Predictive factors for responders to upadacitinib treatment in patients with atopic dermatitis

Figures & data

Table 1. Baseline demographic and disease characteristics of patients with atopic dermatitis (n = 211).

	Upadacitinib 15 mg (n = 159)	Upadacitinib 30 mg (n = 52)	p
Male sex, n (%)	112 (70.4)	38 (73.1)	0.86
Age (years)^a	33.0 [16.0–50.0]	40.5 [31.0–48.0]	0.0688
Body mass index (kg/m2)^a	22.7 [20.3–25.4]	24.1 [21.6–27.1]	0.0229*
Disease duration (years)^a	27.0 [13.0–42.0]	32.5 [22.0–42.25]	0.0411*
Presence of allergic conjunctivitis	33 (20.8)	9 (17.3)	0.691
Presence of allergic rhinitis	43 (27.0)	22 (42.3)	0.0561
Presence of bronchial asthma	42 (26.4)	22 (42.3)	0.0373*
Previous dupilumab	10 (6.3)	9 (17.3)	0.0242*
Previous upadacitinib 15 mg	0	20 (38.5)	<0.01**
Previous baricitinib 4 mg	4 (2.5)	20 (38.5)	<0.01**
Clinical indexes
Total EASI^a	24 [17.4–34.8]	14.6 [10.7–20.3]	<0.01**
EASI of head and neck^a	2.7 [1.2–4.0]	2.8 [1.6–3.6]	0.87
EASI of upper limbs^a	5.6 [4.0–7.8]	2.8 [1.8–4.8]	<0.01**
EASI of lower limbs^a	7.2 [9.6–14.0]	3.6 [1.6–6.8]	<0.01**
EASI of trunk^a	7.2 [5.4–10.5]	4.5 [3.3–7.4]	<0.01**
IGA
Mild (score of 2)	11 (6.92)	12 (23.1)	0.0296*
Moderate (score of 3)	80 (50.3)	29 (55.8)
Severe (score of 4)	68 (42.8)	11 (21.2)
PP-NRS^a	8.0 [7.0–9.0]	6.0 [5.0–8.0]	<0.01**
Laboratory parameters
IgE (IU/mL)^a	2216.5 [432.8–8096.0]	9875.5 [3310.0–18872.5]	<0.01**
TARC (pg/mL)^a	597.25 [1315.0–3688.0]	5762.5 [1718.3–13154.5]	<0.01**
LDH (IU/mL)^a	254 [198.5–317.0]	264.0 [220.0–324.5]	0.128
Eosinophils (/μL)^a	490.0 [269.2–768.0]	431.0 [241.4–665.5]	0.575
Neutrophils (/μL)^a	3729.2[2809.0–4572.7]	4102.4 [3302.5–5181.9]	0.0336*
Lymphocytes (/μL)^a	1664.2 [1319.2–1999.2]	1537.2 [1299.3–1817.7]	0.328
Monocytes (/μL)^a	382.8 [310.8528.0]	438.6 [341.0–569.4]	0.172
Platelets (10³/μL)^a	276.5 [246.5–318.0]	295.5 [271.3–342.8]	<0.01**
ELR^a	0.29 [0.15–0.52]	0.26 [0.16–0.45]	0.96
NLR^a	2.3 [1.5–3.1]	2.6 [2.0–3.4]	0.0788
MLR^a	0.3 [0.2–0.3]	0.3 [0.2–0.4]	0.278
PLR^a	160.6 [117.7–218.5]	189.7 [157.9–231.8]	0.0275*

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

* Statistically significant at p < 0.05, **p < 0.01 by Fisher’s exact test or Mann Whitney U test.

EASI: eczema area and severity index; IGA: investigator’s global assessment; PP-NRS: peak pruritus numerical rating scale; IgE: immunoglobulin E; TARC: thymus and activation-regulated chemokine; LDH: lactate dehydrogenase; ELR: Eosinophil-to-lymphocyte ratio; NLR: neutrophil-to-lymphocyte ratio; MLR: monocyte-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio.

Table 2. Comparison of the background factors between responders and non-responders to upadacitinib 15 mg or 30 mg treatment for atopic dermatitis.

	Upadacitinib 15 mg (n = 159)			Upadacitinib 30 mg (n = 52)
Background factors	Responders (n = 35)	Non-responders (n = 124)	p	Responders (n = 15)	Non-responders (n = 37)	p
Male sex, n (%)	26 (74.3)	86 (69.4)	0.677	9 (60.0)	29 (78.4)	0.19
Presence of allergic conjunctivitis, n (%)	6 (17.1)	27 (21.8)	0.643	1 (6.7)	8 (21.6)	0.257
Presence of allergic rhinitis, n (%)	11 (31.4)	32 (25.8)	0.523	5 (33.3)	17 (45.9)	0.539
Presence of bronchial asthma, n (%)	9 (25.7)	33 (26.6)	1	3 (20.0)	19 (51.4)	0.0622
Presence of previous dupilumab	4 (11.4)	6 (4.8)	0.229	3 (20.0)	6 (16.2)	0.706
Presence of previous upadacitinib 15 mg	NA			3 (20.0)	17 (45.9)	0.118
Presence of previous baricitinib 4 mg	1 (2.9)	3 (2.4)	1	6 (40.0)	14 (37.8)	1
Age (years)^a	39 [17–51]	32 [15–50]	0.368	43.0 [34.0–46.5]	39.0 [31.0–48.0]	0.693
Body mass index (kg/m^2)^a	21.7 [20.5–24.9]	22.7 [20.2–25.6]	0.683	23.9 [21.5–24.8]	24.1 [21.6–27.2]	0.552
Disease duration (years)^a	21.0 [13.5–41.5]	27.0 [13.0–42.0]	0.77	36.0 [26.5–42.0]	30.0 [22.0–42.0]	0.585
Total EASI^a	18.2 [15.4–30.8]	30.0 [17.6–35.4]	0.0125*	12.5 [8.3–17.5]	15.5 [11.0–21.5]	0.17
EASI of head and neck^a	2.4 [0.2–3.4]	2.8 [1.2–4.0]	0.0461*	3.0 [1.2–3.8]	2.7 [1.9–3.5]	0.942
EASI of upper limbs^a	4.6 [3.7–6.3]	5.8 [4.0–8.0]	0.171	2.4 [1.0–4.8]	2.9 [2.0-4.8]	0.304
EASI of lower limbs^a	7.6 [6.3–13.1]	9.6 [7.2–14.0]	0.105	3.2 [1.2–4.4]	4.4 [1.6–9.6]	0.305
EASI of trunk^a	7.2 [5.4–7.2]	7.2 [4.8–10.6]	0.171	4.5 [1.2–7.2]	4.7 [3.6–8.2]	0.161
PP-NRS^a	7.0 [5.0–8.0]	8.0 [7.0–10.0]	0.0139*	7.0 [5.0–8.0]	6.0 [5.0–8.0]	0.501
IgE (IU/mL)^a	626.0 [198.0–2555.8]	2990.5 [774.5–8741.5]	<0.01**	2737.0 [621.5–10249.0]	12039.0 [6604.0–23121.0]	<0.01**
TARC (pg/mL)^a	820.0 [509.8–1416.0]	1479.0 [609.8–4535.0]	0.0534	1916.0 [601.5–6878.5]	6234.0 [2299.0–14894.0]	0.0202*
LDH (IU/mL)^a	217.0 [197.0–285.0]	256.0 [207.0–336.3]	0.107	219.0 [203.5–234.5]	287.0 [238.0–345.0]	<0.01**
Eosinophils (/μL)^a	451.0 [233.2–641.7]	506.4 [288.7–786.25]	0.325	286.0 [203.3–491.9]	491.4 [378.0–670.0]	0.0323*
Neutrophils (/μL)^a	3106.2 [2754.0–3794.2]	3878.4 [2827.3–4605.6]	0.0193*	4379.2 [3848.0–6235.0]	3849.2 [3024.0–5121.5]	0.262
Lymphocytes (/μL)^a	1584.0 [1451.8–1967.1]	1665.1 [1298.7–2019.2]	0.87	1657.2 [1481.5–1825.8]	1472.0 [1279.8–1817.7]	0.403
Monocytes (/μL)^a	361.9 [268.4–410.4]	393.3 [325.0–530.4]	0.0137*	515.2 [340.0–576.3]	430.4 [345.1–558.1]	0.681
Platelets (10³/μL)^a	282.0 [233.0–316.0]	276.0 [258.0–318.0]	0.251	292.0 [269.0–311.0]	298.0[275.0–348.0]	0.364
ELR^a	0.25 [0.15–0.34]	0.31 [0.14–0.56]	0.472	0.21 [0.14–0.34]	0.32 [0.17–0.54]	0.304
NLR^a	2.1 [1.3–2.6]	2.3 [1.6–3.2]	0.0529	2.5 [2.4–4.1]	2.6 [1.9–3.3]	0.613
MLR ^a	0.2 [0.1–0.3]	0.3 [0.2–0.4]	0.0301*	0.3 [0.2–0.4]	0.3 [0.2–0.4]	0.895
PLR^a	167.5 [128.1–186.9]	157.0 [117.5–226.0]	0.581	171.5 [153.7–231.1]	193.9 [170.5–231.0]	0.588

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

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

EASI: eczema area and severity index; PP-NRS: peak pruritus numerical rating scale; IgE: immunoglobulin E; TARC: thymus and activation-regulated chemokine; LDH: lactate dehydrogenase; ELR: Eosinophil-to-lymphocyte ratio; NLR: neutrophil-to-lymphocyte ratio; MLR: monocyte-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio; NA: not applicable.

Table 3. Multiple logistic regression analysis for the association of each variable with responders to treatment with upadacitinib 15 mg (n = 159) or 30 mg (n = 52) for atopic dermatitis.

Dose of upadacitinib		Odds ratio	95% confidential interval	p
15 mg	(Intercept)	0.213	0.00617–7.38	0.393
	Age (years)	1.03	1.0–1.06	0.0483*
	Sex (M = 1, F = 2)	1.37	0.512–3.66	0.532
	Body mass index (kg/m^2)	0.96	0.854–1.08	0.486
	Total EASI	0.931	0.874–0.992	0.0275*
	EASI of head and neck	1.18	0.862–1.62	0.299
	PP-NRS	1.14	0.884–1.46	0.319
	IgE (IU/mL)	1	1.0–1.0	0.707
	Neutrophils (/μL)	1	1.0–1.0	0.238
	Monocytes (/μL)†	1	0.994–1.01	0.318
30 mg	(Intercept)	3.98	0.0126–1260.0	0.638
	Age (years)	0.998	0.928–1.07	0.953
	Sex (M = 1, F = 2)	3.11	0.4810–20.1	0.233
	Body mass index (kg/m^2)	1.09	0.883–1.34	0.4290
	IgE (IU/mL)	1	1.0–1.0	0.0472*
	TARC (pg/mL)	1	1.0–1.0	0.4
	LDH (IU/mL)	0.983	0.966–0.999	0.0381*
	Eosinophils (/μL)	0.999	0.996–1.0	0.401

* Statistically significant at p < 0.05.

^† Since MLR is defined as monocyte to lymphocyte ratio, the variable ‘MLR’ was excluded from the analysis to avoid multicollinearity in 15 mg treatment group.

EASI: eczema area and severity index; PP-NRS: peak pruritus numerical rating scale; IgE: immunoglobulin E; TARC: thymus and activation-regulated chemokine; LDH: lactate dehydrogenase.

Figure 1. The receiver operating characteristic (ROC) curves for evaluating prediction capabilities of individual parameters for responders to upadacitinib 15 mg or 30 mg treatment. The figures present prediction capabilities of baseline total EASI (a) or age (b) for IGA 0/1 response to 15 mg upadacitinib at week 12, and those of baseline IgE (c) and LDH (d) for the same response to 30 mg upadacitinib.

Data availability statement

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