Dupilumab safe, effective for atopic dermatitis in youth with inborn errors of immunity
Click Here to Manage Email Alerts
Key takeaways:
- The series included six patients with unresponsive atopic dermatitis.
- Each patient experienced improvements in Dermatology Life Quality Index by 16 weeks.
- Adverse events all were mild.
Dupilumab was safe and effective in treating a group of six children and young adults with inborn errors of immunity and moderate to severe atopic dermatitis, according to a study published in Pediatric Allergy and Immunology.
However, the biologic was not a definitive treatment for immunodeficiency, Paola Zangari, MD, pediatrician in the clinical and research unit of clinical immunology and vaccinology, IRCCS Bambino Gesú Children’s Hospital, and colleagues wrote.
Topical therapy had failed for these patients, who all had early onset AD. Five patients had elevated blood eosinophils and/or IgE levels, and one had high levels of IL-4 and IL-13. The cohort also had a mean Eczema Area and Severity Index (EASI) score of 24.8.
Four of the patients had a genetically defined inborn error of immunity. One patient had an ARPC1B deficiency, two had a STAT3 deficiency and one had a monogenic STAT6 gain-of-function mutation that caused early onset atopic disease.
Also, one patient had a common variable immunodeficiency (CVID) phenotype, and one had a hyper-IgE syndrome with food allergies, recurrent respiratory infections, severe asthma and IgA nephropathy associated with severe refractory AD.
The patients followed standard dosing of dupilumab (Dupixent; Regeneron, Sanofi) for AD.
Five of the six patients had a long follow-up visit at week 24, and four of the six had a long follow-up visit at week 52.
Significant clinical improvements were apparent in all six patients at week 4, with mean changes of 10.4 points in EASI, 7 points in Dermatology Life Quality Index (DLQI) and 5.1 in Numeric Rating Scale (NRS) for itch intensity.
At week 16, all six patients reported 50% improvements in EASI. At week 24, four out of five patients reported 75% improvements in EASI.
Similarly, four out of six patients reported 50% reductions in NRS, and three out of six reported 50% reductions in DLQI, both at week 4. All six patients saw 50% reductions in DLQI at week 16 as well.
The researchers also noted persistent improvements in AD symptom severity during the follow-up visits, although one patient’s symptoms got worse after week 16 following an upper respiratory tract infection despite earlier cutaneous improvement.
IgE levels fell by 50% for three patients by week 16 as well, with no significant variations in absolute eosinophil count except for one patient who had a transient increase.
The patients in this cohort experienced reductions in itch that were comparable to those seen in randomized clinical trials of children and adolescents with AD who did not have any immunodeficiencies, the researchers continued.
However, the researchers added, patients who did not have any immunodeficiencies had faster improvements in severity based on EASI 75 totals at week 16, possibly due to Th2 imbalances among immunodeficient patients or other immunological pathways that dupilumab does not restore.
The researchers categorized treatment as well tolerated. One patient with a history of mild drug allergies experienced moderate respiratory distress and conjunctivitis, which rapidly resolved with antihistamines and steroids, after the first and second injections.
This patient discontinued dupilumab at first even though there had been improvements in both AD and asthma flares with treatment. When treatment restarted with steroid and antihistamine premedication, the patient did not experience any other adverse events.
Another patient experienced mild conjunctivitis at 3 months. After temporarily halting treatment, the conjunctivitis resolved in 4 weeks.
Based on these findings, the researchers concluded that dupilumab was safe and effective for patients with inborn errors of immunity to use to treat their AD, although it did not provide any benefits for immunodeficiency itself.
The researchers also suggested that dupilumab treatment could represent a valid bridge that could control skin infections and inflammatory complications for patients who are waiting for hematopoietic stem cell transplantation, although careful clinical monitoring would still be necessary.
Further, the researchers called for a comprehensive molecular and immunological characterization of AD with long-term IL4R-alpha inhibition, which could inform therapeutic decisions and tapering strategies, along with larger multicenter studies of the long-term safety and efficacy of dupilumab treatment for these patients.
Perspective
Back to Top
The findings are significant but not surprising. As the authors state, inhibition of IL-4 with dupilumab has been demonstrated to be safe and effective in various inborn errors of immunity, including STAT3 GOF and DOCK8.
The significance of this report is that it expands the clinical impact of dupilumab safety and efficacy in a small case series of patients with primary immune deficiency in addition to the single case reports previously published.
Although I have not used dupilumab in my patients with inborn errors of immunity or primary immune deficiency disorders, this report provides some reassurance that patients with these disorders can benefit from and be treated safely for their severe atopic dermatitis with this biologic.
Patients with severe atopic dermatitis and the diagnoses described in the study may be candidates for treatment with dupilumab if they do not have other contraindications or other alternatives.
As the authors state, this is a small study, and larger numbers of patients are needed to draw more definitive conclusions about safety and efficacy. The study encompasses less than a year of exposure to dupilumab, so following these patients for a longer period may further inform us about risks and benefits. Also, these results cannot be extrapolated to all patients with inborn errors of immunity, since mutations and disorders that were not studied in this report may have different clinical outcomes.
Collapse
Read more about
Click Here to Manage Email Alerts