Early itch relief with upadacitinib predicts later skin clearance in Atopic dermatitis

Figures & data

Table 1. Patient demographics and medical history at baseline (n = 105).

Age (years)^a	35 [15.8–51]
<18 years, n (%)	31 (29.5)
Male, n (%)	73 (69.5)
Body mass index (kg/m²)^a	22.8 [20.0–26.1]
Disease duration (years)^a	22 [13–42]
Comorbidities, n (%)
Allergic conjunctivitis	14 (13.3)
Allergic rhinitis	30 (28.6)
Asthma	28 (26.7)
Cataract	5 (4.8)
Pretreatment, n (%)
Topical treatment alone	78 (74.3)
Systemic corticosteroids	7 (6.7)
Cyclosporine	11 (10.5)
Phototherapy	2 (1.9)
Dupilumab	6 (5.7)
Baricitinib	1 (1)
Clinical indices^a
EASI	23.2 [17.6–32]
IGA	3 [3–4]
ADCT	14.5 [11–19]
PP-NRS	8 [7–9]
Laboratory findings^a
IgE (IU/mL)	2234 [432.8–8368.3]
TARC (pg/mL)	1223 [593.8–3775]
LDH (IU/mL)	248 [196–323]
TEC (number/µL)	431.2 [238.4–755.7]

^a Data provided as the median [interquartile range].

EASI: eczema area and severity index; ADCT: atopic dermatitis control tool; PP-NRS: peak pruritus-numerical rating scale; IGA: investigator’s global assessment; IgE: immunoglobulin E; TARC: thymus and activation-regulated chemokine; LDH: lactate dehydrogenase; TEC: total eosinophil count.

Figure 1. The transition of peak pruritus-numerical rating scale (PP-NRS) in patients with atopic dermatitis treated with upadacitinib 15 mg/day (n = 105). **p < 0.01 versus week 0, analyzed by friedman’s test.

Figure 2. Predictability for week 12 eczema area and severity index (EASI) 100 (a), week 12 investigator’s global assessment (IGA) 0/1 (b), week 24 EASI 100 (c) or week 24 IGA 0/1 (d) by week 2 peak pruritus-numerical rating scale (PP-NRS) value in treatment with upadacitinib 15 mg/day as evaluated by area under the receiver operating characteristic curve (AUC).

Table 2. Optimal threshold for week 2 PP-NRS response to predict clearance of rash at weeks 12 or 24.

Features of threshold	Index of effectiveness	Week 12				Week 24
		Sensitivity	Specificity	AUC	Cutoff value	Sensitivity	Specificity	AUC	Cutoff value
Absolute value of PP-NRS	EASI 90	0.567	0.77	0.658	1	0.48	0.776	0.674	1
	EASI 100	0.7	0.947	0.849	0	0.938	0.775	0.861	1
	IGA0/1	0.773	0.793	0.747	1	0.852	0.566	0.74	2
PP-NRS reduction from week 0	EASI 90	0.433	0.689	0.551	7	0.72	0.534	0.608	6
	EASI 100	0.6	0.681	0.565	7	0.5	0.674	0.572	7
	IGA0/1	0.455	0.683	0.56	7	0.667	0.553	0.589	6

EASI: eczema area and severity index; PP-NRS, peak pruritus-numerical rating scale; IGA: investigator’s global assessment; AUC: area under the curve.

Figure 3. Transition of achievement rates of peak pruritus-numerical rating scale (PP-NRS) ≤ 1 in whole patients (n = 105) and in achievers of week 2 PP-NRS ≤ 1 (n = 35) during treatment with upadacitinib 15 mg/day. **p < 0.01 versus week 0; †p < 0.05, ††p < 0.01 versus week 2; §p < 0.05 versus week 4, analyzed by Fisher’s exact test.

Figure 4. The comparison of achievement rates for eczema area and severity index (EASI) 100 (a), EASI 90 (b), or investigator’s global assessment (IGA) 0/1 (c) between achievers of week 2 PP-NRS ≤ 1 (n = 35) versus non-achievers (n = 70). *p < 0.05, **p < 0.01 versus non-achievers, analyzed by fisher’s exact test.

Figure 5. The comparison of eczema area and severity index (EASI) (a), atopic dermatitis control tool (ADCT) (b) and peak pruritus-numerical rating scale (PP-NRS) (c) between achievers of week 2 PP-NRS ≤ 1 (n = 35) versus non-achievers (n = 70). **, p < 0.01 versus non-achievers, analyzed by Mann-Whitney test.

Table 3. The association of each variable with EASI 100 achievement at each time point, analyzed by multiple logistic regression analysis.

	Week 4			Week 12			Week 24
	Odds Ratio	95% Confidential Interval	p	Odds Ratio	95% Confidential Interval	p	Odds Ratio	95% Confidential Interval	p
(Intercept)	2.63 × 10^–8	0–infinity	0.995	6770	0.537–8.52 x10^7	0.0671	2.31	0.0136–390	0.75
Age (years)	1.01	0.957–1.07	0.644	1.04	0.981–1.1	0.188	1.02	0.979–1.06	0.362
Sex [T.F.]	0.23	0.0281–1.89	0.171	0.664	0.0875–5.05	0.693	0.667	0.146–3.05	0.602
Body mass index (kg/m2)	0.844	0.602–1.17	0.3	0.503	0.297–0.851	0.0104*	0.782	0.6150–0.994	0.0442*
Week 2 PP-NRS≤ 1 achievement	4.25 × 10^8	0–infinity	0.995	38	3.15–459	<0.01**	43.9	4.76–405	<0.01**

*Statistically significant at p < 0.05, **p < 0.01.

EASI: eczema area and severity index; PP-NRS: peak pruritus-numerical rating scale.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.