Study Compares MTX, Cyclosporine A, Dupilumab Survival in Children with Atopic Dermatitis

Lisa van der Rijst, MD

Credit: LinkedIn

The 1-year, 2-year, and 3-year drug survival rate of dupilumab is greater than that of methotrexate (MTX) and cyclosporine A (CsA) in pediatric patients with atopic dermatitis, according to new findings, with those treated with MTX and CsA having a higher discontinuation risk due to ineffectiveness and adverse effects.¹

These findings and others were the results of new research led by Lisa P. van der Rijst, MD, from the National Expertise Center for Atopic Dermatitis at the University Medical Center Utrecht in the Netherlands. The investigators sought in this study to examine the drug survival of these 3 medications among children with atopic dermatitis and to highlight the variables associated with discontinuation.

They highlighted the general lack of drug survival research looking at pediatric patients. The team added that comparative studies between dupilumab, MTX, and CsA survival rates had also been lacking.^2,3

“Therefore, the primary objective of this study was to investigate the 1-year, 2-year, and 3-year drug survival of dupilumab, MTX, and CsA in a multicenter daily practice cohort study of pediatric patients with (atopic dermatitis),” van der Rijst and colleagues wrote. “The secondary objective was to identify characteristics associated with discontinuation of these treatments.”¹

Background and Design

The investigators conducted a cohort study during which they assessed children and adolescents in the 2 - 17 year age bracket who began treatment with MTX, dupilumab, and/or CsA for moderate to severe atopic dermatitis. These individuals had been treated at 5 tertiary care centers found in the Netherlands: Amsterdam University Medical Center, University Medical Center Utrecht, Erasmus MC University Medical Center in Rotterdam, University Medical Center Groningen, and Radboud University Medical Center in Nijmegen.

The time period in which their analysis took place spanned from January 2013 - December 2022. They sourced their data from the Treatment of Atopic Eczema (TREAT) Netherlands registry, the BioDay registry, and available electronic medical records.

Some of the data recorded by the research team included patient demographics such as body weight, age, the age of disease onset, sex, and self-reported allergic conditions such as allergic rhinitis, asthma, allergic conjunctivitis, and allergies to foods. The team additionally took note of medical and treatment history, in addition to subjects’ baseline Eczema Area and Severity Index (EASI) scores.

Some of the other information noted by the investigators include their initial and maximum drug doses, start and stop dates, their administration methods, rationale for treatment cessation, and the implementation of additional medications. MTX and CsA were dosed based on national guidelines: 0.2-0.4 mg/kg per week for MTX and 3-5 mg/kg per day for CsA. Dupilumab was provided to subjects in accordance with FDA-approved dosing guidelines.

The investigators conducted their drug survival analysis through the use of Cox proportional hazard regression models. They carried out both univariable and multivariable analyses conducted to look into factors linked to participants’ discontinuation of medications.

Notable Findings on Drug Survival

Overall, there were 502 treatment episodes in which 362 unique subjects were assessed by the investigators. The research team noted that the average age at initiation of therapy was 12.9 years (SD 3.8), with 54.2% of the episodes involving female participants.

Specifically, there were 192 episodes of treatment with dupilumab, 216 of CsA, and 94 of MTX. For treatment with MTX, the drug survival rates were shown to be 60.7%, 39.3%, and 25.3% at the 1, 2, and 3-year marks. For CsA therapy, they were 43.9%, 21.5%, and 10.4%, respectively. The rates of treatment survival for dupilumab were shown to be 84.1%, 72.3%, and 62.0%, respectively.

The investigators reported that the main reason identified for subjects’ decision to discontinue their medications across all treatments was found to be ineffectiveness, accounting for 35.5% of cases. It was most frequently noted among CsA users. This reason was followed by adverse effects, which were reported by the team in 18.7% of participants.

The research team concluded that MTX and CsA were shown to be independently associated with a higher discontinuation risk due to reported ineffectiveness (hazard ratio [HR], 4.45 for MTX and HR, 10.88 for CsA) and due to adverse effects (HR, 4.39 for MTX and HR, 3.83 for CsA) when compared to treatment with dupilumab.

The team also found that there was an elevated discontinuation risk for subjects aged 12 - 17 years who initiated systemic therapy due to both lack of efficacy (HR, 1.55) and adverse effects (HR, 2.39).

“These results have provided new insight into drug survival resulting from the effectiveness, safety, and tolerability of these systemic treatments, contributing to the optimization of patient outcomes in pediatric patients with (atopic dermatitis),” they wrote.¹

References

1. ^{van der Rijst LP, Kamphuis E, Schuttelaar MLA, et al. Drug Survival of Dupilumab, Methotrexate, and Cyclosporine A in Children With Atopic Dermatitis. JAMA Dermatol. Published online October 16, 2024. doi:10.1001/jamadermatol.2024.3717.}
2. ^{Elsgaard S, Danielsen AK, Thyssen JP, Deleuran M, Vestergaard C. Drug survival of systemic immunosuppressive treatments for atopic dermatitis in a long-term pediatric cohort. Int J Womens Dermatol. 2021;7(5Part B):708-715. doi:10.1016/j.ijwd.2021.07.005.}
3. ^{Law Ping Man S, Bouzillé G, Beneton N, Safa G, Dupuy A, Droitcourt C. Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis: comparison between methotrexate and cyclosporine. J Eur Acad Dermatol Venereol. 2018;32(8):1327-1335. doi:10.1111/jdv.14880.}