Clinical Question: Is azelaic acid or metronidazole a more effective topical treatment for acne rosacea?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: Investigators recruited 251 patients with moderately severe acne rosacea (i.e., 10 to 50 inflamed papules or pustules, persistent erythema, telangiectasia) from specialty centers in the United States. Patients were randomized to treatment with azelaic acid in a 15 percent gel or metronidazole in a 0.75 percent gel, and were told to apply the gel twice daily to the entire face. Randomization, allocation concealment, and blinding appear to have been adequate in this trial, which was sponsored by the manufacturer of azelaic acid.

The primary outcome was the change in the number of inflammatory lesions at 15 weeks. Physician and patient assessments of global improvement on a 7-point scale (0 = clear and 6 = severe disease) also were measured. The groups were similar at baseline, and analysis was by intention to treat. For patients who did not complete the trial, the last observation was carried forward.

The reduced number of inflammatory lesions was greater in the azelaic acid group (12.9 versus 10.7 in the metronidazole group; P = .003), as was the percentage of patients with an improvement of at least 1 on a four-point erythema severity scale (56 versus 42 percent; P = .02; number needed to treat [NNT] = seven). Neither treatment changed the extent of telangiectasia. The global rating was more likely to be clear, minimal, or mild for patients in the azelaic acid group (69 versus 55 percent; P = .02; NNT = seven). Although more patients using azelaic acid noted excellent improvement (40 versus 34 percent), the failure of the authors to report statistical significance may indicate that the improvement was not statistically significant. More patients using azelaic acid withdrew from the study because of adverse effects (four versus none), decreased the dosage (five versus two), or experienced facial skin signs and symptoms (32 versus 9; number needed to harm = 5.3), and were less likely to describe the treatment as tolerable (89 versus 96 percent).

Bottom Line: Azelaic acid in a 15 percent gel appears to offer some modest benefits over 0.75 percent metronidazole gel. Because azelaic acid was not as well tolerated, both medications are reasonable options. The choice depends on patient preference and tolerance. (Level of Evidence: 1b)