Trial Outcomes & Findings for 5-Year Safety Study of Pimecrolimus Cream 1% in Infants 3 - 12 Months of Age With Mild to Moderate Atopic Dermatitis (NCT NCT00120523)

NCT ID: NCT00120523

Last Updated: 2022-02-11

Results Overview

crude incidence of adverse events of primary interest and most frequent adverse events (greater than or equal to 5% crude incidence in either treatment group) in the treatment period

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2418 participants

Primary outcome timeframe

throughout the 5-year study

Results posted on

2022-02-11

Participant Flow

First patient was enrolled into the study on 05 Apr 2004, last patient completed on 04 Oct 2010.

Participant milestones

Participant milestones
Measure	Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Treatment Period STARTED	1205	1213
Treatment Period COMPLETED	836	874
Treatment Period NOT COMPLETED	369	339
Follow-Up Period STARTED	120	70
Follow-Up Period COMPLETED	90	46
Follow-Up Period NOT COMPLETED	30	24

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

5-Year Safety Study of Pimecrolimus Cream 1% in Infants 3 - 12 Months of Age With Mild to Moderate Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pimecrolimus n=1205 Participants 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.	Total n=2418 Participants Total of all reporting groups
Age, Categorical <=18 years	1205 Participants n=5 Participants	1213 Participants n=7 Participants	2418 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	7.1 months STANDARD_DEVIATION 2.71 • n=5 Participants	7.1 months STANDARD_DEVIATION 2.66 • n=7 Participants	7.1 months STANDARD_DEVIATION 2.69 • n=5 Participants
Sex: Female, Male Female	461 Participants n=5 Participants	471 Participants n=7 Participants	932 Participants n=5 Participants
Sex: Female, Male Male	744 Participants n=5 Participants	742 Participants n=7 Participants	1486 Participants n=5 Participants
Region of Enrollment United States	106 participants n=5 Participants	110 participants n=7 Participants	216 participants n=5 Participants
Region of Enrollment Germany	130 participants n=5 Participants	131 participants n=7 Participants	261 participants n=5 Participants
Region of Enrollment Argentina	40 participants n=5 Participants	40 participants n=7 Participants	80 participants n=5 Participants
Region of Enrollment Belgium	20 participants n=5 Participants	16 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Canada	52 participants n=5 Participants	64 participants n=7 Participants	116 participants n=5 Participants
Region of Enrollment Chile	25 participants n=5 Participants	22 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment China	60 participants n=5 Participants	59 participants n=7 Participants	119 participants n=5 Participants
Region of Enrollment Colombia	48 participants n=5 Participants	52 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment Czech Republic	26 participants n=5 Participants	23 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment Ecuador	15 participants n=5 Participants	13 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Spain	51 participants n=5 Participants	48 participants n=7 Participants	99 participants n=5 Participants
Region of Enrollment United Kingdom	32 participants n=5 Participants	27 participants n=7 Participants	59 participants n=5 Participants
Region of Enrollment Greece	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment Guatemala	53 participants n=5 Participants	56 participants n=7 Participants	109 participants n=5 Participants
Region of Enrollment Hong Kong	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Hungary	39 participants n=5 Participants	40 participants n=7 Participants	79 participants n=5 Participants
Region of Enrollment Iceland	97 participants n=5 Participants	98 participants n=7 Participants	195 participants n=5 Participants
Region of Enrollment Netherlands	51 participants n=5 Participants	55 participants n=7 Participants	106 participants n=5 Participants
Region of Enrollment Peru	55 participants n=5 Participants	51 participants n=7 Participants	106 participants n=5 Participants
Region of Enrollment Poland	37 participants n=5 Participants	36 participants n=7 Participants	73 participants n=5 Participants
Region of Enrollment Portugal	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Russian Federation	54 participants n=5 Participants	53 participants n=7 Participants	107 participants n=5 Participants
Region of Enrollment Singapore	12 participants n=5 Participants	13 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Sweden	29 participants n=5 Participants	29 participants n=7 Participants	58 participants n=5 Participants
Region of Enrollment Turkey	26 participants n=5 Participants	28 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment Taiwan	30 participants n=5 Participants	30 participants n=7 Participants	60 participants n=5 Participants
Region of Enrollment Venezuela	39 participants n=5 Participants	39 participants n=7 Participants	78 participants n=5 Participants
Region of Enrollment South Africa	49 participants n=5 Participants	55 participants n=7 Participants	104 participants n=5 Participants

PRIMARY outcome

Timeframe: throughout the 5-year study

Population: complete safety/ITT population of experimental and control

crude incidence of adverse events of primary interest and most frequent adverse events (greater than or equal to 5% crude incidence in either treatment group) in the treatment period

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1205 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Safety Assessed by Adverse Events Acute tonsillitis	8.6 percentage of participants	7.8 percentage of participants
Safety Assessed by Adverse Events Allergy to arthropod bite	5.9 percentage of participants	4.9 percentage of participants
Safety Assessed by Adverse Events Arthropod bite	7.1 percentage of participants	8.8 percentage of participants
Safety Assessed by Adverse Events Asthma	15.1 percentage of participants	14.6 percentage of participants
Safety Assessed by Adverse Events Bronchiolitis	5.4 percentage of participants	5.7 percentage of participants
Safety Assessed by Adverse Events Bronchitis	36.3 percentage of participants	33.8 percentage of participants
Safety Assessed by Adverse Events Bronchospasm	5.2 percentage of participants	6.7 percentage of participants
Safety Assessed by Adverse Events Conjunctivitis	16.5 percentage of participants	16.2 percentage of participants
Safety Assessed by Adverse Events Conjunctivitis allergic	5.0 percentage of participants	6.3 percentage of participants
Safety Assessed by Adverse Events Constipation	6.9 percentage of participants	6.7 percentage of participants
Safety Assessed by Adverse Events Cough	29.9 percentage of participants	30.4 percentage of participants
Safety Assessed by Adverse Events Dermatitis diaper	12.5 percentage of participants	11.3 percentage of participants
Safety Assessed by Adverse Events Diarrhoea	31.9 percentage of participants	31.4 percentage of participants
Safety Assessed by Adverse Events Eczema infected	7.4 percentage of participants	4.5 percentage of participants
Safety Assessed by Adverse Events Eye infection	0.3 percentage of participants	0.3 percentage of participants
Safety Assessed by Adverse Events Food allergy	7.4 percentage of participants	6.0 percentage of participants
Safety Assessed by Adverse Events Gastroenteritis	28.2 percentage of participants	27.1 percentage of participants
Safety Assessed by Adverse Events Gastroenteritis viral	6.1 percentage of participants	5.2 percentage of participants
Safety Assessed by Adverse Events Heat rash	5.5 percentage of participants	4.8 percentage of participants
Safety Assessed by Adverse Events Hypersensitivity	2.0 percentage of participants	1.9 percentage of participants
Safety Assessed by Adverse Events Immunisation reaction	6.5 percentage of participants	5.5 percentage of participants
Safety Assessed by Adverse Events Impetigo	11.9 percentage of participants	10.4 percentage of participants
Safety Assessed by Adverse Events Influenza	6.9 percentage of participants	5.7 percentage of participants
Safety Assessed by Adverse Events Influenza like illness	16.7 percentage of participants	16.6 percentage of participants
Safety Assessed by Adverse Events Laryngitis	5.4 percentage of participants	4.9 percentage of participants
Safety Assessed by Adverse Events Lower respiratory tract infection	3.7 percentage of participants	4.5 percentage of participants
Safety Assessed by Adverse Events Molluscum contagiosum	9.0 percentage of participants	8.2 percentage of participants
Safety Assessed by Adverse Events Nasopharyngitis	59.0 percentage of participants	58.9 percentage of participants
Safety Assessed by Adverse Events Otitis media	34.7 percentage of participants	31.7 percentage of participants
Safety Assessed by Adverse Events Otitis media acute	12.4 percentage of participants	11.6 percentage of participants
Safety Assessed by Adverse Events Pharyngitis	17.8 percentage of participants	19.0 percentage of participants
Safety Assessed by Adverse Events Pneumonia	11.0 percentage of participants	10.8 percentage of participants
Safety Assessed by Adverse Events Pyrexia	48.9 percentage of participants	49.9 percentage of participants
Safety Assessed by Adverse Events Rhinitis	13.9 percentage of participants	13.4 percentage of participants
Safety Assessed by Adverse Events Rhinitis allergic	13.2 percentage of participants	12.7 percentage of participants
Safety Assessed by Adverse Events Rhinorrhoea	6.8 percentage of participants	6.8 percentage of participants
Safety Assessed by Adverse Events Sinusitis	7.6 percentage of participants	8.1 percentage of participants
Safety Assessed by Adverse Events Teething	14.9 percentage of participants	14.9 percentage of participants
Safety Assessed by Adverse Events Tonsillitis	16.9 percentage of participants	16.5 percentage of participants
Safety Assessed by Adverse Events Upper respiratory tract infection	32.0 percentage of participants	31.2 percentage of participants
Safety Assessed by Adverse Events Urinary tract infection	4.3 percentage of participants	5.2 percentage of participants
Safety Assessed by Adverse Events Urticaria	9.5 percentage of participants	10.6 percentage of participants
Safety Assessed by Adverse Events Varicella	25.4 percentage of participants	23.4 percentage of participants
Safety Assessed by Adverse Events Viral rash	3.0 percentage of participants	4.1 percentage of participants
Safety Assessed by Adverse Events Viral upper respiratory tract infection	10.5 percentage of participants	10.4 percentage of participants
Safety Assessed by Adverse Events Vomiting	22.5 percentage of participants	21.3 percentage of participants
Safety Assessed by Adverse Events Wheezing	5.6 percentage of participants	5.3 percentage of participants

PRIMARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication.Patient who do not have a baseline value are excluded from the analysis.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1204 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1208 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Growth Velocity (Height) Baseline (n=1204, n=1208)	68.8 cm Standard Deviation 5.26	68.8 cm Standard Deviation 5.14
Growth Velocity (Height) Week 6 (n=1144, n=1141)	71.3 cm Standard Deviation 4.82	71.3 cm Standard Deviation 4.76
Growth Velocity (Height) Week 26 (n=1092, n=1114)	77.0 cm Standard Deviation 4.37	76.9 cm Standard Deviation 4.46
Growth Velocity (Height) Week 52 (n=999, n=1052)	83.1 cm Standard Deviation 4.23	83.1 cm Standard Deviation 4.30
Growth Velocity (Height) Week 104 (n=924, n=975)	93.0 cm Standard Deviation 4.31	92.9 cm Standard Deviation 4.30
Growth Velocity (Height) Week 156 (n=871, n=919)	100.5 cm Standard Deviation 4.70	100.6 cm Standard Deviation 4.72
Growth Velocity (Height) Week 208 (n=843, n=869)	107.7 cm Standard Deviation 5.46	107.8 cm Standard Deviation 5.25
Growth Velocity (Height) Week 260 (n=833, n=871)	114.4 cm Standard Deviation 5.26	114.5 cm Standard Deviation 5.90

PRIMARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication.Patient who do not have a baseline value are excluded from the analysis.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1203 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Growth Velocity (Weight) Baseline (n=1203, n=1213)	8.2 kg Standard Deviation 1.51	8.2 kg Standard Deviation 1.51
Growth Velocity (Weight) Week 6 (n=1144, n=1144)	8.8 kg Standard Deviation 1.45	8.7 kg Standard Deviation 1.41
Growth Velocity (Weight) Week 26 (n=1093, n=1114)	10.2 kg Standard Deviation 1.43	10.1 kg Standard Deviation 1.39
Growth Velocity (Weight) Week 52 (n=1003, n=1054)	11.6 kg Standard Deviation 1.52	11.6 kg Standard Deviation 1.54
Growth Velocity (Weight) Week 104 (n=928, n=978)	14.1 kg Standard Deviation 1.90	14.1 kg Standard Deviation 1.83
Growth Velocity (Weight) Week 156 (n=873, n=924)	16.3 kg Standard Deviation 2.32	16.3 kg Standard Deviation 2.29
Growth Velocity (Weight) Week 208 (n=843, n=870)	18.6 kg Standard Deviation 2.80	18.7 kg Standard Deviation 2.88
Growth Velocity (Weight) Week 260 (n=833, n=871)	21.1 kg Standard Deviation 3.51	21.4 kg Standard Deviation 3.70

PRIMARY outcome

Timeframe: throughout the 5-year study

Population: Immune system function data analyses were performed on the immunology set (774 patients). Varicella titers were assessed for USA patients only (n= 104, n=108).

number (%) of patients with positive antibody titers to tetanus, hepatitis B, and measles vaccines at baseline, weeks 26 (6 months), 52 (1 year), 104 (2 years), 156 (3 years), 208 (4 years) and 260 (5 years) Varicella antibody titers were measured at the above time points in US patients only.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=383 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=391 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Potential Effect on the Developing Immune System Tetanus Baseline	81.8 % of patients with positive ab titer	85.2 % of patients with positive ab titer
Potential Effect on the Developing Immune System Tetanus week 26	89.5 % of patients with positive ab titer	90.4 % of patients with positive ab titer
Potential Effect on the Developing Immune System Tetanus week 52	91.9 % of patients with positive ab titer	94.0 % of patients with positive ab titer
Potential Effect on the Developing Immune System Tetanus week 104	91.9 % of patients with positive ab titer	94.7 % of patients with positive ab titer
Potential Effect on the Developing Immune System Tetanus week 156	93.5 % of patients with positive ab titer	92.5 % of patients with positive ab titer
Potential Effect on the Developing Immune System Tetanus week 208	89.0 % of patients with positive ab titer	89.5 % of patients with positive ab titer
Potential Effect on the Developing Immune System Tetanus week 260	91.1 % of patients with positive ab titer	88.9 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B Baseline	57.5 % of patients with positive ab titer	53.6 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B week 26	60.7 % of patients with positive ab titer	58.6 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B week 52	59.0 % of patients with positive ab titer	58.5 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B week 104	51.5 % of patients with positive ab titer	51.3 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B week 156	48.5 % of patients with positive ab titer	45.0 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B week 208	39.7 % of patients with positive ab titer	38.5 % of patients with positive ab titer
Potential Effect on the Developing Immune System Hepatitis B week 260	34.6 % of patients with positive ab titer	38.2 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles Baseline	11.4 % of patients with positive ab titer	14.4 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles week 26	37.4 % of patients with positive ab titer	31.6 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles week 52	86.3 % of patients with positive ab titer	86.1 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles week 104	97.3 % of patients with positive ab titer	97.4 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles week 156	98.5 % of patients with positive ab titer	97.0 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles week 208	97.8 % of patients with positive ab titer	95.6 % of patients with positive ab titer
Potential Effect on the Developing Immune System Measles week 260	98.9 % of patients with positive ab titer	96.3 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella Baseline	32.1 % of patients with positive ab titer	17.8 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella week 26	46.5 % of patients with positive ab titer	45.2 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella week 52	72.2 % of patients with positive ab titer	74.2 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella week 104	78.4 % of patients with positive ab titer	88.7 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella week 156	68.4 % of patients with positive ab titer	81.8 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella week 208	86.1 % of patients with positive ab titer	89.4 % of patients with positive ab titer
Potential Effect on the Developing Immune System Varicella week 260	87.1 % of patients with positive ab titer	84.1 % of patients with positive ab titer

SECONDARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication.

IGA = Investigator's global Assessment. CI = Confidence interval for treatment success using binomial distribution: lower CI\<0 is set to 0, upper CI\>100 is set to 100. Treatment success (n): IGA score of 0 or 1 (clear or almost clear). Outcome gives percentage of patients with treatment success.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1205 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 6	61.4 percentage of participants Interval 58.5 to 64.2	59.6 percentage of participants Interval 56.8 to 62.5
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 26	66.4 percentage of participants Interval 63.6 to 69.2	74.5 percentage of participants Interval 71.9 to 77.0
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 52	73.9 percentage of participants Interval 71.2 to 76.6	79.6 percentage of participants Interval 77.2 to 82.1
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 104	79.9 percentage of participants Interval 77.3 to 82.4	83.4 percentage of participants Interval 81.0 to 85.7
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 156	81.9 percentage of participants Interval 79.3 to 84.4	86.1 percentage of participants Interval 83.9 to 88.3
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 208	86.2 percentage of participants Interval 83.8 to 88.5	88.1 percentage of participants Interval 86.0 to 90.2
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Overall IGA Week 260	88.7 percentage of participants Interval 86.6 to 90.9	92.3 percentage of participants Interval 90.5 to 94.1
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 6	68.9 percentage of participants Interval 66.3 to 71.6	71.0 percentage of participants Interval 68.4 to 73.6
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 26	79.5 percentage of participants Interval 77.1 to 81.9	83.8 percentage of participants Interval 81.6 to 86.0
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 52	85.6 percentage of participants Interval 83.4 to 87.7	88.5 percentage of participants Interval 86.6 to 90.4
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 104	92.1 percentage of participants Interval 90.4 to 93.9	94.1 percentage of participants Interval 92.6 to 95.6
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 156	94.2 percentage of participants Interval 92.6 to 95.7	94.3 percentage of participants Interval 92.8 to 95.8
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 208	96.0 percentage of participants Interval 94.7 to 97.3	96.2 percentage of participants Interval 95.0 to 97.5
Investigator's Global Assessment (to Assess Disease Severity) of the Whole Body and of the Face: Treatment Success Rate Facial IGA Week 260	96.6 percentage of participants Interval 95.4 to 97.9	97.2 percentage of participants Interval 96.2 to 98.3

SECONDARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication.

TBSA = Total body surface area; percent BSA affected = (BSA affected/TBSA) x 100.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1205 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Body Surface Area Involved With Atopic Dermatitis Baseline (n=1205, n=1213)	21.1 percentage of TBSA affected Standard Deviation 16.50	21.3 percentage of TBSA affected Standard Deviation 17.19
Body Surface Area Involved With Atopic Dermatitis Week 6 (n=1142, n=1138)	5.5 percentage of TBSA affected Standard Deviation 8.72	6.0 percentage of TBSA affected Standard Deviation 9.10
Body Surface Area Involved With Atopic Dermatitis Week 26 (n=1091, n=1113)	4.3 percentage of TBSA affected Standard Deviation 8.30	3.7 percentage of TBSA affected Standard Deviation 8.50
Body Surface Area Involved With Atopic Dermatitis Week 52 (n=997, n=1048)	3.5 percentage of TBSA affected Standard Deviation 7.69	2.7 percentage of TBSA affected Standard Deviation 6.27
Body Surface Area Involved With Atopic Dermatitis Week 104 (n=922, n=975)	2.4 percentage of TBSA affected Standard Deviation 6.53	1.8 percentage of TBSA affected Standard Deviation 5.17
Body Surface Area Involved With Atopic Dermatitis Week 156 (n=871, n=918)	2.0 percentage of TBSA affected Standard Deviation 5.46	1.4 percentage of TBSA affected Standard Deviation 4.65
Body Surface Area Involved With Atopic Dermatitis Week 208 (n=843, n=868)	1.5 percentage of TBSA affected Standard Deviation 5.16	1.2 percentage of TBSA affected Standard Deviation 4.33
Body Surface Area Involved With Atopic Dermatitis Week 260 (n=833, n=870)	1.1 percentage of TBSA affected Standard Deviation 3.31	0.9 percentage of TBSA affected Standard Deviation 3.69

SECONDARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication. Patients who do not have baseline value are excluded from the analysis.

PIQoL-AD questionnaire (28 questions) was only done in countries where validated questionnaire was available: Germany, Hungary, Netherlands, Spain, UK and US. For the purposes of data presentation, a "Not True" response was coded a value of zero and a "True" a value of one. The total score (i.e., sum of individual questions) was calculated; lower the score, better the QoL. Minimum score = 0; maximum score = 28. If the patient has answered ≤14 questions at a time point, then the patient's total score at the time point was set to missing.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=406 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=405 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Baseline (n=406, n=405)	8.1 units on a scale Standard Deviation 5.04	8.4 units on a scale Standard Deviation 5.25
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 6 (n=378, n=360)	5.8 units on a scale Standard Deviation 4.76	6.0 units on a scale Standard Deviation 5.09
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 26 (n=368, n=363)	4.8 units on a scale Standard Deviation 4.73	5.0 units on a scale Standard Deviation 4.85
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 52 (n=327, n=334)	4.2 units on a scale Standard Deviation 4.45	4.4 units on a scale Standard Deviation 4.94
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 104 (n=302, n=296)	3.7 units on a scale Standard Deviation 4.69	3.9 units on a scale Standard Deviation 5.14
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 156 (n=269, n=266)	3.2 units on a scale Standard Deviation 4.67	3.4 units on a scale Standard Deviation 5.02
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 208 (n=254, n=256)	2.7 units on a scale Standard Deviation 3.93	3.0 units on a scale Standard Deviation 4.88
Parent's Index of Quality of Life - Atopic Dermatitis (PIQoL-AD) Week 260 (n=249, 249)	2.1 units on a scale Standard Deviation 3.22	2.3 units on a scale Standard Deviation 3.80

SECONDARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication.Patients who do not have baseline value are excluded from analysis.

Significant findings are included in the relevant medical history/current medical conditions (prior to study start) or in the AE documentation (after study start.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1205 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 156	62.0 mmHg Standard Deviation 8.11	62.0 mmHg Standard Deviation 8.29
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP - Baseline	94.3 mmHg Standard Deviation 12.40	94.7 mmHg Standard Deviation 12.79
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 6	96.1 mmHg Standard Deviation 11.70	96.3 mmHg Standard Deviation 11.33
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 26	98.6 mmHg Standard Deviation 11.46	98.4 mmHg Standard Deviation 11.49
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 52	99.0 mmHg Standard Deviation 11.33	99.3 mmHg Standard Deviation 11.02
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 104	98.8 mmHg Standard Deviation 10.01	97.9 mmHg Standard Deviation 9.85
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 156	99.0 mmHg Standard Deviation 9.47	98.6 mmHg Standard Deviation 9.75
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 208	99.8 mmHg Standard Deviation 10.10	99.4 mmHg Standard Deviation 9.74
Vital Signs and Physical Examinations: Blood Pressure (BP) Systolic BP- Week 260	100.0 mmHg Standard Deviation 9.51	100.1 mmHg Standard Deviation 9.63
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Baseline	59.2 mmHg Standard Deviation 10.40	59.1 mmHg Standard Deviation 10.26
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 6	60.4 mmHg Standard Deviation 9.47	61.0 mmHg Standard Deviation 9.59
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 26	61.7 mmHg Standard Deviation 9.90	61.6 mmHg Standard Deviation 9.78
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 52	61.9 mmHg Standard Deviation 9.12	61.9 mmHg Standard Deviation 9.23
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 104	61.8 mmHg Standard Deviation 8.14	61.7 mmHg Standard Deviation 7.72
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 208	62.4 mmHg Standard Deviation 8.52	61.8 mmHg Standard Deviation 7.77
Vital Signs and Physical Examinations: Blood Pressure (BP) Diastolic BP - Week 260	61.9 mmHg Standard Deviation 7.24	62.2 mmHg Standard Deviation 7.38

SECONDARY outcome

Timeframe: throughout the 5-year study

Population: Safety/intent-to-treat (ITT) - all randomized patients who received at least one application of study medication.Patients who do not have baseline value are excluded from analysis.

Significant findings are included in the relevant medical history/current medical conditions (prior to study start) or in the AE documentation (after study start.

Outcome measures

Outcome measures
Measure	Pimecrolimus n=1205 Participants Pimecrolimus 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 Participants Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Vital Signs and Physical Examinations: Pulse Baseline	116.7 bpm Standard Deviation 19.43	116.0 bpm Standard Deviation 19.69
Vital Signs and Physical Examinations: Pulse Week 6	114.2 bpm Standard Deviation 18.19	114.5 bpm Standard Deviation 19.45
Vital Signs and Physical Examinations: Pulse Week 26	111.4 bpm Standard Deviation 18.09	111.7 bpm Standard Deviation 18.44
Vital Signs and Physical Examinations: Pulse Week 52	107.7 bpm Standard Deviation 18.63	107.0 bpm Standard Deviation 17.92
Vital Signs and Physical Examinations: Pulse Week 104	101.7 bpm Standard Deviation 15.97	101.8 bpm Standard Deviation 15.91
Vital Signs and Physical Examinations: Pulse Week 156	97.4 bpm Standard Deviation 13.45	97.0 bpm Standard Deviation 13.72
Vital Signs and Physical Examinations: Pulse Week 208	93.4 bpm Standard Deviation 12.78	93.4 bpm Standard Deviation 12.56
Vital Signs and Physical Examinations: Pulse Week 260	90.2 bpm Standard Deviation 12.82	90.4 bpm Standard Deviation 12.25

Adverse Events

Pimecrolimus

Serious events: 247 serious events

Other events: 1162 other events

Deaths: 0 deaths

Topical Corticosteroids

Serious events: 210 serious events

Other events: 1160 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Research

MEDA Pharma GmbH & Co. KG

Phone: +49 6172 888

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pimecrolimus n=1205 participants at risk 1% cream was supplied in 50 g tubes by the sponsor. Elidel was to be applied as a thin layer to the affected skin b.i.d., and rubbed in gently and completely by the primary caregiver	Topical Corticosteroids n=1213 participants at risk Low or medium potency (low potency, e.g. Hydrocortisone acetate; or medium potency, e.g. Fluticasone propionate)TCS supplied locally were to be used according to the country's label as study medication for patients randomized to TCS group. Topical corticosteroids were to be applied as a thin layer to the affected skin only and rubbed in gently.
Infections and infestations Nasopharyngitis	59.0% 711/1205 • Adverse event data were collected throughout the study period of 5 years.	58.9% 715/1213 • Adverse event data were collected throughout the study period of 5 years.
General disorders Pyrexia	48.9% 589/1205 • Adverse event data were collected throughout the study period of 5 years.	49.9% 605/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Bronchitis	36.3% 438/1205 • Adverse event data were collected throughout the study period of 5 years.	33.8% 410/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Otitis media	34.7% 418/1205 • Adverse event data were collected throughout the study period of 5 years.	31.7% 385/1213 • Adverse event data were collected throughout the study period of 5 years.
Gastrointestinal disorders Diarrhoea	31.9% 384/1205 • Adverse event data were collected throughout the study period of 5 years.	31.4% 381/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Upper respiratory tract infection	32.0% 386/1205 • Adverse event data were collected throughout the study period of 5 years.	31.2% 378/1213 • Adverse event data were collected throughout the study period of 5 years.
Respiratory, thoracic and mediastinal disorders Cough	29.9% 360/1205 • Adverse event data were collected throughout the study period of 5 years.	30.4% 369/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Gastroenteritis	28.2% 340/1205 • Adverse event data were collected throughout the study period of 5 years.	27.1% 329/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Varicella	25.4% 306/1205 • Adverse event data were collected throughout the study period of 5 years.	23.4% 284/1213 • Adverse event data were collected throughout the study period of 5 years.
Gastrointestinal disorders Vomiting	22.5% 271/1205 • Adverse event data were collected throughout the study period of 5 years.	21.3% 258/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Pharyngitis	17.8% 215/1205 • Adverse event data were collected throughout the study period of 5 years.	19.0% 231/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Tonsillitis	16.9% 204/1205 • Adverse event data were collected throughout the study period of 5 years.	16.5% 200/1213 • Adverse event data were collected throughout the study period of 5 years.
General disorders Influenza like illness	16.7% 201/1205 • Adverse event data were collected throughout the study period of 5 years.	16.6% 201/1213 • Adverse event data were collected throughout the study period of 5 years.
Eye disorders Conjunctivitis	16.5% 199/1205 • Adverse event data were collected throughout the study period of 5 years.	16.2% 197/1213 • Adverse event data were collected throughout the study period of 5 years.
Gastrointestinal disorders Teething	14.9% 179/1205 • Adverse event data were collected throughout the study period of 5 years.	14.9% 181/1213 • Adverse event data were collected throughout the study period of 5 years.
Respiratory, thoracic and mediastinal disorders Asthma	15.1% 182/1205 • Adverse event data were collected throughout the study period of 5 years.	14.6% 177/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Rhinitis	13.9% 168/1205 • Adverse event data were collected throughout the study period of 5 years.	13.4% 163/1213 • Adverse event data were collected throughout the study period of 5 years.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	13.2% 159/1205 • Adverse event data were collected throughout the study period of 5 years.	12.7% 154/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Otitis media acute	12.4% 150/1205 • Adverse event data were collected throughout the study period of 5 years.	11.6% 141/1213 • Adverse event data were collected throughout the study period of 5 years.
Skin and subcutaneous tissue disorders Dermatitis diaper	12.5% 151/1205 • Adverse event data were collected throughout the study period of 5 years.	11.3% 137/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Impetigo	11.9% 143/1205 • Adverse event data were collected throughout the study period of 5 years.	10.4% 126/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Pneumonia	11.0% 133/1205 • Adverse event data were collected throughout the study period of 5 years.	10.8% 131/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Viral upper respiratory tract infection	10.5% 126/1205 • Adverse event data were collected throughout the study period of 5 years.	10.4% 126/1213 • Adverse event data were collected throughout the study period of 5 years.
Skin and subcutaneous tissue disorders Urticaria	9.5% 114/1205 • Adverse event data were collected throughout the study period of 5 years.	10.6% 129/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Molluscum contagiosum	9.0% 109/1205 • Adverse event data were collected throughout the study period of 5 years.	8.2% 99/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Acute tonsillitis	8.6% 104/1205 • Adverse event data were collected throughout the study period of 5 years.	7.8% 95/1213 • Adverse event data were collected throughout the study period of 5 years.
Injury, poisoning and procedural complications Arthropode bite	7.1% 86/1205 • Adverse event data were collected throughout the study period of 5 years.	8.8% 107/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Sinusitis	7.6% 91/1205 • Adverse event data were collected throughout the study period of 5 years.	8.1% 98/1213 • Adverse event data were collected throughout the study period of 5 years.
Gastrointestinal disorders Constipation	6.9% 83/1205 • Adverse event data were collected throughout the study period of 5 years.	6.7% 81/1213 • Adverse event data were collected throughout the study period of 5 years.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.8% 82/1205 • Adverse event data were collected throughout the study period of 5 years.	6.8% 82/1213 • Adverse event data were collected throughout the study period of 5 years.
Immune system disorders Food allergy	7.4% 89/1205 • Adverse event data were collected throughout the study period of 5 years.	6.0% 73/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Influenza	6.9% 83/1205 • Adverse event data were collected throughout the study period of 5 years.	5.7% 69/1213 • Adverse event data were collected throughout the study period of 5 years.
Immune system disorders Immunisation reaction	6.5% 78/1205 • Adverse event data were collected throughout the study period of 5 years.	5.5% 67/1213 • Adverse event data were collected throughout the study period of 5 years.
Respiratory, thoracic and mediastinal disorders Bronchospasm	5.2% 63/1205 • Adverse event data were collected throughout the study period of 5 years.	6.7% 81/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Eczema infected	7.4% 89/1205 • Adverse event data were collected throughout the study period of 5 years.	4.5% 55/1213 • Adverse event data were collected throughout the study period of 5 years.
Eye disorders Conjunctivitis allergic	5.0% 60/1205 • Adverse event data were collected throughout the study period of 5 years.	6.3% 76/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Gastroenteritis viral	6.1% 73/1205 • Adverse event data were collected throughout the study period of 5 years.	5.2% 63/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Bronchiolitis	5.4% 65/1205 • Adverse event data were collected throughout the study period of 5 years.	5.7% 69/1213 • Adverse event data were collected throughout the study period of 5 years.
Respiratory, thoracic and mediastinal disorders Wheezing	5.6% 68/1205 • Adverse event data were collected throughout the study period of 5 years.	5.3% 64/1213 • Adverse event data were collected throughout the study period of 5 years.
Immune system disorders Allergy to arthropod bite	5.9% 71/1205 • Adverse event data were collected throughout the study period of 5 years.	4.9% 59/1213 • Adverse event data were collected throughout the study period of 5 years.
Skin and subcutaneous tissue disorders Heat rash	5.5% 66/1205 • Adverse event data were collected throughout the study period of 5 years.	4.8% 58/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Laryngitis	5.4% 65/1205 • Adverse event data were collected throughout the study period of 5 years.	4.9% 59/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Oral candidiasis	4.6% 56/1205 • Adverse event data were collected throughout the study period of 5 years.	4.9% 59/1213 • Adverse event data were collected throughout the study period of 5 years.
Infections and infestations Urinary tract infection	4.3% 52/1205 • Adverse event data were collected throughout the study period of 5 years.	5.2% 63/1213 • Adverse event data were collected throughout the study period of 5 years.