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.

Ocular surface disease in moderate‐to‐severe atopic dermatitis patients and the effect of biological therapy

“…Patruno et al. found improvement of ocular symptoms in 46.6% ( n = 7/15) of the patients with DAOSD after prolongation of the dosing interval to 300 mg every 3–4 weeks, without worsening of AD 45 . In addition, Spekhorst et al.…”

“…10 Patruno et al found improvement of ocular symptoms in 46.6% (n = 7/15) of the patients with DAOSD after prolongation of the dosing interval to 300 mg every 3-4 weeks, without worsening of AD. 45 In addition, Spekhorst et al reported persistent AD control in patients who tapered the dosage of dupilumab due to controlled AD. 46 The beneficial effect of dose reduction on DAOSD seems in contrast to the study by Akinlade et al, who pooled data on dupilumab concentrations of phase 3 dupilumab trials from baseline to week 16 and suggested that the incidence of DAOSD may decrease with higher serum concentrations of dupilumab.…”

Lengthening the time intervals between doses of dupilumab in remission atopic dermatitis

“…Driven by numerous evidences on the possible lengthening of the interval between doses after the clearance of the disease, [7][8][9] we decided to do so with our patients on dupilumab therapy.…”

Extending dupilumab dosing intervals in atopic dermatitis: A prospective observational study in a South European tertiary hospital

“…Recently, the possibility of extending intervals to every 3 (Q3W) or 4 weeks (Q4W) has been discussed, with clinical and pharmaco-economic benefits. [1][2][3][4] We conducted a prospective observational study at an AD referral centre to evaluate the persistence rate of tapering dupilumab. Patients with moderate-to-severe AD treated with Q2W dupilumab were tapered to Q3W or Q4W based on clinical decision.…”

“…5 Tapering can also be performed to manage refractory adverse effects such as PFE or conjunctivitis. 1,4 Paradoxical facial erythema is probably related to the immunological shift from a dupilumab's T2-blocked response to a (now) unchecked T1/T17 pathways, which in turn would amplify a T17-response against Malassezia or unmask a T1/T17mediated allergic contact dermatitis. 6,7 We found that resuming on-label dupilumab dosing due to AD worsening with tapering led to a complete reacquisition of response, providing clinicians with encouraging data to try this approach in selected patients.…”