Permethrin 5% cream versus metronidazole 0.75% gel for the treatment of papulopustular rosacea. A randomized double-blind placebo-controlled study

BACKGROUND: Permethrin 5% cream used against human ectoparasites suggests that it may be effective in papulopustular rosacea. METHODS: This study included 63 patients diagnosed as having papulopustular rosacea based on the clinical and histological findings. Patients were randomly assigned into permethrin (n = 23), metronidazole (n = 20) and placebo (n = 20) groups. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and Demodex folliculorum were determined. Twenty-three patients were given permethrin 5% cream (Zalvor 5% skin cream, 20 patients metronidazole 0.75% gel (Roza gel and 20 patients placebo cream (Basis cream, in packages looking identical to those of metronidazole and permethrin creams, and were recommended to apply them to their faces twice a day. All patients were also given SPF 20 cream for protection against sunlight. Two months of treatment were planned, and the patients were invited to the clinic for fortnightly controls. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and D. folliculorum were recorded at each visit. The mean scores of erythema and the mean numbers of papules, pustules and D. folliculorum were determined at baseline and on days 15, 30, 45 and 60. Side effects were also detected. RESULTS: The effect of permethrin 5% cream on D. folliculorum was superior to that of metronidazole 0.75% gel. The effect of permethrin 5% cream on erythema and papules was found to be more effective than placebo and as effective as metronidazole 0.75% gel. However, it had no effect on telangiectasia, rhinophyma and pustules. CONCLUSION: It can be concluded that the application of permethrin 5% cream twice daily for 2 months can be as effective and reliable as metronidazole in the treatment of rosacea and a greater benefit can be gained when it is combined with other systemic and/or topical treatments.     

Treatment of rosacea

A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole.     

Adapalene vs. metronidazole gel for the treatment of rosacea

BACKGROUND: Rosacea is a common, chronic dermatosis that requires long-term therapy. Oral isotretinoin and topical and/or oral antibiotics are effective, but their usage may be limited due to side-effects. OBJECTIVE: The goal of the study was to compare the efficacy of topical adapalene gel (0.1%) and topical metronidazole gel (0.75%) in the treatment of patients with papulopustular rosacea. METHODS: This study included 55 patients with papulopustular rosacea. Diagnostic efforts were focused on clinical and histological features. Patients were randomly assigned to the adapalene (n = 30) and metronidazole (n = 25) groups. Sunlight protection factor 20 cream was used to protect all patients from sunlight. The characteristics and numbers of inflammatory papules, pustules, erythema and telangiectasia were scored at baseline and after 2, 4, 8 and 12 weeks. Side-effects were recorded at each visit. RESULTS: Fifty patients, 27 in the adapalene group and 25 in the metronidzaole group, completed the study. Significant reductions in the total number of inflammatory lesions were found in the adapalene group compared with the metronidazole group. There was no significant difference in the scores of erythema and telangiectasia in the adapalene group. However, a significant reduction in erythema was seen in the metronidazole group. CONCLUSIONS: Adapalene gel is well tolerated and can be used as an alternative for topical treatment of papulopustular rosacea.     

Rosacea: an update

Rosacea is a common chronic cutaneous disorder of unknown etiology which occurs most commonly in middle-aged individuals. Cutaneous manifestations include transient or persistent facial erythema, telangiectasia, edema, papules and pustules that are usually confined to the central portion of the face. The National Rosacea Society's Expert Committee on the Classification and Staging of Rosacea identified four subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous and ocular. Recently, a standard grading system for assessing gradations of the severity of rosacea has been reported. Little is known about the cause of rosacea. Genetic, environmental, vascular, inflammatory factors and microorganisms such as Demodex folliculorum and Helicobacter pylori have been considered. Topical metronidazole and azelaic acid have been demonstrated to be effective treatments for rosacea. Severer or persistent cases may be treated with oral metronidazole, tetracyclines or isotretinoin.     

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.     

Efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole gel in the treatment of acne rosacea

Oral wide-spectrum antibiotics are the linchpin of rosacea treatment. Oral and topical metronidazole, topical tretinoin, and topical benzoyl peroxide may also be used in the treatment of rosacea. We aimed to show that benzoyl peroxide-erythromycin gel is efficient in the treatment of acne rosacea. Fifty-six patients with acne rosacea were enrolled in our study. We administered benzoyl peroxide-erythromycin gel to 27 patients and metronidazole gel to 29 patients. In all the patients, the intensities of erythema, telangiectasia, papules/pustules, and nodules were evaluated before, during and after the treatment. The positivity of Demodex folliculorum from skin scratches was compared between the two groups at each visit. At the end of the therapy on the third examination, in the benzoyl peroxide-erythromycin group, 91.7% of the patients showed marked clinical improvement, and 8.3% of them showed complete remission. In the metronidazole group, 73.3% showed marked clinical improvement, and 26.7% of them showed complete remission. Clinical improvement in the papular component was 65.2% for the benzoyl peroxide-erythromycin group, and 81.5% for metronidazole group. In the first examination, the clinical results of the agents were similar. Although both of the drugs were found to be effective in the second and third examinations, metronidazole gel was more effective than benzoyl peroxide-erythromycin. Both of the drugs were found to be significantly effective especially in treating the papular component of rosacea. Demodex folliculorum was found to be positive in 74.1% of the benzoyl peroxide-erythromycin group and in 62.1% of the metronidazole group at the beginning. In the benzoyl peroxide-erythromycin group, 40.7% of Demodex folliculorum positive patients, became negative by the first examination. This was 17.2% for the metronidazole group. In the benzoyl peroxide-erythromycin group, among the patients who were positive for Demodex folliculorum in the first examination, 37.5% of them became negative. This was 36.7% for the metronidazole group. Benzoyl peroxide-erythromycin gel was superior to metronidazole gel in decreasing Demodex folliculorum by the first examination, but the effect of the two drugs on Demodex folliculorum was similar by the second examination. As a result, topically applied combined benzoyl peroxide-erythromycin gel may be an alternative choice of treatment for acne rosacea.     

A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open‐label clinical trial

Background. There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some reports have indicated beneficial effects of topical pimecrolimus. Aim. To compare the efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the treatment of patients with papulopustular rosacea (PR). Methods. A group of 49 patients with PR was investigated in this single‐centre, randomized, open‐label study. Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the inflammatory lesion count, the severity of facial erythema and telangiectasia, Physician’s Global Assessment (PGA), and safety and tolerability at baseline and at weeks 3, 6, 9 and 12. Results. In total, 48 patients completed the study. Both treatments were very effective in the treatment of PR. There were no significant differences between the treatments in inflammatory lesion counts, overall erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05). Neither treatment produced any clinically relevant improvement in telangiectasia. Conclusion. Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR.     

A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea

Background: Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea. Objective: The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed. Methods: Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial. Results: After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole. Conclusion: Azelaic acid 20% cream provides an effective and safe alternative to metro-nidazole 0.75% cream with the added benefit of increased patient satisfaction. (J Am Acad Dermatol 1999;40:961-5.)     

Use of permethrin in the treatment of rosacea fulminans during pregnancy: One case report

Rosacea fulminans (RF) is a rare dermatological condition which occurs exclusively in women and it is characterized by a sudden onset of painful papules, pustules, cysts, and nodules on the face. A 28‐year‐old woman was referred to our clinic due to a painful facial eruption within the 13th week of her second pregnancy. After physical examination, the diagnosis of RF during pregnancy was established. Several treatments were used: mupirocin ointment, topical zinc oxide, topical erythromycin, oral erythromycin, metronidazole gel, oral metronidazole, oral amoxiciline, and oral prednisone. Finally, the patient was started on 5% permethrin cream with complete clearing of the lesions. Nowadays, a wide range of treatments for rosacea is available: topical metronidazole, oral metronidazole, topical ivermectin, oral tetracyclines, oral isotretinoin, systemic steroids, photodynamic therapy, or pulsed dye laser. However, in pregnant patients, the treatment alternatives are limited. We consider that 5% permethrin cream could be an effective, cheap, and safe treatment not only in regular patients with rosacea but also in pregnant women, representing an important alternative in the context of pregnancy when therapeutic options are limited. To our knowledge, this is the first case of rosacea treated with 5% permethrin cream in monotherapy during pregnancy.     

Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea

BACKGROUND: The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance. OBJECTIVE: We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen. METHODS: A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12. RESULTS: There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was -62% compared with -60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents. CONCLUSION: This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea.     

Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea

Background: Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea. Objective: The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea. Methods: One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period. Results: Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo. Conclusions: The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea.     

Increased density of Demodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea

BACKGROUND: Rosacea is a common chronic dermatosis that evolves in stages. The mite Demodex folliculorum has been implicated in its obscure aetiopathogenesis. AIM: To evaluate the importance of D. folliculorum in the aetiology and course of rosacea. METHODS: We studied 92 consecutive cases of papulopustular rosacea and 92 age- and sex-matched controls. Prevalence and density of D. folliculorum were estimated by microscopic examination of the expressed follicular content. Histological examination and immunohistochemical study of the inflammatory infiltrate were performed in 10 subjects (five with positive D. folliculorum finding and five with negative finding). RESULTS: D. folliculorum was detected in 83 (90.2%) of the 92 rosacea subjects but only 11(11.9%) of the controls. The mean mite density was 2.03 mites/visual field in the rosacea group (range 0-5, SD = 1.2) and 0.16 mites/visual field (range 0-2, SD = 0.52) in the control group. The difference was statistically significant (P < 0.0001) for both mite prevalence and density. Hair follicle infestation was associated with intense perifollicular infiltrate of predominantly (90-95%) CD4 helper/inducer T cells. We observed an increased number of macrophages and Langerhans cells only in those subjects with a positive D. folliculorum finding. CONCLUSIONS: Although Demodex mites do not seem to be the cause of rosacea, they may represent an important cofactor, especially in papulopustular rosacea. Immunohistochemical findings suggest that a delayed hypersensitivity reaction, possibly triggered by antigens of follicular origin, probably related to D. folliculorum, may occur, stimulating progression of the affection to the papulopustular stage.     

Acne and rosacea. New and emerging therapies

The goal of this article is to highlight recent developments in the treatment of acne and rosacea. An update on the use of isotretinoin, minocycline, topical retinoids, and hormones in the treatment of acne are presented. Highlights of research findings that may lead to future acne therapies are discussed. New in the management of rosacea are studies demonstrating the efficacy of 1% topical metronidazole in the treatment of rosacea, reports on the successful maintenance of remissions of rosacea with 0.75% metronidazole gel, and data regarding the controversial association of rosacea with Helicobacter pylori infection.     

Etiopathogenesis, classification, and current trends in treatment of rosacea

Rosacea is a common chronic dermatosis characterized by varying degrees of flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and phymas. Etiology and pathogenesis of rosacea are still unknown. Many possible causes have been described as inducing the disease or contributing to its manifestation, such as genetic predisposition, abnormal vascular reactivity, changes in vascular mediating mechanisms, Helicobacter pylori infection, Demodex folliculorum infestation, seborrhea, sunlight, hypertension, and psychogenic factors. However, none of these factors has been proved. Rosacea shows a wide spectrum of clinical presentations, which vary over time and with age. Successful management of rosacea requires careful patient evaluation and individualized therapy with appropriate variations and modifications, as the severity of the disorder fluctuates. In mild cases of rosacea, patients are instructed to avoid sun, to apply sun-protective creams, and to avoid facial irritants and other triggers that provoke symptoms. At later stage, drug therapy is often necessary. The disease commonly requires long-term treatment with topical or oral medicaments. Surgical correction may be required for rhinophyma and telangiectasia. We reviewed the current literature on the aspects of the pathogenesis, diagnostic criteria, and treatment options for rosacea.     

Laser and intense pulsed light management of couperose and rosacea

Management of couperosis and rosacea has been totally renewed by laser and vascular laser techniques, with efficacy targeted on the telangiectases and to a lesser extent on the erythrosis. Laser management of hypertrophic rosacea or rhinophyma depends on surgical treatment with decortication, continuous CO(2) ablative laser or Erbium, fractionated at high power, then vascular laser treatment for the telangiectases: lasers with pulsed dye, KTP, or pulsed lights for red laser telangiectases and long pulse Nd-Yag laser for blue telangiectases. For papulopustular rosacea, vascular laser treatment (pulsed dye and KTP) and intense pulsed light will be begun once the inflammation has been treated. The major indication for vascular lasers and intense pulsed light is found in erythematotelangiectatic rosacea, with high efficacy for the telangiectases. Diffuse erythrosis is difficult to treat, requiring a high number of laser and/or intense pulsed light sessions.     

Laser and intense pulsed light management of couperose and rosacea

Management of couperosis and rosacea has been totally renewed by laser and vascular laser techniques, with efficacy targeted on the telangiectases and to a lesser extent on the erythrosis. Laser management of hypertrophic rosacea or rhinophyma depends on surgical treatment with decortication, continuous CO(2) ablative laser or Erbium, fractionated at high power, then vascular laser treatment for the telangiectases: lasers with pulsed dye, KTP, or pulsed lights for red laser telangiectases and long pulse Nd-Yag laser for blue telangiectases. For papulopustular rosacea, vascular laser treatment (pulsed dye and KTP) and intense pulsed light will be begun once the inflammation has been treated. The major indication for vascular lasers and intense pulsed light is found in erythematotelangiectatic rosacea, with high efficacy for the telangiectases. Diffuse erythrosis is difficult to treat, requiring a high number of laser and/or intense pulsed light sessions.     

Rosacea and its management: an overview

BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the population. The prevalence of rosacea is highest among fair-skinned individuals, particularly those of Celtic and northern European descent. Since a cure for rosacea does not yet exist, management and treatment regimens are designed to suppress the inflammatory lesions, erythema, and to a lesser extent, the telangiectasia involved with rosacea. OBJECTIVES: This review outlines the treatment options that are available to patients with rosacea. METHODS: Published literature involving the treatment or management of rosacea was examined and summarized. RESULTS: Patients who find that they blush and flush frequently, or have a family history of rosacea are advised to avoid the physiological and environmental stimuli that can cause increased facial redness. Topical agents such as metronidazole, azelaic acid cream or sulfur preparations are effective in managing rosacea. Patients who have progressed to erythematotelangiectatic and papulopustular rosacea may benefit from the use of an oral antibiotic, such as tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the rosacea flare-up under control. Treatment with a topical agent, such as metronidazole, may help maintain remission. Patients with ocular involvement may benefit from a long-term course of an antibiotic and the use of metronidazole gel. A surgical alternative, laser therapy, is recommended for the treatment of telangiectasias and rhinophyma. Patients with distraught feelings due to their rosacea may consider cosmetic camouflage to cover the signs of rosacea. CONCLUSIONS: With the wide variety of oral and topical agents available for the effective management of rosacea, patients no longer need to feel self-conscious because of their disorder.     

Current topical and systemic approaches to treatment of rosacea

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline. Conventionally, 100–200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

Conflicts of interest

None declared.     

The Role of Tetracyclines in Rosacea

There is a great deal of evidence to support the use of tetracycline and doxycycline in the treatment of papulopustular rosacea. Nevertheless, these agents have shared and unique adverse effects and relative contraindications. Recently, subantimicrobial-dose doxycycline was demonstrated to be an effective treatment for rosacea, due to its inherent anti-inflammatory properties. Furthermore, subantimicrobial-dose doxycycline has a more preferable tolerability profile and a lower occurrence of bacterial resistance than traditional-dose doxycycline. To further elucidate the role of tetracycline agents in rosacea, clinical trials that compare these agents with each other as well as with other effective rosacea treatments are called for. Adherence studies comparing oral tetracycline treatment with topical metronidazole treatment may also enhance clinical decision making.     

A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial

OBJECTIVE: To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea. DESIGN: Multicenter, double-blind, randomized, parallel-group study. SETTING: Thirteen US centers. PATIENTS: A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia. INTERVENTIONS: Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks. MAIN OUTCOME MEASURES: Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings. RESULTS: Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group. CONCLUSION: Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema).