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Rapid and sustained improvement in lesion extent and severity versus placebo

DUPIXENT was studied in six Phase 3 clinical trials in adults with moderate-to-severe atopic dermatitis (AD), including more than 2,400 patients worldwide, both as a monotherapy and with TCS for up to 52 weeks1

Rapid improvement compared to placebo + TCS at 16 weeks, sustained over 52 weeks2

CHRONOS: Proportion of adult patients achieving EASI-75 at Week 16 and Week 52*2

At 16 weeks, 69% of patients on DUPIXENT + TCS achieved ≥75% improvement in lesion extent and severity (EASI-75) compared to 23% with placebo + TCS2


Significant improvement in lesion extent and severity was sustained over 52 weeks2

CHRONOS: Proportion of adult patients achieving IGA of 0 or 1 and a reduction of 2 or more points at Week 16 and Week 52†2

At 16 weeks, 39% of patients on DUPIXENT + TCS achieved an IGA score of 0 or 1 with a reduction of ≥2 points compared to 12% with placebo + TCS2,3

CHRONOS: Proportion of adult patients achieving EASI-50 at Week 16 and Week 52*2

Significant improvement in lesion extent and severity versus placebo + TCS was seen over 16 weeks2

At 52 weeks, 79% of patients onDUPIXENT + TCS achieved ≥50% improvement in lesion extent and severity (EASI-50) compared to 30% with placebo + TCS (post-hoc analysis)2

CHRONOS: Proportion of adult patients achieving EASI-90 at Week 16 and Week 52*2

Significant improvement in lesion extent and severity versus placebo + TCS was seen over 16 weeks2

At 52 weeks, 51% of patients on DUPIXENT + TCS achieved ≥90% improvement in lesion extent and severity (EASI-90) compared to 16% with placebo + TCS (post-hoc analysis)2

CHRONOS trial design: A randomised, double-blind, placebo-controlled study of adults with moderate-to-severe atopic dermatitis with prior inadequate response to TCS. 319 patients were randomised to DUPIXENT 300 mg + TCS QW, 106 patients were randomised to DUPIXENT 300 mg + TCS Q2W (licensed dose) and 315 patients were randomised to placebo + TCS for 52 weeks.1 Emollient background regimen/therapy was required during the trial.2


The co-primary endpoints were the proportion of patients with both IGA 0/1 (clear/almost clear) and a ≥2-point reduction from baseline at Week 16 (0–4 scale), and the proportion of patients achieving 75% improvement in EASI (EASI-75) from baseline to Week 16.1


Other evaluated outcomes included: the proportion of patients with improvement of at least 50% and 90% in EASI (EASI-50 and EASI-90, respectively), reduction in itch as measured by the peak pruritus Numerical Rating Scale (NRS), percent change in the SCORing Atopic Dermatitis (SCORAD) scale from baseline to Week 16, mean change from baseline to Week 16 in the Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (a clinically meaningful improvement in DLQI is defined as a ≥4-point improvement on a 0 to 30 scale), and Hospital Anxiety and Depression Scale (HADS) scores. Efficacy was also evaluated at Week 52.1


Efficacy as monotherapy compared to placebo4

Pooled SOLO 1 and 2: Proportion of adult patients achieving EASI-75 at Week 16*4

At 16 weeks, 48% of patients on DUPIXENT achieved a ≥75% improvement in lesion extent and severity (EASI-75) compared to 13% of patients on placebo1,4

Pooled SOLO 1 and 2: Proportion of adult patients achieving IGA of 0 or 1 and a reduction of 2 or more points at Week 16†5

At 16 weeks, 37% of patients on DUPIXENT achieved an IGA score of 0 or 1 with a reduction of ≥2 points in both SOLO 1 and 2 compared to 9% of patients on placebo1,5

Visible results demonstrated in adult patients at Week 16 with DUPIXENT monotherapy

Baseline

Week 16

Baseline

Week 16

Responder:

achieved at least a 75% improvement in lesion extent and severity (EASI score) and an IGA score of 0 or 1 with a reduction of ≥2 points in both SOLO 1 and 2

Baseline

Week 16

Non-responder:

did not achieve at least a 75% improvement in lesion extent and severity (EASI score) or an IGA score of 0 or 1 with a reduction of ≥2 points in both SOLO 1 and 2

Clinical photographs are actual patients treated with DUPIXENT in the SOLO trial and are used with patient consent. Individual results may vary. SOLO 1 and 2 were two randomised, placebo-controlled trials of identical design (SOLO 1, n=671 and SOLO 2, n=708) in adults with moderate-to-severe atopic dermatitis (n=740), randomised to DUPIXENT 300 mg or placebo for 16 weeks.


Co-primary endpoints were the proportion of patients achieving EASI-75 (48% of patients treated with DUPIXENT vs 13% with placebo), and an IGA score of 0 or 1 with a reduction from baseline of ≥2 points at Week 16 (37% of patients treated with DUPIXENT vs 9% with placebo).1


SOLO 1 and 2 trial design: Two randomised, placebo-controlled trials of identical design (SOLO 1, n=671 and SOLO 2, n=708) of adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment, randomised to receive either DUPIXENT 300 mg QW, DUPIXENT 300 mg Q2W (licensed dose) or placebo for 16 weeks.1 Emollient background regimen/therapy was required during the trial.6


The co-primary endpoints were the proportion of patients with both IGA 0/1 (clear/almost clear) and 2 point or higher reduction from baseline at Week 16 (0–4 scale), and the proportion of patients achieving 75% improvement in EASI (EASI-75) from baseline to Week 16.1


Other evaluated outcomes included: the proportion of patients with improvement of at least 50% and 90% in EASI score (EASI-50 and EASI-90, respectively) at Week 16, reduction in itch as measured by the peak pruritus Numerical Rating Scale (NRS) from baseline to Week 16, percent change in the SCORing Atopic Dermatitis (SCORAD) scale from baseline to Week 16, mean change in the Patient Oriented Eczema Measure (POEM) from baseline to Week 16, Dermatology Life Quality Index (DLQI – a clinically meaningful improvement is defined as a ≥4-point improvement on a 0–30 scale), and Hospital Anxiety and Depression Scale (HADS) scores.1


Improvement compared to placebo + TCS following failed ciclosporin therapy7

CAFÉ: Proportion of adult patients achieving EASI-75 at Week 16*7

At 16 weeks, 63% of patients on DUPIXENT + TCS achieved ≥75% improvement in lesion extent and severity (EASI-75) compared to 30% with placebo + TCS7

CAFÉ trial design: A 16-week, Phase 3, double-blind, randomised, placebo-controlled trial of adults with severe atopic dermatitis, who are inadequately controlled by, or intolerant of ciclosporin. A total of 325 patients in Europe were randomised into three treatment groups in the 16-week study to receive either DUPIXENT 300 mg + TCS QW, DUPIXENT 300 mg + TCS Q2W (licensed dose) or placebo + TCS. Patients applied moisturisers at least twice daily for the seven days prior to randomisation and throughout the study; stable doses of prescription moisturisers or moisturisers containing additives were permitted if initiated before screening.7


The primary endpoint was the proportion of patients that achieved a 75% or greater improvement in the Eczema Area and Severity Index (EASI-75) score at 16 weeks from baseline.7


Secondary endpoints included: measures of the impact of DUPIXENT on the persistent itch caused by the disease, health-related quality of life measures, and symptoms of anxiety and depression.7


A clinically meaningful improvement in pruritus is defined as a ≥4-point improvement in NRS.1,3
A clinically meaningful improvement in quality of life is defined as ≥4-point improvement on a 0–30 scale in DLQI.3


*An EASI score is based on a clinician’s weighted score (0 to 72) of four affected areas grading the physical signs of AD (erythema, oedema/papulation, excoriation, lichenification)8–12
An IGA score is based on the clinician’s impression of a patients AD based on severity of erythema, infiltration, papulation and oozing/crusting.8,9


AD, atopic dermatitis; BSA, body surface area; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; HADS, Hospital Anxiety and Depression Scale; IGA, Investigator’s Global Assessment; NRS, Numerical Rating Scale; POEM, Patient-Oriented Eczema Measure; QW, once weekly; Q2W, once every two weeks; SCORAD, SCORing Atopic Dermatitis; TCS, topical corticosteroids.

References

  1. DUPIXENT Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/8553/smpc. Date accessed: July 2021.
  2. Blauvelt A, et al. Lancet. 2017;389(10086):2287–2303.
  3. Blauvelt A, et al. Lancet. 2017;389(10086):2287–2303. Supplementary appendix.
  4. Sanofi Data on File. SAGB.DUP.17.09.1154. September 2017.
  5. Sanofi Data on File. SAGB.DUP.17.09.1168. September 2017.
  6. Simpson EL, et al. New Engl J Med. 2016;375(24):2335–2348.
  7. de Bruin-Weller, et al. Br J Dermatol. 2018;178:1083–1101.
  8. Fattah D, et al. Chair’s presentation. Dupilumab for treating moderate to severe atopic dermatitis (ID1048) presented at the 2nd Appraisal Committee meeting lead team presentation, May 10 2018.
  9. Clinical Review Report: Dupilumab (Dupixent): (Sanofi-Aventis Canada Inc.): Indication: Moderate-to-severe atopic dermatitis (AD) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Jul. Appendix 5, Validity of Outcomes Measures. Available at: https://www.ncbi.nlm.nih.gov/books NBK539234/. Date accessed: July 2021.
  10. © NICE [2018] Dupilumab for treating moderate to severe atopic dermatitis. Available at: https://www.nice.org.uk/guidance/TA534/chapter/1-Recommendations. Date accessed: July 2021. All rights reserved. Subject to notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.
  11. EASI User Guide. HOME – Harmonising Outcome Measures for Eczema website. Available at: http://www.homeforeczema.org/documents/easiuser-guide-dec-2016v2.pdf. Date accessed: July 2021.
  12. Leshem YA, Hajar T, et al. Br J Dermatol. 2015;172(5):1353–1357.