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ORIGINAL ARTICLE
Year : 2007  |  Volume : 52  |  Issue : 4  |  Page : 179-183
Comparative evaluation of effectiveness of adapalene and azithromycin, alone or in combination, in acne vulgaris


Department of Dermatology, Calcutta National Medical College, Kolkata, India

Correspondence Address:
Sabyasachi Banerjee
3/1, Haridas Ghosh Road, P.O. Naihati, Dist. 24 Parganas (N), Kolkata - 743 165
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.37721

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   Abstract 

Introduction: Acne vulgaris, a disorder of the pilosebaceous structure, is a common disorder in adolescents and young adults that is associated with significant morbidity. Aim: The aim of this study was to compare the effects of the drugs adapalene and azithromycin, given separately and in combination in acne vulgaris. Methodology: A total of 61 newly attending cases of inflammatory acne vulgaris were considered the study. They were randomly allocated into three groups. Group 1 received topical adapalene (0.01%) gel, group 2 received oral azithromycin, whereas group 3 was given a combination of these two. The patients were treated for a period of 12 weeks, being reviewed every fortnightly. The results obtained were analyzed in detail using statistical methods. Results: The combination of adapalene and azithromycin caused the highest reduction in the inflamed lesion count followed by azithromycin given singly. Further, monotherapy with adapalene was used. However, this difference in efficacy was small and not statistically significant ( P = 0.717). Azithromycin lead to a rapid reduction in the inflammatory lesion count, but it had negligible action on noninflamed lesions. Conclusion: At the end of 12 weeks of treatment, the three treatment groups showed no statistically significant difference in the efficacy in inflammatory acne.


Keywords: Acne, adapalene, azithromycin, inflammatory


How to cite this article:
Ghoshal L, Banerjee S, Ghosh SK, Gangopadhyay DN, Jana S. Comparative evaluation of effectiveness of adapalene and azithromycin, alone or in combination, in acne vulgaris. Indian J Dermatol 2007;52:179-83

How to cite this URL:
Ghoshal L, Banerjee S, Ghosh SK, Gangopadhyay DN, Jana S. Comparative evaluation of effectiveness of adapalene and azithromycin, alone or in combination, in acne vulgaris. Indian J Dermatol [serial online] 2007 [cited 2019 Oct 22];52:179-83. Available from: http://www.e-ijd.org/text.asp?2007/52/4/179/37721



   Introduction Top


Acne vulgaris is a common dermatological disorder affecting approximately 85% of individuals between 12 and 24 years of age. Although acne is most prevalent in this age group, the disease is reported in 8% of adults aged 25 to 34 years and in 3% aged 35 to 44 years. [1]

Since acne vulgaris occurs mostly on face, the impairment of self-image and self-esteem, clinical depression, social phobia and anxiety factors have been associated with it.

Acne is multifactorial in origin. The major factors concerned are: (i) aberrant follicular keratinization, (ii) androgens, (iii) excess sebum and (iv) Propionibacterium acnes . [2]

The lesions of acne vulgaris may be inflamed (inflamed papules, nodules, pustules, cysts and abscess) or noninflamed (primary lesions: open and closed comedones). However, most of the patients posses both types of lesions at the same time.

Infection with P. acnes plays a major role in the development of inflammatory lesions. Therefore, antibiotics are useful in treatment of inflammatory acne. Topical retinoids are also known to be beneficial in these cases due to their anti-inflammatory action in addition to their comedolytic properties.

In this study, the aim is to compare the efficacy of the newly introduced macrolide: azithromycin given orally as the sole treatment versus a new retinoid adapalene used topically as the sole treatment, versus both given together.

The new international consensus guidelines state that, "topical retinoids, alone or in combination are regarded today as the first line treatment for both comedogenic and mild inflammatory acne vulgaris." [3]

We selected new retinoid adapalene for its highly favorable tolerability profile. Among the available systemic therapies, azithromycin being a broad spectrum antibiotic [4] and since the newer one is less likely to be resistant and has a high affinity for inflammatory tissue, long terminal half-life and good safety profile, its use in treating inflammatory acne vulgaris deserves evaluation.


   Materials and Methods Top


Seventy-five new patients with inflammatory acne vulgaris attending the Dermatology OPD at Calcutta National Medical College, Kolkata were incorporated in this study. Informed consent was obtained from all the patients before being enrolled into the study. For those below the age of 18 years, the consent of the guardian was taken.

Exclusion criteria were (i) patients with purely comedonal acne, (ii) history of hypersensitivity to any ingredients of adapalene (0.1%) gel, (iii) patients below the age of 12 years, (iii) patients with known systemic illness, (iv) pregnant women and lactating mothers, and (v) patients who had underwent any treatment for their acne during last 3 months or those with history of any systemic or topical treatments that may affect acne. These patients were randomly categorized into three treatment groups. Group 1 received only topical adapalene (0.1%) gel once daily at bedtime and 1 FTU for the entire face. Group 2 received only oral azithromycin (500 mg) for three consecutive days in a week. Group 3 received both oral azithromycin and topical adapalene (0.1%) gel.

Patients of all the groups received general face cleansing advice, which included the washing of face with soap for three to four times a day.

At the first visit, detailed history and clinical examination (general and dermatological) were undertaken. For the purpose of counting the lesions, the face was divided into four quadrants: upper, lower, right and left. The patients were reviewed fortnightly. At each review, the lesion count was repeated, and we enquired if there were any adverse effects of therapy. Noninflamed (comedones) and inflamed lesions (papules, pustules, cysts or abscesses) were counted separately.

The therapy was continued for 12 weeks. After completion of the treatment period, the patients were followed-up every 2 weeks for another 4 weeks and were examined as mentioned before.

The data obtained were analyzed in detail using the statistical software SPSS 13.0 for Windows. One-way analysis of variance (ANOVA) was used for analyzing the data, considering visit as replication and effects of the three groups of therapy as the sources of variation.

In addition to that the determination of differences that exist among the means, we wanted to know the means that differed. For that purpose, in other words, in order to compare the efficacy of different treatments groups, we used the Duncan's multiple range test at 5% significance level ( P = 0.05).


   Results Top


The 75 patients, who provided consent to participate, were divided into three groups of 25 members each. In the course of study, a total of 14 patients were lost to follow-up, leaving behind 20, 20 and 21 patients who finally completed the treatment protocol ( P = 0.9).

[Table - 1] shows the break up of the study cases in terms of age, sex and duration of illness.

Among the patients included in the study, 44.26% was male. Majority (52.45%) of the patients belonged to the age group of 16-20 years. Among them, 49.18% had their illness for more than one year at the time of presentation.

The summary of result of counting the facial lesions is as follows [Table - 2].

When ANOVA was performed on the pretreatment data (at the first attendance of the patient), there was no differences ( P = 0.763) in between the groups in terms of the mean number of lesions. We may thus infer that our randomization procedure was appropriately done.

On analyzing the data at the second visit by using the same technique to see if the therapies differed in their effect, it was found that group 1 (adapalene) had the greatest mean value; group 2 (azithromycin) had the least mean value, whereas the group 3 (combination) had an intermediate value.

These findings suggest that monotherapy with azithromycin was more effective on the inflammatory lesions than other regimes as early as the second visit. However, in this study, this early activity was not significantly different from others ( P = 0.103).

The analysis of the outcomes at the sixth visit (end of the treatment period) revealed that the reduction in inflammatory lesion count was the maximum in the group with combination therapy, followed by the group that administered azithromycin only, while the group that was given adapalene only showed the minimum reduction. However, the means of all the treatment groups fell in the same subset (when Duncan's multiple range test was applied) and again the difference in lesion reduction between the groups failed to be significant ( P = 0.717).

We may thus infer that at the end of treatment period (12 weeks) that all the groups underwent similar improvement with respect to inflammatory lesions.

The effect of three treatment modalities on noninflamed lesions (comedones) at the end of the treatment period was also analyzed by the same techniques.

From the DMRT of "comedones," it was found that the effects of adapalene monotherapy and combination therapy fell in the same subset, implying that both the regimes are relatively similar in effect, whereas drug azithromycin (which formed a different subset) was different from others. The order of effectiveness was: adapalene > combination >> azithromycin. This relationship was highly significant ( P < 0.001). Pre and post treatment changes in acne have been highlighted in [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4],[Figure - 5],[Figure - 6].

From these results, it is safe to conclude that the drug azithromycin had very little comedolytic effect, while other two regimes had good and almost similar effect on noninflamed lesions.

All the treatment regimens were generally well tolerated with a similar, low incidence of adverse events.


   Discussion Top


In this study, a peak in the incidence of acne vulgaris was found to be in the age group of 16-20 years. This finding corroborates with the findings of a pioneer epidemiological study on acne, in which a peak was found in the incidence between 14 and 17 years in the case of females and 16-19 years in case of males. [5]

There was no statistical difference amongst the three treatment groups with regard to the reduction in the inflammatory lesion count at the end of the treatment period ( P = 0.717). In other words, this implies that all the therapies reduced the inflammatory lesions to a similar extent, as measured at the end of the treatment period. This can be attributed to the anti-inflammatory properties of adapalene and some other retinoids, particulary when applied for a long duration. This observation was corroborated by several previous studies that found significant anti-inflammatory action in the topical usage of adapalene. [6],[7],[8],[9]

However, the overall quantitative reduction in inflammatory lesion was the greatest in the group treated with combination therapy, as observed in the results of Duncan's multiple range test performed on the results at the end of the treatment period. Although not statistically significant ( P = 0.717), it shows a trend and effectively correlates with the findings of a previously conducted study. [10]

Although the treatment group 3 (combination of topical adapalene and oral azithromycin) showed more improvement in terms of inflammatory lesion count than the other two groups, small number of cases in the present study might have prevented this trend from assuming statistical significance.

An improvement in the inflammatory lesions was observed more rapidly (as early as the second visit, i.e., after 4 weeks of therapy) in the groups of patients treated with azithromycin, alone or in combination. The faster reduction in acne lesions when azithromycin was added to the therapeutic regime, suggests that the usage of this drug from the beginning of treatment could lead to a faster clinical response than that achieved by topical therapy alone. Thus, the addition of azithromycin to the anti-acne regimen may be considered by the dermatologist, particularly when faster reduction is being requested for. However, this observation is statistically was not significant ( P = 0.103), again may be due to a small number of subjects in the study.

Furthermore, the use of adapalene in combination with azithromycin (and other antibiotics as well), may offer the potential to reduce the duration of antibiotic treatment and to possibly reduce the potential for antibiotic resistance, which is an ever increasing clinical problem. [11],[12]

Topical adapalene has a very good comedolytic effect, while oral azithromycin has a negligible one. Therefore, in case of purely comedonal acne, monotherapy with adapalene should be sufficient.


   Acknowledgement Top


We are grateful to Dr. Soumen Sahoo, B.Sc, M.Stat, Ph.D, Reader, Department of Fishery Economics and Statistics, West Bengal Board of Animal Husbandry and Fishery Sciences, for his kind guidance during the statistical analysis of the data.

 
   References Top

1.Bergfield WF. Topical retinoids in the management of acne vulgaris. J Drug Dev Clin Pract 1996;8:151-60.  Back to cited text no. 1    
2.Abell E. Inflammatory diseases of the epidermal appendages and of cartilage. In : Elder D, Elenitsas R, Jaworsky C, Johnson B Jr, editors. Lever's Histopathology of the Skin. 8 th ed. Lippincott Raven: Philadelphia; 1997. p. 403-4.  Back to cited text no. 2    
3.Thielitz A, Helmdach M, R φpke EM, Gollnick H. Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of anti acne agents. Br J Dermatol 2001;145:19-27.  Back to cited text no. 3    
4.Neu HC. Clinical microbiology of azithromycin. Am J Med 1991;91:12S-8S.  Back to cited text no. 4    
5.Stern RS. The prevalence of acne on the basis of acne on the basis of physical examination. J Am Acad Dermatol 1992;26:931-5.  Back to cited text no. 5    
6.Michel S, Jomard A, Demarchez M. Pharmacology of adapalene. Br J Dermatol 1998;139:3-7.  Back to cited text no. 6    
7.Cunliffe WJ, Danby FW, Dunlap F, Gold MH, Gratton D, Greenspan A. Randomized, controlled trial of the efficacy and safety of adapalene gel 0.1% and tretinoin cream 0.05% in patients with acne vulgaris. Eur J Dermatol 2002;12:350-4.  Back to cited text no. 7    
8.Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: A meta-analysis of five randomized trials. Br J Dermatol 1998;139:48-56.  Back to cited text no. 8    
9.Ellis CN, Millikan LE, Smith EB, Chalker DM, Swinyer LJ, Katz IH, et al . Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris. Br J Dermatol 1998;139:41-7.  Back to cited text no. 9    
10.Cunliffe WJ, Meynadier J, Alirezai M, George SA, Coutts I, Roseeuw DI, et al . Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle. J Am Acad Dermatol 2003;49:S218-26.  Back to cited text no. 10    
11.Eady EA. Bacterial resistance in acne. Dermatology 1998;196:59-66.  Back to cited text no. 11    
12.Espersen F. Resistance to antibiotics used in dermatological practice. Br J Dermatol 1998;139:4-8.  Back to cited text no. 12    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
 
 
    Tables

  [Table - 1], [Table - 2]

This article has been cited by
1 Problems in the reporting of acne clinical trials: A spot check from the 2009 Annual Evidence Update on Acne Vulgaris
Ingram, J.R., Grindlay, D.J.C., Williams, H.C.
Trials. 2010; 11(art 77)
[Pubmed]



 

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