triggers lead to increased flushing and a sensation
of burning or stinging in the skin and have led
to the suggestions that the cause is related to
aberrant changes within the innate immunity and
neurovascular systems.
Table 2
Investigator Global Assessment scale
Ivermectin
One potential factor implicated in cutaneous
inflammation is the presence on the skin of the
mite Demodex folliculorum, which resides in hair
follicles. Patients with rosacea have between 35%
and 50% more Demodex on affected areas of skin
than those without the disease; 5 however, the
presence of the mite in the skin of unaffected
individuals casts doubt on its pathological role.
Furthermore, treatment of rosacea with either oral
or topical antibiotics does not lead to a reduction in
the population of the mite. Moreover, it has often
been assumed that the efficacy of antibiotics in
rosacea is primarily due to an anti-inflammatory
rather than an antibacterial effect. However, this
seems implausible given than more effective anti-
inflammatory agents such as topical steroids are
contra-indicated in rosacea and may actually worsen
the condition.
There is emerging evidence to suggest that
a bacterium, Bacillus oleronius, found in the
intestines of Demodex, may have a pathological
role in rosacea. Indeed, antigenic proteins isolated
from the bacterium have been shown to stimulate
an inflammatory response in patients with
papulopustular rosacea and the organism was
sensitive to the antibiotics normally used to treat
rosacea. 6
Ivermectin is a semi-synthetic macrocyclic lactone
with broad-spectrum anti-parasitic activity, although
it also possesses direct anti-inflammatory effects
by reducing inflammatory cytokines such as IL-1b
and TNF-a and upregulating the anti-inflammatory
cytokine, IL-10. 7
The drug is available as a 1% topical cream
(Soolantra ® ) for the treatment of inflammatory
lesions of rosacea (that is, papulopustular)
in adults.
Score Grade Description
0
Clear
No inflammatory lesions/
erythema
Almost clear
1
Very few small papules/
pustules, very mild
erythema
Mild
2
Few small papules/
pustules, mild erythema
Moderate
3
Several small or large
papules/pustules,
moderate erythema
4
Severe
Numerous small and/or
large papules/pustules,
severe erythema
Clinical efficacy
Two identical Phase III randomised, double-blind,
placebo-controlled trials have been undertaken in
patients with moderate to severe rosacea (see Table
1). Patients were randomised in a 2:1 fashion to
Table 1
Efficacy of ivermectin 1% in placebo-controlled trials
Outcome measure
Study 1
Study 2
Ivermectin 1%
(n = 451) Vehicle
(n = 232) Ivermectin 1%
(n = 459) Vehicle
(n = 229)
Inflammatory lesion
counts mean absolute
(%) change from
baseline 20.5*** (64.9) 12 (41.6) 22.2 (65.7) 13.4 (43.4)
% IGA** 38.4 *** 11.6 40.1 18.8
% Patient reported
improvement
(‘excellent’ and ‘good’) 68*** 39 66 34
*Details provided in reference 8. **Assessed at week 12. Figures represent the proportion of patients achieving a treatment success, defined
as a score of 0 or 1 (‘clear’ or ‘almost clear’ respectively. ***p < 0.001 vs vehicle.
hospitalpharmacyeurope.com | 2018 | Issue 90 | 27