Analysis of predictive factors influencing dupilumab continuation rate in adult patients with atopic dermatitis: results from an Italian multicenter study

Figures & data

Table 1. Clinical and demographic characteristics of the study population.

Total patients n		659
Males [n (%)]		345 (52.3)
Females [n (%)]		314 (47.7)
Age (Mean ± SD)		42.8 (±19.9)
Patients residing in Lazio [n (%)]*		481 (87.1)
Patients residing outside Lazio [n (%)]*		71 (12.9)
Previous CsA administration	Yes [n (%)]	366 (55.6)
	No [n (%)]	292 (44.4)
Age at onset	Child (0–11) [n (%)]	328 (49.8)
	Adolescent (11–17) [n (%)]	58 (8.8)
	Adult (18–64) [n (%)]	216 (32.8)
	Older adult (>65) [n (%)]	51 (7.6)
Clinical disease phenotype (n = 359)	Classic phenotype [n (%)]	177 (49.3)
	Prurigo nodularis [n (%)]	26 (7.2)
	Nummular eczema [n (%)]	19 (5.3)
	Generalized phenotype [n (%)]	131 (36.5)
	Psoriasis-like dermatitis [n (%)]	6 (1.7)
Difficult-to-treat anatomical site involvement (n = 122)	Head and neck involvement [n (%)]	12 (9.8)
	Hands involvement [n (%)]	17 (13.9)
EASI (baseline) [mean(±(SD)]		29.2 (7.6)
Itch-NRS (baseline) [mean(±(SD)]		8.3 (1.9)
DLQI (last follow-up visit) [mean(±(SD)]		15.9 (7.5)
Overall AEs	Tot observation [n (%)]	31/659 (4.7)
	Cutaneous [n (%)]	16 (51.6)
	Ocular [n (%)]	14 (45.2)
	Other (reflux esophagitis) [n (%)]	1 (3.2)
Drug discontinuation*		115/580 (19.8)
Reasons for drug discontinuations	Stable efficacy [n (%)]	24 (20.8)
	Inefficacy [n (%)]	34 (29.6)
	Compliance [n (%)]	20 (17.4)
	Pregnancy [n (%)]	3 (2.6)
	Covid-19 [n (%)]	1 (0.9)
	Death [n (%)]	1 (0.9)
	Other concomitant diseases [n (%)]	5 (4.3)
	Not available data [n (%)]	6 (5.2)
	Other reasons [n (%)]	12 (10.4)
	Adverse Events [n (%)]	Tot observations	9 (7.8)
		Ocular adverse events (conjunctivitis, xerosis)	5 (55.6)
		Cutaneous adverse events (injection-site reaction) n (%)	4 (44.4)

*Sum does not always match the total due to missing data.

Figure 1. Kaplan–meier survival plots. (a) Overall discontinuation and (b) discontinuation due to AEs and inefficacy were considered failure events for drug survivor function (analysis time = days).

Figure 2. Characterization over time of the mean EASI score during dupilumab treatment.

Table 2. Dupilumab efficacy at specified time points considering the overall study population.

Overall study population
	Baseline	Week 16	Week 48	Week 64	Week 80	Week 96	p Value*
Number of patients	659	659	362	410	210	155
EASI (mean ± SD)	29.2 (7.6)	5.5 (5.4)	3.8 (4.7)	3.9 (4.7)	2.6 (3.4)	2.9 (4.5)	<.0001
DLQI (mean ± SD)	15.9 (7.5)	3.1 (3.4)	2.4 (2.9)	2.2 (3.0)	1.7 (2.2)	2.1 (4.6)	<.0001
NRS-itch (mean ± SD)	8.3 (1.9)	3.4 (3.7)	2.0 (2.4)	2.6 (3.6)	1.7 (2.3)	1.7 (2.2)	<.0001

* Paired t test for the comparison between baseline EASI, DLQI and itch-NRS and the corresponding last follow-up visit scores for each patient.

Table 3. Univariable and multivariable Cox proportional hazard regression model predicting overall drug discontinuation (Prob > chi2 = 0.0000) and discontinuation due to AEs and inefficacy (Prob > chi2 = 0.0000).

		Overall drug discontinuation				Drug discontinuation due to AEs and inefficacy
		HR	Std. Err	P>|z|	95% conf. interval	HR	Std. Err	P>|z|	95% conf. interval
Univariable analysis
Disease phenotype	Eczematous	Ref				Ref
	Erythrodermic	0.756	0.249	0.398	0.396–1.445	0.503	0.291	0.325	0.161–1.565
	Prurigo-like	1.146	0.616	0.800	0.399–3.286	0.672	0.702	0.704	0.0867–5.207
	Nummular eczema	2.208	1.000	0.080	0.909–5.367	2.586	1.683	0.144	0.722–9.262
	Psoriasis-like	2.029	2.071	0.488	0.274–15.010	4.841	5.068	0.132	0.622–37.674
Anatomical disease localization	Flexural areas	Ref				Ref
	Head/neck	4.56e-16	1.24e-08	1.000	0	4.53e-17	4.59e-09	1.000	0
	Portrait dermatitis	1.039	1.076	0.970	0.136–7.909	4.61e-17	8.72e-09	1.000	0
	Hand eczema	0.703	0.532	0.642	0.159–3.097	4.62e-17	5.03e-09	1.000	0
Baseline EASI score		0.976	0.014	0.103	0.947–1.1004	0.995	0.022	0.845	0.953–1.040
EASI score (last follow-up visit)		1.128	0.015	0.000	1.099–1.158	1.157	0.024	0.000	1.112–1.205
Male		Ref				Ref
Female		1.353	0.283	0.148	0.898–2.039	1.621	0.533	0.142	0.851–3.089
Early AD onset (<18 years)		Ref				Ref
Adult AD onset (≥18 years)		1.59	0.337	0.028	1.052–2.409	1.728	0.579	0.103	0.895–3.336
Age at treatment initiation		1.011	0.005	0.027	1.001–1.021	1.017	0.007	0.030	1.001–1.032
No prior use of cyclosporin		Ref				Ref
Prior use of cyclosporin		0.978	0.208	0.919	0.644–1.485	1.008	0.335	0.980	0.525–1.934
Residence country	Lazio	Ref				Ref
	Outside Lazio	1.160	0.349	0.621	0.643–2.092	1.686	0.713	0.216	0.736–3.865
Multivariable analysis
Baseline EASI score		1.019	0.027	0.482	0.966–1.075	1.060	0.048	0.191	0.971–1.158
EASI score (last follow-up visit)		1.133	0.016	0.000	1.103–1.164	1.157	0.024	0.000	1.110–1.205
Male		Ref				Ref
Female		1.263	0.335	0.379	0 .751–2.123	1.236	0.563	0.640	0.507–3.018
Early AD onset (<18 years)		Ref				Ref
Adult AD onset (≥18 years)		1.349	0.480	0.400	0.672–2.711	0.915	0.576	0.888	0.266–3.142
Age at treatment initiation		1.002	0.009	0.818	0.984–1.019	1.006	0.016	0.697	0.975–1.037
No prior use of cyclosporin		Ref				Ref
Prior use of cyclosporin		1.101	0.322	0.741	0.620–1.955	1.324	0.711	0.602	0.461–3.797

HR: hazard ratio; Std. Err: standard error; conf. interval: confidence interval. Statistically significant p value are in bold.

Data availability statement

Enquiries related to the data generated or analyzed during this study can be directed to the corresponding author.