Näytönastekatsaukset

Upadacitinib therapy in adults with moderate to severe atopic dermatitis: effectiveness compared to placebo

Näytönastekatsaukset

30.5.2023

Krista Nuotio

Level of evidence: A

Oral upadacitinib at the dose of 15-30mg daily alone or in combination with topical treatment increases the proportion of adult patients with moderate-to-severe atopic dermatitis achieving EASI75 response at week 16, when compared to placebo (15 mg: 60.1-69.6 %, 30 mg: 72.9-79.7%, and placebo 13.3-26.4%).

In addition, upadacinitib compared to placebo increases the proportion of patients achieving EASI90, with improvement in peak score on numerical rating scale (NRS) for pruritus and improves quality of life. The evidence is based on 3 RCTs, applicability of the evidence is high.

Table 1. Description of the included studies
Reference	Study type	Population	Intervention and comparison	Outcomes	Risk of bias
RCT=randomized controlled trial; EASI=Eczema Area and Severity Index, IGA=Investigator Global Assessment, NRS=Numeric Rating Scale, SCORAD=SCORing Atopic Dermatitis, BSA=Body Surface Area, POEM=Patient-Oriented Eczema Measure, AE=Adverse Event, DLQI=Dermatology Life Quality Index, vIGA-AD=validated Investigator's Global Assessment for Atopic Dermatitis, ADerm-IS=Atopic Dermatitis Impact Scale; ADerm-SS=the Atopic Dermatitis Symptom Scale, HADS-A=Hospital Anxiety and Depression Scale, anxiety; HADS-D=Hospital Anxiety and Depression Scale, depression.
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	2 RCTs	Patients 12-75 years of age with moderate to severe atopic dermatitis (EASI ≥ 16 and an IGA score of ≥ 3), an inadequate response to topical treatments or using systemic treatment. Multicenter study n1=847 n2=836	Upadacitinib 15mg or upadacitinib 30mg vs. placebo	Primary: EASI-75 and vIGA-AD Secondary: NRS, EASI-90, ADerm-IS, ADerm-SS, EASI-100, POEM, DLQI, HADS-A, HADS-D	Low
«Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up):»2	RCT	Patients 12-75 years of age with moderate to severe atopic dermatitis (EASI ≥ 16 and an IGA score of ≥ 3, onset ≥ 3yrs before baseline) Multicenter study N=901	Upadacitinib 15mg with topical treatment or upadacitinib 30mg with topical treatment vs. Placebo with topical treatment Choice of topical treatment aligned with potency was at the investigator's discretion.	Primary outcome: EASI-75, vIGA-AD Secondary outcomes: WP-NRS, EASI-90, EASI-100, EASI.	Low

Table 2. Additional comments for included studies
Reference	Comments
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	N of adolescents=228 The study was sponsored by pharma.
«Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up):»2	N of adolescents=116 Choice of topical corticosteroids (TCS) aligned with potency was at the investigator's discretion; the protocol recommended triamcinolone acetonide 0·1% cream or fluocinolone acetonide 0·025% ointment as medium potency TCS and hydrocortisone 1% cream as low potency TCS. The study was sponsored by pharma.

Results

Results are shown for upadacitinib 15 and 30 mg.

Table 3. Outcome 1: EASI-75 (number and proportion of patients achieving EASI-75)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	ARR (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids; UPA=upadacitinib
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	RCT 1, UPA 15 mg, no concomitant TCS allowed (281 /281)	16	196 (69.6)	46 (16.3)	53.3 (46.4-60.2)
	RCT 1, UPA 30 mg, no concomitant TCS allowed (285 /281)	16	227 (79.7)	46 (16.3)	63.4 (57.1-69.8)
	RCT 2, UPA 15 mg, no concomitant TCS allowed (276/278)	16	166 (60.1)	37 (13.3)	46.9 (39.9- 53.9)
	RCT 2, UPA 30 mg, no concomitant TCS allowed (282/278)	16	206 (72.9)	37 (13.3)	59.6 (53.1-66.2)
«Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up):»2	UPA 15 mg, concomitant TCS allowed (300 / 304)	16	194 (64.6)	80 (26.4)	38.1 (30.8 - 45.4)
	UPA 30 mg, concomitant TCS allowed (297/304)	16	229 (77.1)	80 (26.4)	50.6 (43.8-57.4)
Level of evidence: High

Table 4. Outcome 2: EASI-90 (number and proportion of patients achieving EASI-90)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	ARR (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids; UPA=upadacitinib
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	RCT 1, UPA 15 mg, no concomitant TCS allowed (281 /281)	16	149 (53.1)	23 (8.1)	45.1 (38.6-51.7)
	RCT 1, UPA 30 mg, no concomitant TCS allowed (285 /281)	16	187 (65.8)	23 (8.1)	57.8 (51.5-64.1)
	RCT 2, UPA 15 mg, no concomitant TCS allowed (276/278)	16	117 (42.4)	15 (5.4)	36.9 (30.6-43.3)
	RCT 2, UPA 30 mg, no concomitant TCS allowed (282/278)	16	165 (58.5)	15 (5.4)	53.1 (46.7-59.4)
«Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up):»2	UPA 15 mg, concomitant TCS allowed (300 / 304)	16	128 (42.8)	40 (13.2)	29.5 (22.8-36.3)
	UPA 30 mg, concomitant TCS allowed (297/304)	16	187 (63.1)	40 (13.2)	49.9 (43.3-56.4)
Level of evidence: High

Table 5. Outcome 3: IGA (Investigator's Global Assessment (IGA) score achieved 0/1)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	ARR (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids; UPA=upadacitinib
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	RCT 1, UPA 15 mg, no concomitant TCS allowed (281 /281)	16	135 (48.1)	24 (8.4)	39.8 (33.2-46.4)
	RCT 1, UPA 30 mg, no concomitant TCS allowed (285 /281)	16	177 (62.0)	24 (8.4)	53.6 (47.2-60.0)
	RCT 2, UPA 15 mg, no concomitant TCS allowed (276/278)	16	107 (38.8)	13 (4.7)	34.0 (27.8-40.2)
	RCT 2, UPA 30 mg, no concomitant TCS allowed (282/278)	16	147 (52.0)	13 (4.7)	47.4 (41.9-53.7)
«Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up):»2	UPA 15 mg, concomitant TCS allowed (300 / 304)	16	119 (64.6)	33 (10.9)	28.5 (22.1-34.9)
	UPA 30 mg, concomitant TCS allowed (297/304)	16	174 (58.6)	33 (10.9)	47.6 (41.1-54.0)
Level of evidence: High

Table 6. Outcome 4: Pruritus (Improvement in weekly average of worst daily pruritus NRS ≥ 4 points from baseline, assessed if NRS was at least 4 at baseline)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	Absolute difference (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids; UPA=upadacitinib
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	RCT 1, UPA 15 mg, no concomitant TCS allowed (281 /281)	16	143/274 (52.2)	32/272 (11.8)	40.5 (33.5-47.5)
	RCT 1, UPA 30 mg, no concomitant TCS allowed (285 /281)	16	168/280 (60.0)	32/272 (11.8)	48.2 (41.3-55.0)
	RCT 2, UPA 15 mg, no concomitant TCS allowed (276/278)	16	113/270 (41.9)	25/274 (9.1)	32.6 (25.8-39.4)
	RCT 2, UPA 30 mg, no concomitant TCS allowed (282/278)	16	167/280 (59.6)	25/274 (9.1)	50.4 (43.8-57.1)
«Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up):»2	UPA 15 mg, concomitant TCS allowed (300 / 304)	16	149/288 (51.7)	44/294 (15.0)	36.8 (29.7-43.8)
	UPA 30 mg, concomitant TCS allowed (297/304)	16	186/291 (63.9)	44/294 (15.0)	48.8 (41.9-55.7)
Level of evidence: high

Table 7. Outcome 5: Quality of life (Dermatology Life Quality Index (DLQI) score reduction ≥ 4, assessed if DLQI was at least 4 at baseline and age at least 16)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	Absolute difference (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids; UPA=upadacitinib
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	RCT 1, UPA 15 mg, no concomitant TCS allowed (281 /281)	16	192/254 (75.4)	73/250 (29.0)	46.7 (39.0-54.4)
	RCT 1, UPA 30 mg, no concomitant TCS allowed (285 /281)	16	210/256 (82.0)	73/250 (29.0)	53.2% (45.9-60.5)
	RCT 2, UPA 15 mg, no concomitant TCS allowed (276/278)	16	180/251 (71.7)	71/250 (28.4)	42.8 (35.0-50.6)
	RCT 2, UPA 30 mg, no concomitant TCS allowed (282/278)	16	195/251 (77.6)	71/250 (28.4)	49.0 (41.4-56.5)
Level of evidence: high

Table 8. Outcome 6: POEM (Patient-Oriented Eczema Measure (POEM) score reduction ≥ 4, assessed if POEM was at least 4 at baseline)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	Absolute difference (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids; UPA=upadacitinib
«Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from t»1	RCT 1, UPA 15 mg, no concomitant TCS allowed (281 /281)	16	209/278 (75.0)	63/276 (22.8)	52.3 (45.2-59.4)
	RCT 1, UPA 30 mg, no concomitant TCS allowed (285 /281)	16	228/280 (81.4)	63/276 (22.8)	58.6 (51.9-65.3)
	RCT 2, UPA 15 mg, no concomitant TCS allowed (276/278)	16	190/268 (70.9)	77/268 (28.7)	42.1 (34.5-49.8)
	RCT 2, UPA 30 mg, no concomitant TCS allowed (282/278)	16	225/269 (83.5)	77/268 (28.7)	54.7 (47.7-61.7)
Level of evidence: high

References

Guttman-Yassky E, Teixeira HD, Simpson EL ym. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet 2021;397:2151-2168 «PMID: 34023008»PubMed
Reich K, Teixeira HD, de Bruin-Weller M ym. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2021;397:2169-2181 «PMID: 34023009»PubMed