Effectiveness of dupilumab compared to placebo in treatment of adult patients with atopic dermatitis
Näytönastekatsaukset
30.5.2023
Level of evidence: A
Dupilumab (initial dose of 600 mg followed by 300 mg every other week) alone or in combination with topical treatments compared to placebo increases the proportion of adults with moderate to severe atopic dermatitis reaching EASI-75 at week 16 when compared to placebo (48–66% vs. 13–25%).
In addition, there is high quality evidence that compared to placebo dupilumab increases proportion of patients with improvement in peak score on numerical rating scale (NRS) for pruritus and improves quality of life.
The efficacy evidence is based on 5 RCTs with low risk of bias, applicability of the evidence is high.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; IGA=Investigator's Global Assessment score; EASI=Eczema Area and Severity Index, SCORAD=SCORing Atopic Dermatitis, GISS= Global Individual Sign Score, SASSAD=Six Area Six Sign Atopic Dermatitis, POEM=Patient Oriented Eczema Measure, DLQI=Skin or AD-specific health-related quality of life, QoL=quality of life, AE=adverse events, SAE= serious adverse events, TCS=topical corticosteroid. *Not included in the results section of this evidence summary. | |||||
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | MA including 7 RCTs | Patients ≥12 years with uncontrolled moderate-to-severe atopic dermatitis (IGA≥3, EASI≥12). N of adults (≥18) 1678 and N of adolescents (12-17 years)* 167. | Adults and adolescent with weight at least 60 kg: initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week; Adolescent with weight less than 60 kg: initial dose of 400 mg (two 200 mg injection) followed by 200 mg given every other week vs. placebo+usual care | Primary: SCORAD 75; EASI 50 or 75; and pruritus and safety (AEs) Secondary: f.ex. IGA, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL) at 16 weeks | Low |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | MA including 11 RCTs on dupilumab | Patients ≥12 years with uncontrolled moderate-to-severe atopic dermatitis (IGA≥3, EASI≥12). N of patients 3529. | Dupilumab (75 mg/150 mg/200 mg/300 mg weekly, 200 mg/300 mg every two weeks, 100mg/300mg every 4 weeks, 300mg every 8 weeks) vs. placebo | Primary: EASI 75, SCORAD, SASSAD, POEM, DLQI, AE, SAE Secondary pruritus | Low |
| «Blauvelt A, de Bruin-Weller M, Gooderham M ym. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, rando»3 | RCT | Patients ≥18 years with uncontrolled moderate-to-severe atopic dermatitis (IGA≥3, EASI≥16) and an inadequate response to TCS. N of patients 740. | Dupilumab 300 mg once weekly, dupilumab 300 mg every 2 weeks, or placebo once weekly. All groups used TCS and when needed topical calcineurin inhibitors. | Primary: IGA, EASI-75. Secondary f.ex. EASI-50, EASI-90, SCORAD, GISS and pruritus and safety (AEs), sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL) at 16 weeks | Low |
| «de Bruin-Weller M, Thaçi D, Smith CH ym. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or whe»4 | RCT | Patients ≥18 years with uncontrolled moderate-to-severe atopic dermatitis (IGA≥3, EASI≥20), an inadequate response to TCS and and either inadequate response to ciclosporin A or not eligible for ciclosporin A. N of patients 325. | Dupilumab 300 mg once weekly, dupilumab 300 mg every 2 weeks, or placebo once weekly. All groups used TCS once daily to active lesion. | Primary: EASI-75 at week 16. Secondary f.ex: SCORAD, pruritus, GISS, DLQI, POEM, EASI-50, EASI-90. | Low |
| «Simpson EL, Bieber T, Guttman-Yassky E ym. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016;375:2335-2348 »5 | 2 RCTs | Patients ≥18 years with uncontrolled moderate-to-severe atopic dermatitis (IGA≥3) and an inadequate response to TCS. N of patients 1379. | Dupilumab 300 mg once weekly, dupilumab 300 mg every 2 weeks, or placebo once weekly. | Primary: IGA Secodary: EASI-50, 75, and 90, pruritus, SCORAD, GISS, DLQI, POEM, anxiety and depression. | Low |
| Reference | Comments |
|---|---|
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | Search performed in MEDLINE, Cochrane Controlled Trials Register, and EMBASE until 2/2020. Seven RCTs were included. In some studies topical treatment was allowed, separate analysis not included. Risk of bias was assessed as low for all included studies. All studies were sponsored by pharma. |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | Meta-analysis of systemic treatments in the management of atopic dermatitis. Only results of dupilumab vs. placebo are shown in this evidence summary. Search performed in MEDLINE, Cochrane Controlled Trials Register, and EMBASE, and Global Resource of Eczema Trials (GREAT) until 2/2020. Risk of bias was assessed as low for nearly all included studies, all studies were sponsored by pharma. One study included adolescents. |
| «Blauvelt A, de Bruin-Weller M, Gooderham M ym. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, rando»3 | All patients received concomitant topical corticosteroids. Topical calcineurin inhibitors could be used in body locations considered inadvisable for topical corticosteroids. |
| «de Bruin-Weller M, Thaçi D, Smith CH ym. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or whe»4 | All eligible patients applied medium-potency TCS once daily to active lesion areas, or low-potency TCS on areas of thin skin (e.g. face, neck, intertriginous and genital areas). Patients could receive rescue medication, including potent or very potent TCS, topical calcineurin inhibitors or systemic medication, if medically necessary. |
| «Simpson EL, Bieber T, Guttman-Yassky E ym. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016;375:2335-2348 »5 | Two identical RCTs. Prohibited concomitant medications included topical glucocorticoids and calcineurin inhibitors, immunomodulating biologic agents, systemic glucocorticoids, and nonsteroidal systemic immunosuppressants. |
Results
The results are shown for dupilumab 300 mg every two weeks.
| Reference | Number of studies and number of patients (I/C) | Follow-up time (weeks) | Absolute number of events (%) I | Absolute number of events (%) C | Mean difference or risk difference (95% CI) |
|---|---|---|---|---|---|
| I=intervention; C=comparison; CI=confidence interval; MD=mean difference; RD=risk difference, TCS=topical corticosteroids | |||||
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | 5 RCTs N= 1675 (731/944) | 16 | 391 (53.5) | 173 (18.3) | MD -30.72 (-34.64 – -26.79) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 2 RCTs concomitant topical treatment allowed N= 636 (213/423) | 16 | 140 (65.7) | 105 (24.8) | RD 0.40 (0.28-0.52) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 3 RCTs no concomitant topical treatment allowed N= 1042 (521/521) | 16 | 251 (48.2) | 68 (13.1) | RD 0.35 (0.3-0.4) |
| Level of evidence: high | |||||
| 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; NA=not applicable. | |||||
| «Blauvelt A, de Bruin-Weller M, Gooderham M ym. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, rando»3 | RCT, concomitant topical treatment allowed N= 740 (106/305) | 16 | 42 (40) | 35 (11) | 29 (18.6-38.5) |
| «de Bruin-Weller M, Thaçi D, Smith CH ym. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or whe»4 | RCT, concomitant topical treatment allowed N=325 (107/108) | 16 | 49 (45.8) | 13 (12.0) | NA, p< 0.001 vs. placebo |
| «Simpson EL, Bieber T, Guttman-Yassky E ym. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016;375:2335-2348 »5 | RCT 1, no concomitant topical treatment allowed N=671 (224/224) | 16 | 80 (36) | 17 (8) | NA |
| RCT 2, no concomitant topical treatment allowed N=708 (233/236) | 16 | 70 (30) | 17 (7) | NA | |
| Level of evidence: moderate. The level of evidence is downgraded due to imprecision (confidence intervals not reported). | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time (weeks) | Absolute number of events (%) I | Absolute number of events (%) C | Risk ratio (95% CI) |
|---|---|---|---|---|---|
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | 4 RCTs N= 1553 (670/883) | 16 | 253 (37.8) | 97 (11.0) | 3.46 (2.79-4.30) |
| Level of evidence: high | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) or mean change I | Absolute number of events (%) or mean change C | Risk ratio or SMD (95% CI) |
|---|---|---|---|---|---|
| I=intervention; C=comparison; CI=confidence interval; TCS=topical corticosteroids; SMD=standardized mean difference; *Improvement in peak score on numerical rating scale (NRS) for pruritus ≥ 4 point, Absolute number of events; **NRS pruritus mean changes, range between different studies. | |||||
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | 5 RCTs N= 1612 (711/901) | 16 weeks | 316 (44.4)* | 143 (15.9)* | RR 2.96 (2.37-3.70) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 2 RCTs concomitant topical treatment allowed N=636 (213/423) | 16 | -53.9 – -56.2** | -25.4 – -28.6** | SMD: -0.8 (-0.97 – -0.62) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 3 RCTs no concomitant topical treatment allowed N=1042 (521/521) | 16 | -40.1 – -51.0** | 5.15 – -26.1** | SMD: -0.79 (-1.07 – -0.52) |
| Level of evidence: high | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean change* I | Mean change* C | MD or SMD (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval; MD=mean difference, SMD= standardized mean difference; * range between different studies. | |||||
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | 5 RCTs N=1678 (734/944) | 16 | -9.3 – -9.7 | -1.3 - -5.3 | MD -4.8 (-5.55- -4.06) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 2 RCTs concomitant topical treatment allowed N=636 (213/423) | 16 | -9.5 – -9.7 | -4.5 - -5.3 | SMD: -0.89 (-1.09—-0.69) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 3 RCTs no concomitant topical treatment allowed N=907 (457/460) | 16 | -9.3 – -9.5 | -3.6 – -5.3 | SMD: -0.70 (-0.93 – -0.48) |
| Level of evidence: high | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time (weeks) | Mean change* I | Mean change* C | SMD (95% CI) |
|---|---|---|---|---|---|
| I=intervention; C=comparison; CI=confidence interval; SMD=standardized mean difference. *Range between different studies. | |||||
| «Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 »1 | 5 RCTs 1678 (734/944) | 16 | -9.8 – -12.4 | -1.1 – -5.1 | -7.29 (-8.78 – -5.02) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 2 RCTs concomitant topical treatment allowed N=636 (213/423) | 16 | -11.90 – -12.40 | -4.30 – -4.70 | -1.17 (-1.35 – -0.99) |
| «Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 »2 | 3 RCTs no concomitant topical treatment allowed N=1042 (521/521) | 16 | -9.80 – -11.60 | -1.10 – -5.10 | -0.86 (-1.08 – -0.64) |
| Level of evidence: high | |||||
References
- Agache I, Song Y, Posso M ym. Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines. Allergy 2021;76:45-58 «PMID: 32691892»PubMed
- Siegels D, Heratizadeh A, Abraham S ym. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021;76:1053-1076 «PMID: 33074565»PubMed
- Blauvelt A, de Bruin-Weller M, Gooderham M ym. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017;389:2287-2303 «PMID: 28478972»PubMed
- de Bruin-Weller M, Thaçi D, Smith CH ym. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol 2018;178:1083-1101 «PMID: 29193016»PubMed
- Simpson EL, Bieber T, Guttman-Yassky E ym. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016;375:2335-2348 «PMID: 27690741»PubMed