Takaisin Tulosta

Tralokinumab in the treatment of adult atopic dermatitis

Additional information
Tanja Laukkala and Raija Sipilä
30.5.2023

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. Tra...»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 p...»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. Tra...»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 p...»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. Tra...»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 p...»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. Tra...»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 p...»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. Tra...»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 p...»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. Tra...»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 p...»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. Tra...»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 p...»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. Tra...»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 p...»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

  1. 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
  2. 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