Patients’ preferences for systemic treatment of atopic dermatitis: safety and efficacy count the most

Figures & data

Table 1. Attributes and attribute levels.

Attribute	Attribute level
Probability of achieving clear or almost clear skin after 16 weeks of therapy	20%
	40%
	60%
Probability of significant improvement in itch after 16 weeks of therapy	20%
	40%
	60%
Time to onset of itch relief	2 days
	1 week
	2 weeks
Increased risk of the following side effects	Conjunctivitis, injection-site reaction, oral herpes
	Nausea, elevation in lipids, herpes zoster
	Nephrotoxicity, hypertension, increased susceptibility to infections
Application method	Tablets taken once to twice per day
	Syringe or pen administered into the subcutaneous fatty tissue every 2 weeks by the patient or a trained person.
	Syringe or pen administered into the subcutaneous fatty tissue every 4 weeks by the patient or a trained person
Frequency of laboratory tests	Not routinely required
	Every 4 weeks
	Every 12 weeks

Table 2. Characteristics of the study cohort.

Characteristic
Total cohort, n (%)	182 (100)
Sex, n (%)
Female	137 (75.3)
Male	43 (23.6)
Age (years)
Mean ± SD (range)	41.6 ± 13.7 (18–73)
18–40	86 (47.3)
>40	96 (52.8)
Comorbidity^a, n (%)
Atopic diseases^b	119 (65.4)
Cardiovascular diseases^c	28 (15.4)
Metabolic diseases^d	17 (9.3)
Psychiatric diseases^e	34 (18.7)
Immune-mediated diseases^f	16 (8.8)
Current therapy^a,g, n (%)
Topical therapy	164 (90.1)
Phototherapy	20 (11.0)
Systemic therapy	45 (24.7)
Cyclosporine A	1 (0.5)
Biologics	33 (18.1)
Dupilumab	32 (17.6)
Tralokinumab	1 (0.5)
JAK inhibitors	4 (2.2)
Baricitinib	3 (1.6)
Upadacitinib	1 (0.5)
Other^h	9 (4.9)

^aMultiple answers were permitted. ^bAtopic diseases other than AD included food allergies (n = 70), allergic rhinitis or rhinoconjunctivitis (n = 98) and asthma (n = 58). ^cCardiovascular diseases comprised arterial hypertension (n = 23) as well as myocardial infarction, stroke, coronary artery disease, peripheral artery disease or any other cardiovascular diseases (n = 6). ^dMetabolic diseases included hypercholesterolemia or hyperlipidemia (n = 12) and diabetes mellitus (n = 5). ^ePsychiatric diseases implied depression (n = 27), anxiety disorder (n = 15) and other psychiatric disorders (n = 1). ^fImmune-mediated diseases other than AD were alopecia areata (n = 7), vitiligo (n = 6), axial spondyloarthritis (n = 1), vasculitis (n = 2) und multiple sclerosis (n = 1). Autoimmune diseases of the thyroid gland were not subsumed in this category. ^gTwo patients reported current treatment with 2 systemic medications in parallel, cyclosporine A + acitretin (n = 1) and dupilumab + systemic glucocorticoids (n = 1). ^hOther treatments comprised acitretin (n = 1) and systemic glucocorticoids (n = 8). AD, atopic dermatitis; JAK, Janus kinase; n, number; SD, standard deviation.

Table 3. Patient-reported outcomes.

Characteristic
Total cohort, n (%)	182 (100)
PO-SCORAD
Mean ± SD (range)	47.8 ± 16.4 (1–87.5)
≤40	51 (28.0)
>40	131 (72.0)
BSA
Mean ± SD (range)	37.5 ± 25.0 (0–100)
≤10	26 (14.3)
>10	156 (85.7)
POEM
Mean ± SD (range)	15.6 ± 7.4 (0–28)
0–16	101 (55.5)
17–28	81 (44.5)
Peak pruritus, previous 24 h^a
Mean ± SD (range)	4.7 ± 2.9 (0–10)
≤6	119 (65.4)
>6	63 (34.6)
Average pruritus, previous 48 h^a
Mean ± SD (range)	4.4 ± 2.8 (0–10)
≤6	131 (72.0)
>6	51 (28.0)
Average sleep disturbance, previous 48 h^a
Mean ± SD (range)	4.0 ± 3.2 (0–10)
≤6	130 (71.4)
>6	52 (28.6)
DLQI
Mean ± SD (range)	11.4 ± 7.6 (0–30)
≤10	89 (49.2)
>10	92 (50.8)
HADS
Mean ± SD (range)	19.1 ± 3.6 (11–28)
HADS-Depression
Mean ± SD (range)	9.6 ± 2.0 (4–15)
0–7	20 (12.0)
8–10	93 (56.0)
11–21	53 (32.0)
HADS-Anxiety
Mean ± SD (range)	9.3 ± 2.5 (5–15)
0–7	45 (26.3)
8–10	71 (41.5)
11–21	55 (32.2)

^aAssessed on a numeric rating scale (NRS) from 0 to 10. BSA, Body Surface Area; DLQI, Dermatology Life Quality Index; h: hour; HADS: Hospital Anxiety and Depression Scale; POEM, Patient-Oriented Eczema Measure; PO-SCORAD, Patient-Oriented SCORing of Atopic Dermatitis.

Figure 1. Preferences for systemic treatment of AD. Relative importance scores (RIS) averaged across the study cohort (a). PWU for type of side effects (b) and application method (c). Bars: means with standard deviations. AD: atopic dermatitis; PWU: Part-Worth Utility; RIS: Relative Importance Scores.

Figure 2. Treatment preferences according to sex, age and psychiatric comorbidity. (a) No significant differences were found with respect to sex. (b) Patients ≤ 40 years of age put more emphasis on the probability of clear skin (p = 0.004) and of itch improvement (p = 0.012) but regarded the type of side effect less relevant (p = 0.002). Older patients had greater concern about “nephrotoxicity, hypertension and increased susceptibility to infections” (p = 0.003) and were more willing to accept “nausea, elevation in lipids and herpes zoster” (p = 0.035). (c) Presence of a psychiatric comorbidity was associated with higher preferences for the probability of clear skin (p = 0.029) and less interest in the type of side effects (p = 0.020). Patients with psychiatric comorbidity were less afraid of “nephrotoxicity, hypertension and increased susceptibility to infections” (p = 0.008) and disliked injections every 4 weeks more (p = 0.033) than other participants. Bars: means with standard deviations. PWU: Part-Worth Utility; RIS: Relative Importance Scores. *p < 0.05, **p < 0.01.

Figure 3. Treatment preferences dependent on current systemic therapy, DLQI and PO-SCORAD. (a) Patients receiving non-biologic drugs placed significantly more value on the time to onset of itch relief than others (p = 0.004 compared to patients on biologics; p = 0.002 compared to those without systemic treatment). Participants treated with biologics were more willing to accept “conjunctivitis, injection-site reaction and oral herpes” (p = 0.001 compared to non-biologic treatment; p = 0.013 compared to participants without systemic treatment). Those receiving non-biologic drugs were less interested in avoidance of “nephrotoxicity, hypertension and increased susceptibility to infections” (p = 0.039 compared to no systemic therapy; p = 0.019 compared to biologics). Compared to those without a systemic therapy, patients treated with biologics were less interested in an oral therapy (p = 0.009) and favored a subcutaneous treatment regimen more (every 2 weeks: p = 0.020; every 4 weeks: p = 0.019). Participants treated with non-biologic agents disliked a subcutaneous medication every other week more than those with biologics (p = 0.042). (b) Health-related quality of life had no significant impact on RIS. However, participants with a DLQI ≤10 attached greater importance to avoidance of “nephrotoxicity, hypertension and increased susceptibility to infections” (p = 0.015) and were more willing to accept “conjunctivitis, injection-site reaction and oral herpes” (p = 0.007). (c) PO-SCORAD >40 was associated with higher preferences for skin clearance (p = 0.015) and itch relief (p = 0.033) and less concern about the type of side effects (p = 0.026). Participants with a PO-SCORAD ≤40 worried more about “nephrotoxicity, hypertension and increased susceptibility to infections” (p = 0.004) and less about “conjunctivitis, injection-site reaction and oral herpes” (p = 0.015). Bars: means with standard deviations. DLQI: Dermatology Life Quality Index; PO-SCORAD: Patient-Oriented SCORing of Atopic Dermatitis; PWU: Part-Worth Utility; RIS: Relative Importance Scores. *p < 0.05, **p < 0.01.

Table 4. Multivariate linear regression models assessing the impact of patient and disease characteristics on RIS of treatment attributes.

	Probability of (almost) clear skin at week 16		Probability of significant itch improvement at week 16		Time to onset of itch relief		Type of side effects		Application method		Frequency of laboratory tests
Independent variables	β	p	β	p	β	p	β	p	β	p	β	p
Male^a	4.594	0.032	1.439	0.310	−1.640	0.064	−5.008	0.080	0.348	0.855	0.266	0.761
Age >40 years^b	−5.505	0.001	−3.168	0.012	0.347	0.666	8.048	0.001	−0.599	0.660	0.877	0.203
Psychiatric comorbidity^c	3.669	0.086	1.601	0.234	0.663	0.518	−5.606	0.031	0.233	0.895	−0.560	0.452
Systemic treatment^d	2.854	0.174	1.016	0.438	1.507	0.136	−4.885	0.069	−0.439	0.761	−0.053	0.946
DLQI	−0.005	0.974	−0.047	0.621	0.026	0.701	−0.131	0.490	0.167	0.226	−0.010	0.840
PO-SCORAD	0.067	0.313	0.022	0.602	0.009	0.793	−0.034	0.707	−0.033	0.587	−0.031	0.271
Constant	16.985	<0.001	14.733	<0.001	8.073	<0.001	38.482	<0.001	14.014	<0.001	7.713	<0.001

The RIS was defined as the dependent variable; sex, age, psychiatric comorbidity, systemic treatment, DLQI and PO-SCORAD were used as independent variables. β represents the unstandardized regression coefficient. For continuous variables (DLQI, PO-SCORAD), a positive β-value indicates that the attribute gains importance with an increase in the characteristic, whereas a negative β-value indicates a loss of importance with an increase in the characteristic. For all other variables, a positive β indicates a higher importance assigned to the attribute compared to the reference group. Statistically significant findings are highlighted in bold. Reference categories: ^afemale, ^bage ≤40 years, ^cno psychiatric comorbidity, ^dcurrently no systemic treatment. DLQI and PO-SCORAD were incorporated as linear values. DLQI, Dermatology Life Quality Index; PO-SCORAD, Patient-Oriented SCORing of Atopic Dermatitis; RIS, Relative Importance Score.

Table 5. Multivariate linear regression models assessing the impact of patient and disease characteristics on PWU for levels of the attributes “type of side effects” and “application method”.

	Type of side effects						Application method
	Conjunctivitis, injection-site reaction, oral herpes		Nausea, elevation in lipids, herpes zoster		Nephrotoxicity, hypertension, increased susceptibility to infections		Oral medication once or twice daily		Subcutaneous injections every two weeks		Subcutaneous injections every four weeks
Independent variables	β	p	β	p	β	p	β	p	β	p	β	p
Male^a	−8.636	0.426	−3.185	0.719	11.822	0.386	21.341	0.049	−10.607	0.091	−10.734	0.046
Age >40 years^b	13.400	0.162	19.775	0.025	−33.176	0.007	−7.061	0.432	2.524	0.630	4.537	0.326
Psychiatric comorbidity^c	−16.263	0.148	−16.407	0.098	32.670	0.014	13.927	0.238	−2.015	0.769	−11.913	0.039
Systemic treatment^d	8.440	0.414	−27.058	0.007	18.619	0.165	−23.222	0.023	10.683	0.086	12.539	0.012
DLQI	−2.025	0.011	−0.696	0.337	2.721	0.005	0.462	0.581	−0.304	0.522	−0.158	0.696
PO-SCORAD	−0.020	0.957	0.133	0.647	−0.113	0.802	−0.093	0.801	0.099	0.653	−0.006	0.973
Constant	44.456	0.027	69.283	<0.001	−113.740	<0.001	−8.769	0.626	−10.672	0.309	19.441	0.028

The PWU was defined as the dependent variable; sex, age, psychiatric comorbidity, systemic treatment, DLQI and PO-SCORAD were used as independent variables. β represents the unstandardized regression coefficient. For continuous variables (DLQI, PO-SCORAD), a positive β-value indicates that the attribute gains importance with an increase in the characteristic, whereas a negative β-value indicates a loss of importance with an increase in the characteristic. For all other variables, a positive β indicates a higher importance of the attribute compared to the importance assigned by the reference group. Statistically significant findings are highlighted in bold. Reference categories: ^afemale, ^bage ≤40 years, ^cno psychiatric comorbidity, ^dcurrently no systemic treatment. DLQI and PO-SCORAD were incorporated as linear values. DLQI, Dermatology Life Quality Index; PO-SCORAD, Patient-Oriented SCORing of Atopic Dermatitis; PWU, Part-Worth Utility.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. Additionally, the used model can be provided upon request.