Only one RCT was located that compared an oral antibiotic with benzoyl peroxide.158 Although the study was underpowered to conclusively state equivalence, similar efficacy was found between 5% benzoyl peroxide and oral oxytetracycline, 250 mg twice daily, at 6 weeks. The oral agent was more effective against acne of the trunk. The AHRQ review located eight RCTs that compared topical antibiotics with 5% benzoyl peroxide and searches found one additional trial.58,130,158,161-165 In the three RCTs located, 5% benzoyl peroxide was found to be more active against NIL in moderate acne than 1% clindamycin58,161,162 over 10-12 weeks. Two studies also found it to be more active against IL,161,162 although the third found no difference.58 Benzoyl peroxide was also more active against both NIL and IL than 1% meclocycline.164 Compared with erythromycin, benzoyl peroxide was more active against NIL and similarly active against IL.130,163 All RCTs providing data showed benzoyl peroxide to cause more local irritation.
Three RCTs compared 20% azelaic acid with oral tetracycline (variable dose)73,74 in patients with mild-to-severe acne. No significant differences were reported in any lesion counts except in the smallest trial, which was very small and suffered from high dropouts in the azelaic acid group. A 20-week RCT of 20% azelaic acid compared with 2% topical erythromycin was located through additional searches.76 No differences between the comparators were found.
Nine RCTs were located examining combinations of 0-025% tretinoin and 1% clindamycin against either tretinoin,166 clindamycin,166 167 or both168 169 (see Web Table 13.10). One additional RCT compared 2% erythromycin/0-05% tretinoin against both agents individually.170 Numerically, the combination produced greater mean percentage reductions in NIL than either agent alone, but the only statistically significant results were against clindamycin in two studies.166,167 Against IL, the combination shows greater activity numerically than either agent, but it reached significance only against tretinoin.166
Combinations of antibiotics and benzoyl peroxide were examined in nine RCTS (see Web Table 13.11); the antibiotics were clindamycin,58,161 erythromycin,130,171-173 meclocycline164 and metronidazole.165 In the five studies that used an antibiotic alone as a comparator, the combination was shown to be more active against both IL and NIL.58 130 161 171 Six studies used benzoyl peroxide alone as a comparator.58,130,161,164,165 The data were equivocal, with some studies showing a greater effect for the combination and others showing no difference. Combinations of 5% benzoyl peroxide with 3% erythromycin has greater activity against P. acnes than 3% erythromycin and results in significantly greater clinical improvement.66 One study compared 5% benzoyl peroxide plus 2% metronidazole against an oral antibiotic (oxytetracycline), but, because it was of only 6 weeks duration, unfairly biased the results against the oral antibiotic.165 A 16-week study was the only one that compared concomitant use of 5% benzoyl peroxide with an oral antibiotic (oxytetracycline 0-5 g, 1 g and 1-5 g) but did not clearly state whether patients were randomly allocated to treatment.174 The response was considered to be adequate in 2/23 patients with 5% benzoyl peroxide alone and in 6/24, 8/19 and 12/17 of patients using 5% benzoyl peroxide plus oxytetracycline 0-5 g, 1 g and 1-5 g, respectively.
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