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ORIGINAL ARTICLE
Year : 2021  |  Volume : 7  |  Issue : 1  |  Page : 20-23

Topical 0.1% adapalene gel versus 0.1% adapalene and 2.5% benzoyl peroxide combination gel in the treatment of mild-to-moderate acne vulgaris: An open-label randomized controlled pilot study


Department of Dermatology, Government Medical College, Kannur, Kerala, India

Date of Submission08-May-2020
Date of Decision23-Feb-2021
Date of Acceptance02-Jun-2021
Date of Web Publication25-Jun-2021

Correspondence Address:
Thyvalappil Anoop
Department of Dermatology, Government Medical College, Kannur - 670 503, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_29_20

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  Abstract 


Introduction: The combination of adapalene (ADA) benzoyl peroxide (BPO) offers a safe and effective alternative avoiding long-term antibiotic use in the management of acne vulgaris. Aims: The aim of this study was is to compare the clinical efficacy and tolerability of 0.1% ADA with combination of 0.1% ADA and 2.5% BPO in the treatment of mild-to-moderate acne vulgaris. Methods: All patients were instructed to apply the given topical medications to whole face, excluding lips and eyelids, once a day at night after washing and moistening the facial skin. Follow-up was done once every 4 weeks up to 12 weeks from the start of treatment. Efficacy of treatment arms was assessed by 4 parameters, namely percentage change of total lesion counts (TLCs), Acne severity index, success rate, and response rate. Statistical analysis was performed using the SPSS software version 16.0. Data were analyzed using the Chi-square test, Fisher's exact test, and Mann–Whitney U test. P < 0.05 was considered to indicate statistical significance. Results: Thirty-eight patients were in Group A (ADA-BPO) and 38 patients in Group B (ADA alone). At the end of 12 weeks, Group A had significantly less TLC as well as significant percentage change in total lesions than Group B. Group A was significantly better than Group B in TLC response rate also. Conclusions: The combination gel of 0.1% ADA and 2.5% BPO was superior to 0.1% ADA gel in terms of efficacy. Tolerability was comparable for both the drugs.

Keywords: Acne vulgaris, adapalene, benzoyl peroxide


How to cite this article:
Amrutha MP, Bifi J, Anoop T, Ajayakumar S, Radhakrishnan K, Rajiv S. Topical 0.1% adapalene gel versus 0.1% adapalene and 2.5% benzoyl peroxide combination gel in the treatment of mild-to-moderate acne vulgaris: An open-label randomized controlled pilot study. Indian J Drugs Dermatol 2021;7:20-3

How to cite this URL:
Amrutha MP, Bifi J, Anoop T, Ajayakumar S, Radhakrishnan K, Rajiv S. Topical 0.1% adapalene gel versus 0.1% adapalene and 2.5% benzoyl peroxide combination gel in the treatment of mild-to-moderate acne vulgaris: An open-label randomized controlled pilot study. Indian J Drugs Dermatol [serial online] 2021 [cited 2021 Dec 3];7:20-3. Available from: https://www.ijdd.in/text.asp?2021/7/1/20/319360




  Introduction Top


Acne vulgaris is a chronic skin disease affecting approximately 80% of young adults and adolescents.[1] Topical treatment is the sole treatment in many patients with acne vulgaris and are a part of therapeutic regimen in almost all patients.[2] Nowadays, the most popular topical agents are retinoids such as adapalene (ADA), benzoyl peroxide (BPO), azelaic acid, and topical antibiotics.[2],[3]

The novel combination of ADA - BPO formulation offers a safe and effective alternative avoiding long-term antibiotic use.[4] The primary effect of ADA is the prevention of comedogenesis with secondary effects consisting of comedolysis, keratolysis, reduction of inflammation, and limitation of host tissue damage. The primary effect of BPO is to reduce the number of Propionibacterium acnes within follicles.[5] We did this randomized open-label study to compare clinical efficacy and tolerability of 0.1% ADA and 2.5% BPO combination with 0.1% adaplene alone in mild-to-moderate acne vulgaris.


  Methods Top


This was a hospital-based randomized open-label clinical study conducted in the department of dermatology at a tertiary care center in North Kerala. Institutional ethical and research committee clearance was obtained. Consecutive patients with mild-to-moderate acne vulgaris between 15 and 35 years age, who had not taken treatment 1 month before enrolment in the study were recruited. Patients with severe acne requiring systemic treatment, pregnant and lactating women, and psychiatric patients were excluded. The treatment method was randomly allocated using lots. All odd numbers went to Group A (combination of 0.1% ADA with 2.5% BPO) and even numbers to Group B (0.1% ADA). All patients were instructed to apply the given topical medications to whole face, excluding lips and eyelids, at night after washing and moistening the facial skin. Same brand medications were given for all the patients. After randomization and recruitment, baseline clinical evaluation was done using a set proforma. Total lesion count (TLC) was assessed during each visit. Acne severity index (ASI = Papules + (2 × pustules) + (0.25 × comedones) was calculated using the formula (Burke and Cunliffe).[6] Digital photographs were taken under standard settings after taking written consent.

Efficacy of the two drugs was compared using change in ASI, percentage reduction of lesion from baseline, investigator global assessment (IGA), and calculation of response rate. IGA scoring was done to identify success rate [the percentage of patients rated “clear” (Score 0) or “almost clear” (Score 1) on the IGA scale]. Response rate was defined as the percentage of patients who achieved at least 50% reduction in lesion counts.

Tolerability was assessed by erythema, scaling (Desquamation), dryness, and burning (stinging) sensation. At each visit, investigator rated these factors on a scale ranging from 0 (none) to 3 (severe). Statistical analysis was performed using the Statistical analysis was performed using SPSS for windows, version 16.0. Chicago, SPSS Inc. Data were analyzed using Chi-square test, Fisher's exact test, and Mann–Whitney U test. P < 0.05 was considered to indicate statistical significance.


  Results Top


A total of 76 patients participated in the study. Thirty-eight patients were in Group A (ADA-BPO) and 38 patients in Group B (ADA alone). There were six dropouts in Group A and 5 dropouts in Group B who did not complete the study. Twenty-five males and 51 females were included in the present study (M 32.8%, F 67.1%). The study excluded patients outside the specified age group of 15–35 years. Majority were in 15–20 years in both groups (A 23 [60.5%], B 21 [55.2%]). The study included patients with IGA Score 2 and 3 (i.e., mild and moderate acne) and excluded those with severe acne. Proportion of mild and moderate acne was comparable between the groups (P = 0.08).

Median TLC was not significantly different at the beginning of the study (P = 0.831). Routine follow-up visit at 4 weeks and 8 weeks showed no difference in either treatment arms (P = 0.272, 0.18). However, at the end of 12 weeks, Group A (ADA-BPO) had significantly less TLC than Group B (ADA alone) (P = 0.024) [Figure 1].
Figure 1: Total lesion count

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Percentage changes in lesion counts from baseline were compared in all follow-up visits. This was calculated as ([present lesion count – baseline lesion count]/baseline lesion count) ×100. When there was a reduction in lesion count from baseline, the value obtained was negative. At the end of the study, after 12 weeks, superiority of Group A (ADA-BPO) than Group B (ADA alone) in achieving significant percentage change in total lesions was established (Group A – 61.5%, Group B – 54.29% and P = 0.02).

Median ASI at onset was not significantly different between Group A and Group B (Group A 20.5, Group B 19.75 and P = 0.32). However, after the completion of the study, statistical analysis showed significantly low ASI in Group A (ADA-BPO) (Group A – 6.38, Group B – 9.0 and P = 0.007) [Figure 2]. Analysis after 12 weeks also showed Group A (ADA-BPO) to be better in achieving significant change in ASI than Group B (ADA alone) (Group A – 66.67%, Group B – 56.25% and P = 0.014) [Figure 3].
Figure 2: Acne severity index

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Figure 3: Percentage change in acne severity index

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Percentage of patients who achieved at least 50% reduction in lesion counts after 12 weeks in both treatment groups was compared. After the completion of the study, 93.8% in Group A (ADA-BPO) had shown response with more than 50% reduction in TLC. On the other hand, only 66.7% patients in Group B (ADA alone) achieved similar reduction in TLC. Group A was significantly better than Group B in TLC response rate (P = 0.006).

Percentage of patients who were declared treatment success after 12 weeks (i.e. clear (0) or almost clear (1) in IGA), in both the treatment groups were compared. After 12 weeks treatment, 56.2% patients were declared successful in Group A as compared to 21.2% in Group B. Success rate was significantly better in Group A (ADA-BPO) than in Group B at the end of the study (P = 0.007).

Treatment-related side effects were analyzed as erythema, scaling, dryness, and burning. After the completion of the study, both groups were comparable with respect to the incidence of erythema (P = 0.197). The incidence of scaling also showed similar trend during and after the treatment period (P = 0.7177 and 0.587 respectively).

However, dryness as a side effect was significantly more in ADA-BPO treatment arm after 4 weeks when compared to ADA alone (P = 0.016). At the end of the study, no significant difference could be established with respect to the incidence of dryness between the drugs studied (P = 0.369). Burning was an infrequent side effect in both groups. After 12 weeks, there was no statistical significant difference in the incidence of burning between the two modalities of treatment studied (P = 0.488 and 0.649, respectively).

Eleven patients did not complete the study. There were total six dropouts in Group A and five dropouts in Group B. During data analysis, the data available from the number of patients who had completed the study at each stage were analyzed. In Group A, three people did not come for first follow-up at the 4th week and another three people discontinued by skipping the second follow-up visit at the 8th week. In Group B, two people did not come for the first review at the 4th week and another three people skipped second review at the 8th week. The reason for dropout at 4 weeks was not related to treatment-related adverse events or worsening of lesions. All the three patients who discontinued at the 8th week in Group A had moderate (Grade 2) erythema, scaling, and dryness at the 4th week. All the three patients in Group B, who discontinued at the 8th week had moderate (Grade 2) scaling at the 4th week. Photographs of the patients in both the groups, before and after 12 weeks of treatment, are shown in [Figure 4] and [Figure 5].
Figure 4: Before and after 12 weeks of treatment with 0.1% adapalene gel

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Figure 5: Before and after 12 weeks of treatment with combination of 0.1% adapalene and 2.5% benzoyl peroxide gel

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  Discussion Top


The study included patients with IGA Score 2 and 3 (i.e., mild and moderate acne). We excluded patients outside the specified age group of 15–35 years. Majority were in 15–20 years in both groups. Efficacy of treatment arms was assessed by four parameters, namely percentage change of lesion counts, change in ASI, success rate, and response rate.

In our study, reduction in TLC at 12 weeks with ADA-BPO treatment (Group A) was 61.55% in contrast to 54.29% reduction in with ADA alone treatment (Group B) (P = 0.023). In the North American study by Gold et al., there was a statistically significant reduction in TLC with ADA-BPO combination compared to ADA alone after 12 weeks treatment (P < 0.05).[7] Multicenter randomized controlled trials (RCT) by Thiboutot et al. showed 51.0% reduction in TLC with ADA-BPO treatment and 35.4% reduction in TLC with ADA alone treatment (P < 0.001).[8] Transatlantic RCT by Gollnick et al. showed 65.4% reduction in TLC with ADA-BPO and 52.3% reduction with ADA alone (P < 0.001).[9] The pooled analysis of above three studies by Tan et al. showed 59% reduction in TLC with ADA-BPO combination and 47% reduction in TLC with ADA alone after 12 weeks (P < 0.05).[10] All these four studies and our study also showed statistically significant reduction in TLC percentage after 12 weeks of treatment with ADA-BPO in comparison to ADA alone.

Our study showed statistically significant reduction in ASI and significant percentage reduction in ASI in AD-BPO (Group A) compared to ADA alone (Group B). Our study showed that after 12 weeks treatment 56.2% were declared successful in Group A as compared to 21.2% in Group B (P = 0.007). Thiboutot et al. showed that success rate of ADA-BPO combination (27.5%) was superior to ADA alone (15.5%) at 12 weeks (P = 0.008).[8] Gollnick et al. also showed that ADA-BPO combination (37.9%) achieved superior success rate than ADA alone (21.8%) (P < 0.001).[9] The pooled analysis of above studies by Tan et al. again showed that ADA-BPO combination gave superior success rate (33.1%) than ADA alone (20%) after 12 weeks (P < 0.05).[10]

After the completion of the study, 93.8% in Group A (ADA-BPO) had shown response with more than 50% reduction in TLC. On the other hand, only 66.7% patients in Group B (ADA alone) achieved similar reduction in TLC. Group A was significantly better than Group B in TLC response rate (P = 0.006). Thiboutot et al. showed that TLC response rate of ADA-BPO combination (52.3%) was superior to ADA alone (34.5%) at 12 weeks with statistical significance (P = 0.001).[8]

Thiboutot et al. showed that the safety and tolerability results of ADA - BPO were comparable with those of ADA. Local cutaneous tolerability was good for all treatments, with all mean tolerability scores at each visit and worst postbaseline scores for erythema, dryness, scaling, and burning/stinging <1 (mild). A majority of subjects in all of the groups experienced mild or no irritation. The most frequently reported related adverse event was dry skin: 9.4% for ADA - BPO, 10.1% for ADA.[8]

In the study by Gold et al., the side effects were reported as transient, occurred mainly within the first 2 weeks of treatment, and were mostly of mild-to-moderate severity. The mean worst scores for all tolerability signs and symptoms were all below Grade 1 (mild). The overall safety of ADA - BPO combination gel was comparable with ADA monotherapy and BPO monotherapy. Most treatment-related adverse events were cutaneous, mild to moderate in severity, and resolved without residual effects. Dry skin was reported as the most common adverse event in the ADA - BPO combination gel group.[7]

Gollnick et al. showed that local cutaneous tolerability was good for both treatments, with all mean tolerability scores at each visit and worst postbaseline scores for erythema, dryness, scaling, and burning consistent with mild scores (score of <1).[9] Peak scores at week 1 were generally higher for ADA – BPO, but tolerability profiles were then comparable at subsequent visits. A majority of subjects in all of the groups experienced mild or no irritation. The overall incidence of subjects experiencing at least one adverse event was 48% for ADA – BPO and 39% for ADA. The difference in related adverse events among the groups was mainly driven by an increase in dry skin: 21.2% for ADA – BPO, 14.1% for ADA[9]

Our study also showed similar results. The mean tolerability scores at each visit and worst scores for erythema, dryness, scaling, and burning were consistent with mild scores (score of <1). However, erythema was the most common side effect. Dryness was significantly more common in ADA-BPO combination group at 4 weeks. However, in subsequent follow ups, dryness was not different between the groups. Small sample size and short follow-up period are the limitation of our study.


  Conclusions Top


In the present 12 weeks' study, comparing two treatment modalities for mild-to-moderate acne in 15–35 years age group, combination gel of 0.1% ADA and 2.5% BPO was superior to 0.1% ADA gel. Combination gel of 0.1% ADA and 2.5% BPO achieved statistically significant superior results than 0.1% ADA gel monotherapy in treating lesions of mild-to-moderate acne vulgaris after. Combination gel of 0.1% ADA and 2.5% BPO achieved statistically significant superior results than 0.1% ADA gel monotherapy in treating lesions of mild-to-moderate acne vulgaris after 12 weeks. Large scale studies with larger sample size may be required to validate the above results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Thiboutot D, Pariser DM, Egan N, Flores J, Herndon JH Jr., Kanof NB, et al. Adapalene gel 0.3% for treatment of acne vulgaris: A multicentre, randomized, double blind, controlled, phases III trial. Adapalene gel 0.3% was effective and well tolerated in the treatment of acne. J Am Acad Dermatol 2006;54:242-50.  Back to cited text no. 1
    
2.
Piskin S, Uzunali E. A review of the use of adapalene for the treatment of acne vulgaris. Ther Clin Risk Manag 2007;3:621-4.  Back to cited text no. 2
    
3.
Iraji F, Sadeghinia A, Shahmoradi Z, Sidat AH, Jooya A. Efficacy of topical azelaic acid gel 20% in the treatment of mild moderate acne vulgaris. Indian J Dermatol Venereol Leprol 2007;73:94-6.  Back to cited text no. 3
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4.
Kubba R, Baja AK, Thappa DM, Sharma R, Vedamurthy M, Dhar S, et al. Antibiotic resistance in acne. Indian J Dermatol Venereol Leprol 2009;75 Suppl S1:37-8.  Back to cited text no. 4
    
5.
Layton AM, Eady EA. Benzoyl peroxide and adapalene fixed combination: A novel agent for acne. Br J Dermatol 2009;161:971-6.  Back to cited text no. 5
    
6.
Layton AM. Disorders of sebaceous glands. In: Burns T, Breathnach S, Cox N, Griffith C, editors. Rook's Textbook of Dermatology. 8th ed. Oxford: Blackwell Publishing; 2010. p. 42.1-42.88.  Back to cited text no. 6
    
7.
Gold LS, Tan J, Cruz-Santana A, Papp K, Poulin Y, Schlessinger J, et al. A North American study of adapalene-benzoyl peroxide combination gel in the treatment of acne. Cutis 2009;84:110-6.  Back to cited text no. 7
    
8.
Thiboutot DM, Weiss J, Bucko A, Eichenfield L, Jones T, Clark S, et al. Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: Results of a multicenter, randomized double-blind, controlled study. J Am Acad Dermatol 2007;57:791-9.  Back to cited text no. 8
    
9.
Gollnick HP, Draelos Z, Glenn MJ, Rosoph LA, Kaszuba A, Cornelison R, et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: A transatlantic, randomized, double-blind, controlled study in 1670 patients. Br J Dermatol 2009;161:1180-9.  Back to cited text no. 9
    
10.
Tan J, Gollnick HP, Loesche C, Ma YM, Gold LS. Synergistic efficacy of adapalene 0.1%-benzoyl peroxide 2.5% in the treatment of 3855 acne vulgaris patients. J Dermatolog Treat 2011;22:197-205.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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