Evaluation of the efficacy of subantimicrobial dose doxycycline in rosacea: a systematic review of clinical trials and meta‐analysis

Summary Background Low‐dose doxycycline (SDD) is an antimicrobial agent that appears to improve common inflammatory skin diseases. Few data are available regarding the overall effectiveness, appropriate length of treatment and optimal patient selection for rosacea. We therefore reviewed the efficacy of sub‐antimicrobial doses of SDD in papulopustular rosacea (PPR) and aimed to determine the most suitable patients for this approach. Methods From July to September 2019, we carried out a comprehensive search of literature from five databases, using a combination of “rosacea” AND “doxycycline”. Results Our search yielded 532 potentially relevant studies. Our meta‐analysis showed no significant difference between SDD and a comparator (RR: 1.12, 95 % CI: 0.78–1.62, I 2 = 86 %). Subgroup analysis of studies comparing doxycycline with placebo yielded a clear difference in favor of doxycycline (RR: 1.45, 95 % CI: 1.22–1.72, I 2 = 31 %), while subgroup analysis of studies comparing active drugs revealed no difference between interventions (RR: 0.52, 95 % CI: 0.17–1.63, I 2 = 90 %). Conclusions There is strong evidence that SDD is more effective than placebo. However, other drugs such as minocycline or isotretinoin have shown outcomes at least similar to that of SDD. We suggest that the anti‐inflammatory properties of SDD may be of more value for mild cases of rosacea than for moderate to severe cases, for which higher (antimicrobial) doses of doxycycline may be a more suitable choice.