ORIGINAL ARTICLE A COMPARATIVE STUDY OF EFFECACY AND SAFETY OF COMBINATION OF TOPICAL CLINDAMYCIN AND 0.1% ADAPALENE WITH 1% CLINDAMYCIN AND 2

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1 A COMPARATIVE STUDY OF EFFECACY AND SAFETY OF COMBINATION OF TOPICAL CLINDAMYCIN AND 0.1% ADAPALENE WITH 1% CLINDAMYCIN AND 2.5% BENZOYL PEROXIDE IN MILD TO MODERATE ACNE IN A TERTIARY CARE HOSPITAL Revathi T. N 1, Geetha A 2, Shilpa K 3, Shwetha H 4, Mandara Harikar 5 HOW TO CITE THIS ARTICLE: Revathi T. N, Geetha A, Shilpa K, Shwetha H, Mandara Harikar. A Comparative Study of Effecacy and Safety of Combination of Topical Clindamycin and 0.1% Adapalene with 1% Clindamycin and 2.5% Benzoyl Peroxide in Mild To Moderate Acne in a Tertiary Care Hospital. Journal of Evidence based Medicine and Healthcare; Volume 1, Issue 14, December 08, 2014; Page: ABSTRACT: BACKGROUND: Topical combination therapy in acne targets different pathogenic factors in acne, produces greater and faster results, minimizes adverse effects and improves compliance. The present study was done to compare efficacy and safety of two different topical combination therapies in mild to moderate acne. OBJECTIVES: To compare efficacy to topical combination of 1% Clindamycin and 0.1% Adapalene with 1% Clindamycin and 2.5% Benzoyl peroxide in mild to moderate acne. To compare safety of topical combination of 1% Clindamycin and 0.1% Adapalene with 1% Clindamycin and 2% Benzoyl peroxide and mild to moderate acne. METHODOLOGY: A prospective comparative study was conducted at Victoria Hospital in Department of Dermatology of BMCRI on 120 patients diagnosed with mild to moderate acne on face (as per Indian Acne Alliance grading for severity of acne). They were randomly assigned into 2 groups (A and B) of 60 each, group A having received combination of topical 1% clindamycin and 0.1% adapalene and group B having received combination of topical 1% clindamycin and 2.5% benzoyl peroxide and were followed up at end of 4, 8, 12 weeks Efficacy was assessed by spot counting of acne lesions at each follow ups and any reduction in their numbers was compared with baseline lesion counts and expressed as percentage reduction. At baseline total number of lesions was taken as 100%. Percentage reduction in lesion counts was expressed as improvement in acne and Graded. Safety and Tolerability assessment: Dryness, erythema, burning, peeling and irritation were noted and graded at each follow ups. RESULTS: Significant greater reduction in mean percentage of total (70% vs 51%), non-inflammatory (68% vs 49%) and inflammatory (77% vs 57%) acne lesion counts was seen in group A than group B at 12 weeks, (p<0.001-for all types of lesion counts). was better tolerated than group B in terms of lesser irritation. CONCLUSION: Greater and early treatment response with less irritation is noticed with the combination of topical 1% clindamycin and 0.1% adapalene as compared to combination of topical 1% clindamycin and 2.5% benzoyl peroxide. Thus, combination of topical 1% clindamycin and 0.1% adapalene is superior to combination of topical 1% clindamycin and 2.5% benzoyl peroxide in treatment of mild to moderate acne vulgaris. KEYWORDS: Acne vulgaris; clindamycin 1%; adapalene 0.1%; benzoyl peroxide 2.5%; Randomized controlled trial; topical combination therapy and acne; efficacy, safety and tolerability; meta analysis. J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1783

2 INTRODUCTION: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. It is characterized by seborrhea, the formation of open and closed comedones, erythematous papules and pustules and in more severe cases nodules, deep pustules and pseudocysts. In many cases, degrees of scarring will ensue. 1 Acne is often an early manifestation puberty. 2 It develops earlier in females than in males, which may reflect the earlier onset of puberty in females. Prevalence being 56% in boys and 45% in girls between years of age group. 1 Adolescence is a time of significance physical, emotional and social development, which may predispose individuals to psychiatric or psychosocial complications 3. Acne affects 85% of individuals between 12 and 24 years of age mostly on the face resulting in impairment of self image, self-esteem, clinical depression, social phobia and anxiety. 4 Acne has multifactorial pathogenesis mainly follicular epidermal hyper proliferation, excess sebum production, inflammation and activity of Propionibacterium acnes. (P.acnes) 2 Choice of therapy is largely determined by the severity and extent of disease but should be tempered by patient s choice and cost. 5 Topical antibacterials such as clindamycin are bacteriostatic for P. acnes. They have also been demonstrated to have anti-inflammatory activities though inhibition of lipase production by P.acnes, as well as inhibition of leukocyte chemotaxis. 6 Topical retinoids function to normalize the maturation of follicular epithelium, reduce inflammation and enhance the penetration of other topical medications. 7 Adapalene, in addition to displaying typical retinoid effects, also has anti-inflammatory properties and interefers with polymorphonuclear leukocyte function and arachidonic acid metabolism. 8 It is stable in sunlight and it tends to be less irritating. 7 Benzoyl peroxide (BPO) has been used in the treatment of acne since many years. It has been postulated that the mechanism of action of benzoyl peroxide in acne is related to its antimicrobial activity against P.acnes and to its peeling and comedolytic effects. 9 Benzoyl peroxide has the advantage that bacterial resistance does not develop. 10 It has been shown that lower concentration of benzoyl peroxide (2.5%) can be equally efficacious to higher concentrations of benzoyl peroxide in reducing acne lesions and also the low concentration of benzoyl peroxide has reduced cutaneous side effects such as burning, erythema and peeling. 11 Different topical anti acne agents targeting different pathogenic factors are available and thus combining them enhances therapeutic efficacy, makes it user friendly and minimizes adverse effects. 12 Combination of topical retinoids with antimicrobial agents has a complimentary mechanism of action. Adapalene has comedolytic and anti-inflammatory action. It also allows topical antimicrobial agents to penetrate more effectively into the sebaceous follicle and treat bacterial colonization. 13 The combination thus results in reducing both comedones and inflammatory acne lesion counts, resulting in significantly greater and faster results, reduce the duration of antibiotic therapy and the potential for developing bacterial resistance. 14 Topical clindamycin and benzoyl peroxide have synergistic antimicrobial action. Clindamycin has anti-inflammatory action. Benzoyl peroxide has keratolytic action and improves penetration of clindamycin. 15 Thus, clindamycin 1% and benzoyl peroxide 2.5% combines a low J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1784

3 concentration of benzoyl peroxide with clindamycin phosphate that demonstrates efficacy against inflammatory and non-inflammatory lesions of acne. Once daily use of this combination product with a low potential for cutaneous irritation may lead to increased patient adherence to treatment and thus to improved clinical outcomes. 16 In view of its common nature and devastating effects of acne on face mainly in adolescents and relatively less data available in this domain, the comparative study between two topical combination therapies for acne on face has been taken up. OBJECTIVES OF STUDY: 1. To compare efficacy of topical combination of 1% clindamycin and 0.1% Adapalene with 1% clindamycin and 2.5% benzoyl peroxide in mild to moderate acne. 2. To compare safety of topical combination of 1% clindamycin and 0.1% Adapalene with 1% clindamycin and 2.5% benzoyl peroxide in mild moderate acne. Review of Literature: Acne vulgaris is a self limited disorder of the pilosebaceous unit that is seen primarily in adolescents. Most cases of acne present with pleomorphic lesions, consisting of comedones, papules, pustules and nodules. Although the course of acne may be self-limiting, the sequelae can be life long, with pitted or hypertrophic scar. 2 Anatomy of the Pilosebaceous Unit: The hair follicle and associated gland comprise the pilosebaceous unit. The sebaceous gland is holorine, its secretion is formed by the complete disintegration of the glandular cells. 17 The gland consists of series of lobes each with a duct lined by keratinizing squamous epithelium. The lobule ducts converge near the main sebaceous duct, which normally opens into the pillary canal whose epithelium is continuous with the surface epidermis. Ultrastructure, Histochemistry and Immunochemistry of the sebaceous gland and duct: Undifferentiated sebaceous cells at the periphery of the gland are rich in ribonucleoproteins and stain with basic dyes. As the cells move towards the center of each lobe they contain more lipids and become progressively acidophilic. All cells have numerous mitochondria, usually appearing as short or wavy rods. The undifferentiated cells contain coarse, osmium staining particles around the nucleus; as differentiated proceeds, the particles increase in number and size and develop lipid droplets in their centres, which gradually enlarge. This complex corresponds to the golgi body; at completion of sebaceous synthesis it is no longer recognizable. Physiology of Sebum Secretion: Sebaceous glands are present at birth and sebum production is relatively high at this time. The level of sebum excretion at birth is similar to that in adults. It soon declines and remains low until puberty, at which time it again increases under the influence of androgens. The level of sebum production at the end of puberty remains constant throughout adulthood. Sebum production declines in women after menopause and in men during 6 th to 7 th decade. 18 J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1785

4 Sebum is a slightly yellow viscous fluid. It is a complex mixture of lipids: 19 Wax esters (26%), squalene (12%); derived from sebaceous gland. Triglycerides and free fatty acids (57.5%); formed in infundibulum due to esterase activity of P. acnes and Propionibacterium granulosum on acyl glycerols. Cholesterol esters (3%), Cholesterol (1.5%). Pathogenesis of Acne Vulgaris: Pathophysiology of acne involves a complex interaction of multiple factors both internal and external to the pilosebaceous apparatus. Sebum and Acne: Excess sebum production is a prerequisite for the development of acne. The level of sebum secretion correlates well with the severity of acne. Sebaceous gland activity is predominantly dependent on androgenic sex hormones of gonadal or adrenal origin: Excessive androgen production Increased availability of free androgen which may be associated with a relative reduction of sex hormone binding globulin (SHBG) Amplified target response mediated either through 5 reduction of testosterone to dihydrotestosterone (DHT). An increased capacity of the intracellular receptor to bind androgens. EFFECT OF HORMONES ON SEBACEOUS GLAND CELLS: Sex steroids: Sebocytes are target cells for several neuro hormones. Androgen receptors are present on both the sebaceous gland and sebaceous duct. The majority of potent androgens are produced by peripheral target tissues. The biological activity of testosterone on the skin is the main induced by its conversion to Dihydrotestosterone (DHT) by the enzyme 5 reductase (20) Altered Follicular Keratinisation: One of the first step in the production of acne is the formation of micro come done. This begins in the keratinized lining of the upper portion of the follicle, the infundibulum. It occurs when the corneocytes which are normally shed into the lumen of the follicle and extruded through the follicular ostium, are retained and accumulate leading to hyperkeratosis. Increased cohesiveness of the cells is responsible. Several factors have been implicated in the induction of keratinocyte hyperpoliferation: Androgen simulation. Decreased linoleic acid. Increased interleukin 1 activity. Environmental factors affecting Acne Vulgaris: Hot and humid climate aggravate acne, due to increased sweating causing ductal hydration. People working with oils, occupation as cooks, halogenated hydrocarbons can aggravate acne. UV radiation, external application of oils, pomades can cause acneiform eruptions. Some studies show that diet could play a role in the pathogenesis of acne by increasing ILGF, resulting in unregulated growth of follicular epithelium, increased sebum production and synthesis of androgens from gonads. Milk not only contains IGF- 1, but also increases endogenous secretion of IGF-1. J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1786

5 Genetic Factors: Although acne is not an inherited condition, there is an inherited predisposition. Several genes are believed to be involved, of which only the gene for CYP4501A1 and gene for steroid 21 hydroxylase are documents. There is high concordance in identical twins. Patients with persistent acne have a strong family history of persistence acne, in contrast to patients with adolescent acne. Epidemiology of Acne Vulgaris: Acne is often an early manifestation of puberty; in the very young patient the predominant lesions are comedones. In girls, the occurrence of acne may precede menarche by more than 1 year. The greatest numbers of cases are seen during the middle to the late teenage period. Afterward, the incidence steadily decreased. However, particularly in women, acne may persist through the third decade or even later. 2 Prevalence being 56% in boys and 45% in girls between years of age group. 1 Grading of Acne vulgaris: Grading systems bases on the clinical appearance of lesions as well as lesions counting are useful in assessing the severity of acne vulgaris. Grade of Acne Predominant Lesions Type and Number of Lesions Comedones<30 1- Mild Comedones Papules<10 No scarring 2- Moderate Papules Comedones any number Papules>10 Nodules/Cysts<3 Scarring +/- 3-Severe Many nodules Comedones any number Papules any number Nodules/Cysts>3 Scarring+ Table 1: Indian Acne Alliance Grading for Severity of Acne 36 Psychosocial effects of Acne: Acne is associated with greater psychological burden than a variety of disparate chronic disorders. Besides anxiety and depression, acne patients are prone to low self esteem, low self-confidence, low self-assertiveness, embarrassment, social inhibition, affectation, shame, altered body image, psychosomatic symptoms (pain and discomfort) obsessive compulsiveness and suicidal ideation. Treatment of Acne Vulgaris: Aims of treatment: Correct the altered pattern of follicular keratinization. Decrease sebaceous gland activity. Decrease the follicular bacterial population, particularly P. acnes. Reduce inflammation. J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1787

6 The management of acne starts with education. Treatment procedures involve detailed patient discussion, acne assessment and appropriate prescribing based on the history, acne severity, lesions type, psychological effects of the disease and cause of the disease. The cause of the acne should be discussed, as should the goals and outcomes (Including the patients expectations) of therapy. RECENT ADVANCES IN ACNE VULGARIS: Recent advances in the treatment of Acne vulgaris: Recent developments in topical treatment encompass newer formulations and combinations of conventional treatments as well as emerging topical therapies. Synergistic topical combination therapies in acne: Combination of benzoyl peroxide 2.5% or 5% with nadifloxacin, adapalene and salycilic acid. Newer formulations: Formulation technology has focused on novel systems for drug delivery, including microspone/spheres, liposomes, nanoemulsions and aerosol foams. Microsphere encapsulation eliminates the rapid delivery of high concentrations of active drug to the application site, while it facilitates controlled release of potentially irritating drugs. The encapsulation also enables the use of convenient topical combination regimens with a strong oxiding agent such as benzoyl peroxide, leading to improved treatment outcomes and minimal irritation. Microsphere formulations of topical tretinoin and benzoyl peroxide, currently in the market, have demonstrated good efficacy and tolerability. Retinoic acid loaded, solid, lipid nanoparticles formulation is designed to increase it s tolerability without reducing efficacy. The nano-emulsion gel formulation of Adapalene clindamycin combination appears to be more efficacious and better tolerated than the conventional formulation in Indian acne patients. Study Groups Clindamycin 1% and benzoyl peroxide 5% combination gel Mean percentage reduction in Non-inflammatory lesion counts at 11 weeks Mean percentage reduction in inflammatory lesion counts at 11 weeks 61% + 3% 36% + 4% Clindamycin 1% gel 39% + 4% 30% + 4% Benzoyl peroxide 5% gel 35% + 5% 9% + 6% Vehicle 5% + 7% -11% + 8% Table 2: Results of the study done by Looking bill et al, in mean percentage reduction of acne lesion counts J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1788

7 Acne lesions counts Total lesion counts Inflammatory lesion counts Noninflammatory lesion count Clindamycin 1.2% Benzoyl peroxide 2.5% Clindamycin 1.2% gel Benzoyl peroxide 2.5% gel Vehicle 47.9% 40.4% 41.6% 41.6% 54.6% 46.2% 47.5% 29% 43.2% 36.2% 37.4% 24% P Value < < < Table 3: Results of the study done by Thiboutot et al, in mean percentage reduction of acne lesion counts Mean percentage reduction in acne lesions Inflammatory lesions Non-inflammatory lesions Benzoyl peroxide 5% [29.37, 37.40] [14.06, 24.18] Clindamycin 1% - 1.2% 21.5 [17.47, 25.57] 9.99 [5.01, 14.96] 5% Benzoyl peroxide with salicylic acid [50.72, 59.72] [39.33, 46.10] 5% Benzoyl peroxide with 1% lindamycin [37.23, 44.24] [22.16, 30.26] Table 4 (a): Results of metal analysis done by Seidler et al Placebo 7.26 [3.03, 17.55] 6.65 [-0.68, 13.98] Types of acne lesions Inflammatory lesions Noninflammatory lesions Benzoyl peroxide 5% 43.75% [41.13, 46.32] 30.88% [25.61, 36.16] Clindamycin 1% - 1.2% 45.91% [42.77, 49.05] [27.86, 37.35] 5% Benzoyl peroxide with salicylic acid 51.77% [43.08, 60.45] [40.49, 55.01] Table 4 (b): Results of meta analysis by Seidler et al 5% Benzoyl peroxide with 1% lindamycin 55.58% [53.59, 57.56] [37.02, 43.58] Placebo 26.76% [21.65, 31.88] [11.70, 22.39] J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1789

8 METHODOLOGY SOURCE OF DATA: Patients suffering from mild to moderate acne on face attending Dermatology OPD in teaching hospitals attached to Bangalore Medical College and Research Institute, Bangalore. METHODS OF COLLECTION OF DATA: Study design: Prospective Comparative Study. Study period: November 2001 to May Place of study: Out patients in Department of Dermatology in teaching hospitals attached to Bangalore Medical College and Research Institute, Bangalore. Sample size: 120 patients having mild to moderate acne vulgaris on face. Inclusion Criteria: 1. Patients aged years of either sex. 2. Patients with mild to moderate acne on face above jaw line (Indian Acne Alliance Grading). 3. Women of child bearing potential were required to have a negative urine pregnancy test result and to agree to use an effective form of contraception for the duration of study (12 weeks). 4. Patients who gave consent and were willing for follow up. Exclusion Criteria: 1. Other variants of acne: chloracne, oil acne, tropical acne, mechanical acne severe variants like acne conflobata and acne fulminans. 2. Drug induced acne. 3. If at follow up the disease progressed and required systemic therapy. 4. Patients who were not willing to give informed consent and follow up. 5. Pregnant and lactating mother. 6. Patients with known hypersensitivity to any of the components of the drug. Study Procedure: After obtaining clearance and approval from the institutional ethics committee, 120 patients suffering from mild to moderate acne on face fulfilling the inclusion/exclusion criteria were enrolled in the study after obtaining informed consent. RESULTS: Disposition of Patients: The present prospective, randomized, comparative study which was done at Victoria hospital, in the Department of Dermatology of Bangalore Medical College and Research Institute to evaluate the efficacy and safety of two different topical combination therapies in mild to moderate acne vulgaris on face revealed the following results. J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1790

9 Age in years > Total Mean + SD Table 5: Distribution of cases of acne based on age of the patients in the 2 groups studied Gender Male Female Total Table 6: Distribution of cases of acne based on gender of the patients in the 2 groups studied Region Urban Rural Total Table 7: Regional distribution of the patients in the 2 groups studied Occupation Student Employed Housewife Total Table 8: Occupation distribution of the patients in the 2 groups studied J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1791

10 Mean Duration of Acne in years < > Total Table 9: Distribution of the mean duration of acne in the 2 groups studied Grade of Acne Grade I [Mild Acne] Grade II [Moderate Acne] Total Table 10: Distribution of the grade of acne in the 2 groups studied Duration Baseline weeks weeks weeks <0.001** Significance Baseline-4 weeks <0.001** <0.001** - Baseline-8 weeks <0.001** <0.001** - Baseline-12 weeks <0.001** <0.001** - Table 11: Comparison of the mean number of non-inflammatory acne lesion counts from baseline to 12 weeks in the 2 groups studied Duration Baseline weeks * 8 weeks * 12 weeks <0.001** Significance Baseline-4 weeks <0.001** <0.001** - Baseline-8 weeks <0.001** <0.001** - Baseline-12 weeks <0.001** <0.001** - Table 12: Comparison of the mean number of inflammatory acne lesion counts from baseline to 12 weeks in the 2 groups studied J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1792

11 Duration Baseline weeks weeks * 12 weeks <0.001** Significance Baseline-4 weeks <0.001** <0.001** - Baseline-8 weeks <0.001** <0.001** - Baseline-12 weeks <0.001** <0.001** - Table 13: Comparison of the mean number of total acne lesion counts from baseline to 12 weeks in the 2 groups studied Duration Baseline- 4 weeks Baseline- 8 weeks <0.001** Baseline- 12 weeks <0.001** Table 14: Comparison of the mean percentage reduction in total acne lesion counts in the 2 groups studied Duration Baseline- 4 weeks Baseline- 8 weeks <0.001** Baseline- 12 weeks <0.001** Table 15: Comparison of the mean percentage reduction in noninflammatory acne lesion counts in the 2 groups studied Duration Baseline- 4 weeks Baseline- 8 weeks <0.001** Baseline- 12 weeks <0.001** Table 16: Comparison of the mean percentage reduction in inflammatory acne lesion counts in the 2 groups studied J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1793

12 Grade Excellent (>75% reduction in acne lesion count) Good (50-75% reduction in acne lesion count) Fair (25-50% reduction in acne lesion count) Poor (<25% reduction in acne lesion count) Worse (Increase in acne lesion count) Table 17: Comparison of Grading of Improvement in acne at the end of 4 weeks in the 2 groups studied Grade Excellent (>75% reduction in acne lesion count) Good (50-75% reduction in acne lesion count) Fair (25-50% reduction in acne lesion count) Poor (<25% reduction in acne lesion count) Worse (Increase in acne lesion count) Table 18: Comparison of Grading of Improvement in acne at the end of 8 weeks in the 2 groups studied <0.001** Grade Excellent (>75% reduction in acne lesion count) Good (50-75% reduction in acne lesion count) Fair (25-50% reduction in acne lesion count) Poor (<25% reduction in acne lesion count) Worse (Increase in acne lesion count) Table 19: Comparison of Grading of Improvement in acne at the end of 12 weeks in the 2 groups studied <0.001** J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1794

13 Safety and tolerability parameter Dryness No dryness Mild dryness Moderate dryness Severe dryness Table 20: Comparison of cumulative local dryness of skin between the 2 groups studied Safety and tolerability parameter Erythema No erythema Mild erythema Moderate erythema Severe erythema <0.001** Table 21: Comparison of cumulative local erythema of skin between the 2 groups studied Safety and tolerability parameter Burning sensation No burning sensation Mild burning sensation Moderate burning sensation Severe burning sensation * Table 22: Comparison of cumulative local burning sensation of skin between the 2 groups studied Safety and tolerability parameter Peeling No Peeling Mild Peeling Moderate Peeling Severe Peeling Table 23: Comparison of cumulative local peeling of skin between the 2 groups studied J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1795

14 Safety and tolerability parameter Irritation No irritation Mild irritation Moderate irritation * Severe irritation Table 24: Comparison of cumulative local irritation sensation of skin between the 2 groups studied J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1796

15 CONCLUSION: Greater and early treatment response with less irritation is noticed with the combination of topical 1% clindamycin and 0.1% Adapalene treated group as compared to the combination of topical 1% clindamycin and 2.5% benzoyl peroxide treated group. This can be attributed to the predominant comedolytic and anti-inflammatory action of Adapalene. Thus, the combination of topical 1% clindamycin and 0.1% Adapalene is superior to the combination of topical 1% clindamycin and 2.5%benzoyl peroxide in the treatment of mild moderate acne vulgaris. SUMMARY: A prospective, randomized, study was conducted to compare the efficacy and safety of combination of topical 1% clindamycin and 0.1% Adapalene with the combination of topical 1% clindamycin and 2.5% benzoyl peroxide in mild to moderate acne vulgaris on face. A total of 120 patients suffering from mild to moderate acne on face fulfilling the inclusion and exclusion criteria were enrolled in the study after taking approval and clearance from the institutional ethics committee. Written informed consent from the patients or parents/guardians of the patients was obtained and the patients were randomized into 2 groups (A and B) of 60 each. received combination of topical 1% clindamycin and 0.1% adaplaene and Group B received combination of topical 1% clindamycin and 2.5% benzoyl peroxide for a period of 12 weeks and were evaluated for efficacy and safety. J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1797

16 The study population included 67 boys and 53 girls. Majority of the study population were students between the age group of 16 to 20 years and had a history of mild to moderate acne for 1 to 2 years. Thus the 2 groups (A and B) were matched in terms of mean age, gender, regional distribution, occupation, duration of acne and grade of acne. 1 patient in group A and 2 patients in group B did not report for the 4 th week and further follow up. Thus, 59 patients in group A and 58 patients in group B were included for efficacy and safety assessment. Both the groups showed statistically significant reduction in the mean number of total, non-inflammatory and inflammatory acne lesion counts. After 4 th week, combination of topical 1% clindamycin and 0.1% Adapalene group showed significantly greater reduction in all lesion types throughout the study period with a p < Dryness, erythema, burning peeling and irritation of skin were the most commonly reported side effects. Combination of topical 1% clindamycin and 0.1% Adapalene was significantly better tolerated with less irritation as compared to the combination of topical 1% clindamycin and 2.5% benzoyl peroxide. Combination of topical 1% clindamycin and 0.1% Adapalene produced a significantly greater overall improvement in acne as compared to the combination of topical 1% clindamycin and 2.5% benzoyl peroxide. BIBLIOGRAPHY: 1. Layton A.M. Disorders of the Sebaceous Glands. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook s Textbook of Dermatology.8 th edn. USA: Wiley- Blackwell Publication: P Zaenglein AL, Graber EM, Thiboutot DM, Strauss JS. Acne Vulgaris and acneiform eruptions In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller As, Leffell DJ, editors. Fitzpatrick s Dermatology in General Medicine. 7 th edn. USA: McGraw Hill; P James WD. Acne. New England J of Medicine 2005; 325: Ghoshal L, Banerjee Sk, Ghosh SK, Gangopadhyay DN, Jana S. Comparative evalution of effectiveness of adapalene and azithromycin, alone or in combination, in acne vulgais. Indian J Dermatology 2007; 52 (4): Thiboutot D. New treatment and therapeutic stratergies for acne. Arch Fam Med 2000; 9: Tan HH. Antibacterial therapy for acne: A guide to selection and use of systemic agents. Am J Clin Dermatol, 2003; 4: Burkhart C, Morrell D, Goldsmith L. Dermatological Pharmacology. In: Brunton LL, Chabner BA, Knollman BC editors. Goodman and Gilman s. The Pharmacological Basis of Therapeutics. 12 th ed. New York: McGraw Hill; 2011.p Waugh J, Noble S, Scott LJ. Adapalene: a review of its use in the treatment of acne vulgaris. Drugs. 2004; 64 (13): Robertson DB, Maibach HI. Dermatologic Pharmacology. In: Katzung BG, Masters SB, Trevor AJ editors. Basic and Clinical Pharmacology. 11 th ed. New York: Tata McGraw Hill; 2010/9.p J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1798

17 10. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of acne: A report from a global alliance to improve outcomes in acne. J Am Acad Dernatol 2003; 49:S Mills OH Jr, Kligman AM, Pochi P, Comite H. Comparing 2.5%, 5% and 10% benzoyl peroxide on inflammatory acne vulgaris. Int Dermatol 1986; 25 (10): Kubba R, Bajaj AK, Thappa DM, Sharma R, Vedamurthy M, Dhar S, et al. Indian Acne Alliance Consensus Document. Indian J Dermatol Venerol Leprol 2009; 75:S20-S Kligman AM. The growing importance of topical retinoids in clinical dermatology:a retrospective and prospective analysis. J Am Acad Dermatol 1998; 39 (2pt 3): S Wolf JE, Kaplan D, Kraus SJ, Loven KH, Rist T, Swinyer LJ, et al. Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: A multicenter, randomized, investigator-blinded study. American Academy of Dermatology 2003; 49 (3): S Bikowski BJ. Clinical experience results with clindamycin 1% Benzoyl peroxide 5% gel as monotherapy and in combination. Journal of Drugs in Dermatology 2005; 4(2): Thiboutot D, Zaenglein A, Weiss J, Webster G, Calvarese B, Chen D et al An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the oncedaily treatment of moderate to servere acne vulgaris: Assessment of efficacy and safety in 2813 patients. J AM ACAD DERMATOL 2008; 59(5); Haider, Shaw, JC. Treatment of acne vulgaris. JAMA 2004; 292: Pochi PE, Strauss JS, Downing DT, Downing DT. Age related Changes in sebaceous gland activity. J invest Dermatol 1979; 73: Lookingbill DP, Chlker DK, Lindholm JS, Katz HI, Kempers SE, Huerter CJ, Swinehart JM, Schelling DJ, Klauda HC. Treatment of acne with a combination clindamycin-benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: Combined results of two double-blind investigations. Journal of the American Academy of Dermatology 1997; 37 (4): Sawleshwarkar SN, Salgaonkar V, Oberai CM. Multicenter study to evaluate efficacy and irritation potential of benzoyl peroxide 4% cream in hydrophase (brevoxyl) in acne vulgaris. Indian Journal of Dermatology, Venerology and Leprology 2003; 69 (1): Langer A, Chu A, Goulden V, Ambroziak M. A randomized, single-blind comparison of topical clindamycin with benzoyl peroxide and adapalene in the treatment of mild to moderate facial acne vulgaris. Br J Dermatol. Jan 2008; 158 (1): Zouboulis CC, Fischer TC, Wohlrab J, Jo Barnard, Alio AB. Study of the efficacy, tolerability and safety of two fixeddose combination gel in the management of acne vulgaris. Cutis 2009; 84: J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1799

18 AUTHORS: 1. Revathi T. N. 2. Geetha A. 3. Shilpa K. 4. Shwetha H. 5. Mandara Harikar PARTICULARS OF CONTRIBUTORS: 1. Assistant Professor, Department of Skin and STD, Bangalore Medical College and Research Institute, Bangalore. 2. Professor, Department of Skin and STD, Bangalore Medical College and Research Institute, Bangalore. 3. Assistant Professor, Department of Skin and STD, Bangalore Medical College and Research Institute, Bangalore. 4. Resident, Department of Skin and STD, Bangalore Medical College and Research Institute, Bangalore. 5. Student, Department of Skin and STD, Bangalore Medical College and Research Institute, Bangalore. NAME ADDRESS ID OF THE CORRESPONDING AUTHOR: Dr. Revathi T. N, Assistant Professor, Department of Skin & STD, Bangalore Medical College & Research Institute, Bangalore. Date of Submission: 01/12/2014. Date of Peer Review: 02/12/2014. Date of Acceptance: 02/12/2014. Date of Publishing: 05/12/2014. J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 1/Issue 14/Dec 08, 2014 Page 1800