JADE COMPARE
Cibinqo efficacy in combination with medicated topical therapy vs placebo and dupilumab1,2
This pivotal Phase III clinical trial evaluated the efficacy and safety of Cibinqo in combination with medicated topical therapy vs placebo in 838 patients with moderate-to-severe AD, with a direct head-to-head comparison with dupilumab as an active comparator for itch relief at Week 2.1,2
STUDY DESIGN1,2
*Patients used non-medicated emollient twice daily, starting at least 7 days before randomisation and continued throughout the trial.
†Patients used medicated topical therapy (once daily) such as low- or medium-potency topical corticosteroids, calcineurin inhibitors, or PDE4 inhibitors, starting on Day 1 and as per protocol guidance, to treat active lesions during the study.
Co-primary endpoints:
- EASI-75 response at Week 12 vs placebo (defined as a 75% improvement in EASI score from baseline)
- IGA 0/1 response with ≥2-point improvement at Week 12 vs placebo
Secondary endpoints:
- PP-NRS4 response of either dose of Cibinqo vs dupilumab and placebo at Week 2 (defined as an improvement of ≥4 points from baseline in the severity of PP-NRS)
- IGA 0/1 response with ≥2-point improvement and EASI-75 response at Week 16 vs placebo
- EASI-90 response at Week 12 vs placebo
- Score on the Patient-Oriented eczema Measure (POEM; scores range from 0–28 with higher scores indicating greater severity)
- Score on the Dermatology Life Quality Index (DLQI; scores range from 0–30 with higher scores indicating greater impairment)
- Change in the subjective assessment of sleep loss on the SCOring Atopic Dermatitis (SCORAD; scores range from 0–103 with higher scores indicating greater severity) sleep loss subscale
The primary analysis of efficacy was performed in the modified intention-to-treat-population, which included all the patients who had undergone randomisation and received at least 1 dose of a trial drug or placebo.
Baseline characteristics*2
|
Cibinqo 200 mg,
OD (N=226) |
Cibinqo 100 mg,
OD (N=238) |
Dupilumab 300 mg,
every other week (N=242) |
Placebo (N=131) |
Age, years |
38.8 ±14.5 |
37.3 ±14.8 |
37.1 ±14.6 |
37.4 ±15.2 |
Female sex, n (%) |
122 (54.0) |
118 (49.6) |
134 (55.4) |
54 (41.2) |
|
- 161(71.2)
-
9 (4.0)
- 53 (23.5)
-
3 (1.3)
|
- 182 (76.5)
-
6 (2.5)
- 48 (20.2)
- 2(0.8)
|
- 176 (72.7)
- 14 (5.8)
- 46 (19.0)
- 6 (2.5)
|
- 87 (66.4)
-
6 (4.6)
- 31 (23.7)
- 7 (5.3)
|
Duration of AD, years |
23.4 ±15.6 |
22.7 ±16.3 |
22.8 ±14.8 |
21.4 ±14.4 |
IGA score, n (%)
- 0, clear
- 1, almost clear
- 2, mild
- 3, moderate
- 4, severe
|
- 0
- 0
- 0
- 138 (61.1)
- 88 (38.9)
|
- 0
- 0
- 0
- 153 (64.3)
- 85 (35.7)
|
- 0
- 0
- 0
- 162 (66.9)
- 80 (33.1)
|
- 0
- 0
- 0
- 88 (67.2)
- 43 (32.8)
|
EASI score |
32.1 ±13.1 |
30.3 ±13.5 |
30.4 ±12.0 |
31.0 ±12.6 |
BSA involvement, %
|
50.8 ±23.0 |
48.1 ±23.1 |
46.5 ±22.1 |
48.9 ±24.9 |
PP-NRS score |
7.6 ±1.5 |
7.1 ±1.7 |
7.3 ±1.7 |
7.1 ±1.8 |
SCORAD score |
69.3 ±12.7 |
66.8 ±13.8 |
67.9 ±11.4 |
67.9 ±12.0 |
POEM score |
21.5 ±5.3 |
20.9 ±5.3 |
21.2 ±5.5 |
20.4 ±6.1 |
DLQI score |
16.3 ±6.6 |
15.5 ±6.4 |
15.6 ±6.7 |
15.2 ±6.9 |
Coexisting medical conditions
-
Asthma
- Allergic conjunctivitis
- Food allergy
|
- 82 (36.3)
- 18 (8.0)
- 39 (17.3)
|
- 79 (33.2)
- 21 (8.8)
- 36 (15.1)
|
- 75 (31.0)
- 26 (10.7)
- 36 (14.9)
|
- 8 (36.6)
- 14 (10.7)
- 14 (10.7)
|
*Plus-minus values are means ±SD. Percentages may not total 100 due to rounding.
†Race was reported by the patients.
Inclusion/exclusion criteria2,3
INCLUSION CRITERIA2
- ≥18 years of age
- Clinically diagnosed with chronic AD for ≥1 year, confirmed by Hanifin and Rajka criteria of AD at the screening and baseline visits. Criteria for AD diagnosis include ≥3 of the basic features of pruritus: typical morphology and distribution, including flexural lichenification or linearity in adults and facial and extensor involvement in infants and children; chronic or chronically relapsing dermatitis; and personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis); along with ≥3 of 23 minor features specified in the criteria
- Have a documented history of inadequate response to treatment with topical medications or require systemic therapies to control their disease
- Moderate-to-severe AD defined as BSA ≥10%, IGA ≥3, EASI ≥16 and PP-NRS ≥4 at the baseline visit
EXCLUSION CRITERIA2,3
- Active forms of other inflammatory skin diseases
- Prior treatment with any systemic JAK inhibitors
- Prior treatment with dupilumab and/or a history of hypersensitivity, intolerance, AE, or allergic reaction associated with prior exposure to the excipients of dupilumab
- Vaccination with, or exposure to, a live or attenuated vaccine within 6 weeks prior to the first dose
- Participation in other clinical studies involving investigational drug(s) within 8 weeks prior to study entry
- Uncontrolled, clinically significant laboratory abnormality that could affect study interpretation
- Any major psychiatric condition
- Unwillingness to discontinue current AD medications prior to the study
- Requiring treatment with prohibited medications during the study
- Medical history of thrombocytopenia, coagulopathy or platelet dysfunction, or Q wave interval abnormalities
- Presence or history of certain infections, cancers, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
- Pregnant or breastfeeding women
- Women of childbearing potential who are unwilling to use contraception
PRIMARY ENDPOINT – SKIN CLEARANCE
Significantly more patients achieved skin clearance with Cibinqo vs placebo1,2
In 12 weeks, 70.3% of patients treated with Cibinqo 200 mg achieved EASI-75 vs 27.1% with placebo (P<0.001).1,2
Proportion of patients achieving EASI-75 (in combination with medicated topical therapy)2
EASI-75 at Week 12
|
no./Total no. (%, 95% CI) |
Cibinqo 200 mg |
154/219 (70.3%; 64.3–76.4) |
Cibinqo 100 mg |
138/235 (58.7%; 52.4–65.0) |
Dupilumab |
140/241 (58.1%; 51.9–64.3) |
Placebo |
35/129 (27.1%; 19.5–34.8) |
EASI-75 response is defined as a 75% improvement in EASI score from baseline.
Analyses shown are between Cibinqo and placebo. Results are not to be interpreted as evidence of superiority, noninferiority, or similarity between Cibinqo and dupilumab
For most patients, particularly those with severe disease, the recommended starting dose is 200 mg.
In 12 weeks, 48.4% of patients treated with Cibinqo 200 mg achieved IGA 0/1 vs 14.0% with placebo (P<0.001).1,2
Proportion of patients achieving IGA 0/1 (in combination with medicated topical therapy)2
IGA 0/1 at Week 12 |
no./Total no. (%, 95% CI) |
Cibinqo 200 mg |
106/219 (48.8%; 41.8–55.0 |
Cibinqo 100 mg |
86/235 (36.6%; 30.4–42.8) |
Dupilumab 300 mg |
88/241 (36.5%; 30.4–42.6) |
Placebo |
18/129 (14.0%; 8.0–19.9) |
IGA response is defined as an IGA score of 0 or 1 and a ≥2-point improvement from baseline.
Analyses shown are between Cibinqo and placebo. Results are not to be interpreted as evidence of superiority, noninferiority, or similarity between Cibinqo and dupilumab
KEY SECONDARY ENDPOINT – ITCH REDUCTION
Rapid itch relief with Cibinqo 200 mg vs dupilumab at Week 21,2
Cibinqo 200 mg was superior to dupilumab at Week 2 in the proportion of patients achieving PP-NRS4, with significantly higher itch response* seen as early as Day 4 after the first dose.1,2
- 49.1% (111/226) of patients achieved PP-NRS4 with Cibinqo 200 mg at Week 2
Proportion of patients achieving PP-NRS4 (combination therapy)1–3
*PP-NRS4 is defined as an improvement of ≥4 points from baseline in the severity of PP-NRS. Cibinqo 200 mg was compared with dupilumab in the key secondary head-to-head endpoint, PP-NRS4 at Week 2. This endpoint was further analysed as prespecified multiplicity-controlled analysis and showed superiority to dupilumab down to Day 4.
SECONDARY ENDPOINT – SKIN CLEARANCE
Help your patients achieve a higher threshold of skin clearance, EASI-901,3
46.1% (101/219) of patients achieved EASI-90 with Cibinqo 200 mg.
Proportion of patients achieving EASI-90 (in combination with medicated topical therapy)1,3
EASI-90 at Week 12 |
no./Total no. (%, 95% CI) |
Cibinqo 200 mg |
101/219 (46.1%; 39.5–52.7) |
Cibinqo 100 mg |
86/235 (36.6%; 30.4–42.8) |
Dupilumab 300 mg |
84/241 (34.9%; 28.8–40.9) |
Placebo |
13/129 (10.1%; 4.9–15.3) |
EASI-90 is defined as a 90% improvement in EASI score from baseline.
Data limitations: EASI-90 at all scheduled points are prespecified secondary endpoints not controlled for multiplicity; treatment differences could represent chance findings.
Analyses shown are between Cibinqo and placebo. Results are not to be interpreted as evidence of superiority, noninferiority, or similarity between Cibinqo and dupilumab.
SECONDARY ENDPOINT – PATIENT REPORTED OUTCOMES
Cibinqo demonstrated a greater improvement in the frequency of patient-reported AD symptoms at Week 12 vs placebo1,3
7.5 point greater improvement in POEM scores reported with Cibinqo 200 mg vs placebo at Week 12 (nominal P<0.0001).
POEM outcomes at Week 12 (in combination with medicated topical therapy)1,3
Data limitations: Change from baseline in POEM is a prespecified secondary endpoint not controlled for multiplicity; therefore treatment differences could represent chance findings.
Analyses shown are between Cibinqo and placebo. Results are not to be interpreted as evidence of superiority, noninferiority, or similarity between Cibinqo and dupilumab.
Cibinqo demonstrated improvement in patient-reported health-related quality of life at Week 121,3
86.4% (190/220) of patients reported at least a 4-point improvement in DLQI score with Cibinqo 200 mg at Week 12.
DLQI outcomes at Week 12 (in combination with medicated topical therapy)1,3
Data limitations: Change from baseline in DLQI is a prespecified secondary endpoint not controlled for multiplicity; therefore treatment differences could represent chance findings.
Analyses shown are between Cibinqo and placebo. Results are not to be interpreted as evidence of superiority, noninferiority, or similarity between Cibinqo and dupilumab.
Cibinqo demonstrated improved patient-reported sleep disruption compared with placebo at Week 121,3
62.4% greater improvement in reported SCORAD sleep loss subscale with Cibinqo 200 mg vs placebo at Week 12 (nominal P≤0.0001).
SCORAD sleep loss subscale at Week 12 (in combination with medicated topical therapy)1,3
SCORAD sleep loss subscale is a component of the SCORAD questionnaire.
Data limitations: Change from baseline in SCORAD sleep loss is a prespecified secondary endpoint not controlled for multiplicity; therefore treatment differences could represent chance findings.
Analyses shown are between Cibinqo and placebo. Results are not to be interpreted as evidence of superiority, noninferiority, or similarity between Cibinqo and dupilumab.
Explore more
Safety
3,128 patients were treated with Cibinqo in clinical studies in AD representing 2,089 patient-years of exposure.1
View safety guidance
References: 1. Cibinqo (abrocitinib) Summary of Product Characteristics.
Dosing
Learn more about flexible dosing in patients on Cibinqo.
Discover oral once-daily dosing
** This is an optional area where footnotes can live.
AD=atopic dermatitis;
AE=adverse event;
BSA=body surface area;
CI=confidence interval;
DLQI=Dermatology Life Quality Index;
EASI=Eczema Area and Severity Index;
IGA=Investigator’s Global Assessment;
LSM=least squares mean;
JAK=Janus kinase;
OD=once daily;
PDE4=Type 4 cyclic nucleotide phosphodiesterase;
POEM=Patient-Oriented Eczema Measure;
PP-NRS=Peak Pruritus Numerical Rating Scale;
SCORAD=SCORing Atopic Dermatitis;
SD=standard deviation.
Prescribing information:
Cibinqo (abrocitinib) Prescribing Information (Great Britain) – 200 mg film-coated tablets.
Cibinqo (abrocitinib) Prescribing Information (Great Britain) – 100 mg film-coated tablets.
Cibinqo (abrocitinib) Prescribing Information (Great Britain) – 50 mg film-coated tablets.
References: 1. Cibinqo (abrocitinib) Summary of Product Characteristics.
2. Bieber T,
et al. N Eng J Med 2021;384:1101–1112.
3. Bieber T,
et al. N Eng J Med 2021;384:1101–1112 Supplementary appendix.
PP-CIB-GBR-0062. November 2021
Cibinqo Risk Minimisation Programme (RMP) materials, including a Patient Card and Prescriber Brochure, are available from
https://www.medicines.org.uk/emc. Patients treated with Cibinqo should be given the Patient Card.
