figure 1
Mean percentage change in inflammatory lesions;
ivermectin vs metronidazole
(adapted from reference 10)
0
-10
0
Baseline
Week 3
Week 6
Week 9
Week 12
Week 16
-20
-30
-32.5
-40
-30.5
-50
-60
-49.2
-55.6
-70
-59.8
-67.1
-66.3
-80
-73.7
-75.1
-90
p < 0.001
Ivermectin 1%
Metronidazole 0.75%
ivermectin 1% cream or vehicle, applied to the
whole of the face, daily at bedtime for 12 weeks and
were not permitted to use other rosacea treatments
and advised to avoid recognised rosacea triggers. For
the studies, 96% of patients were Caucasian and 67%
female, with a mean age of 50 years.
A 5-point investigator global assessment (IGA)
scale (see Table 2) was used to determine treatment
success. At entry, 79% of patients had an IGA
score of 3 (that is, moderate) with the remainder
(21%) having a score of 4 (that is, severe). The
co-primary endpoints in both trials were ‘treatment
success’ (defined as the percentage of patients
‘clear’ and ‘almost clear’) and absolute change
from baseline in inflammatory lesion counts at
week 12.
The data in Table 1 demonstrate that topical
ivermectin is effective, yet what is more relevant
is its comparison with currently used rosacea
treatments such as metronidazole or azelaic acid.
While there are no studies directly comparing
ivermectin with azelaic acid, both studies in Table 1
were extended for 40 weeks. All patients originally
assigned to ivermectin continued with the same
treatment for the next 40 weeks and patients given
placebo were switched to azelaic acid 15%, which
was applied twice a day. The results, shown in Table
3, demonstrate that a larger proportion of patients
treated with ivermectin 1% achieved an IGA score
of ‘clear/”almost clear’ at week 52, compared with
those given azelaic acid 15% in both trials.
No statistical analysis was undertaken in this
extension trial because patients given ivermectin 1%
had an extra 12 weeks of treatment.
Ivermectin 1% has also been compared with
-83
Key points
• Rosacea is a chronic
inflammatory skin
condition affecting up to
10% of the population.
• Papulopustular
rosacea is characterised
by the presence of
inflammatory papules
and pustules on the
cheeks, forehead and
chin.
• One possible trigger for
rosacea is the presence
on the skin of the
parasitic mite Demodex.
• Topical ivermectin 1%
is an anti-parasitic agent
that is effective against
Demodex.
• Clinical studies suggest
that topical ivermectin
cream is more effective
than currently
available treatments at
reducing the number
of inflammatory
lesions in patients
with mild to moderate
papulopustular rosacea.
Table 3
Proportion of patients achieving ‘clear/almost clear’
in both extension trials
(see reference 9 for details)
Comparison
Study 1
Clear/almost clear (%) Study 2
Clear/almost clear (%)
Ivermectin 1% 71.1 (n = 349) 76.0 (n = 358)
Azelaic acid 15% 59.4 (n = 175) 57.9 57.9 (n = 164)
28 | Issue 90 | 2018 | hospitalpharmacyeurope.com
metronidazole gel 0.75% in an investigator blinded
trial. A total of 962 patients were randomised (1:1)
to ivermectin 1% or metronidazole 0.75% cream.
The primary efficacy endpoint was the percentage
change in inflammatory lesion counts from
baseline to week 16, and the data are shown in
Figure 1.
The trial was extended for another 40 weeks to
compare the time to relapse for both treatments.
Patients who achieved an IGA score of 0 (clear) or 1
(almost clear) on either therapy were enrolled in the
follow-up study. The median time to relapse (an IGA
score of ≥2) was 115 days for ivermectin vs 85 days
with metronidazole (p < 0.0365). 11
Adverse effects
From the trial data, ivermectin 1% cream appears
to be very well tolerated. The incidence of reported
adverse effects was similar to vehicle (36.5%
for ivermectin vs 39.4% for vehicle). The most
commonly reported adverse effects were a sensation
of burning, skin irritation and dry skin, although
none of these effects occurred in more than 1% of
patients using ivermectin 1%.
Place in therapy
Mild-to-moderate papulopustular rosacea is
managed with topical metronidazole or azelaic
acid and although a Cochrane review concluded
that ivermectin is slightly more effective than
metronidazole, 12 it noted the lack of direct
comparative studies with azelaic acid. Nevertheless,
a recent network meta-analysis of ivermectin with
current topical rosacea treatments concluded that
the drug appears to be more effective than the
other therapeutic agents. 13 Ivermectin therefore
represents an effective and alternative first-line
treatment option for patients with mild to moderate
papulopustular rosacea.
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