We updated our searches, to July 2014, of: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974) and Science Citation Index (from 1988). We searched five trials registers and checked reference lists for further relevant studies.
SELECTION CRITERIA: Study selection, data extraction, risk of bias assessment and analyses were carried out independently by two authors.
MAIN RESULTS: We included 106 studies, comprising 13,631 participants. Sample sizes of 30-100 and study duration of two to three months were most common. More women than men were included, mean age of 48.6 years, and the majority had
papulopustular rosacea, followed by
erythematotelangiectatic rosacea.A wide range of comparisons (67) were evaluated. Topical interventions:
metronidazole,
azelaic acid,
ivermectin,
brimonidine or other topical treatments. Systemic interventions: oral
antibiotics, combinations with topical treatments or other systemic treatments, i.e.
isotretinoin. Several studies evaluated
laser or light-based treatment.The majority of studies (57/106) were assessed as 'unclear risk of bias', 37 'high risk ' and 12 'low risk'. Twenty-two studies provided no usable or retrievable data i.e. none of our outcomes were addressed, no separate data reported for
rosacea or limited data in abstracts.Eleven studies assessed our primary outcome 'change in quality of life', 52 studies participant-assessed changes in
rosacea severity and almost all studies addressed adverse events, although often only limited data were provided. In most comparisons there were no statistically significant differences in number of adverse events, most were mild and transient. Physician assessments including investigators' global assessments, lesion counts and
erythema were evaluated in three-quarters of the studies, but time needed for improvement and duration of remission were incompletely or not reported.The quality of the body of evidence was rated moderate to high for most outcomes, but for some outcomes low to very low.Data for several outcomes could only be pooled for topical
metronidazole and
azelaic acid. Both were shown to be more effective than placebo in
papulopustular rosacea (moderate quality evidence for
metronidazole and high for
azelaic acid). Pooled data from physician assessments in three trials demonstrated that
metronidazole was more effective compared to placebo (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.29 to 3.02). Four trials provided data on participants' assessments, illustrating that
azelaic acid was more effective than placebo (RR 1.46, 95% CI 1.30 to 1.63). The results from three studies were contradictory on which of these two treatments was most effective.Two studies showed a statistically significant and clinically important improvement in favour of topical
ivermectin when compared to placebo (high quality evidence). Participants' assessments in these studies showed a RR of 1.78 (95% CI 1.50 to 2.11) and RR of 1.92 (95% CI 1.59 to 2.32),which were supported by physicians' assessments. Topical
ivermectin appeared to be slightly more effective than topical
metronidazole for
papulopustular rosacea, based on one study, for improving quality of life and participant and physician assessed outcomes (high quality evidence for these outcomes).Topical
brimonidine in two studies was more effective than vehicle in reducing
erythema in
rosacea at all time points over 12 hours (high quality evidence). At three hours the participants' assessments had a RR of 2.21 (95% CI 1.52 to 3.22) and RR of 2.00 (95% CI 1.33 to 3.01) in favour of
brimonidine. Physicians' assessments confirmed these data. There was no rebound or worsening of
erythema after treatment cessation.Topical
clindamycin phosphate combined with
tretinoin was not considered to be effective compared to placebo (moderate quality evidence).Topical
ciclosporin ophthalmic
emulsion demonstrated effectiveness and improved quality of life for people with
ocular rosacea (low quality evidence).Of the comparisons assessing oral treatments for
papulopustular rosacea there was moderate quality evidence that
tetracycline was effective but this was based on two old studies of short duration. Physician-based assessments in two trials indicated that
doxycycline appeared to be significantly more effective than placebo (RR 1.59, 95% CI 1.02 to 2.47 and RR 2.37, 95% CI 1.12 to 4.99) (high quality evidence). There was no statistically significant difference in effectiveness between 100 mg and 40 mg
doxycycline, but there was evidence of fewer adverse effects with the lower dose (RR 0.25, 95% CI 0.11 to 0.54) (low quality evidence). There was very low quality evidence from one study (assessed at high risk of bias) that
doxycycline 100 mg was as effective as
azithromycin. Low dose
minocycline (45 mg) was effective for
papulopustular rosacea (low quality evidence).Oral
tetracycline was compared with topical
metronidazole in four studies and showed no statistically significant difference between the two treatments for any outcome (low to moderate quality evidence).Low dose
isotretinoin was considered by both the participants (RR 1.23, 95% CI 1.05 to 1.43) and physicians (RR 1.18, 95% CI 1.03 to 1.36) to be slightly more effective than
doxycycline 50-100 mg (high quality evidence).
Pulsed dye laser was more effective than
yttrium-
aluminium-garnet (
Nd:YAG) laser based on one study, and it appeared to be as effective as
intense pulsed light therapy (both low quality evidence).
AUTHORS' CONCLUSIONS: