Patients with atopic dermatitis maintain positive outcomes with reduced dupilumab dosages
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Key takeaways:
- There were no significant changes in disease severity scores among the different study cohorts whether they maintained their dupilumab dose or received extended dose intervals.
- Numeric Rating Scale pruritis scores significantly increased temporarily but remained low among patients whose dose intervals were extended.
- Median dupilumab levels remained stable among patients who remained on a biweekly dosing schedule but significantly decreased among those whose dose intervals were extended.
Patients with persistently controlled atopic dermatitis continued to experience stable and low disease activity after receiving reduced dosages of dupilumab, according to a study published in Allergy.
These findings show that patient-centered dosing regimens can be successful, Lotte S. Spekhorst, MD, of the department of dermatology and allergology and National Expertise Center for Atopic Dermatitis at University Center Utrecht, the Netherlands, and colleagues wrote in the study.
The observational cohort study involved 90 adults (65.6% male; mean age, 42.4 years; standard deviation, 16.4 years) with AD. At baseline, these patients had a median Eczema Area and Severity Index (EASI) score of 17.9 (interquartile range [IQR], 12.4-25.3) and a median Numeric Rating Scale (NRS) pruritis score of 7 (IQR, 5-8).
Patients were treated subcutaneously with dupilumab (Dupixent, Sanofi Genzyme/Regeneron), including a loading dose of 600 mg and maintenance doses of 300 mg administered every 2 weeks.
After a year of treatment, which the researchers called the first timepoint (T1), median EASI scores fell to 2.7 (IQR, 1-5.4). Individual patients who tallied EASI scores of 7 or less for 6 months, which the researchers considered controlled disease, were eligible for dose reduction.
First, dose intervals were extended to every 3 weeks. If AD remained controlled, intervals were extended to every 4 weeks, corresponding to a 50% dose reduction (group B, n = 30). Continued control led to extensions to every 6 weeks (66% reduction) and then 8 weeks (75% reduction; group C, n = 30). Participants remained on dosages for at least 3 months before intervals were extended.
Thirty patients did not achieve control after 52 weeks or wished to continue their standard dosage (group A). In this group, 50% of the patients had controlled AD at T1, 40% had controlled AD at an individually defined second timepoint and 50% had controlled AD at an individually defined third timepoint.
After at least 3 months of doses every 4 weeks, defined as the second timepoint (T2), 83.3% of group B and 86.7% of group C had controlled AD. After at least 3 months of doses every 6 or 8 weeks, defined as the third timepoint (T3), 93.3% of group C had controlled AD.
Overall, patients experienced significant decreases in NRS pruritis scores by T1 with a median score of 2 (IQR, 1-4; P < .001).
Specifically, 65.4% of patients in group A experienced stable NRS pruritis scores of 4 or less at T1, 70% were stable at a second individually defined timepoint and 68.8% were stable at a third. Meanwhile, 79.2% of group B and 88% of group C had NRS pruritis scores of 4 or less at T2, with 66.7% of group C at a score of 4 or less at T3.
However, group B saw a significant increase in median NRS pruritis score from 2 (IQR, 1-3) at T1 to 3 (IQR, 2-4) at T2, although there was no significant difference between T1 and T3 (median, 1.5; IQR, 0.6-3.9).
Group C experienced similar significant changes in median NRS pruritis scores from 2 (IQR, 1-3) at T1 to 1 (IQR, 0-3.5) at T2 and to 3 (IQR, 1-5) at T3 (P = .03).
The researchers also measured serum dupilumab levels, which remained stable for group A but were significantly higher than levels found for group B at T2 and group C at T3 (both, P < .001).
In group B, these levels significantly decreased from a median of 88.9 mg/L (IQR, 65.3-127) at T1 to 24.1 mg/L (IQR, 17.1-45.6) at T2 (P < .001). Group C experienced decreases from a median of 82 mg/L (IQR, 66.8-101) at T1 to 25.8 mg/L (IQR, 20.3-48.8) at T2 and 12.5 mg/L (IQR, 1.7-22.3) at T3 (P < .001).
The researchers measured 19 serum biomarkers as well, with significant decreases in PARC/CCL18 (P = .001) and TARC/CCL17 (P = .001) during the first year of treatment and levels that remained low in all three groups at all time points during the following year.
Despite small changes in NRS pruritis scores that remained low in groups B and C, the researchers said that disease activity and severity biomarkers also remained low and stable for patients with extended dose intervals, indicating the potential for personalized dupilumab treatment for patients with controlled AD in clinical practice.
Perspective
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Individual patients can vary widely in terms of their disease severity and responses to treatment, so it is not surprising that there is a range of potential dosing regimens that can keep patients with moderate to severe AD well controlled.
These findings align with my own experience, in which some patients may need more frequent dosing, whereas others maintain their response with less frequent dosing or even interruptions in treatment.
Doctors can use these findings to consider a tailored approach to treating each patient. If a patient would like to try less frequent dosing, then this study provides support for that possibility, with the knowledge it can be effective for some patients.
Next steps in this research would be to understand if there are specific characteristics, potentially biomarkers, that can help to predict response to treatment and to different treatment regimens.
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