Once-daily topical brimonidine tartrate gel 0·5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies

Abstract

Background: Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective α(2) -adrenergic receptor agonist with vasoconstrictive activity.

Objective: To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety.

Methods: In study A, 122 subjects were randomized to receive a single application of BT 0·07%, 0·18%, 0·5% or vehicle. In study B (4-week treatment and 4-week follow-up), 269 subjects were randomized to receive BT 0·5% once daily, BT 0·18% once daily, vehicle once daily, BT 0·18% twice daily or vehicle twice daily. Evaluations included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), Chroma Meter measurements and adverse events.

Results: In study A, a single application of topical BT gel reduced facial erythema in a dose-dependent fashion. A significant difference between BT 0·5% and vehicle in Chroma Meter redness value was observed from 30min to 12h after application. In study B, BT 0·5% once daily had a statistically superior success profile (defined as a two-grade improvement on both CEA and PSA over 12h) compared with vehicle once daily on days 1, 15 and 29 (all P<0·001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events.

Conclusions: Once-daily BT gel 0·5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea.

Fig 1

Study A. Percentage of total subjects who had one-grade or two-grade improvement on Clinician’s Erythema Assessment (CEA), Patient’s Self-Assessment (PSA) and both CEA and PSA for 12 h after a single application. **P < 0·001 vs. vehicle gel; *P < 0·05 vs. vehicle. BT, brimonidine tartrate.

Fig 2

Study A. Median change in Chroma Meter a* (redness) values at each time point after a single application. **P < 0·001 vs. vehicle; *P < 0·05 vs. vehicle. BT, brimonidine tartrate.

Fig 3

Study A. Standardized photographs of a subject with moderate erythema (a) before, and (b) 30 min, (c) 3 h and (d) 10 h after a single application of brimonidine tartrate gel 0·5%.

Fig 4

Study B. Study flow chart. BT, brimonidine tartrate; QD, once daily; BID, twice daily.

Fig 5

Study B. Success rate (two-grade improvement on both Clinician’s Erythema Assessment and Patient’s Self-Assessment) on day 29 (intent-to-treat–last-observation-carried-forward). **P < 0·001 vs. vehicle once daily on day 29; *P < 0·05 vs. vehicle once daily on day 29. BT, brimonidine tartrate; QD, once daily; BID, twice daily.

Fig 6

Study B. Success rate (two-grade improvement on both Clinician’s Erythema Assessment and Patient’s Self-Assessment) on days 1 and 29 (intent-to-treat–last-observation-carried-forward). **P < 0·001 vs. vehicle QD. BT, brimonidine tartrate; QD, once daily.

Fig 7

Study B. Percentage of subjects having one- or two-grade improvement on both Clinician’s Erythema Assessment (CEA) and Patient’s Self-Assessment (PSA) at 3 h on day 29 (intent-to-treat–last-observation-carried-forward). **P < 0·001 vs. vehicle. BT, brimonidine tartrate; QD, once daily.