpson, EL, Siegfried, EC, et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022;400(10356):908-919. doi:10.1016/S0140-6736(22)01539-2

5. McGovern, G. Experts: Current Treatment Regimens and the Future for Plaque Psoriasis, Atopic Dermatitis. Pharmacy Times. February 26, 2024. Accessed June 10, 2024. https://www.pharmacytimes.com/view/experts-current-treatment-regimens-and-the-future-for-plaque-psoriasis-atopic-dermatitis