| Abramovits, 2006225 | MAS063DP emollient cream self-administered three times per day
(morning, afternoon and evening) to affected areas and those
areas prone to be affected for up to 50 days | Vehicle emollient cream self administered three times per day
(morning, afternoon and evening) to affected areas and those
areas prone to be affected for up to 50 days | | | Not stated | 218 participants (n = 145
MAS063DP, n = 73 vehicle) | Age ≥ 18 years; diagnosed with mild to moderate
atopic dermatitis according to the Hanifin and Rajka8 criteria and Rajka
and Langeland228
scale; score of at least 40 mm on a VAS scale for itch
(100-mm scale, with 0 mm = no itch,
100 mm = worst possible itch); women of
child-bearing potential had a negative test for pregnancy and
had to agree to use adequate birth control throughout the
study | (Primary) EASI score at day 22
EASI score at other time
points
Itch (target lesion) on a VAS
Percentage of
affected body surface area
IGA of clinical response from
baseline
Need for rescue medication in event of a
flare
Adverse events
Participant global assessment
of clinical improvement from baseline | Other outcomes: participant assessment of itch over total body
(improvement from baseline on a 4-point scale, with
1 = worse to 3 = total
resolution); participant opinion of acceptability of the study
cream | MAS063DP was statistically
(p < 0.0001) more
effective than vehicle in all outcomes at all time points.
Incidence of rash: 2.1% in the MAS063DP group vs. 5.5% in the
vehicle group. Two participants discontinued MAS063DP because of
an adverse event. Participant global assessment: day 22
– MAS063DP group 77% vs. vehicle group 21% had a
participant global assessment of ‘good
improvement’ or better (chi-square test
p < 0.0001). More
participants had an improvement in itch over their total body in
the MAS063DP group than in the vehicle group
(p < 0.0001) | Method of randomisation was described and is good. Allocation
concealment not reported. Intention-to-treat population used in
the analyses and compared with the per-protocol population |
| Amichai 2009196 | Liquid soap (Axera) containing 12% ammonium lactate and 20% urea
was used once daily for 3 weeks whilst showering | Placebo commercial liquid soap used for 3 weeks | | The placebo soap had a similar odour and cleaning properties to
the intervention soap. All patients continued all other systemic
or topical medication but avoided any other soap or
emollients | | 36 patients randomised [n = 24
group A (active), n = 12 group
B (placebo)] | Male or female; mild to moderate stable atopic dermatitis
diagnosed according to criteria proposed by the UK Working
Party;9 age
range of participants was 3–40 years but the paper does
not state if this was a specific inclusion criterion | Scaling, skin dryness and redness (score of 0–4, with
0 = none, 1 = mild,
2 = moderate, 3 = severe and
4 = worsened)
Patient-assessed subjective
itch [score of 0–3, with 0 = none,
1 = mild only (occasional),
2 = moderate (many times during the day) and
3 = severe (troublesome itching both day and
night]
Patient assessment of liquid soap (based on the
parameters of skin smoothness, odour quality and stickiness
using a score of 1–3, with 1 = very
good, 2 = good, 3 = bad) | | After 3 weeks there were significant improvements in
investigator-rated scaling, skin dryness and redness in the
study group compared with the placebo group (scaling
p < 0.0001, skin
dryness p < 0.0001,
redness p = 0.03). Subjective
patient itch improved in the study group compared with the
control group
(p < 0.001) | No description of randomisation method, allocation concealment
or blinding. Not stated whether intention-to-treat principle was
used |
| Arenberger 2010, 2011,230,231 | Combination of levomenol (0.3 g/100 g cream) and
heparin (20,000 IU/100 g cream) cream (group A)
applied to the affected eczematous areas twice daily for 8
weeks | Levomenol cream (0.3 g/100 g cream) (group B)
applied to the affected eczematous areas twice daily for 8
weeks | Heparin cream (20,000 IE/100 g cream) (group C)
applied to the affected eczematous areas twice daily for 8
weeks | Group D = base cream vehicle, applied to the
affected eczematous areas twice daily for 8 weeks. Base vehicle
was a cortisone-free cream base manufactured as an oil-in-water
emulsion | Not stated | 280 patients were screened and 278 participants were randomised
(n= 79 group A,
n = 80 group B,
n = 78 group C,
n = 41 group D) | Adults and children with atopic eczema (no specific inclusion
criteria based on severity of the atopic dermatitis); age up to
60 years (inclusion of children was explicitly approved of) | (Primary) Itching (100-mm VAS)
Severity of eczema (SCORAD
index)
Physician-rated global assessment
(VAS)
Participant-rated global assessment (verbal rating
scale – ‘no activity’,
‘low’, ‘moderate’,
‘good’ and ‘very
good)’
Participant-rated global tolerability
(‘very bad’, ‘bad’,
‘acceptable’, ‘good’,
‘very good’)
Adverse effects
Local
tolerance (included the assessment of eczemas,
blisters/urticaria, ulcers, excoriation and folliculitis) | | Severity (SCORAD index) and pruritus: combination treatment
(group A) was superior to the treatments alone and the control
group (analysis of covariance
p < 0.00000007). The
improvement in pruritus in the combination treatment group
approximately equated to the cumulative effect of the two
individual treatments. Mean improvements in itching: group A
–41.3 mm, group B –13.3 mm,
group C –21.3 mm, group D +0.6 mm (95%
CIs for comparisons: group A vs. B 7.1 to 13.5, group A vs. C
2.9 to 9.2, group A vs. D 10.4 to 18.3) | Method of randomisation described (ratio
2 : 2 : 2 : 1).
Allocation concealment achieved. Physicians, patients,
statistician and the study sponsor were fully blinded until
statistical assessment was complete. Intention-to-treat
population used for the analyses |
| Belloni 2005224 | MAS063D (Atopiclair) cream applied the first time following
visit 1 and then three times a day for 5 weeks | Vehicle-only cream applied the first time following visit 1 and
then three times a day for 5 weeks | | The vehicle-only cream was described as the emollient cream base
that is used as the vehicle for MAS063D | Not stated | 30 participants | Fair/light skin without recent suntan; age > 16
years; mild to moderate eczema (Hanifin and Rajka8 criteria referenced
but not specifically stated as being used); grading according to
the Rajka and Langeland228 criteria of 3.0–7.5;
> 20% cutaneous body surface area involvement;
written informed consent given; female sexually active
participants required to test negative in a pregnancy test and
to agree to use birth control during the study and for 2 weeks
afterwards | Severity of atopic dermatitis (graded according to the Rajka and
Langeland228
criteria)
Percentage of body surface area
affected
Area and severity using the EASI
score
Participant-assessed itch score using a VAS
(10 cm, without anchor points)
Hours of
sleep
Adverse events observed by clinicians or reported
by participants | Questions to the participants were given in a consistent way
according to the structure of the case report form | In the vehicle-only group there was a significant change in itch
score (p < 0.05) at
visit 4 (end of treatment) compared with baseline. There were no
significant changes for any of the other outcomes assessed. In
the MAS063D group, statistically significant improvements
between visits 1 and 4 were found for the itch score, affected
area score and EASI score. In the MAS063D group, 33% of
participants stated that they ‘would’ use the
cream again and 60% stated that they ‘may’ use
it again. In the vehicle group, 60% of participants stated that
they ‘may’ use the cream again and 33% stated
that they ‘would not’ use it again | Method of randomisation and allocation concealment both
described and adequate. Intention-to-treat population used for
the analyses |
| Berardesca 2001200 | Skin lipid mixture containing ceramide-3, cholesterol, palmitic
acid and oleic acid in a water-in-oil vehicle with nanoparticles
(Reposital®/Alfason®
Repair/Lactobase Repair®/Nouriva™
Repair; Yamanouchi) applied one to two times a day until healing
occurred or for a maximum of 8 weeks | Skin lipid mixture (see intervention A) and topical
corticosteroids applied one to two times a day until healing
occurred or for a maximum of 8 weeks | | | Not stated | 91 participants with atopic eczema out of 508 in total for the
trial (n = 206 allergic contact
dermatitis, n = 283 irritant
contact dermatitis) | Atopic eczema, irritant contact dermatitis or allergic contact
dermatitis | Overall disease severity (visual 4-point scale, with
0 = none, 1 = mild,
2 = moderate,
3 = severe)
Dryness (visual 4-point
scale, with 0 = none, 1 = mild,
2 = moderate,
3 = severe)
Scaling (visual 4-point
scale, with 0 = none, 1 = mild,
2 = moderate,
3 = severe)
Erythema (visual 4-point
scale, with 0 = none, 1 = mild,
2 = moderate,
3 = severe)
Pruritus (visual 4-point
scale, with 0 = none, 1 = mild,
2 = moderate,
3 = severe)
Fissuring (visual 4-point
scale, with 0 = none, 1 = mild,
2 = moderate, 3 = severe) | | (Only for the participants with atopic eczema) Compared with
baseline, both groups improved in all measures taken at week 4
and week 8. Between the two groups: statistically significant
improvement in favour of combined therapy for dryness and
scaling | Whether a true method of randomisation was used is unclear as
the term ‘randomised’ is not used. Allocation
concealment was not mentioned and seems unlikely.
Intention-to-treat analysis not stated |
| Bigliardi 2007216 | 1% Naltrexone cream applied when experiencing severe pruritus
for up to 28 days | Placebo cream (vehicle for naltrexone – Excipial cream;
Galderma) applied when experiencing severe pruritus for up to 28
days | | Participants were allowed to use topical corticosteroids as
rescue medication except in the itching intensity measuring
periods | Switzerland | 45 participants | Age ≥ 18; atopic eczema; bouts of itching
recorded as > 50 mm on a 100-mm VAS
(strong intensity) | Location of pruritus attacks (participant recorded)
Itch
sensation during attacks
Use of rescue
medication
Side
effects
SPID = SUMi = 1
to
n[VAS(i) – VAS(Baseline)]
where i = 1 is the first pruritus measurement
and n is the last measurement. The mean of
three itching attacks was calculated for each time point | No residual (carry-over) effect found in the analysis | Naltrexone cream had a 29.4% better effect than the placebo
cream for sum of the pruritus intensity difference (per-protocol
set). Naltrexone cream = median 46 minutes for a
reduction of 50% in itching; placebo
cream = median 74 minutes for a reduction of 50%
in itching | Method of randomisation and allocation concealment not reported.
Full analysis set used for the analysis but not defined |
| Bissonnette 2010195 | Urea 5% moisturiser applied twice a day, morning and evening, on
the trunk and limbs for 42 days | Urea 10% lotion | | The base emollients of the two treatments have different
compositions so this study compares two completely different
treatments | Not stated | 100 participants (n = 50, 5%
urea; n = 50, 10% urea) | Age ≥ 18 years; diagnosed with atopic eczema
(SCORAD score of ≤ 30) | Efficacy (SCORAD index)
Safety (5-point tolerance scale,
with 1 = very good, 2 = good,
3 = average, 4 = poor,
5 = very poor)
Safety (evaluation of
adverse events) | | Mean SCORAD score: 5% urea – day 0 to day 42 reduction
19.76%, 10% urea – day 0 to day 42 reduction 19.23%
(p < 0.001). No
difference between the treatments in reduction of SCORAD scores.
Both treatments were well tolerated (three withdrawals because
of adverse events). For cosmetic acceptability, significantly
more participants preferred the 5% urea moisturiser than the 10%
urea lotion | Method of randomisation and allocation concealment were not
stated. Intention to treat not used but data to be included in
the analyses were clearly described |
| Bissonette 2012220 | Synthetic compound 2-isopropyl-5-[(E)–2-phenylethenyl]
benzene-1,3-diol (WBI-1001) 0.5% cream applied twice daily for 4
weeks | Synthetic compound 2-isopropyl-5-[(E)–2-phenylethenyl]
benzene-1,3-diol (WBI-1001) 1% cream applied twice daily for 4
weeks | Placebo – vehicle cream applied twice daily for 4
weeks | WBI-1001 shows non-steroidal anti-inflammatory properties | Not stated | 37 participants (numbers allocated to each group not
stated) | Between 1% and 10% of the body surface area affected (excluding
the face, groin, scalp and genital regions); EASI score of
< 12; IGA score of 2 (mild) or 3 (moderate) | Severity of eczema (EASI score)
Severity of eczema
(SCORAD index)
IGA
Affected body surface
area
Pruritus (10-cm VAS)
Adverse events | The efficacy analyses should be considered as post hoc as they
were carried out before database lock | No serious adverse events were reported. The pharmacokinetic
analyses showed that WBI-1001 was only minimally absorbed. The
severity of eczema was significantly reduced in the WBI-1001
groups compared with the placebo group as measured by SCORAD and
EASI, IGA and pruritus | Method of randomisation not described. Allocation concealment
not reported, Intention-to-treat analysis not reported. Not
stated which parties were blinded |
| Boguniewicz 2008227 | MAS063DP (Atopiclair) cream applied to skin affected by atopic
eczema, skin that had been affected by atopic eczema in the past
or skin that could reasonably be affected by atopic eczema
during the course of the study. Cream applied three times daily
(morning, afternoon and evening) for 43 days | Vehicle cream applied to skin affected by atopic eczema, skin
that had been affected by atopic eczema in the past or skin that
could reasonably be affected by atopic eczema during the course
of the study. Cream applied three times daily (morning,
afternoon and evening) for 43 days | | It is stated that the emollient base of the vehicle cream was
‘similar’ to the MAS063DP base | USA | 142 participants (n = 72
MAS063DP, n = 70 vehicle) | Girls and boys aged from 6 months to 12 years; diagnosed with
atopic eczema according to the Hanifin and Rajka8 criteria; IGA of 2
(mild) or 3 (moderate); at least 5% body surface area affected
by atopic eczema at study entry; a sore of at least
40 mm on a VAS from 0 to 100 mm for itch;
participant/caregiver agreement to refrain from using other
topical and systemic medications (including phototherapy) | (Primary) IGA at day 22
(Secondary) IGA at other time
points
(Secondary) Participant/caregiver assessment of
pruritus on a VAS
(Secondary) EASI score at all time
points
(Secondary) Participant/caregiver assessment of
global response from baseline
(Secondary) Onset of itch
relief and duration of action
(Secondary) Need for rescue
medication in the event of a flare | | MAS063DP is safe and effective monotherapy in infants and
children with mild to moderate atopic eczema. MAS063DP applied
three times daily resulted in rapid improvement with resolution
of pruritus and was well tolerated | Method of generation of the randomisation procedure was
described and was adequate. Allocation concealment was not
reported. Intention-to-treat analysis was carried out |
| De Belilovsky 2011198 | 2% Sunflower oleodistillate emollient cream (Stelatopia) applied
to the entire body twice a day for 3 weeks | Hydrocortisone butyropropionate cream
(CENEO®; Pensa) (1 mg/g) applied to
the affected lesions twice a day for 3 weeks | | | Spain | 80 participants
(n = 40emollient group,
n = 40 hydrocortisone
group) | Age 4 months to 4 years; mild to moderate atopic eczema
(clinical definition = acute lesions in the
folds of the elbows and/or knees and/or surfaces of the limbs
and/or cheeks); SCORAD score between 15 and 60 | (Primary) SCORAD score measured at days 0, 7 and
21
(Secondary) IGA of eczema flare-ups at day
21
(Secondary) Quality of Life (IDLQI and Dermatitis
Family Impact questionnaires)
(Secondary) Individual
components of the SCORAD assessment (extent of lesions,
erythema, oedema/papulation, oozing/crusting, excoriation,
lichenification, dry skin in healthy areas, pruritus, sleep
loss) | | SCORAD, hydrocortisone vs. emollient: day 0: 37.2 vs. 36.9, day
7: 18.9 (–49%) vs. 19.2 (–48%), day 21: 11
(–70%) vs. 9.4 (–75%)
(p < 0.01 vs. day 0).
Quality of life (IDLQI/Dermatitis Family Impact): improvement at
day 21: hydrocortisone group 65%/67%, emollient group 72%/75%
(p < 0.01 vs. day
1) | Method of randomisation only partially described. Allocation
concealment not reported. Intention-to-treat analysis not
reported |
| Dolle 2010215 | 6% Miltefosine solution (Miltex®; Baxter
Oncology GmbH) applied topically (two drops of solution per
affected lesion) once daily for the first week, then twice daily
for the second and third weeks | 1% Hydrocortisone solution (Hydrogelan®;
GALENpharma GmbH) applied topically (two drops of solution per
affected lesion) once daily for the first week, then twice daily
for the second and third weeks | | All of the participants had moderate to severe atopic eczema (as
per the SCORAD index) | Not stated | 16 participants (only 12 participants consented to skin
biopsies) | Atopic eczema according to the diagnostic criteria of Hanifin
and Rajka;8 age
≥ 18; two comparable skin lesions | (Primary) Local clinical response: decline by
> 1.5 in TIS score (score of 0–3 for
each of erythema, oedema/papulations, excoriations, with
0 = none, 1 = mild,
2 = moderate,
3 = severe)
Transepidermal water
loss
Maximum temperature of the treated
lesions
Epidermal atrophy (measured by transepidermal
thickness)
CD4+ T-cell infiltration of the
lesions
FoxP3+ protein
expression | All assessed lesions had a TIS score of 5–7 before
treatment | Both treatments caused a significant decrease in TIS score;
however, only miltefosine showed a carry-over effect after
stopping treatment. Both treatments reduced the infiltration of
CD4+ T cells | Method of randomisation and allocation concealment not reported.
Intention-to-treat analysis not reported |
| Draelos 2009190 | Abolene (over-the-counter moisturiser) with triamcinolone 0.1%
cream for moderate eczema applied twice daily for 4 weeks | MimyX (prescription device moisturiser) with triamcinolone 0.1%
cream for moderate eczema applied twice daily for 4 weeks | | Moisturiser put on top of topical corticosteroid. Participants
allowed to use their preferred cleanser throughout the trial. No
other moisturisers allowed on the limbs for the duration of the
trial | Not stated | 60 participants, 30 with dermatologist-assessed mild eczema, 30
with dermatologist-assessed moderate eczema | Symmetrical mild to moderate eczema (as assessed by a
dermatologist) of the arms or legs | (Primary) Abolene and MimyX parity in treating mild
eczema
(Secondary) Abolene and MimyX parity in treating
moderate eczema in combination with triamcinolone cream | | Parity between the over-the-counter moisturiser Abolene and the
prescription device moisturiser MimyX was proven. This was based
on investigator and participant assessments | Method of randomisation and allocation concealment not reported.
Intention-to-treat principle not used for the analyses |
| Draelos 2011201 | Hyaluronic acid-based emollient foam (Hylatopic) applied twice
daily to the target site for 4 weeks | Ceramide-containing emulsion cream (EpiCeram) applied twice
daily to the target site for four weeks | | Split-body study. Patients were randomised to apply intervention
A to one limb and intervention B to the opposite limb. Patients
were instructed to treat all of the non-target areas with the
randomised barrier therapy for that side of the body to yield a
split-body design | | 20 subjects randomised | Age ≥ 18 years; investigator-assessed mild to
moderate atopic dermatitis defined by IGA with symmetrically
distributed target lesions on the arms or legs – each
target lesion required a minimum score of 3 on a 6-point target
lesion severity scale (0 = none,
1 = minimal, 2 = mild,
3 = moderate, 4 = moderately
severe, 5 = severe) at baseline; minimum total
body surface area involvement, including the
investigator-evaluated target lesions, of 10%; participant
agreed to avoid all other topical medications and moisturisers
during the study period and for 2 weeks prior to study
enrolment | Investigator-assessed overall eczema
severity
Investigator-assessed erythema, scaling,
lichenification, excoriation, itching, stinging and
burning
Subject-evaluated skin appearance for redness,
peeling, dryness, stinging/burning and overall skin
irritation
Survey to report which features of the two
products the subjects favoured (including spreadability,
moisturisation, soothing ability, skin absorption and lack of
odour)
Subject-assessed belief of which product was most
effective, which they would be willing to pay for and which they
preferred | A 6-point ordinal rating scale was used for both investigator
and subject assessments (0 = none,
1 = minimal, 2 = mild,
3 = moderate, 4 = moderately
severe, 5 = severe) | Both formulations showed a statistically significant improvement
in clinical signs and symptoms of atopic dermatitis by week 4
(p < 0.001). The
hyaluronic acid-based formulation showed a statistically
significant improvement in overall severity by week 2
(p = 0.016) whereas the
ceramide-containing emulsion cream did not
(p = 0.155). Subjects
significantly favoured the hyaluronic acid foam in terms of
ability to spread, ability to moisturise, ease of use and lack
of odour. The foam was also favoured for effectiveness and the
ability to soothe | Method of randomisation and allocation concealment not
described. The authors reported that the study was double blind.
The evaluating investigator was blinded but it is not clear
which other parties were blinded |
| Foelster-Holst 2010222 | SRD441 (a topical matrix metalloproteinase inhibitor)
(1 mg/g) applied to all affected body areas and commonly
affected sites twice daily for up to 28 days | Vehicle applied to all affected body areas and commonly affected
sites twice daily for up to 28 days | | | Germany, Bulgaria, Finland | 93 participants (n = 45 SRD441
group, n = 48 vehicle
group) | Age ≥ 18 years; dermatologist-confirmed
diagnosis of atopic eczema; mild to moderate atopic eczema at
randomisation (IGA of 2 or 3); ≤ 20% of total
body surface area affected; current exacerbation of atopic
eczema (requiring a ‘step up’ in
medication) | (Primary) Success rate at day 21 (success defined as IGA of 0 or
1) (0 = clear, 1 = almost clear,
2 = mild, 3 = moderate,
4 = severe, 5 = very
severe)
(Secondary) Time to resolution of primary
exacerbation (IGA of 0 or 1)
(Secondary) IGA score at
each visit
(Secondary) Participant-assessed total
pruritus over previous 24 hours (‘none’,
‘mild’, ‘moderate’,
‘severe’)
(Secondary) Number of subjects
requiring rescue medication
(Secondary) Quality of life
(DLQI – 10-question questionnaire with scoring for each
question as follows: 3 = very much,
2 = a lot, 1 = a
little)
Safety (adverse events, physical examinations,
clinical laboratory measures, change from baseline in
investigator’s visual assessment) | | Success rate (IGA): no significant difference between groups at
day 21 – SRD441 11.1%, vehicle 12.5%
(p = 1.000). Secondary outcomes
did not show any clinical or other significant differences. In
total, 18 participants withdrew because of an adverse event
(n = 7 SRD441,
n = 11 vehicle). Number (%)
of participants reporting an adverse event: SRD441 27 (60.0),
vehicle 34 (70.8) | Method of randomisation and allocation concealment reported.
Intention-to-treat population used for the analyses but not
defined |
| Gandy 2011221 | CHD-FA 3.5% in an emollient buffered to pH 4.8 applied twice
daily for 4 weeks to affected areas | Placebo emollient buffered to pH 4.8 applied twice daily for 4
weeks to affected areas | | Epizone A® emollient buffered with acetic
acid used as needed | Not stated | 36 (n = 18 CHD-FA,
n = 18, placebo) | Healthy males or females with known eczema; age
> 2 years; females using a reliable
contraception method if of childbearing age; written informed
consent | Investigator-assessed global response to treatment [7-point
scale, with 0 = completely clear,
1 = almost clear (about 90%),
2 = marked improvement (75%),
3 = moderate improvement (50%),
4 = slight improvement (25%),
5 = no change (moderate to severe disease)
6 = worse]
Investigator assessment of
severity of disease (5-point scale, with
0 = absent, 1 = mild,
2 = moderate, 3 = moderately
severe, 4 = severe)
Severity of eczema
assessed by the participant (VAS from 0 to
100 mm)
Blood tests (liver function tests, full
blood count, kidney function tests)
Clinical examination
and electrocardiography
Adverse events
Laboratory
investigations | | All safety parameters stayed within normal limits. There were
significant differences for severity and erythema compared with
baseline in the placebo and CHD-FA groups. There was a
significant difference for scaling compared with baseline in the
placebo group | No description of randomisation process or allocation
concealment. The title states that this was a double-blind trial
but there is no description of who was blinded. It is unclear if
the intention-to-treat population was used or not. It is stated
that two patients were excluded from the analysis for using
concomitant medications; however, the number in the data tables
appears to be the number randomised |
| Giordano-Labadie 2006192 | Moisturising milk (Exomega) applied all over the body twice a
day for 2 months | Standard cleansing bar (A-Derma) applied all over the body twice
a day for 2 months | | At least 1 week washout of no application of topical therapy
prior to randomisation for all participants. Only topical
corticosteroids were allowed during the study | Not stated | 76 participants
(n = 37 = Exomega
milk, n = 39 standard cleansing
bar) | Age 6 months to 2 years; mild to moderate atopic eczema (SCORAD
score < 35) | Severity of eczema (SCORAD)
Tolerance
(0 = excellent/no side effects,
1 = satisfactory/minor unwanted side effects,
2 = mediocre/occurrence of unwanted side effects
requiring reduction of frequency of application,
3 = unsatisfactory/occurrence of unwanted side
effects requiring stoppage of treatment)
Topical steroid
use
Quality of life (CDLQI; max. score 30) | | SCORAD: after 2 months decrease in SCORAD index in Exomega milk
group not statistically significantly
(p = 0.051). There was a
significant difference between groups at 2 months for xerosis
(p = 0.01) and pruritus
(p = 0.01) in favour of the
treatment group. There was a significant improvement in quality
of life after 2 months in the Exomega milk group
(p = 0.0011). Good to
excellent tolerance: 97% participants | Method of randomisation, allocation concealment and
intention-to-treat analysis not described |
| Griffiths 2002124 | Cipamfylline cream (1.5 mg/g), maximum application of
2 g (four fingertip units) per day for up to 14
days | Hydrocortisone 17-butyrate 0.1% cream, maximum application of
2 g (four fingertip units) per day for up to 14
days | Vehicle of cipamfylline cream, maximum application of
2 g (four fingertip units) per day for up to 14
days | | Canada, Denmark, the Netherlands and the UK | 103 participants (n = 54
cipamfylline/vehicle group,
n = 49
cipamfylline/hydrocortisone 17-butyrate group) | Men and women aged ≥ 18 years, diagnosis of
atopic eczema according to the Hanifin and Rajka8 criteria; stable,
symmetrical lesions of atopic eczema on both arms with a minimum
total severity score of 6 for a selected larger lesion; women of
childbearing potential had a negative pregnancy test and used
adequate contraception throughout the study | (Primary) Investigator-assessed absolute change in TSS from
baseline to end of treatment (TSS = severity of
erythema, oedema/papulation, oozing/crusting, excoriations,
lichenification on a 4-point scale, with
0 = absent, 1 = mild,
2 = moderate,
3 = severe)
(Secondary)
Investigator-assessed overall response to treatment since
commencement of treatment as recorded on days 3, 7, 14
(‘worse’, ‘no change’,
‘minimal improvement’, ‘moderate
improvement’, ‘marked improvement’ or
‘completely cleared’)
(Secondary)
Participant-assessed overall response to
treatment
(Secondary) Participant-assessed cosmetic
acceptability (‘unacceptable’,
‘acceptable’, ‘good’ or
‘very good’)
(Secondary)
Participant-assessed severity of pruritus of the target lesions
on a 10-cm VAS (ranging from ‘no itching’ to
‘worst possible itching’)
(Secondary)
Proportion of participants relapsing defined as the requirement
for treatment of atopic dermatitis on the target lesions | | There was a statistically significant reduction in the TSS from
baseline to the end of treatment for all three treatments
(p < 0.002). In the
cipamfylline/vehicle group the difference between treatments was
statistically significant in favour of cipamfylline (1.67, 95%
CI 1.06 to 2.28;
p < 0.001). In the
cipamfylline/hydrocortisone 17-butyrate group the difference
between treatments was statistically significant in favour of
hydrocortisone 17-butyrate (–2.10, 95% CI –1.27
to –2.93;
p < 0.001) | Randomisation procedure described. Allocation concealment
appears to have happened, although this is not as clear.
Intention-to-treat population was used and clearly defined |
| Grimalt 2007191 | Emollient (Exomega lotion) applied twice a day (after morning
cleansing and before bed in the evening) for 6 weeks in
sufficient amount on the dry, non-inflammatory areas of the skin
over the whole body | Control (no emollient) | | Both groups applied topical corticosteroids of high (micronised
desonide 0.1% cream) or moderate (desonide 0.1% cream) potency
on the inflammatory lesions according to the
investigators’ regular practice | Not stated | 173 participants randomised
(n = 91 emollient group,
n = 82 control group) | Male and female infants aged < 12 months with
moderate to severe atopic eczema with a SCORAD score of
20–70 | (Primary) Steroid-sparing effect (measured as amount of topical
corticosteroid used)
(Secondary) Severity of eczema
(SCORAD)
(Secondary) Participant and parent quality of
life (French version of the IDLQI and Dermatitis Family
Impact)
Physician-assessed global tolerance (only for
emollient group) on a 4-point scale from 1 = no
sign of tolerance to 4 = intolerance signs
leading to treatment discontinuation
Adverse events | | The amount of topical corticosteroid used in 6 weeks decreased
by 7.5% (not significant) and 42%
(p < 0.05) in the
control and the emollient group, respectively. The SCORAD index
and infant and parent quality of life significantly improved
(p < 0.0001) in
both groups | Some information given about the method of randomisation and the
reason for not blinding the study is also stated.
Intention-to-treat population used for the analysis, although it
was not fully described |
| Guéniche 2006213 | V. filiformis bacterial extract in a base cream
containing glyceryl mono/distearate and polyethylene glycol
stearate, isoparaffin cyclopentadimethylsiloxane (5% V.
filiformis biomass) was applied in a thin layer to
an investigator-defined area twice daily for 4 weeks | Base cream containing glyceryl mono/distearate and polyethylene
glycol stearate, isoparaffin cyclopentadimethylsiloxane was
applied in a thin layer to an investigator-defined area twice
daily for 4 weeks | | Base cream not designed specifically for atopic skin. Areas for
treatment were symmetrical: left side/right side | Not stated | 13 participants | Atopic dermatitis; mild to moderate according to Rajka and
Langeland228
criteria; 5–60% total body surface area involvement | Investigator-assessed erythema,
oedema–induration–papulation, excoriations and
lichenification (4-point scale from 0 to 3) and estimated total
body surface area affected (0–100%) in four body areas:
head and neck, trunk, upper limbs and lower
limbs
Participant-assessed itch intensity (in previous 24
hours on a 10-cm VAS, with 0 cm = no
itch and 10 cm = worst itch
imaginable)
mEASI (includes an assessment of itch) (max.
score 90)
Investigator-assessed global evaluation of
clinical response (cleared = 100% improvement,
excellent = 90–99% improvement,
marked = 75–89% improvement,
moderate = 50–74% improvement,
slight = 30–49% improvement, no
appreciable improvement = 0–29%
improvement, worse = worsening of the
condition)
Adverse events (any undesirable experience
that occurred during the trial) | | A beneficial effect was seen after 2 weeks of treatment, which
increased after this point | Method of randomisation and allocation concealment not reported.
Intention-to-treat population defined but it is not clear which
analyses were carried out using this population |
| Guéniche 2008214 | 5% V. filiformis lysate cream applied twice
daily in a thin layer on predefined areas for 30 days | Vehicle cream applied twice daily in a thin layer on predefined
areas for 30 days | | | Not stated | 75 (n = 37 5% V.
filiformis lysate cream,
n = 38 vehicle cream) | Age 6–70 years; diagnosis of mild atopic eczema
according to the Hanifin and Rajka8 criteria; history of atopy (e.g.
allergic rhinitis and/or allergic asthma, atopic eczema, type I
sensitivity to aeroallergens); presenting with dry and/or
scaling skin | Severity of eczema (SCORAD index)
Participant-assessed
pruritus (VAS)
Participant-assessed sleep loss
(VAS)
Transepidermal water loss
Skin microflora
(counts per 1 cm2 of skin
surface)
Adverse events | | Severity of eczema: 5% V. filiformis lysate
cream compared with vehicle –
p = 0.0044 in favour of 5%
V. filiformis lysate cream. Pruritus: 5%
V. filiformis lysate cream compared with
vehicle – p = 0.0171 in
favour of 5% V. filiformis lysate cream. Sleep
loss: 5% V. filiformis lysate cream
significantly decreased sleep loss from day 0 to day 29
(p = 0.0074). Skin
microflora: 5% V. filiformis lysate cream
reduced S. aureus on the skin. Skin barrier:
transepidermal water loss decreased significantly in both groups
from baseline with no difference between the groups | Both randomisation and allocation concealment described.
Intention-to-treat principle used for the analysis |
| Hamada 2008234 | Camellia oil spray (Atopico® Skin Health Care
Oil) applied as often as desired for 2 weeks (then used purified
water spray for 2 weeks) | Purified water spray applied as often as desired for 2 weeks
(then used camellia oil spray for 2 weeks) | | No modification to participants’ standard care | Japan | 42 participants | Patients with atopic dermatitis who fulfilled the atopic
dermatitis criteria of the Japanese Dermatological Society;26 severity less
than moderate, which was based on the atopic dermatitis
guideline of the Ministry of Health, Labour and Welfare in
Japan | Change in eczema severity evaluated by the
physician
Change of applied ointment dose assessed by the
patient
Moisturising affect assessed by the
patient
Frequency of use of the spray assessed by the
patient
Effectiveness of the treatment assessed by the
patient
Itch score assessed by the patient | | Changes in the severity of clinical manifestations: no
difference between groups. Participants’ impressions of
the treatments: significant difference between groups in favour
of the camellia oil spray
(p < 0.01) | Method of randomisation not described. Allocation concealment
not reported. Intention-to-treat population does not appear to
have been used for the analyses |
| Hashizume 2013236 | 1% AHYP in a cream with aqua, squalane, glycerin, glyceryl
stearate, stearic acid, steareth-20, cetyl alcohol, arginine,
dimethicone, sorbitan stearate, 1,2-hexanediol, caprylyl glycol
and phenoxyethanol applied to one forearm twice daily for 4
weeks | Control cream containing aqua, squalane, glycerin, glyceryl
stearate, stearic acid, steareth-20, cetyl alcohol, arginine,
dimethicone, sorbitan stearate, 1,2-hexanediol, caprylyl glycol
and phenoxyethanol applied to the other forearm twice daily for
4 weeks | | The study was carried out in winter. Subjects were asked not to
use any other new medicines to treat their skin apart from their
usual treatment and not to change or add any emollient or
medicine during the study | Japan | Slight atopic dermatitis diagnosed by a dermatologist in
accordance with the atopic dermatitis treatment guidelines of
the Japanese Dermatological Association26 | Transepidermal water loss
Pruritus change (pruritus
intensity evaluated using a 100-mm VAS, with
0 mm = no itch and
100 mm = maximum
itch)
Dermatological observations
Safety | | | No adverse events were observed. Transepidermal water loss was
increased in the control cream-treated region of the forearm
(p < 0.05) after 4
weeks whereas there was no change in the AHYP-treated region of
the forearm. Pruritus intensity was decreased in the
AYHP-treated forearm between 0 and 4 weeks
(p < 0.05) but there
was no change in the control-treated forearm | Randomisation method and allocation concealment not described.
The study was blinded but method of blinding and parties blinded
were not stated. Intention-to-treat population not
described |
| Herzog 2011237 | SRD174 cream (nalmefene hydrochloride monohydrate, a
μ-opiate receptor antagonist; strength 0.95% w/w
anhydrous nalmefene base with isopropyl myristate, glycerol,
hydroxyethylcellulose and phenoxyethanol supplied in a 10-g
tube). When the subject experienced an itch of
≥ 40 on a 101-point VAS during the treatment
periods he or she had to identify a target area of highest
intensity and treat both the target area and other areas of
bothersome itch. The severity of the target area itch was then
assessed using the 101-point VAS at 15, 30, 45 and 60 minutes
and 2, 3, 4, 6 and 8 hours after administration of the trial
medication Once a recording of itch intensity was complete (8
hours) another area could be treated. Subjects could treat more
than one episode of itch in a day provided (1) the episodes were
> 8 hours apart and (2) the total amount of
study drug used in a day was less than one tube
(10 g) | Vehicle cream, identical to the SRD174 cream but without the
nalmefene. When the subject experienced an itch of
≥ 40 on a 101-point VAS during the treatment
periods he or she had to identify a target area of highest
intensity and treat both the target area and other areas of
bothersome itch. The severity of the target itch was then
assessed using the 101-point VAS at 15, 30, 45 and 60 minutes
and 2, 3, 4, 6 and 8 hours after administration of the trial
medication Once a recording of itch intensity was complete (8
hours) another area could be treated. Subjects could treat more
than one episode of itch in a day provided (1) the episodes were
> 8 hours apart and (2) the total amount of
study drug used in a day was less than one tube
(10 g) | | SRD174 cream is white to off-white and supplied in a collapsible
aluminium tube. The vehicle cream had the same ingredients with
the exception that it contained no nalmefene. All labelling and
packaging for the two study drugs was identical. Subjects
applied either vehicle or SRD174 in the first treatment period
of 7 days and the opposite treatment for the second treatment
period of 7 days following a washout period (length of washout
not stated). During the assessment period (0–8 hours)
following treatment, subjects were asked not to reapply the
study medication to the target itch or other areas. Subjects
were also asked not to apply any emollients or rescue medication
during this time and particularly for at least the first 4
hours. If itch intensity was < 40 on the VAS
they were asked not to apply trial medication. They were asked
to wait for the itch to alleviate spontaneously or for it to
worsen such that the VAS score was ≥ 40. They
would then be eligible to apply the study medication. When
waiting was not acceptable, the subjects could use their
standard emollient or moisturiser. This would be recorded as a
concomitant medication | Not stated | 136 subjects were screened and 62 were randomised
(n = 31 SRD174 in the first
treatment phase, n = 31 vehicle
in the first treatment phase) | Male and female; age ≥ 18 years; recurrent,
persistent episodes of moderate to severe atopic dermatitis
pruritus defined as ≥ 40 on a 101-point pruritus
VAS; active and pruritic atopic dermatitis covering a body
surface area ≤ 20%; subjects had adequately
recorded at least three episodes of moderate to severe pruritus
defined as VAS score of ≥ 40 in the 7 days prior
to randomisation | (Primary) Period mean of the SPID from 0 to 4 hours based on
participant assessment of itch intensity at 15, 30, 45 and 60
minutes and 2, 3 and 4 hours post study drug administration
compared with baseline
(Secondary) SPID from 0 to 8
hours
Pruritus intensity difference at each assessed time
point
Change in EASI score during each time
period
IGA during each treatment period
Quality of
sleep recorded during each treatment period
Average daily
pruritus score during each treatment period
Eppendorf
Itch Questionnaire | Other secondary end points included pruritus relief; time to
achieve a > 30%, > 50% and 80%
reduction of itch sensation; time to reduction of itch sensation
to VAS score of < 40; and use of rescue
medication for pruritus | Least square means (SDs) for SPID: SRD174 210.7 (20.4), vehicle
212.1 (20.2), difference –1.3 (95% CI –25.9 to
23.3). None of the secondary efficacy end points demonstrated a
statistically significant or clinically important difference
between the test product and the vehicle. The SRD174 cream was
well tolerated but there was a higher incidence of adverse
events in the SRD174 group: SRD174 22 (36.7% of subjects),
vehicle 14 (23.3% of subjects) | Randomisation method described. Allocation concealment not
described. Study was double blind but it was not clear who was
blinded. Intention-to-treat analysis was used |
| Januchowski 2009218 | Vitamin B12 cream (0.07% by weight of cyanocobalamin
in a moisturising base) applied for 4 weeks | Placebo cream (moisturising base only) applied for 4 weeks | | | Not stated | 22 | Age 6 months to 18 years; eczema; ability to understand the
consent process | Severity of eczema (modified SCORAD index, max. score 27) | | Treatment with topical vitamin B12 significantly
improved the skin in comparison to the placebo cream at 2 weeks
(p = 0.02) and 4 weeks
(p = 0.01) | Method of randomisation described but slightly unclear.
Allocation concealment was unclear. Intention-to-treat analysis
not reported |
| Katsuyama 2005229 | ‘Oil-in-water’ cream containing 17% moisturiser,
0.2% farnesol (3,7,11-tri-methyl-2,6,10-dodecatrien-1-ol,
molecular weight 222.37) and 5% xylitol
(xylo-pentane-1,2,3,4,5-pentol, molecular weight 152.15) was
applied to the left or right forearm for 7 days | (Placebo) ‘Oil-in-water’ cream containing 17%
moisturiser was applied to the left or right forearm for 7
days | | | Not stated | 17 participants | Atopic eczema of mild to moderate severity on the arms | Dermatologist-assessed changes in skin condition (dryness,
scaling excoriation, redness and papules)
Skin
conductance
Transepidermal water loss
Skin
microflora | | Ratio of S. aureus in the total bacteria at the
test site after 1 week: farnesol and xylitol cream significantly
decreased compared with before application
(p = 0.007) and with placebo
cream (p = 0.045). Mean skin
conductance of farnesol and xylitol cream test patches was
significantly increased after application compared with before
application (p = 0.0001) and
with placebo cream
(p = 0.002) | No description of method of randomisation or allocation
concealment. Intention-to-treat population not reported |
| Korting 2010212 | Oil-in-water cream with 4% sodium bituminosulfonate (Ichthosin
cream) (pale sulfonated shale oil) applied three times a day for
4 weeks | Vehicle cream (propylene glycol, glycerol monostearate, cetyl
alcohol, medium-chain triglycerides, macrogol-1000-glycerol
monostearate, white vaselin (‘white soft
paraffin’, Ichthyol-Gesellschaft, Hamburg, Germany),
purified water and, for adjustment for colour, caramel and
quinoline yellow) applied three times a day for 4 weeks | | Skin-care products were allowed on unaffected skin. Concomitant
medications of any kind were not allowed | Germany | 99 participants (n = 51 pale
shale oil, n = 48 vehicle)
(safety population) | Caucasian; mild to moderate atopic eczema (total score of
≤ 21); age 0–12 years | (Primary) Total score – erythema, crusts, excoriations,
scales, lichenification and itch (each scored from 0 to 5, with
0 = non-existent, 1 = very mild,
2 = mild, 3 = moderate,
4 = severe, 5 = very
severe)
Topographical distribution
(0 = not affected,
1 = 1–33%,
2 = 34–66%,
3 = 67–100%) for the areas of face and
neck, head, torso front, torso back, arms, hands and wrists,
legs, feet. Topographical score halved as in EASI. Total score
max. = 42
(Secondary) Reduction of total
score after 1 and 2 weeks of treatment
(Secondary)
Reduction in signs and symptoms after 1, 2 and 4 weeks of
treatment
(Secondary) Reduction in topographical
distribution after 1, 2 and 4 weeks
Participant- and
investigator-assessed tolerability of the study treatment
(‘very good’, ‘good’,
‘medium’, ‘moderate’ or
‘bad’)
Adverse events | | Total score: baseline – vehicle cream 13.0
SD ± 3.1, shale oil cream 13.4
SD ± 3.7; 1 week – vehicle cream
reduction of 1.3 SD ± 5.9, shale oil
cream reduction of 5.6 SD ± 4.3; 4 weeks
– vehicle cream 11.7 SD ± 8.6,
shale oil cream 4.5 SD ± 7.4
(p < 0.0001).
Tolerability (at end of treatment): better in the shale oil
group than in the vehicle cream group according to investigators
(p < 0.0001) and
participants/parents
(p = 0.0051) | Method of randomisation described. Allocation concealment not
reported. Intention-to-treat population used for the efficacy
analyses and defined |
| Lee 2008210 | Rosmarinic acid-containing cream (0.3% rosmarinic acid) applied
to the elbow flexures twice daily, in the morning and evening,
for 8 weeks | Vehicle cream applied to the elbow flexures twice daily, in the
morning and evening, for 8 weeks | | Use of topical or systemic corticosteroids strictly forbidden
during the trial | Korea | 21 | Affected by eczematous lesions on elbows (this was taken as
moderate atopic eczema according to the SCORAD index); diagnosis
of atopic eczema according to the criteria of Hanifin and
Rajka8 | Severity of eczema (SCORAD index)
Local
pruritus
Transepidermal water loss
Safety | | SCORAD index: erythema on antecubital fossa significantly
reduced at weeks 4 and 8
(p < 0.05).
Transepidermal water loss on the antecubital fossa significantly
reduced at 8 weeks compared with before treatment
(p < 0.05).
Participant questionnaire: improvements in dryness, pruritus and
general eczema symptoms | The method of randomisation was not described. Allocation
concealment was not reported. Intention-to-treat analysis not
reported |
| Loden 2001193 | Glycerine 20% cream applied twice daily for 30 days over one
part of the body identified as dry by the dermatologist | Urea cream (4% urea and 4% sodium chloride) applied twice daily
for 30 days over one part of the body identified as dry by the
dermatologist | Placebo cream (same as the glycerine cream with water replacing
the glycerine) applied twice daily for 30 days over one part of
the body identified as dry by the dermatologist | The urea cream did not have the same constituents as the
glycerine and placebo creams. The participants were asked to
replace their normal moisturisers with the treatment cream | Not stated | 110 | Atopic dermatitis according to the criteria of Hanifin and
Rajka8 and with
no other significant concurrent illness and no known allergy to
ingredients in the test creams | Dryness of the skin [scaling, roughness, redness and cracks
(fissures) in the identified area were scored from 0 to 4 and
the sum of the severity score was calculated; max. score
16]
Transepidermal water loss
Skin
capacitance | | No difference in transepidermal water loss was found between the
glycerine cream and the placebo cream, whereas a lower value was
found in the urea cream group. No difference in skin capacitance
was found. The clinical assessment of dryness showed urea to be
superior to glycine in treating eczema | Details of randomisation and blinding are not given and there is
no mention of intention-to-treat analysis |
| Loden 2002194 | Glycerine 20% cream. Participants used as much cream as desired
and at least once daily for 30 days | Urea 4% cream. Participants used as much cream as desired and at
least once daily for 30 days | Placebo cream. Participants used as much cream as desired and at
least once daily for 30 days | Participants were allowed to continue to use topical
corticosteroids but noted their use in their diary | Not stated | 197 participants randomised
(n = 68 glycerine group,
n = 63 urea group,
n = 66 placebo group) | Atopic dermatitis | Participant-assessed degree of smarting, stinging, itching and
dryness/irritation on a 5-point scale (0–4) after 2
weeks of treatment
Participant-assessed skin dryness at
the end of treatment (14-cm VAS)
Dermatologist-assessed
dry skin [DASI: scaling, roughness, redness and cracks
(fissures) in the worst affected area in each of four body
regions were scored from 0 to 4 and the size of the area
involved was estimated; DASI = sum of the
severity score × percentage area
affected (max. score of 1600)] | | Adverse skin reactions such as smarting were felt significantly
less among participants using glycerine cream then among
participants using urea cream (10% vs. 24% severe or moderate
smarting; p < 0.0006).
No differences were found regarding skin reactions such as
stinging, itching and dryness/irritation. There were equal
effects on skin dryness as judged by the participants and the
dermatologist | No details were given about the method of randomisation.
Allocation concealment and intention-to-treat analysis were not
reported |
| Miller 2011199 | Glycyrrhetinic acid-containing barrier repair cream composed of
glycyrrhetinic acid 2%, hyaluronic acid, Vitis
vinifera (grapevine) extract, telmesteine and
Butyrospermum parkii (Shea butter). The
smallest amount needed to cover the area was used so that it
would rub in easily. The cream was applied three times daily
(morning, afternoon and evening) to all affected areas for 3
weeks | Ceramide-dominant barrier repair cream consisting of a
3 : 1 : 1 molar mixture of a
synthetic ceramide, free fatty acids and cholesterol. The
smallest amount needed to cover the area was used so that it
would rub in easily. The cream was applied three times daily
(morning, afternoon and evening) to all affected areas for 3
weeks | Petrolatum-based skin protectant moisturiser (over the counter).
The smallest amount needed to cover the area was used so that it
would rub in easily. The moisturiser was applied three times
daily (morning, afternoon and evening) to all affected areas for
3 weeks | Subjects were given a study treatment diary and were instructed
to note the times that they administered the treatment doses
each day. Each moisturiser was distributed in a plain white jar
so that subjects and investigators were blinded | USA | 39 | Age 2–17 years; mild to moderate atopic eczema; a rating
of 2–3 on a 5-point IGA severity scale as well as
≥ 1% of overall body surface area involvement
including facial and intertriginous skin | IGA (scale 0–4)
Body surface area involvement
(scale 0–100)
Investigator’s global
assessment of improvement (scale 0–6)
Itch
intensity (VAS with no itch on the left and most intense itch on
the right)
EASI (scale 0–72)
Subject
global assessment of improvement (0 = completely
clear and 6 = worsening of disease) | | There were no statistically significant differences between the
groups at any time point. The petroleum-based moisturiser was 47
times more cost-effective than the other two treatments | Method of randomisation and allocation concealment not reported.
Investigators and subjects were blinded but this was limited as
the physical properties of the treatments were different.
Intention-to-treat principle was applied |
| Misery 2005223 | Lipiderm cream containing 1% raffinose (Tefirax) applied as
frequently as necessary for 3 days and when needed for
persistent symptoms of pruritus | Lipiderm cream without raffinose applied as frequently as
necessary for 3 days and when needed for persistent symptoms of
pruritus | | Tefirax had blue packaging and the Lipiderm cream had red
packaging | France | 11 participants | Diagnosed with atopic dermatitis; age between 6 and 60 years;
presence of pruritus; atopic eczema on the body without
infection | (Primary) Intensity of pruritus (VAS from 0 to
10)
Assessment of improvement of study treatment area
between 5 minutes before treatment and 5 minutes after
application of treatment
Amount of study treatment
used
Investigator assessment of erythema, xerosis,
lichenification, scaling, exudation, presence of pustules (rated
individually on a 6-point scale, with
0 = absent, 0.5 = presence
suspected, 1 = very mild,
2 = mild, 3 = moderate,
4 = severe)
Adverse events
Amount
of repeated application because of the recurrence of
pruritus | | Six participants reported good efficacy results with Tefirax;
four participants reported symptom improvements for both Terifax
and Lipiderm; and one participant reported no improvement for
either cream. No significant difference found between the study
treatments. This could be because of the small size of the
study | Intention-to-treat population not described |
| Mora 2004232 | Lantigen B (a topical suspension of bacterial antigens), 1 drop
per year of age, given twice a day for 3 consecutive months in
the external acoustic duct | Placebo (physiological solution), 1 drop per year of age, given
twice a day for 3 consecutive months in the external acoustic
duct | | | Not stated | 80 children were followed up for a period of 1 year. Number
randomised is not explicitly stated | Recurrent external auditory atopic dermatitis; age 2–6
years at the time of the first examination | Severity [Rajka and Langeland228 scale, which considers the
intensity (itch level – mild, moderate, severe), extent
(affected percentage of the total external ear surface –
< 20%, 20–60%, > 60%)
and course (length of remission – > 3
months of remission in 1 year, < 3 months in 1
year and persistent) of the lesions, each on a scale of
1–3; severe atopic eczema 8–9, moderate
5–7, mild 3–4]
Frequency of allergies
(skin-prick test)
Total serum IgE | | In the Lantigen B group, using the Wilcoxon test, there was an
improvement in the clinical items measured. Participants were
allowed to receive concomitant medications to treat acute
episodes, which may have partly contributed to the positive
results obtained | Method of randomisation not stated and concealment of allocation
not reported. Intention-to-treat analysis not reported |
| Msika 2008123 | Emollient containing 2% sunflower oleodistillate applied twice
daily for 21 days (groups B, D and E) | Topical 0.05% corticosteroid (desonide) applied for 21 days:
groups A and B = twice daily, groups C and
D = once daily (morning), group
E = once every other day (morning) | | | Not stated | 86 participants (group A
n = 18, group B
n = 17, group C
n = 15, group D
n = 17, group E
n = 19 | Age 4 months to 48 months; free from application of topical
corticosteroids for the 8 days prior to study entry;
inflammatory phase moderate to severe atopic eczema | Severity of eczema (SCORAD index)
Investigator global
evaluation (‘completely agree’, ‘quite
agree’, ‘not very agree’, ‘not
agree’, ‘no opinion’)
Quality of
life (DLQI and Dermatitis Family Impact)
Tolerance | | All of the groups improved (SCORAD index and quality of life) at
the end of treatment. Therefore, the emollient cream twice a day
combined with topical corticosteroid once every other day was as
effective as topical corticosteroid once or twice a day on its
own (topical corticosteroid-sparing effect). The emollient cream
had a significant impact on quality of life and lichenification
and excoriation | Method of randomisation unclear and allocation concealment not
reported. Intention-to-treat analysis not reported |
| Palombo 2004208 | Imbibed pill mask containing the chitosan-derived
anti-inflammatory compound ATOBIOL (5 mg/g) solubilised
in a lamellar active emulsion of tocotrienols and hyaluronic
acid applied 3 minutes after washing using a bath oil
(hydrogenated polydecene, silica dimethyl silylate, oleth-3)
twice a day for 8 weeks | Lamellar active emulsion of the chitosan-derived compound
ATOBIOL (5 mg/g) applied 3 minutes after washing using a
bath oil (hydrogenated polydecene, silica dimethyl silylate,
oleth-3) twice a day for 8 weeks | Petroleum ointment applied 3 minutes after washing using a bath
oil (hydrogenated polydecene, silica dimethyl silylate, oleth-3)
twice a day for 8 weeks | After 8 days of treatment, all participants were given
triamcinolone 0.1% ointment twice a week and lamellar gel only
twice a day | Not stated | 36 participants (n = 15 pill
mask group, n = 12 vehicle
group, n = 9 petroleum ointment
group) | Children | Clinical score (erythema, scaling, crusting and pruritus on a
VAS) | | After 4 weeks: improvement from starting point – 58% in
pill mask group vs. the petroleum group, 82% in pill mask group
vs. lamellar gel group, 64% in petroleum group vs. lamellar
group | Method of randomisation and allocation concealment not reported.
Intention-to-treat analysis not reported. Lack of blinding
reported |
| Patrizi 2008226 | MAS063DP (Atopiclair) applied to all areas of eczema three times
a day for 43 days | MAS060 (Atopiclair light), which is in an oil-in-water
formulation with no preservatives and at a lower concentration
(specifically for the paediatric population), applied to all
areas of eczema three times a day for 43 days | Vehicle applied to all areas of eczema three times a day for 43
days | Participants could not use topical or systemic treatments or
phototherapy in the washout or study period | Italy | 60 participants (n = 20
MAS063DP, n = 20 MAS060,
n = 20 vehicle) | Age 2–17 years; diagnosed with atopic eczema according
to the Hanifin and Rajka8 criteria; IGA of 2 (mild) or 3 (moderate) at study
entry; ≥ 5% affected body surface area | (Primary) IGA at day 22 (on a scale from 0 to 5, with
0 = clear, 5 = severe
disease)
(Secondary) Participant-/caregiver-assessed
pruritus (0–100-mm VAS)
(Secondary) IGA at days
8, 15, 29 and 43
(Secondary) EASI score (max. score
72)
(Secondary) Use of rescue
medication
(Secondary) Participant-/caregiver-assessed
acceptability of study treatment | | IGA at day 22: difference between groups – MAS063DP
compared with MAS060
p < 0.0001, MAS063DP
compared with vehicle
p = 0.001, MAS060 compared with
vehicle not significant. Statistically significant results
maintained until the end of the study | Method of randomisation described and adequate. Allocation
concealment not reported. Description of blinding adequate |
| Patrizi 2012239 | 1 mg/cm2 AR-GG27 cream (Dermolichtena;
Giuliana SpA) containing aqua, PEG-8 Beeswax, caprylic/capric
triglyceride, dicaprylyl ether, isostearyl isostearate,
diisopropyl sebacate, glycerin, Butyrospermum
parkii butter, Zea mays,
Calendula officinalis extract, tapioca
starch, glycyrrhetinic acid, rhizobian gum, sodium hyaluronate,
sorbityl furfural palmitate, citric acid, sodium hydroxymethyl
glycinate, betain, inositol, trehalose, bisabolol,
phenoxyethanol, allantoin, diethylhexyl syringylidenemalonate,
carbomer, beta-sitosterol, pentaerythrityl tetra-di-t-butyl
hydroxycinnamate, dimethylmethoxy cromanol, Olea
europea leaf extract, Rosmarinus
officinalis extract and tocotrienols. Cream was
applied twice daily (approx. 12 hours apart) on the affected and
perilesional areas for a period of 30 days | 1 mg/cm2 placebo cream containing aqua, PEG-8
Beeswax, caprylic/capric triglyceride, isostearyl isostearate,
glycerin, tapioca starch, carbomer, citric acid, sodium
hydroxymethylglycinate, phenoxyethanol. Cream applied twice
daily (approx. 12 hours apart) on the affected and perilesional
areas for a period of 30 days | | Treatment with topical steroids or topical calcineurin
inhibitors had to be stopped for at least 15 days. Any general
therapy and phototherapy or sun exposure was stopped at least 30
days before. Emollients were stopped at least 7 days before. No
other local or systemic treatments were allowed as well as sun
exposure, during the trial | Not stated | 60 patients were enrolled and randomised
(n = 30 AR-GG27,
n = 30 placebo) | Patients aged between 2 months and 15 years; normal social and
dietary habits; affected by pityriasis alba located on the face
and/or limbs and/or the trunk; atopic dermatitis previously
diagnosed on the basis of the Hanifin and Rajka8 criteria; xerosis
was present as well as pruritus | IGA – average change between the 15th day of treatment
and baseline in the two groups
Overall disease severity
based on IGA (erythema, excoriation,
desquamation)
Effectiveness of AR-GG27 for pityriasis
alba (based on the severity of three clinical signs: erythema,
excoriation and desquamation using a subjective 5-point scale,
with 0 = absent, 1 = almost
absent, 2 = mild, 3 = moderate
and 4 = severe)
Changes in pruritus
severity using a 10-cm VAS, with
0 cm = no itching and
10 cm = worst imaginable
itching
Safety | | Statistically significant difference in the group treated with
AR-GG27 compared with placebo after 15 days
(p = 0.0007) and 30 days
(p = 0.005). Itching was
reduced after 15 days in the AR-GG27 group compared with placebo
(p = 0.01) in the whole
trial population and also in those who had itching at
baseline | Randomisation method not described. Allocation concealment not
described. Patients, caregivers, investigators and clinical
staff were blinded to treatment. Intention-to-treat analysis was
used |
| Patzelt-Wenczler 2000233 | Kamillosan cream (containing 2% ethanolic extract of camomile
flowers) applied to the affected areas of the arm twice
daily | Hydrocortisone 0.5% cream applied to the affected areas of the
arm twice daily | Vehicle cream applied to the affected areas of the arm twice
daily | Participants randomised as follows: group 1: left
arm = Kamillosan, right
arm = hydrocortisone; group 2: left
arm = Kamillosan, right
arm = placebo; group 3: left
arm = hydrocortisone, right
arm = Kamillosan; group 4: left
arm = placebo, right
arm = Kamillosan. Additional treatment of eczema
was not allowed | Not stated | 72 participants | Atopic eczema on both arms (must have pruritus, lichenification
in the joint flexures and chronic course); moderate eczema (sum
score of pruritus, erythema and desquamation of
≥ 3 on a scale from 0 to 9) | Efficacy (sum scores of pruritus, erythema and
desquamation
Individual symptoms (oedema,
papules/pustules, lichenification, excoriation, fissures
(4-point scale, with 0 = missing,
1 = low, 2 = marked,
3 = severe)
Investigator-assessed global
assessment (each arm separately: ‘very
good/good’, ‘satisfactory’,
‘insufficient’,
‘unassessable’)
Tolerability (unspecified
interrogated adverse events) | | After 2 weeks of treatment, Kamilosan was slightly superior to
0.5% hydrocortisone and there was a marginal difference compared
with placebo | Method of randomisation described. Allocation concealment not
stated. Intention-to-treat analysis not reported |
| Shibagaki 2005206 | A bath additive containing a diamide derivative, eucalyptus
extract, oat extract and oily moisturising ingredients such as a
synthetic pseudoceramide; 30 ml in
180–200 l of hot water for 5 minutes for four or
more times a week for 3–6 weeks | A bath additive containing eucalyptus extract, oat extract and
oily moisturising ingredients such as a synthetic pseudoceramide
(intervention A without the diamide derivative); 30 ml
in 180–200 l of hot water for 5 minutes four or
more times a week for 3–6 weeks | | | Japan | 21 | Participants with atopic dermatitis; lesion with dryness; no
complications affecting the evaluation of the study | Skin scores (from 0 = none to
4 = severe) of dryness, desquamation, itching
and scratch marks, erythema and papules pre and post
intervention
Transepidermal water loss on the flexural
area of the forearm pre and post intervention
Stratum
corneum hydration on the flexural area of the forearm pre and
post intervention
Investigator
evaluation
Participant
self-evaluation
Comprehensive evaluation
Itching
scores (from 0 = none to
4 = severe) before, during and after bathing pre
and post intervention from itching diary in participants who
used additive four or more times a week | A comprehensive evaluation was conducted using skin scores,
investigator evaluation and participant self-evaluation;
however, further details of the manner in which these
assessments were combined were not provided | | Method of randomisation not described. Allocation concealment
not reported. Intention-to-treat principle not used |
| Simpson 2011202 | CRM containing ceramides, humectants, emollients and occlusives
to be applied twice daily on the designated side of the body
with no moisturiser on the other side | No moisturiser applied to the side of the body that was not
designated to CRM | | Subjects were instructed to continue their routine course of
care with topical steroids. They were then instructed to apply
CRM to the designated side of the body and no moisturiser to the
other side of the body | USA | 127 patients were enrolled and randomised. A subset of 42
patients was enrolled for corneometry/transepidermal water loss
measurements | Male or female; age ≥ 3 years; diagnosed with
mild to moderate atopic dermatitis as rated by IGA | mEASI (adapted to a split-body design in which the constant
weighted values were reduced by 50%)
Skin hydration
(transepidermal water loss)
Patient satisfaction | | A more rapid decrease in overall disease severity was observed
on days 7, 14 and 21
(p < 0.05) compared
with steroid treatment alone | Method of randomisation and allocation concealment not
described. Single-blinded (evaluator) study. Intention-to-treat
analysis not reported |
| Stern 2002209 | Black seed oil 15% ointment applied twice daily for 28 days | No further description of ‘base treatment’,
applied twice daily for 28 days | | Total length of trial 4 weeks; no additional creams or ointments
were allowed on either arm | Germany | 20 | ‘Volunteers’ | Severity/intensity and pruritus
Transepidermal water
deficit
Skin moisture/hydration of stratum
corneum
pH value
Subjective rating of easiness of
application and properties for care | | No significant differences between black seed oil ointment and
‘base treatment’. No differences in subjective
rating of easiness of application and properties for care
between black seed oil and ‘base treatment’ but
smell of black seed oil was remarked on (in negative sense) | No adequate description of the method of randomisation,
allocation concealment and blinding |
| Stücker 2004217 | Topical vitamin B12 cream (0.07% cyanocobalaminin
DAB) applied twice daily (morning and evening) for 8 weeks | Placebo cream applied twice daily (morning and evening) for 8
weeks | | | Germany | 48 | Age 18–70 years; atopic eczema for at least 2 years;
three/four major criteria of the UK Working Party criteria9 fulfilled | (Primary) Placebo-corrected efficacy (modified SASSAD score,
max. score per body half 240, ‘exudation’
changed to ‘infiltration’)
Investigator
assessment of efficacy
Participant assessment of
efficacy
Assessment of tolerability of the treatment | One investigator took all of the efficacy measurements to
minimise variability | Modified SASSAD score: topical vitamin B12-treated
side 55.34 SD ± 5.74 SEM,
placebo-treated side 28.87 SD ± 4.86 SEM
(p < 0.001). End of study:
investigator- and participant-assessed ratings of the treatments
– topical vitamin B12
‘good’ = 58%, ‘very
good’ = 59%; placebo –
‘moderate’ = 89%,
‘poor’ = 87% | Method of randomisation described and adequate. Allocation
concealment not reported. Intention-to-treat analysis was
unclear; missing values were replaced by last value carried
forward |
| Sugarman 2009126 | Ceramide-dominant barrier repair formulation applied to the
eczema lesions twice daily for 28 days | Fluticasone propionate 0.05% (hydrocortisone 2.5% for the face
and body folds) applied to the eczema lesions twice daily for 28
days | | All participants used Cetaphil lotion twice daily on unaffected
skin | Not stated | 121 participants (n = 59
ceramide formulation, n = 62
fluticasone propionate) | Dermatologist-diagnosed moderate to severe atopic eczema
(severity measured by SCORAD index); age 6 months to 18
years | (Primary) Severity (SCORAD index) at 28 days
(0 = none,
72 = severe)
(Primary) Pruritus score at
28 days (scale 0–10, with 0 = none,
10 = severe)
(Primary) Sleep habit at 28
days (scale 0–10, with 0 = none,
10 = severe)
(Secondary)
Participant-/family-assessed improvement (no change, improved,
worsening)
IGA (scale 0–4, with
0 = clear, 1 = almost clear,
2 = mild, 3 = moderate,
4 = severe)
(Secondary) Excellent
improvement as per the IGA and SCORAD index | | Ceramide formulation improved clinical disease severity,
decreased pruritus and improved sleep habits at 14 and 28 days
of treatment. Fluticasone propionate showed a significantly
greater improvement at 14 days but at 28 days there was no
significant difference | Method of randomisation and allocation concealment not stated.
Intention-to-treat principle used for the analyses |
| Thumm 2000211 | 20% Sea buckthorn kernel oil cream (H.
rhamnoides) applied for 28 days | 10% Sea buckthorn kernel oil cream (H.
rhamnoides) applied for 28 days | Placebo: 20% Miglyol cream (caprylic/capric triglyceride)
applied for 28 days | Cream for all three groups was based on bees wax, glycerine and
paraffin | Germany | 58 | Clinical diagnosis according to Hanifin and Rajka8 criteria; atopic
dermatitis with light to severe symptoms; SCORAD score of
< 60 | Dermatologist assessment of percentage of affected skin
areas
A clinician-rated score that assessed redness,
oedema/papules, exudates/scabbing, excoriation, lichenification
and dryness
Participant-reported extent of pruritus and
sleep loss on a VAS
Transepidermal water
deficit
Moisture in the stratum corneum
DLQI
– measuring quality of life
Participant diaries:
daily reporting on VAS scale of redness, pruritus, dryness and
general well-being | | Skin condition improved by all preparations. SCORAD score
increased in all three groups
(p > 0.05).
Transepidermal water loss decreased in all three groups
(p < 0.05). Skin
moisture increased in all three groups
(p < 0.05). Quality of
life improved in all three groups
(p < 0.05). Redness,
itching, dryness and general condition improved in all three
groups but the worst results were seen in the placebo group | No reporting on randomisation procedure nor on allocation
concealment |
| Tripodi 2009207 | Emollient cream with furfuryl palmitate and the antioxidants
superoxide dismutase, 18-beta-glycyrrhetinic acid, vitamin E and
alpha-bisabolol. Applied twice a day for 2 weeks only on
eczematous skin, one fingertip unit per area the size of two
adult hands with fingers together | Emollient cream with the antioxidants superoxide dismutase,
18-beta-glycyrrhetinic acid, vitamin E and alpha-bisabolol.
Applied twice a day for 2 weeks only on eczematous skin, one
fingertip unit per area the size of two adult hands with fingers
together | | | Not stated | 117 participants (n = 57
furfuryl palmitate group,
n = 60 emollient group) | Age 3 months to 14 years; diagnosed with atopic eczema according
to the UK Working Party criteria;9 no topical or systemic treatments
at least 1 week prior to starting the study; no changes to
participants’ usual lifestyle and dietary habits 1 week
before and thought the study period | Severity of eczema (SCORAD index: mild eczema
< 25, moderate eczema 25–50, severe
eczema > 50)
Efficacy (by questionnaire:
‘worsening’, ‘inexistent’,
‘poor’, ‘good’, ‘very
good’)
Tolerability (by questionnaire:
‘poor’, ‘good’ or ‘very
good’)
Atopic status (skin-prick tests for
standard panel of commercial extracts including D.
pteronyssinus, Parietaria judaica,
olive, cat dander, Alternaria, hen’s
egg, wheat and cod fish; prick by prick method used for
cow’s milk) | | Both groups: significant reduction
(p < 0.001) in SCORAD
score after 14 days. Per-protocol analysis: emollient
cream = bigger reduction. Intention-to-treat
analysis of treatment success (≥ 20% reduction
in SCORAD score): furfuryl palminate group 29% (number needed to
treat = 2.4, 95% Cl 1.6 to 4.6), emollient group
70%. Emollient cream without furfuryl palminate found to be more
effective by parents and paediatricians.
Tolerability = no differences between
groups | Method of randomisation described and adequate. Allocation
concealment described. Intention-to-treat population reported
and described |
| Udompataikul 2011238 | LA in a ceramide and linoleic acid lipid base formulation
(Eucerin) consisting of 0.025% LA, 12.00% omega-6-fatty acids,
0.05% ceramide 3 and 10.00% glycerine was applied twice daily on
one side of the body for 6 weeks | Hydrocortisone 1% cream was applied on the opposite side of the
body for 4 weeks followed by the cream base for 2 weeks. The
number of times a day that the treatments were applied was not
stated | | The LA cream also contained paraffinum liquidum, octyldodecanol,
hydrogenated castor oil, dimethicone, Glycyrrhiza
inflata, sorbitan isostearate, methoxy PEG-22 and
45/dodecyl glycol copolymer and BHT. The cream base lotion
consisted of 10% propylene glycol, 5% mineral oil, 2%
cetostearyl, 0.05% BHT and 0.1% ethylenediaminetetra-acetic acid
disodium. A washout period of up to 4 weeks was required for
patients taking oral medications (e.g. corticosteroids and
antihistamines). A washout period of up to 2 weeks was required
for patients receiving topical medications (corticosteroids,
calcineurin inhibitors and moisturisers) | Not stated | 30 patients randomised, 26 completed the protocol | Children aged 2–15 years; mild to moderate atopic
dermatitis diagnosed by the Hanifin and Rajka8 criteria (mild to
moderate was defined as scores of 1–40 on the SCORAD
index); skin lesions on both flexural areas of the body;
included patients had to have been through a washout of up to 4
weeks if they were taking oral medications (e.g.
corticosteroids, antihistamines) and up to 2 weeks if they were
receiving topical medications (corticosteroids, calcineurin
inhibitors and moisturisers) | SCORAD index (modified as each treatment was on a different side
of the body – scores multiplied by 2)
Global
self-evaluation (graded as ‘excellent’,
‘good’, ‘fair’ and
‘minimal or no change’)
Adverse
events
Relapse rate – measured using a survival
analysis programme | | Baseline SCORAD index – about 28 on both sides. Response
rate to both agents: 73.33%. No statistically significant
difference between groups in reduction of SCORAD index. More
rapid resolution of oedema and erythema in the
hydrocortisone-treated side but this was not significant. There
was no significant difference for the LA-treated side. Relapse
rate was higher in the hydrocortisone group than in the LA group
but this was not significant. No side effects were observed in
either group | Method of randomisation not described. Allocation was concealed
as assignment of treatment group was carried out by a third
party. The study was single blind (investigator). Not stated
whether intention-to-treat population was used |
| Wiren 2009197 | Canoderm 5% cream (lipid content around 20%). Moisturiser was to
be applied to the identified area (previously treated with
topical corticosteroid in the acute phase) twice daily until
relapse of eczema or for 6 months | No treatment – patients had to abstain from using any
topical formulation until relapse of eczema or for 6 months | | There was an acute phase to the study that involved patients
being randomised to betamethasone cream [either
Betnoderm® 0.01% (ACO HUD AB) or
Betnovat® 0.01% (GlaxoSmithKline)] on an
identified area for 3 weeks. Those achieving ‘cleared
eczema’ according to the assessment of a dermatologist
(except lichenification) could then be randomised again to
either emollient (intervention A) or no treatment (intervention
B) in a maintenance phase lasting 6 months. Other body areas
could be treated with topical treatment throughout the
study | Sweden | Acute phase n = 55
(n = 27 Betnoderm,
n = 28 Betnovat).
Maintenance phase n = 44
(n = 2 emollient,
n = 22 no treatment) | Age 18–65 years; atopic eczema diagnosed according to
the Hanifin and Rajka8 criteria or by the clinic; one lesion that was
typical on an easily inspected site (e.g. arms, legs, chest);
degree of eczema at identified site with a score of
≥ 6 (Atopic Dermatitis Severity Index) | Time to relapse of atopic eczema, calculated as the time from
entry into the maintenance phase until a relapse
occurred
(Secondary) Transepidermal water loss after 3
weeks of the maintenance phase | | Maintenance phase: median time to relapse – emollient
> 180 days (length of study), no treatment 30
days. Eczema free during the whole maintenance phase: emollient
68%, no treatment 32% | Method of randomisation and allocation concealment not reported.
Blinding not stated. Intention-to-treat population used for the
analyses and defined |
