Conjoint analysis: a novel, rigorous tool for determining patient preferences for topical antibiotic treatment for acne. A randomised controlled trial

BACKGROUND: Acne vulgaris is an extremely common skin disorder that can be treated effectively with drugs that are currently available. Poor compliance, however, is a major factor in the high failure rates seen in acne treatment. Compliance might be enhanced by considering patient preferences for acne medications. Conjoint analysis is well suited for the study of patient preferences in healthcare, but is novel to the field of dermatology. OBJECTIVES: The study aimed to determine and compare patient preferences for four topical antibiotics used for 1 week, once or twice daily, to treat acne vulgaris. METHODS: A randomised, phase IV, single-centre, cross-over study was performed using conjoint analysis and a traditional patient questionnaire. Over 4 weeks, the patients used each of four topical antibiotics for 1 week: erythromycin/zinc solution, clindamycin phosphate lotion, benzoyl peroxide (BP)/erythromycin gel (each applied twice daily) and clindamycin phosphate gel (applied once daily). The conjoint analysis examined five different attributes of acne medications: form, storage, product life once opened, method of application and regimen (each with two or three possible options). From 108 possible permutations of the five attributes, 16 hypothetical medications were selected at random and described on printed cards. Pre- and post-treatment, the patients ranked the cards in order of preference and rated each hypothetical product based on their likelihood to use it. For each patient, product 'utilities' were then calculated by multiple regression. The patients also completed a patient acceptability questionnaire, by which they rated the product acceptability after 1 week of treatment with each of the four topical antibiotics. The patients later ranked the medications in order of preference after using all four treatments. Adverse events were recorded in diary cards to assess tolerability. RESULTS: Of 67 patients recruited, 64 used all four medications and completed the study. The conjoint analysis found that a gel formulation, room temperature storage, product life of up to 18 months once opened, application with fingers and once-daily regimen were the options ranked first for the five product attributes. According to the ranking order (out of 108) for the combination of attributes representing the four study medications, clindamycin phosphate gel had the highest rankings (6 and 1 pre- and post-treatment, respectively) and BP/erythromycin gel had the lowest rankings (93 and 70 pre- and post-treatment). The rankings of clindamycin phosphate lotion and erythromycin/zinc solution worsened from pre- to post-treatment, indicating a shift in patient preference after they experienced products 'in-use' during the study. Based on the questionnaire, clindamycin phosphate gel was liked best by the highest proportion of patients (33%). In terms of overall satisfaction, the order of preference was: (i) clindamycin phosphate gel, (ii) clindamycin phosphate lotion, (iii) BP/erythromycin gel and (iv) erythromycin/zinc solution. Adverse events related to medication occurred most frequently with erythromycin/zinc solution and BP/erythromycin gel. Clindamycin phosphate gel was the only product not associated with any episodes resulting in a change of medication or dose. CONCLUSIONS: Conjoint analysis provided a convenient, reliable tool for assessing patient preferences for topical antibiotics used to treat acne. The patients clearly preferred a gel formulation that could be applied with the fingers once daily and stored at room temperature for as long as 18 months. One product (clindamycin phosphate gel) combined all five of the preferred attributes, a preference confirmed by the simulated product rankings. These findings of the conjoint analysis are consistent with the safety profiles and the results of the traditional questionnaire.     

A single centre, open-label, cross-over study of pharmacokinetics comparing topical zinc/clindamycin gel (Zindaclin) and topical clindamycin lotion (Dalacin T) in subjects with mild to moderate acne

Zinc/clindamycin gel (Zindaclin 1%) gel, is a new once-daily topical acne treatment (Strakan Ltd) containing clindamycin phosphate equivalent to 1% clindamycin and zinc acetate in a formulation, which leads to a reduced systemic absorption of clindamycin through the skin. The objective of the study was to compare the systemic absorption of clindamycin from zinc/clindamycin gel and clindamycin lotion (Dalacin T topical lotion, Pharmacia Ltd) after repeated twice-daily topical administration for two periods of 5 days with an intervening gap of 2 weeks in 24 subjects with mild to moderate acne. Plasma Cmax, and AUC0-12 of clindamycin measured after single and multiple applications of zinc/clindamycin gel were between 30% and 50% lower than for clindamycin lotion. As zinc/clindamycin gel is a topical treatment for acne, the lower systemic bioavailability may be beneficial because there may be a correspondingly lower risk of systemic events in zinc/clindamycin gel-treated subjects.     

A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin lotion formulation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris

BACKGROUND: A successful phase III pilot study compared the efficacy and safety of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel) applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T lotion) applied twice daily in the treatment of moderate to severe acne vulgaris. OBJECTIVES: We aimed to follow up this study. METHODS: The two treatment regimens were compared in a multicentre, single-blind, randomized 12-week investigation of patients with moderate to severe acne vulgaris. RESULTS: At week 12, the mean percentage reduction in non-inflamed lesions (open and closed comedones) was greater in the CTG group compared with the CLN group (P = 0.05). Absolute reductions in open and closed comedones were also greater in the CTG group, consistent with the comedolytic activity of tretinoin. There was a significantly greater absolute reduction in inflamed lesions (pustules, papules and nodules) from baseline to both end-point (last observed efficacy outcome; P = 0.043) and week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of the calculated overall acne severity score, considering all five lesion subtypes, demonstrated a significantly greater mean percentage reduction in the CTG group compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P < 0.01). The more subjective assessment of overall acne severity according to the Cook scale also demonstrated a significantly greater mean reduction in the CTG group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more rapid effect on the onset of improvement compared with CLN; a 50% reduction in total lesion counts by day 60 was found in 77% of patients on CTG compared with 56% receiving CLN (P = 0.003). This was largely due to the reduction in open comedone counts (P = 0. 0006). For all other variables, CTG was at least as effective as CLN. Both treatments were well tolerated. CONCLUSIONS: A single daily topical application of Velac gel was superior to Dalacin T lotion applied twice daily in reducing overall acne scores, and was faster acting. The simpler dosing regimen of Velac gel and its rapid effect are likely to have a positive effect on both patient compliance and cost.     

Systemic absorption of clindamycin hydrochloride after topical application

Clindamycin has become a highly popular drug for the topical therapy of acne; however, the extent to which it is systemically absorbed from the skin has has not been established. We measured the serum level and urinary excretion of clindamycin on the third day and the twenty-seventh day of therapy in thirteen patients who were applying 1% clindamycin hydrochloride topically for acne. There was no detectable antibiotic in the serum of any subject (less than 0.4 microgram/ml); in contrast, clindamycin was found in the urine of ten of the thirteen patients. There was marked intersubject variation in the urinary excretion of the drug, ranging from less than 10 to 500 micrograms/day. However, there was a highly significant correlation (p less than 0.0001) for a given subject between excretion values on days 3 and 27. There was no correlation between urinary excretion of clindamycin and either racial pigmentation or severity of acne in this relatively small group of patients. After topical application of 1% clindamycin hydrochloride, an average of 4% to 5% of clindamycin appears to be absorbed systemically, but greater amounts are absorbed in some individuals.     

Treatment of acne with topical antibiotics: lessons from clinical studies

BACKGROUND: Over the past 20 years, major concerns have been repeatedly expressed over antibiotic-resistant acne in Europe and in the U.S.A. However, the clinical significance of these resistance patterns is poorly defined so that topical antibiotics remain one of the cornerstones of acne management. OBJECTIVES: To determine whether we are facing decreased efficacy of topical formulations of erythromycin and clindamycin in clinical trials of therapeutic interventions for acne. METHODS: To review systematically the results of the clinical trials investigating topical formulations of erythromycin and clindamycin for the treatment of inflammatory acne and to establish whether or not there is a decrease in the efficacy of these topical antibiotic formulations since their widespread introduction in the mid 1970s. RESULTS: Of the 50 eligible controlled trials identified using a systematic electronic database search strategy, 45 (90%) incorporated a lesion count, making comparison across trials possible. Analysis of clinical studies investigating the effect of topical erythromycin in acne patients indicates a significant decrease in the effect of this antibiotic on inflammatory and noninflammatory lesion count over time (r = -2.140, P = 0.001 and r = -2.032, P = 0.001, respectively). Efficacy of topical clindamycin remained stable during the study period. CONCLUSIONS: There is a gradual decrease in the efficacy of topical erythromycin in clinical trials of therapeutic intervention for acne, which is probably related to the development of antibiotic-resistant propionibacteria.     

Results of a randomised, multicentre study comparing a new water-based gel of clindamycin 1% versus clindamycin 1% topical solution in the treatment of acne vulgaris

Several topical formulations of clindamycin phosphate are currently marketed for the treatment of acne vulgaris. This 12 week, multi-centre, investigator-blind, randomised, active and placebo-controlled, parallel group study assessed the clinical efficacy and safety of clindamycin 1% gel once-a-day vs clindamycin 1% solution twice-a-day, and to demonstrate its superiority vs its vehicle alone. A total of 592 subjects were included. After 12 weeks, a 65% reduction in inflammatory lesion count was observed with both active treatments. The gel was superior to its vehicle for total and inflammatory lesion reduction, Global Assessment of Improvement, and Global Severity Grade at final visit (all p < 0.01). No difference was found between the 2 active treatments for any of the evaluated criteria. Local tolerance in each active treatment group was slightly better with clindamycin gel (1.9% of subjects) relative to 3.1% in the topical solution group. In conclusion, the new water-based gel once-a-day formulation of clindamycin 1% is an effective, safe, and convenient alternative to the twice-a-day topical solution formulation in the treatment of acne vulgaris.     

Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure

Erythromycin resistant (EmR) propionibacteria were isolated from the skin surface of 51% of patients treated with oral erythromycin and 42% of patients treated with topical clindamycin compared with 3% of untreated control subjects (P less than 0.001). Amongst the topical clindamycin-treated patients, there was a higher incidence of EmR propionibacterial carriage in those patients who had previously been treated with oral erythromycin (64%) than in patients with no known previous exposure to erythromycin (20%; 0.01 greater than P greater than 0.001). Patients responding to oral erythromycin treatment carried EmR propionibacteria less frequently (24%) than patients who were not responding or who had relapsed (70%; P less than 0.001). These observations suggest that the use of oral erythromycin and/or topical clindamycin encourages the development of resistant propionibacteria and that the emergence of resistant strains is associated with therapeutic failure in erythromycin-treated patients. In total 63 resistant isolates were obtained from 52 subjects. There were 42 strains of Propionibacterium acnes, 16 strains of Propionibacterium granulosum and five strains of Propionibacterium avidum. The majority of isolates were inducibly or constitutively resistant to macrolide (e.g. erythromycin), lincosamide (e.g. clindamycin) and streptogramin B type antibiotics. Therefore, the isolates are phenotypically indistinguishable from the majority of EmR bacteria in which resistance is due to methylation of 23S ribosomal RNA.     

Acne treatment with topical erythromycin and zinc: effect of Propionibacterium acnes and free fatty acid composition

A double-blind investigation has been conducted to examine the effect of topical 4% erythromycin/1.2% zinc acetate solution and its vehicle on quantitative bacterial counts (skin surface washings) of propionibacterium acnes and the free fatty acids of the skin surface. The logarithmic counts for P. acnes in the erythromycin/zinc group showed a significant reduction (98%) following 10 weeks of therapy. This compared with a 43% change shown for the vehicle-control group. A significant reduction (69%) in the percentage of free fatty acids in the surface lipids was seen at week 4 in the erythromycin/zinc group as compared to the control group. Triglyceride levels were significantly increased at all time points for the erythromycin/zinc group as compared to the control group. There was also a significant decrease (69%) in inflammatory lesions shown for the erythromycin/zinc treatment group at week 8 as compared to a 9% reduction in the control group.     

Effects of treatment with erythromycin 1.5 percent topical solution or clindamycin phosphate 1.0 percent topical solution on P. acnes counts and free fatty acid levels

Twenty healthy subjects (7 men and 13 women) with average baseline P. acnes counts equal to or greater than 1.0 x 10(5) were treated twice a day for eleven days in a randomized, double-blind study with either erythromycin 1.5 percent topical solution or clindamycin phosphate 1.0 percent topical solution. P. acnes counts and free fatty acid (FFA) measurements were performed before treatment, and on Days 4 and 11 of treatment. Statistically significant reductions in P. acnes counts were produced in both groups over the course of the study. There were no statistically significant changes in FFA, free fatty acid/fatty ester (FFA/FE) ratios or triglyceride levels. With erythromycin there were greater reductions in FFA and FFA/FE ratios and greater increases in triglycerides than with the clindamycin group, but the differences between the treatment groups were not significant. No adverse reactions were reported.     

Antimicrobial susceptibility and genetic characteristics of Propionibacterium acnes isolated from patients with acne

Background Propionibacterium acnes is an important target in acne management. Antibiotic resistance has increased, reducing its clinical efficiency. Objective To study the prevalence, antimicrobial susceptibility patterns, and resistance mechanisms of P. acnes isolated from patients with acne. Methods Skin swabs were collected from 83 patients. Agar dilution determined the minimum inhibitory concentrations of five antibiotics. Polymerase chain reaction and DNA sequencing were used to identify mutations. Results P. acnes was isolated in 80 of 83 patients (96%), and 27 patients had resistance to antibiotics (33.7%). The mean age was older in the antibiotic‐resistant group (20.8 ± 5.8 vs. 18.3 ± 3.7, P = 0.02). Resistance to trimethoprim–sulfamethoxazole was 26.3%, erythromycin 12.5%, and clindamycin 7.5%. All clindamycin‐resistant strains had cross‐resistance to erythromycin, and 40% erythromycin‐resistant strains had cross‐resistance to trimethoprim–sulfamethoxazole. All strains were sensitive to tetracycline and doxycycline. The use of topical erythromycin or clindamycin was a risk factor to carry resistant strains (P = 0.02, P = 0.04, respectively). Resistance to trimethoprim–sulfamethoxazole was associated with acne severity (P = 0.02). Six of the 10 erythromycin‐resistant strains had a mutation in the peptidyl transferase region of the 23S rRNA gene: one A2058G and five A2059G. No strain carrying mutation G2057A was found. Conclusions Resistance to trimethoprim–sulfamethoxazole was the most common pattern found, and further studies are required to clarify its resistance mechanism. A certain tetracycline resistance was expected, but interestingly all strains remained sensitive. Resistance to erythromycin and clindamycin were influenced using topical formulations. Mutation A2059G was related to high resistance to erythromycin. Antibiotic resistance is increasing, and new strategies are needed.     

Double-blind, randomized, vehicle-controlled clinical trial of once-daily benzoyl peroxide/clindamycin topical gel in the treatment of patients with moderate to severe rosacea

BACKGROUND: Systemic antibiotics such as tetracycline are well accepted as effective in treating the inflammatory papular/pustular phase of rosacea but may be associated with systemic side-effects. Few controlled data on the use of topical antibiotics in rosacea are available. OBJECTIVE: We evaluated the efficacy and tolerability of a fixed combination of 5% benzoyl peroxide and 1% clindamycin in a topical gel for the treatment of rosacea. Methods This was a 12-week, double-blind, vehicle-controlled, randomized, prospective, parallel-group study in 53 patients with moderate to severe rosacea. RESULTS: The mean percentage reduction in papules and pustules from baseline to the end of treatment was 71.3% in the benzoyl peroxide/clindamycin group (n = 26) and 19.3% in the vehicle group (n = 26; P = 0.0056). A significant (P = 0.0141) difference in favor of benzoyl peroxide/clindamycin was evident by the third week of treatment. Severity scores for erythema, papules/pustules, and flushing/blushing decreased more with benzoyl peroxide/clindamycin than with vehicle. Overall rosacea severity, Physician Global Assessment, and Patient's Global Assessment at the end of treatment were all significantly improved with benzoyl peroxide/clindamycin compared with vehicle (P = 0.0101, 0.0026, and 0.0002, respectively). Application site reactions were reported in four patients (14.8%) in the benzoyl peroxide/clindamycin group. CONCLUSION: A once-daily topical application of a combination of 5% benzoyl peroxide and 1% clindamycin is effective and well tolerated in patients with moderate to severe rosacea.     

Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac®) and a proprietary 0.025% tretinoin gel formulation (Aberela®) in the topical control of facial acne

Background A formulation containing agents affecting the non-inflammatory as well as the inflammatory lesions of acne vulgaris at the same time would be efficient, probably showing a high efficacy and possibly a considerable shortening of the duration of treatment. One single formulation would simplify drug administration thereby enhancing patient compliance and possibly leading to improved therapeutic results. In two studies this seems to have been corroborated for the fixed clindamycin phosphate-tretinoin gel formulation. Objective This study was designed to assess whether the recently developed fixed formulation of 1.2% clindamycin phosphate and 0.025% tretinoin in a gel base (Velac®), further referred to as Clindamycin phosphate Tretinoin Gel is at least as effective as a proprietary 0.025% tretinoin gel formulation (Aberela®, Janssen Cilag Ab, Sollentuna, Sweden; further defined as tretinoin) showing an additional anti-inflammatory effect in the treatment of moderate to severe acne vulgaris. Methods In a double-blind, randomised study 72 patients were treated with CTG and 73 with tretinoin gel in a once daily regimen for 12 weeks. Responses, irritation as well as possible systemic and other adverse effects were recorded after 4, 8 and 12 weeks of treatment and the improvement, compared to baseline, assessed in all included patients. An additional assessment of the safety parameters was carried out at week 2. Parameters of efficacy were the various acne lesion counts, the overall acne severity grade and the calculated totals of acne lesion counts. Results CTG was statistically significantly more effective than tretinoin at the P= 0.05 level in the papular and the total mean inflammatory lesion counts as well as in the estimated or calculated mean overall acne severity scores. CTG and tretinoin gel were equally effective in the remaining parameters: open and closed comedones, the calculated total mean comedone, the pustule as well as the nodule lesion counts. The onset of action was faster for CTG than for tretinoin gel and evident in all assessed parameters except in open comedone lesion counts. In the calculated total mean acne lesion counts, half of all acne lesions had disappeared by week 6 of treatment with CTG, whereas this was recorded at week 9 for tretinoin gel. No clinically relevant changes in the parameters of safety as a consequence of treatment were observed, although the burning component of irritation was shown to be significantly less for CTG than for tretinoin gel. The observed adverse effects were considered minor. Treatment had to be discontinued in five patients on CTG and three on tretinoin. Conclusion The addition of clindamycin to tretinoin, as in CTG, enhances the comedolytic efficacy of tretinoin in moderate to severe acne of the face, maintaining at the same time its anti-inflammatory efficacy thus accelerating resolution of all types of acne lesions without affecting the safety of response to both components.     

Topical clindamycin therapy for acne vulgaris. A cooperative clinical study

Eleven institutions participated in an eight-week controlled clinical study to evaluate treatment of acne vulgaris with topical clindamycin hydrochloride and clindamycin phosphate. Three hundred fifty-eight patients with comparable baseline pustule, papule, and nodule counts applied 1%, clindamycin hydrochloride, 1% clindamycin phosphate, or a hydroalcoholic vehicle twice daily. Every two weeks, lesions were counted, and patients' evaluations of their acne conditions were scored. By week 8, pustule and papule counts in the groups who were receiving clindamycin were significantly lower than those in the group receiving placebo. Also, more patients who were receiving clindamycin thought their acne improved by week 8 (with significantly higher change-in-acne scores) than did the patients receiving placebo. Patients receiving clindamycin reported 12 episodes of diarrhea; only one episode was considered to be treatment related. These results substantiate the clinical impression that topical clindamycin is effective treatment for acne.     

Effect of a topical erythromycin—zinc formulation on sebum delivery. Evaluation by combined photometric—multi-step samplings with Sebutape®

Zinc displays‘in vitro’some antiandrogen activity through an inhibition of the 5α-reductase activity. The clinical relevance of this effect is unknown, particularly during zinc therapy of acne. As sebum production could he a pharmacological target, a sensitive method was used for measuring the rate of sebum delivery to the skin surface during treatment with a topical 4% crythromy-cin-1·2% zinc acetate formulation. A series of four successive 1-h samplings with Sebutape® was taken to derive the rate of sebum output from the slope of the regression line given by cumulative data. As a control the classical photometric method was used. Such combined evaluation revealed a sebosuppressive effect for the topical zinc formulation tested.     

Erythromycin 2% gel in comparison with clindamycin phosphate 1% solution in acne vulgaris

One hundred two patients with mild to moderate facial acne vulgaris completed a 12-week, investigator-masked, randomized, parallel-group comparison of a gel formation of erythromycin (2%) with clindamycin phosphate 1% solution. Patients were evaluated at a baseline visit and after 4, 8, and 12 weeks of twice-daily treatment. Both medications significantly reduced the numbers of papules and open and closed comedones. No significant differences in lesion count reductions were detected between the treatment groups after 8 and 12 weeks of treatment. By the end of 12 weeks, 48% of the patients in the erythromycin group and 47% in the clindamycin group had good or excellent responses to treatment. No patient was terminated from the study for side effects. Most patients, 65% in the erythromycin 2% gel group and 67% in the clindamycin phosphate 1% solution group, had a favorable impression of the overall cosmetic characteristics of their study medication.     

A comparison of clindamycin phosphate 1 percent topical lotion and placebo in the treatment of acne vulgaris

The efficacy and skin tolerance of 1 percent clindamycin phosphate lotion were compared with those of the placebo for the lotion in a randomized, double-blind, 12-week study in forty-six patients with moderate to severe acne vulgaris. Patients using the 1 percent clindamycin lotion experienced reductions in numbers of pustules, papules, open comedones, and nodulocystic lesions. Papule counts were also reduced in placebo-treated patients. The group using clindamycin lotion had significantly greater reductions in pustule counts at week 12 and papule counts at week 3 than the placebo-treated group. Nearly 90 percent of the evaluable patients at week 12 experienced improvement or marked improvement in their acne according to the physician's evaluation, regardless of treatment group. Both regimens were well tolerated. Although diarrhea was reported by eight patients (three taking clindamycin, five receiving placebo), no patients discontinued the protocol because of diarrhea. This study demonstrated the efficacy of 1 percent clindamycin topical lotion in the treatment of moderate to severe acne vulgaris.     

Inhibition of erythromycin-resistant propionibacteria on the skin of acne patients by topical erythromycin with and without zinc

Summary Propionibacteria resistant to high concentrations of erythromycin [minimal inhibitory concentration (MIC)≥0·5 mg/ml) are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w·v erythromycin with and without 1–2% w/v nine acetate to reduce the numbers of erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the erythromycin/zinc complex and erythromycin alone produced highly significant reductions in total propionibacteria (P<0·01) and in the number of erythromycin-resistant strains (P<0·01 at 8 weeks). After 12 weeks, resistant propionibacteria were re-acquired, or acquired de novo. by three patients treated with erythromycin alone and four patients treated with the erythromycin/zinc complex. In contrast, changes in numbers of Micrococcaceae were slight and. after 12 weeks, erythromycin-resistant strains were predominant in both treatment groups. In vitro MIC determinations suggested that this finding might be explained by the exceptionally high degree of erythromycin resistance displayed by some staphylococcal strains (MIC>4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Krythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (F<0·001). In particular, 11 of 12 patients who harboured >10³ c.f.u. erythromycin-resistant propionibacteria/cm² skin pretreatment (seven on the erythromycin/zinc complex and five on erythromycin alone) showed clinical improvement, with a>50% reduction in acne grade and/or lesion count. These results show that topical 4% w/v erythromycin with and without zinc eradicates erythromycin-resistant propionibac-teria in vivo, and is thus therapeutlcally effective in patients who harbour such strains.     

Clinical efficacy and safety of a topical combination of retinaldehyde 0.1% with erythromycin 4% in acne vulgaris

The objective of this randomized, controlled, multicentre study was to assess the efficacy and safety of a topically applied retinaldehyde 0.1% gel in combination with a topical erythromycin 4% lotion for the treatment of acne vulgaris. Treatment consisted of applying either retinaldehyde or its vehicle every morning and erythromycin every evening for 8 weeks. Efficacy parameters were sequential lesion counts for papules and pustules, and a 6-point semiquantitative scale for comedones and microcysts. Safety parameters were local tolerance and adverse events. Of 74 recruited patients, 73 were appraisable for efficacy and safety. In both treatment groups, papules and pustules were reduced significantly at the end of treatment (P < 0.001), and no statistical difference was observed between the groups. Comedones and microcysts were significantly improved with retinaldehyde combined with erythromycin (P = 0.005), but not with erythromycin alone. However, no statistical difference between the groups could be demonstrated (test power, 50%). Local tolerance of the combined treatment group was very satisfactory, as only a few patients experienced local irritation. In conclusion, retinaldehyde combined with erythromycin appears to be a valuable topical therapy in polymorphic acne.     

Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ψ

OBJECTIVES: Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (beta-CD) is investigated in 66 acne vulgaris patients. METHODS: This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/beta-CD complex hydrogel formulation (0.025%), RA/beta-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. RESULTS: After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/beta-CD complex hydrogel formulation, 4.1 with the RA/beta-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/beta-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/beta-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/beta-CD complex in the moisturizing base. CONCLUSION: The topical RA/beta-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/beta-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/beta-CD complex in acne vulgaris. We conclude that the topical RA/beta-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris.     

Effect of topical benzoyl peroxide/clindamycin versus topical clindamycin and vehicle in the reduction of Propionibacterium acnes

Propionibacterium acnes is one of the primary factors involved in the pathogenesis of acne vulgaris; proliferation of this bacteria is present in all patients with inflammatory lesions. Combination topical therapy with agents that have different but complementary antimicrobial mechanisms of action has the potential to increase efficacy and to prevent the emergence of resistant organisms. The onset of action and effectiveness of 3 topical preparations (benzoyl peroxide 5%/clindamycin phosphate 1% gel, clindamycin phosphate 1% solution, and vehicle gel) in reducing P acnes were compared in a randomized, open-label, evaluator-blinded, comparative trial involving 60 healthy volunteers who were free of acne but had high levels of facial P acnes. Treatment with benzoyl peroxide 5%/clindamycin phosphate 1% gel significantly (P<.001) reduced P acnes levels by >1 log10/cm2 from baseline (91% inhibition) 24 hours after application. Progressive declines were observed throughout the 2-week study period, with a 3 log10/cm2 reduction (99.9% inhibition) from baseline in P acnes at the end of the 2-week treatment period. In contrast, significant (P<.05) reductions from baseline in P acnes levels following treatment with clindamycin phosphate 1% solution were only observed at the last assessment period (2 weeks), with an average reduction of 0.64 log10/cm2 (77% inhibition). Patients receiving vehicle gel had no measurable reductions in P acnes from baseline. These results demonstrate that topical benzoyl peroxide 5%/clindamycin phosphate 1% gel produces rapid and clinically relevant reductions in P acnes greater than those produced by single-agent therapy. This activity is likely responsible for the quick onset of clinical efficacy produced by this combination regimen.