Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis

Abstract

Strategies on long‐term management of patients affected by atopic dermatitis (AD) undergoing treatment with dupilumab achieving good clinical response (GCR) or experiencing dupilumab‐related adverse events (AEs) are scant. Data of patients who implemented longer than scheduled dupilumab dosing interval due to GCR (at least 52 weeks of treatment and controlled AD activity [Eczema Area Severity Index ≤7 and Dermatology Life Quality Index ≤5 for at least 6 months]) or AEs (dupilumab‐related and treatment‐resistant conjunctivitis) were retrospectively collected. Dupilumab was tapered to Q3W or Q4W based on physician‐patient shared decision. At baseline (T0) and each follow‐up (week 16 [T1] and week 32 [T2]) disease severity was assessed. A total of 59 patients implemented longer than scheduled dosing interval (44 GCR, 15 AEs). Among these, 50 (35 GCR and 15 conjunctivitis) patients switched to 300 mg Q3W, while nine GCR subjects to Q4W. In the GCR group Q3W, 34 and 31 patients maintained clinical response at T1 and T2, whereas eight and seven Q4W subjects maintained clinical response at the same timepoints, respectively. No significant differences in AD severity were observed between T1 and T2 in both groups. Contrariwise, one Q3W and one Q4W patients at T1, and three Q3W and one Q4W subjects at T2, returned to dupilumab labeled dosage due to AD worsening. In conjunctivitis group, dupilumab Q3W was maintained in eight and four patients at T1 and T2, respectively. Three patients at T1 and three at T2 subjects returned to the labeled interval due to conjunctivitis remission. Four patients at T1 and four subjects at T2 interrupted dupilumab due to the persistence of conjunctivitis. A longer dupilumab dosing interval may be a valuable option in patients with a GCR and may be a useful strategy to reduce treatment‐related conjunctivitis, also with pharmacoeconomic benefit.

Appropriate Injection Intervals of Dupilumab in Patients With Adult Atopic Dermatitis: A Step Toward Developing Guidelines for Daily Practice

“…In our study, we prolonged the interval to 3 to 4 weeks without any observed flare-ups or notable exacerbation of the disease. In line with our results, Patruno et al 3 showed that patients with interval extended to 3 to 4 weeks due to GCR maintained mean disease severity scores up to week 32 after tapering. Spekhorst et al 4 adopted a gradual tapering approach, starting with a dosage interval of every 3 weeks and progressing sequentially to Q4W, Q6W, and Q8W, contingent on a state of controlled disease (EASI score ≤7).…”

Appropriate Injection Intervals of Dupilumab in Patients With Adult Atopic Dermatitis: A Step Toward Developing Guidelines for Daily Practice

“…In our study, we prolonged the interval to 3 to 4 weeks without any observed flare-ups or notable exacerbation of the disease. In line with our results, Patruno et al 3 showed that patients with interval extended to 3 to 4 weeks due to GCR maintained mean disease severity scores up to week 32 after tapering. Spekhorst et al 4 adopted a gradual tapering approach, starting with a dosage interval of every 3 weeks and progressing sequentially to Q4W, Q6W, and Q8W, contingent on a state of controlled disease (EASI score ≤7).…”

Therapeutic Modulation of Dupilumab in Patients with Severe Atopic Dermatitis®: Clinical Effectiveness in Real Life

“…The mean time before treatment extension was 28 months, more than 2 years, longer than reported in the few studies on the subject currently in the literature. 3–6,8–11 At the end of the analysis of the cases observed at 8 months, only two patients returned to the standard dosage, confirming the effectiveness of this strategy.…”

“…All selected patients had to have achieved EASI £ 7 and DLQI £ 5 for at least 6 months and to have been on dupilumab treatment for at least 52 weeks. 4 The mean EASI remained stably below the threshold of significance with a minimal mean elevation at the second visit. 4 In the work of Spekhort and colleagues, the only one currently in the literature prospectively constructed, a group of 90 adult atopic patients treated with dupilumab for 52 weeks and with a clinically significant response (EASI £ 7) for at least 6 months were randomized into three groups of 30 patients; group A without treatment prolongation, group B dose prolongation at 4 weeks, and group C in case of persistent response after the first follow-up visit of group B at 6-8 weeks.…”

“…4 The mean EASI remained stably below the threshold of significance with a minimal mean elevation at the second visit. 4 In the work of Spekhort and colleagues, the only one currently in the literature prospectively constructed, a group of 90 adult atopic patients treated with dupilumab for 52 weeks and with a clinically significant response (EASI £ 7) for at least 6 months were randomized into three groups of 30 patients; group A without treatment prolongation, group B dose prolongation at 4 weeks, and group C in case of persistent response after the first follow-up visit of group B at 6-8 weeks. 8 In groups A, B, and C, EASI and NRSp remained below the threshold of clinical significance at the two follow-up visits following spacing (EASI £ 7 and NRSp £ 4); however, in groups B and C, an increase in the mean NRSp value was observed after therapeutic prolongation.…”

“…4,10 However, the increase in reported flares was also not particularly significant, and all studies that analyzed safety agreed on a reduction in ocular adverse events. 3–6,8–11…”

Appropriate Injection Intervals of Dupilumab in Patients With Adult Atopic Dermatitis: A Step Toward Developing Guidelines for Daily Practice

“…In our study, we prolonged the interval to 3 to 4 weeks without any observed flare-ups or notable exacerbation of the disease. In line with our results, Patruno et al 3 showed that patients with interval extended to 3 to 4 weeks due to GCR maintained mean disease severity scores up to week 32 after tapering. Spekhorst et al 4 adopted a gradual tapering approach, starting with a dosage interval of every 3 weeks and progressing sequentially to Q4W, Q6W, and Q8W, contingent on a state of controlled disease (EASI score ≤7).…”

Therapeutic Modulation of Dupilumab in Patients with Severe Atopic Dermatitis®: Clinical Effectiveness in Real Life

“…The mean time before treatment extension was 28 months, more than 2 years, longer than reported in the few studies on the subject currently in the literature. 3–6,8–11 At the end of the analysis of the cases observed at 8 months, only two patients returned to the standard dosage, confirming the effectiveness of this strategy.…”

“…All selected patients had to have achieved EASI £ 7 and DLQI £ 5 for at least 6 months and to have been on dupilumab treatment for at least 52 weeks. 4 The mean EASI remained stably below the threshold of significance with a minimal mean elevation at the second visit. 4 In the work of Spekhort and colleagues, the only one currently in the literature prospectively constructed, a group of 90 adult atopic patients treated with dupilumab for 52 weeks and with a clinically significant response (EASI £ 7) for at least 6 months were randomized into three groups of 30 patients; group A without treatment prolongation, group B dose prolongation at 4 weeks, and group C in case of persistent response after the first follow-up visit of group B at 6-8 weeks.…”

“…4 The mean EASI remained stably below the threshold of significance with a minimal mean elevation at the second visit. 4 In the work of Spekhort and colleagues, the only one currently in the literature prospectively constructed, a group of 90 adult atopic patients treated with dupilumab for 52 weeks and with a clinically significant response (EASI £ 7) for at least 6 months were randomized into three groups of 30 patients; group A without treatment prolongation, group B dose prolongation at 4 weeks, and group C in case of persistent response after the first follow-up visit of group B at 6-8 weeks. 8 In groups A, B, and C, EASI and NRSp remained below the threshold of clinical significance at the two follow-up visits following spacing (EASI £ 7 and NRSp £ 4); however, in groups B and C, an increase in the mean NRSp value was observed after therapeutic prolongation.…”

“…4,10 However, the increase in reported flares was also not particularly significant, and all studies that analyzed safety agreed on a reduction in ocular adverse events. 3–6,8–11…”

Appropriate Injection Intervals of Dupilumab in Patients With Adult Atopic Dermatitis: A Step Toward Developing Guidelines for Daily Practice

“…In our study, we prolonged the interval to 3 to 4 weeks without any observed flare-ups or notable exacerbation of the disease. In line with our results, Patruno et al 3 showed that patients with interval extended to 3 to 4 weeks due to GCR maintained mean disease severity scores up to week 32 after tapering. Spekhorst et al 4 adopted a gradual tapering approach, starting with a dosage interval of every 3 weeks and progressing sequentially to Q4W, Q6W, and Q8W, contingent on a state of controlled disease (EASI score ≤7).…”

Therapeutic Modulation of Dupilumab in Patients with Severe Atopic Dermatitis®: Clinical Effectiveness in Real Life

“…The mean time before treatment extension was 28 months, more than 2 years, longer than reported in the few studies on the subject currently in the literature. 3–6,8–11 At the end of the analysis of the cases observed at 8 months, only two patients returned to the standard dosage, confirming the effectiveness of this strategy.…”

“…All selected patients had to have achieved EASI £ 7 and DLQI £ 5 for at least 6 months and to have been on dupilumab treatment for at least 52 weeks. 4 The mean EASI remained stably below the threshold of significance with a minimal mean elevation at the second visit. 4 In the work of Spekhort and colleagues, the only one currently in the literature prospectively constructed, a group of 90 adult atopic patients treated with dupilumab for 52 weeks and with a clinically significant response (EASI £ 7) for at least 6 months were randomized into three groups of 30 patients; group A without treatment prolongation, group B dose prolongation at 4 weeks, and group C in case of persistent response after the first follow-up visit of group B at 6-8 weeks.…”

“…4 The mean EASI remained stably below the threshold of significance with a minimal mean elevation at the second visit. 4 In the work of Spekhort and colleagues, the only one currently in the literature prospectively constructed, a group of 90 adult atopic patients treated with dupilumab for 52 weeks and with a clinically significant response (EASI £ 7) for at least 6 months were randomized into three groups of 30 patients; group A without treatment prolongation, group B dose prolongation at 4 weeks, and group C in case of persistent response after the first follow-up visit of group B at 6-8 weeks. 8 In groups A, B, and C, EASI and NRSp remained below the threshold of clinical significance at the two follow-up visits following spacing (EASI £ 7 and NRSp £ 4); however, in groups B and C, an increase in the mean NRSp value was observed after therapeutic prolongation.…”

“…4,10 However, the increase in reported flares was also not particularly significant, and all studies that analyzed safety agreed on a reduction in ocular adverse events. 3–6,8–11…”