Multicenter study to evaluate efficacy and irritation potential of benzoyl peroxide 4% cream in hydrophase base (Brevoxyl) in acne vulgaris

Introduction

Acne vulgaris is a multifactorial disease affecting the pilosebaceous unit of the skin. It is the most common problem of adolescence reaching its peak incidence and severity arounc 16-18 years. Etiologic factors in acne vulgari; include: 1)Excessive sebum secretion 2) Abnorma follicular keratinization leading to comedogenesi 3) Proliferation of Propionibacterium acnes, or anaerobic bacterium and 4) Inflammation.

Although there is no known predictable cure for the disease numerous topical and systemic therapies are available that can substantially contro its activity in most cases. Benzoyl peroxide has c proven record as an effective topical acne therapy.[1] It has comedolytic and potent antibacteria activity and has been reported to suppress sebum secretion.[2] It is finely ground crystals, which do cause local irritation and sensitization. Attempts to overcome this problem have resulted in the formulation of aqueous and gel vehicles containing lower concentrations of benzoyl peroxide. There has been continued interest in formulating a stable soluble benzoyl peroxide product. The advantages would be less irritation locally and better efficacy at a lower concentration. A multicenter study was carried out to assess the efficacy and irritation potential of Brevoxyl, a new 4% benzoyl peroxide cream in hydrophase base.

Subjects and Methods

A multicenter, open - labeled, non-comparative study of 4% benzoyl peroxide cream in hydrophase base applied topically in patients with acne vulgaris was carried out by 100 dermatologists from various parts of India. Eligible patients were patients with acne vulgaris on the face. Before the study entry, one-week washout period was given for any type of topical treatment for acne vulgaris. Exclusion criteria were: Pregnant females and patients with known hypersensitivity to benzoyl peroxide. Acne vulgaris grading was done as follows: Grade I - A few to moderate comedones + a few papules, Grade II - A few to moderate papules + a few pustules, Grade III - A few to moderate pustules + nodule/cyst and scarring.

All the patients were given 4% benzoyl peroxide cream in hydrophase base to be applied on ace. Systemic antibiotics were given to some patients if found necessay by the investigator.

Assessment by investigators

All the patients were evaluated at the baseline and at the end of week one, two, four, six and assessment at week 12 was optional. The assessment of the irritation potential and efficacy was performed according to the following scale:

Irritation potential

1. - =No irritation

2. + =Minimal irritation

3. + + =Moderate irritation

4. +++ =Severe irritation

Efficacy

a) 0 =Same

b) 1 = Poor

c) 2 = Fair

d) 3 = Good

e) 4 = Very good

Assessment by patients

Every patient was asked to opine about the following details at the end of study:

1) Irritation-none, some or troublesome.

2) Dryness of skin-none, some or troublesome.

3) Improvement in acne -none, satisfactory or very satisfactory.

4) Willingness to continue medicine -yes or no.

Statistical analysis

Demographic data of all patients who completed the study were analyzed by using descriptive methods and will be reported in the result part. For efficacy analysis, observation by patients and doctors at pre-treatment and at the end of week 1, 2, 4 and 6 were compared.

Safety analysis

At each of the visits (week 1, 2, 4 and 6), adverse result if any were recorded by the doctors. Patients were also asked to report dryness and irritation after application of 4% benzoyl peroxide in hydrophase base.

Results

A total of 630 patients were enrolled it the study. The age group of the patients in this study ranged from 13-34 years with mean age 21.06 years 54.4% of the total patients were males. Duration of the acne ranged from 2 months to 7 years. 48.6% of total patients had grade Il acne followed by 35.1 % who had grade I acne. Grade III acne was seen in only 16.3% of total patients. A total of 567 patients completed the study [Table - 1]

Investigators′ assessment

According to doctors assessment regarding overall efficacy of 4% benzoyl peroxide in hydrophase base in treating acne showed that at the end of 6′h week 85.6% had good to very good effect of treatment [Table - 1]. At the end of 2^d week of treatment 36.9% showed good to very good improvement followed by 43.6% of patients showing fair response. The profile of side effects observed by doctors revealed that 53.8% of total patients did not have any irritation. 34.6% of patients had minimal irritation whereas only 11.6% had moderate to severe irritation (Diagram I).

Patients′ assessment

According to assessment in the improvement of acne after treatment reported by the patients, data showed that 72% of patients had satisfactory improvement at the end of 6-weeks. 23.6% reported very satisfactory improvement and only 4.4% reported an unsatisfactory response (Diagram 2). Assessment of irritation after treatment with 4% benzoyl peroxide in hydrophase base showed that 53.8% of patients did not report any irritation. 41.4% had some irritation whereas only 4.8% patients reported troublesome irritation [Table - 3]. Dryness of skin after treatment with 4% benzoyl peroxide in hydrophase base was assessed. No dryness was reported in 44.4% of patients. Only 3.2% reported troublesome dryness whereas some dryness was reported by 52.4% of the total number of patients.

Discussion

Acne therapy aims at reduction of sebum production, correcting the abnormal ductal keratinization, reducing the colony of P acnes and prevents the release of inflammatory mediators that are basically responsible for the pathogenesis of acne.

The benzoyl peroxide, an oxidant, anti-inflammatory and keratolytic agent is used over the skin as an antibacterial agent. In 1972, Fulton showed its action against the Propionibacterium acnes, reducing its population and , therefore, indirectly, the production of free fatty acids.[3] It can irritate the skin and bleaches the skin and hair.

Due to the discovery of the action of benzoyl peroxide on the Propionibacterium acnes, many investigators have been conducting clinical studies with benzoyl peroxide in the treatment of acne. The present study evaluated the efficacy and irritation potential of 4% benzoyl peroxide in hydrophase base (Brevoxyl 4% cream) in the treatment of acne vulgaris. All stable benzoyl peroxide formulations contain suspended crystalline particles of benzoyl peroxide, which are water insoluble. After application of traditional formulations water and other volatile solvents evaporate leaving behind a residue containing benzoyl peroxide particles. The hydrophase base of Brevoxyl contains dimethyl isosorbide that is water-soluble but is much less volatile than water. The solvent dimethyl isosorbide dissolves the crystals of benzoyl peroxide, which helps in reducing the irritation and also improving biovailability.[4] Evidence from this study indicates that only a small percentage of patients reported irritation after the use of unique brnzoyl peroxide containing solvent dimethyl isosorbide. A satisfactory response was reported as early as two weeks and most of the patients had a very satisfactory response after six weeks and were willing to continue the treatment. This supports the theory that the hydrophase formulation in Brevoxyl helped to decrease the irritation associated with use of benzoyl peroxide.

Acknowledgement

The authors wish to thank the following doctors for their contribution in conducting the study.

Dr.Shreyash Kamath, Dr. M. V. Sriram, Dr. G. Nirmaladevi, Dr. C. N. Mohana Vala, Dr. Pravinkumar R. Shetty, Dr. Bipin B. Deshpande, Dr. S.N. Marathe, Dr. Ashok Lawakh, Dr. Kannan Shah, Dr. Deepak Parikh, Dr. Sudhesh T. Choudhary, Dr. Yogesh B. Shah, Dr. Rekha Lanjekar, Dr. Soman Peter, Dr. Susy Alias Samson, Dr. Kribha Mohan, Dr. D. Prabhavathy, Dr. Radha V. Naik, Dr. Mini Raja N.A., Dr. Rafeeq Moideen, Dr. P. Narasimha Rao, Dr. Muhammed, Dr. M. Kurthikeyar, Dr. K. Ganapathy Sundar, Dr. G. Ravichandran, Dr. U.R. Dhanalokshmi, Dr. Hanumathaiah, Dr. M.K. Shetty, Dr. A.C. Ramesh, Dr. Sharath Kumar, Dr. M.G . Gopal, Dr.Kalpana Sarangi, Dr. R.D.Kharkar, Dr. Rajendra Mehta, Dr. Raju Shah, Dr. Bhartiya Pravin, Dr. H.S. Chopade, Dr. Sunil Tolat, Dr. Bina Rabadia, Dr. Vivek Jain, Dr. R. Muthukumaran, Dr. Abdul Razak, Dr. Anita Shojan, Dr. C.M. Harid, Dr. George Chakola, Dr. Jeyakimari Jeevan, Dr. N. Bola, Dr. Anita Shojon, Dr. C.M.Harid, Dr. Jeraldin Join, Dr. Rohini Gupta, Dr. Rai Parikh, Dr. Jitendra Parikh, Dr. S. S. Rajendran, Dr. V. Harshan, Dr. P Kannan, Dr. K.S. Duraisingh, Dr. Judith Christopher, Dr. A. Seelvani Dr. T Subramaniam, Dr. J. Thadeus, Dr. Sandip Dey, D Gaitri Bharadwaj, Dr. Kasare T G., Dr. Rekha Solanki, D` Sikander M. Rathod, Dr. Harshit Ranpara, Dr. Neel Bhuptani, Dr. Satish K.M., Dr. C.J. Gururaja Das, Dr. K; Upadhya, Dr. C. Murugan, Dr. S.G.Parasramani, Dr. R.1 Gadgil, Dr. Mahesh Patil, Dr. Sara Prasad, Dr. PLK D′ Silvc Dr. Asif Qureshi, Dr. Ketan Shah, Dr.V. Eswaramoorthy, D S.Byravarathinam, Dr. C.K. Prasad, Dr. Moolly Kutty Francis Dr. C.Sargunan, Dr. Suneel Kumar, Dr. P Deeksha, Dr.P Gomanthy, Dr. Chandini Prabhakar, Dr. Veeranna, D Hemant Kumar, Dr. Ravindra N.C., Dr. Ram Kumar Gulall Dr. Asheesh Batra, Dr. Gyaneshwar Kalla, Dr. M.C. Singh Dr. S.K.Bose, Dr. Sanchita Karmehen, Dr. Y.B.Sharma Dr.K.K.Rajababu, Dr.M. Siva Ram Prasad, Dr. Sudhi Nikhare, Dr. Rajesh Kumar, Dr. H.J.Shridhar, Dr. Y.S Marfatia, Dr.N.R.Nagabhusana.

The authors wish to thank Mr. Kailash Gandewas for his assistance in statistical analysis of the data. This study was supported by Stiefel India Ltd.