Lisätietoa aiheesta

Tralokinumab in the treatment of adult atopic dermatitis

Additional information

30.5.2023

Tanja Laukkala and Raija Sipilä

Tralokinumab has been compared to placebo. The evidence is based on 3 RCTs, but the quality of evidence varies among outcomes, 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; IGA=Investigator's Global Assessment score; EASI=Eczema Area and Severity Index, POEM50= 50% improvement in POEM (Patient-Oriented Eczema Measure) score; SAE=serious adverse effects; TCS=topical corticosteroids; q2w=every 2 weeks
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	2 RCTs	Patients ≥ 18 years with moderate to severe atopic dermatitis (EASI ≥ 12 at screening and ≥ 16 at baseline, IGA score of ≥ 3) for ≥ 1 year, an inadequate response to topical treatments n1=802 n2=794	Subcutaneous tralokinumab 300 mg, after a 600 mg loading dose on day 0, or placebo every other week.	Primary: IGA score of 0 (clear skin) or 1 (almost clear skin) and EASI-75 at week 16.	Low
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT	Patients ≥ 18 years with moderate-to-severe atopic dermatitis (EASI score ≥ 12 at screening and ≥ 16 at baseline, IGA score of ≥ 3) for ≥ 1 year and an inadequate response to topical medications or documented systemic treatment in the past year. N=380.	Subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed after day 0. Loading dose of 600 mg tralokinumab or placebo.	Primary: IGA score of 0 or 1 and EASI-75 at week 16.	Low

Table 2. Additional comments for included studies
Reference	Comments
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	Two identical 52-week, multinational, randomized, double-blind, placebo-controlled trials. Patients were randomized to treatment and placebo groups 3 : 1. Rescue treatment for AD could be provided at the discretion of the investigator. For the purpose of efficacy analysis, patients who received rescue treatment during the initial treatment period were considered nonresponders in the primary analysis but were permitted to continue their assigned study treatment if rescue consisted of topical medications. After a 16-week initial treatment period, tralokinumab-treated patients who achieved the prespecified criteria for clinical response of IGA score of 0 or 1, or ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) were rerandomized 2:2:1 to tralokinumab 300 mg every 2 weeks (Q2W) or every 4 weeks (Q4W), or placebo for a 36-week maintenance treatment period. The study was sponsored by pharma.
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	A double-blind, randomized, placebo-controlled 32-week trial conducted across 63 sites in Europe and North America. Supplied topical corticosteroids were advised to be used as needed, once daily to areas with active lesions [mometasone furoate 0.1% cream; Europe class 3 (potent)]. The study was sponsored by pharma.

Results

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
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	RCT 1 no concomitant TCS allowed N= 798 (601/197)	16	150 (25.0%)	25 (12.7%)	12.1 (6.5 - 17.7)
	RCT 2 no concomitant TCS allowed N=792 (591/201)	16	196 (33.2%)	23 (11.4%)	21.6 (15.8 - 27.3)
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT concomitant TCS allowed N= 380 (253/127)	16	141 (56.0%)	45 (35.7%)	20.2 (9.8–30.6)
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
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	RCT 1 no concomitant TCS allowed N= 798 (601/197)	16	87 (14.5%)	8 (4.1%)	10.3 (6.4 - 14.1)
	RCT 2 no concomitant TCS allowed N=792 (591/201)	16	108 (18.3%)	11 (5.5%)	12.7 (8.3-17.0)
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT concomitant TCS allowed N= 380 (253/127)	16	83 (32.9%)	27 (21.4%)	11.4 (2.1–20.7)
Level of evidence: moderate The quality of evidence is downgraded due to imprecision (wide confidence intervals and possible lack of clinically meaningful difference).

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)
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	RCT 1 no concomitant TCS allowed N= 798 (601/197)	16	95 (15.8%)	14 (7.1%)	8.6% (4.1–13.1)
	RCT 2 no concomitant TCSallowed N=792 (591/201)	16	131(22.2%)	22(10.9%)	11.1% (5.8–16.4)
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT concomitant TCS allowed N= 380 (253/127)	16	98 (38.9%)	33 (26.2%)	12.4% (2.9–21.9)
Level of evidence: moderate The quality of evidence is downgraded due to imprecision.
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids

Table 6. Outcome 4: Pruritus (Improvement in weekly average of worst daily pruritus NRS ≥ 4 points from baseline to week 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	ARR (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; TCS=topical corticosteroids
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	RCT 1 no concomitant TCS allowed N= 798 (601/197)	16	119 (20.0%)	20 (10.3%)	9.7 (4.4 - 15.0)
	RCT 2 no concomitant TCS allowed N=792 (591/201)	16	144 (25.0%)	19 (9.5%)	15.6 (10.3 - 20.9)
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT concomitant TCS allowed N= 380 (253/127)	16	113 (45.4%)	43 (34.1%)	11.3 (0.9–21.6)
Level of evidence: moderate The quality of evidence is downgraded due to imprecision.

Table 7. Outcome 5: Quality of life (Dermatology Life Quality Index (DLQI) score reduction ≥ 4)
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
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	RCT 1 no concomitant TCS allowed N= 798 (601/197)	16	258 (44.6%)	60 (31.6%)	13.0 (5.4 - 20.5)
	RCT 2 no concomitant TCS allowed N=792 (591/201)	16	325 (56.3%)	54 (27.3%)	28.9 (21.4 - 36.3)
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT concomitant TCS allowed N= 380 (253/127)	16	207 (83.5%)	81 (65.9%)	17.6 (8.0–27.1)
Level of evidence: moderate The quality of evidence is downgraded due to inconsistency.

Table 8. Outcome 6: POEM (adjusted mean change from baseline in Patient-Oriented Eczema Measure (POEM) score)
Reference	Number of studies and number of patients (I/C)	Follow-up time, weeks	Mean change (SE) I	Mean change (SE) C	Difference (95% CI)
I=intervention; C=comparison; CI=confidence interval; SE=standard error; TCS=topical corticosteroids; POEM maximum score 28 points.
«Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III tria»1	RCT 1 no concomitant TCS allowed N= 798 (601/197)	16	-7.6 (0.35)	-3.0 (0.66)	-4.6 (-6.0- -3.1)
	RCT 2 no concomitant TCS allowed N=792 (591/201)	16	-8.8 (0.33)	-3.7 (0.66)	-5.1 (-6.5 - -3.6)
«Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo»2	RCT concomitant TCS allowed N= 380 (253/127)	16	-11.8 (0.46)	-7.8 (0.66)	-4.0 (-5.6- -2.4)
Level of evidence: high

References

Wollenberg A, Blauvelt A, Guttman-Yassky E ym. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol 2021;184:437-449 «PMID: 33000465»PubMed
Silverberg JI, Toth D, Bieber T ym. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol 2021;184:450-463 «PMID: 33000503»PubMed