Efficacy and safety of 5% imiquimod cream compared to 10%

(1)

Journal of General - Procedural Dermatology & Venereology Journal of General - Procedural Dermatology & Venereology Indonesia

Indonesia

Volume 3

Number 2 June Edition Article 4

6-30-2019

Efficacy and safety of 5% imiquimod cream compared to 10%

KOH solution for elimination of molluscum contagiosum lesions KOH solution for elimination of molluscum contagiosum lesions in adults

in adults

Marsha Bianti

Department of Dermatology and Venereology Universitas Indonesia, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Agung Muhammad Rheza

Arinda Marina

Rizka Farah Hilma

Sarah Mahri

See next page for additional authors

Follow this and additional works at: https://scholarhub.ui.ac.id/jdvi

Part of the Dermatology Commons, Integumentary System Commons, and the Skin and Connective Tissue Diseases Commons

Recommended Citation Recommended Citation

Bianti, Marsha; Rheza, Agung Muhammad; Marina, Arinda; Hilma, Rizka Farah; Mahri, Sarah; Nuary, Teffy;

and Rihatmadja, Rahadi (2019) "Efficacy and safety of 5% imiquimod cream compared to 10% KOH solution for elimination of molluscum contagiosum lesions in adults," Journal of General - Procedural Dermatology & Venereology Indonesia: Vol. 3: No. 2, Article 4.

DOI: 10.19100/jdvi.v3i2.107

Available at: https://scholarhub.ui.ac.id/jdvi/vol3/iss2/4

This Article is brought to you for free and open access by UI Scholars Hub. It has been accepted for inclusion in Journal of General - Procedural Dermatology & Venereology Indonesia by an authorized editor of UI Scholars Hub.

(2)

Efficacy and safety of 5% imiquimod cream compared to 10% KOH solution for Efficacy and safety of 5% imiquimod cream compared to 10% KOH solution for elimination of molluscum contagiosum lesions in adults

elimination of molluscum contagiosum lesions in adults

Authors Authors

Marsha Bianti, Agung Muhammad Rheza, Arinda Marina, Rizka Farah Hilma, Sarah Mahri, Teffy Nuary, and Rahadi Rihatmadja

This article is available in Journal of General - Procedural Dermatology & Venereology Indonesia:

https://scholarhub.ui.ac.id/jdvi/vol3/iss2/4

(3)

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 19 Evidence - Based Case Report

Efficacy and safety of 5% imiquimod cream compared to 10% KOH solution for adult molluscum contagiosum

Marsha Bianti, Agung Muhammad Rheza, Aninda Marina, Rizka Farah Hilma Sarah Mahri, Teffy Nuary, Rahadi Rihatmadja

Email: [email protected]

Abstract

Background: Molluscum contagiosum (MC) is a benign infection caused by the Molluscipox virus that most often affects children and sexually active adolescents. Various topical therapeutic options are available, however, no single intervention is convincingly effective. Potassium hydroxide (KOH) solution is widely used but its usefulness is hampered with adverse effects. Newer preparation, 5% imiquimod cream seems to be as, if not more, effective. However, it is not legally available yet in Indonesia.

Aim: To assess the efficacy and safety of 5% imiquimod cream in treating adult molluscum contagiosum.

Methods: Literature search was done through Pubmed, EBSCO, dan Cochrane databases. Inclusion criteria included articles in English, available in free full text and matched with the clinical question as well as providing the clinical outcome of papules clearance within 12 weeks.

Results: There were three articles found to be related to the clinical question and they were critically appraised for their validity, importance, and applicability.

Conclusion: Only two studies were valid and further assessed for their importance and applicability. In regards to importance, imiquimod has fewer side effects than KOH, yet it was not constantly shown to be superior to KOH in curing MC lesions. We conclude that KOH solution is the preferred treatment of MC in adults.

Keywords: imiquimod, KOH, molluscum contagiosum, safety, efficacy

Background

Molluscum contagiosum (MC) is a benign viral infection that often affects children, sexually active adolescents, and the immunocompromised of all ages.¹ It is a self-limiting epidermal papular condition caused by the Molluscipox virus.

Although it is self-limiting and may resolve spontaneously, it is somewhat troublesome to patients. First, the lesions are cosmetically unattractive. Secondly, even though most of MC cases are asymptomatic, pruritus is sometimes significant, particularly in those with underlying atopic dermatitis. Lastly, it may persist for months to years and recurrencences are common.

MC is characterized by smooth, dome-shaped, discrete, opalescent papules with a central core;

some develops surrounded areas of scales and

erythema (molluscum dermatitis).² It is a sexually transmitted diseases in adults. The prevalence of MC has risen significantly in the past decades.

This appears to be parallel to the overall increase of other sexually transmitted diseases and HIV infection.² Assessment for risk and benefits for MC therapy is important. In immunocompetent individual, lesion will generally resolve without complication.

Many modalities have been used but sound scientific evidences supporting them is lacking.³ Topical therapeutic modalities include topical cantharidin, retinoid creams, imiquimod cream, salicylic acid, trichloroacetic acid, KOH solution, cidofovir, silver nitrate paste and tape stripping.

Imiquimod and KOH were considered common for

(4)

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 19 treating MC. A Cochrane Database analysis in

2009 regarding treatments for MC found no single intervention was convincingly effective.³ Newer Cochrane review that had been published after we corroborated the question concluded similarly.⁴

Case Illustration

A 26-year-old male came to our clinic with a complaint of whitish papules with central umbilication around genital area for 2 months duration. He also complained of mild itch. There was history of promiscuity, but his HIV screening test was non-reactive. Dermoscopic examination revealed white-yellowish area consistent with MC He asked for effective and safe medication and refused manual extraction procedure. He preferred not to be treated with KOH because his partner had received such treatment and experienced side effects. The doctor thinks that 5% imiquimod cream is a good alternative, but unsure if it is as effective with fewer side effects than the widely available preparation.

Clinical Question

Is 5% imiquimod cream more effective and safer than 10% KOH solution in clearing molluscum contagiosum papules in adults?

P : adults with molluscum contagiosum I : 5% imiquimod cream

C : 10% KOH solution

O : complete clearance of papules Clinical question type: therapy

Methods

Literature search through Pubmed, EBSCO, dan Cochrane was done on April 6th 2017 using keywords ‘molluscum contagiosum’ AND

‘imiquimod’ AND ‘KOH’ OR ‘potassium hydroxide’

AND ‘treatm ent’. Inclusion criteria were articles in English, available in free full text and matched with our clinical question. The desired outcome was complete clearing of papules in 12 weeks clinically. (Appendix 1)

Results

Selection

Seven articles were obtained from literature searching. First selection was based on title/abstract, with elimination of same articles.

The remaining was re-assessed based on inclusion criteria. Three articles were suitable for our EBCR clinical question and were critically appraised using CEBM critical appraisal worksheet. (www.cebm.net/critical-appraisal/).

Critical Appraisal

Three relevant studies by Seo et al., Chatra et al., and Metkar et al. were critically appraised for their validity, importance, and applicability.

Comparisons of the studies were summarized below (Table 1, Table 2 and Table 3).

It is important to note that all the studies lack of validity. Randomization was not concealed and clinicians were not blind to treatment. Two studies found that the use of imiquimod will increase the risk of failure (ARI 20% and 30%, respectively).

Are the valid results of this randomised trial important?

Table 1. Clearing of Lesions

RRR ARR NNT

CER EER CER-EER

CER

CER-EER 1/ARR

Seo et al.

3/13= 0,23 6/14= 0,43 0,23-0,43 0,23

= -0,87

0,23-0,43=

0,2 (20%)  ARI 1/0,2 = 5 Chatra

et al.

3/20 = 0,15 10/20 = 0,5 0,15-0,5 0,15

= -2,3

0,15-0,5= 0,35 (35%)

 ARI 1/0,35 = 2,85 ~ 3 CER: Control Event Rate, EER: Experimental Event Rate, RRR: Relative Risk Reduction, ARR: Absolute Risk Reduction, ARI: Absolute Risk Increase, NNT: Number Needed to Treat

(5)

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 20 Table 2. Side Effect

CER EER RRR ARR NNT

CER-EER/ CER CER-EER 1/ARR Seo et al. 6/14 = 0.43 6/13= 0.46 0.43-0.46

0.43

= -0.69

0.43-0.46 = 0.03 (3%)  ARI

1/0.03 = 33.33 ~ 33 Chatra et

al.

10/20 = 0.5 4/20 = 0.2 0.5-0.2 0.5

= 0.6 (60%)

0.5-0.2= 0.3 (30%)  ARR

1/0.3 = 3.33 ~ 3

CER: Control Event Rate, EER: Experimental Event Rate, RRR: Relative Risk Reduction, ARR: Absolute Risk Reduction, ARI: Absolute Risk Increase, NNT: Number Needed to Treat

Can you apply this valid, important evidence about therapy in caring for your patient?

Table 3. Critical Appraisal

Seo et al. Chatra et al.

Do these results apply to your patient?

Is your patient so different from those in the study that its results cannot apply?

No Quite, in the scenario the

patient was adult Is the treatment feasible in your

setting?

No, due to availability No What are your patient’s potential benefits and harms from the therapy?

Benefits: none Harms:

- based on absolute risk calculation, there was no superiority of using imiquimod (ARI 20%).

- Imiquimod proved to have slightly more side effects (ARI 3%)

Benefits:

- Imiquimod prove to be safer than KOH (ARR 30%).

Harms:

- In terms of clearing of lesion, imiquimod was not convincingly superior to KOH. (ARI 35%).

Are your patient’s values and preferences satisfied by the regimen and its consequences?

Do your patient and you have a clear assessment of their values and preferences?

Yes Yes

Are they met by this regimen and its consequences?

No No

Study by Chatra et al. pointed that imiquimod was somewhat safer (NNT 3). However, Seo et al.

found that imiquimod might cause more side effects.⁵

Result

Three articles were obtained from literature searching, two of them were randomized controlled trial (Seo et al. and Chatra et al.), whereas one was nonrandomized comparative study (Metkar et al.)therefore, it was not valid and no longer assessed for importance and applicability.^5-7

In Seo study, 30 subjects were divided into two study groups.⁵ Out of 30 patients, 3 patients were noncompliant and did not follow up, thus only 27 were analyzed based on per protocol analysis.

(6)

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 21 Results showed there was no significant

difference between MC treatment using 5%

imiquimod cream and 10% KOH solution at 12 weeks of observation. Complete clearance of lesions was found only in 57% patients treated with imiquimod, while in patients treated with KOH had 77% rate of clearance. The reduction in number of lesions at the end of week 12 was statistically significant in each group (p < 0.05).

However, comparison of the number of the lesions between two groups was not statistically different (p = 0.413). The incidence rate of side effects in imiquimod group was slightly higher than KOH group (46% vs 42%). The side effects were observed on the sites of application and they included erythema, ulceration, scaling, and hyperpigmentation. However, it was transient and tolerable.

Chatra study recruited 40 pediatric patients.⁶ This study showed statistically significant results where KOH was more effective than imiquimod in treating MC at the end of 12 weeks (p = 0.019).

Imiquimod group showed complete clearance in 50% patients, while KOH group demonstrated similar outcome in 85% patients. Out of 20 patients who received KOH solution, 10 (50%) showed adverse effects, whereas of the 20 patients who received imiquimod, it was only in 4 subjects (20%). The result was significant statistically with p =0.18. The side effects observed after treatment with KOH were pigmentary disturbance and burning sensation.

Discussion

Publication of studies involving imiquimod and KOH were apparently lacking, therefore any conclusion of superior efficacy of one group over another can not be over emphasized. Two out of three studies selected for this paper were randomized controlled trial studies but neither were blinded. Blinding could not be done because of difference in the mode of application; imiquimod was applied directly on the lesion, while KOH was applied with cotton swab or toothpick. This could lead to bias in the results. Study by Metkar, was not randomized, therefore its validity was not appraised.⁷

All studies have comparable sample size, ranging from 20 to 40 subjects. This number was too small for a clinical trial and might not represent the target population. In most studies, the setting was not clearly defined. Only study by Metkar stated

dermatology department in tertiary care center as the clinical setting.⁷ The age of the subjects ranged from 1-36 years (Seo et al.)⁵, 1-18 years (Chatra et al.)⁶, and 1-40 years (Metkar et al.)⁷. Only the second study singled out subjects in the pediatric population, while in the first and third the age was more diverse. These differences were not considered serious problem because MC is one of the most common cutaneous viral infection that can be found both in children or adult.

From all studies, both imiquimod and KOH have good efficacy in clearing the lesions. Marked superiority was found only in one study (Chatra et al.), while the other showed only marginal results, even the p values were not significant (p > 0.05).

In terms of safety, most studies showed KOH to have more adverse effect than imiquimod. One study showed imiquimod has more adverse effects slightly than KOH (46% vs 42%). Yet, adverse effects of KOH were transient and tolerable. Therefore, no specific recommendation is available for adult with MC, but due to price and availability, KOH seems to be more superior. In pediatric patients, these adverse effects of KOH were less tolerable because of the child pain threshold is relatively low. Thus, the use of imiquimod is more recommended for children with MC, despite the fact that imiquimod is more expensive and not well distributed.

Conclusion

Based on critical appraisal, only two studies were valid and further assessed for their importance and applicability. In regard to importance, imiquimod has fewer side effects than KOH, yet it was not constantly shown to be superior to KOH in curing MC lesions. We conclude that KOH solution is the preferred treatment of MC in adults.

References

1. Nguyen HP, Franz E, Stiegel KR, Hsu S, Tyring SK. Treatment of molluscum contagiosum in adult, pediatric, and immunodeficient populations. J Cutan Med Surg. 2014;18:299-306.

2. Piggott C, Friedlander SF, Tom W. Poxvirus Infections. In: Goldsmith LA, Kats SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K.

(Eds.) Fitzpatrick’s dermatology in general medicine. New York: McGraw-Hill. 2012;

2:2417-20.

3. Van der Wouden JC, van der Sande R, van Suijlekom-Smit LW, Berger M, Butler CC,

(7)

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 22 Koning S. Interventions for cutaneous

molluscum contagiosum. Cochrane Database Syst Rev. 2009;4:CD004767.

4. Van der Wouden JC, van der Sande R, Kruithof EJ, Sollie A, van Suijlekom-Smit LW, Koning S. Interventions for cutaneous molluscum contagiosum (Review). Cochrane Database Syst Rev. 2017;5:CD004767.

5. Seo SH, Chin HW, Jeong DW, Sung HW. An open, randomized, comparative clinical and histological study of imiquimod 5% cream vs.

10% potassium hydroxide solution in the treatment of molluscum contagiosum. Ann Dermato. 2010;22:156-62

6. Chatra N, Sukumar D, Bhat RM, et al. A comparative study of 10% KOH solution and 5% imiquimod cream for the treatment of Molluscum contangiosum in the pediatric age. Indian Dermatol Online J. 2015;6:75-80 7. Metkar A, Pande S, Khopkar U. An open,

non-randomized, comparative study of imiquimod 5% cream vs. 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Indian J Dermatol Venereol Leprol. 2008;74:614-8

(8)

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 23 Appendix 1. Literature Searching Strategy

Inclusion criteria:

- Articles that matched with clinical question - Available in free full

text

- Written in English language

**Reading time:

April 6th-8th 2017

*Searching time:

April 6th 2017, 15.00 PM

Filter for same articles

3 1

Pubmed Cochrane

Imiquimod Molluscum

contagiosum A N D

A N

D KOH

EBSCO

3

A N

D Treatment O

R

Potassium Hydroxide

3

Screening through title and abstract

Metkar, et al (2008) Seo, et al (2010) Chatra, et al (2015)

Reading the full text**

Critical appraisal of 3 articles 3