Key Risk Factors Uncovered for AD Recurrence After Dupilumab Discontinuation

Patients who discontinue dupilumab treatment after their atopic dermatitis has cleared remain susceptible to relapse and thereby require longer-term management and monitoring, according to a new study.¹ Several independent risk factors are implicated in the greater risk of disease recurrence following treatment discontinuation, the authors explained in Frontiers in Medicine.

“Dupilumab controls symptoms while in use, but relapses may occur after discontinuation of use,” they wrote. “How to choose the most appropriate treatment regimen for different populations, which can ensure sustained efficacy while minimizing the probability of disease recurrence, and thus reduce the burden of disease on patients has become a key issue that needs to be urgently resolved.”

There were 141 patients with atopic dermatitis included in this analysis, who received care at the dermatology outpatient clinic at Sichuan Provincial People’s Hospital in Chengdu, China, between January 1, 2021, and December 31, 2023. The latter date was the cohort termination time, and patients were followed retrospectively from medication discontinuation until disease recurrence or the study end date. These follow-ups were every 2 weeks.

Patients' mean (SD) age was 37.3 (20.7) years, and 42.6% were female patients. To be included, they had to have been treated with dupilumab for at least 4 weeks, received the standard induction dose of dupilumab (600 mg for body weight ≥ 30 kg; 300 mg for body weight < 30 kg), received the standard maintenance dose of dupilumab (300 mg every 2 weeks for body weight ≥ 30 kg; 300 mg every 2 weeks for body weight < 30 kg), and have complete medical records and follow-up information.

Overall, the investigators saw a recurrence rate of 23.4% (95% CI, 16%-30%) and a median time to relapse of 29 weeks (range, 22-59). No patient deaths were attributed to recurrence of atopic dermatitis, but 1 patient death was reported during the follow-up period, and this was linked to serious complications.

The highest risks of recurrence were seen in patients who had comorbid conjunctivitis (HR, 7.912; 95% CI, 1.280-48.895; P = .026), were treated with dupilumab for fewer than 16 weeks (HR, 5.871; 95% CI, 2.154-16.003; P = .001), had a body mass index (BMI) of 28 kg/m² (HR, 5.653; 95% CI, 2.331-13.713; P < .001), were male (HR, 5.634; 95% CI, 1.727-18.373; P = .004), and had a familial predisposition to allergy (HR, 3.438; 95% CI, 1.351-8.747; P = .01).

Risk factors that did not reach statistical significance were having comorbid urticaria (HR, 1.035) or comorbid allergic rhinitis (HR, 1.023), despite their noted modestly increased risks of atopic dermatitis recurrence. Factors that were negatively associated with risk of recurrence were comorbid asthma (HR, 0.935), previous corticosteroid treatment (HR, 0.880), age older than 60 (HR, 0.763), disease duration of 10 or more years (HR, 0.761), and comorbid chronic bronchitis (HR, 0.416).

Explaining the strengths of their findings, the study investigators highlighted several examples of where their results echoed previous research on links between risk factors and atopic dermatitis recurrence. There was a greater risk of reduced drug survival during dupilumab treatment in a setting that included male sex (HR, 2.34; 95% CI, 1.14-4.78; P = .02) and susceptibility to allergic rhinitis (HR, 2.61; 95% CI, 1.37-5.00; P = .004).² Another previous study showed male sex (P = .002) and high BMI (P < .000) to be potential determinants of atopic dermatitis severity. Also, several other studies have demonstrated that female gender and a BMI below 24 kg/m² may predispose individuals to better responses to dupilumab.^3-5

The investigators expressed their concern both for the lack of early intervention in the setting of atopic dermatitis relapse and for the disease status of these patients, and they noted that subsequent management and treatment in this setting should encompass reassessment, potential dupilumab reinitiation, and transitioning to another treatment regimen if needed. However, they also add that their results show how dupilumab maintained its effectiveness when reinitiated in their study population, that this treatment course was effective in older and younger patients—which reflects a real-world population, and that they believe these data reflect “modifiable factors leading to [atopic dermatitis] relapse and provide insight into the risk profiles associated with relapse at different stages of disease."

References

1. Chen M, Wen X, Liu J, et al. Recurrence and influencing factors of moderate-to-severe atopic dermatitis after dupilumab withdrawal: a retrospective cohort analysis. Front Med (Lausanne). 2025:12:1585368. doi:10.3389/fmed.2025.1585368
2. Wollenberg A, Ariens L, Thurau S, van Luijk C, Seegräber M, de Bruin-Weller M. Conjunctivitis occurring in atopic dermatitis patients treated with dupilumab–clinical characteristics and treatment. J Allergy Clin Immunol Pract. 2018;6(5):1778-1780.e1. doi:10.1016/j.jaip.2018.01.034
3. Gu C, Wu Y, Luo Y, et al. Real-world efficacy and safety of dupilumab in Chinese patients with atopic dermatitis: a single-centre, prospective, open-label study. J Eur Acad Dermatol Venereol. 2022;36(7):1064-1073. doi:10.1111/jdv.18109
4. Stingeni L, Bianchi L, Antonelli E, et al. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: a multicentre Italian real-world experience. J Eur Acad Dermatol Venereol. 2022;36(8):1292-1299. doi:10.1111/jdv.18141
5. Mastorino L, Richiardi I, Gelato F, et al. Predisposition to conjunctivitis and male sex reduces drug survival of dupilumab in adults and adolescents. Expert Opin Biol Ther. 2024;24(8):863-868. doi:10.1080/14712598.2024.2372367