- Email: [email protected]
Ingenol mebutate gel for the treatment of molluscum contagiosum: An open-label comparative pilot study
LETTER RESEARCH Ingenol mebutate gel for the treatment of molluscum contagiosum: An open-label comparative pilot study
LETTER Table I. Demographics and treatment outcomes of the patients
Characteristics*
To the Editor: Molluscum contagiosum (MC) is a common contagious cutaneous viral disease caused by the MC virus. Although MC resolves spontaneously, the demand exists for a rapid, less painful, and safe treatment due to its contagious nature, pruritus, cosmesis, and pain.1 Ingenol mebutate gel has recently been approved for the treatment of actinic keratosis by inducing direct and rapid cell death and immune responses.2 Although ingenol mebutate has the potential for the treatment of other cutaneous diseases, there has been a single case report of MC treated with ingenol mebutate in English literature.3 Our aim was to perform a pilot study of ingenol mebutate gel for patients with MC lesions. The Pusan National University Hospital Ethics Committee (H1902-005-076) approved the study. From 2015 to 2017, 19 patients with MC lesions were enrolled in the Dermatology Departments of Pusan National University Hospitals (Busan and Yangsan); of these, 10 patients were randomly assigned to the ingenol mebutate group and 9 to the imiquimod group. In the ingenol mebutate group, 0.015% ingenol mebutate gel was applied to the top of the lesion once daily for 3 consecutive days per week. In the imiquimod group, 5% imiquimod cream was applied directly on the lesion once daily 5 times per week. They were applied until the lesions disappeared completely. We observed significantly reduced MC lesions all throughout the follow-up period in the ingenol mebutate group, but at week 2, there was no significant decrease of lesions in the imiquimod group (Table I). Compared with the imiquimod group, the ingenol mebutate group showed significantly fewer lesions at weeks 2, 4, 8, and 12. The complete clearance rate of 90% in the ingenol mebutate group was higher than the 33.3% rate of the imiquimod group at week 12. Furthermore, significantly less time was needed to complete clearance and perilesional erythema in the ingenol mebutate group than in the imiquimod group. Representative clinical course of MC after ingenol mebutate application is presented in Fig 1. Crusts on the MC lesions were more frequently observed in the ingenol mebutate group (9 of 10) than in the J AM ACAD DERMATOL
Age, yz Malex Duration, moz Locationz Face Trunk Extremities Groin Number of lesions Week 0 Week 2 Week 4 Week 8 Week 12 Complete clearancex Week 2 Week 4 Week 8 Week 12 Time to Perilesional erythema, wk Complete clearance, wkz
Ingenol mebutate (n = 10)
Imiquimod (n = 9)
5.6 (1.7-8.0)y 4.3 (1.7-8.0)y 4 (40.0)y 5 (55.6)y y 8.5 (2.0-24.0) 6.4 (2.0-24.0)y y
y
P valuey
.173y .414y .453y y
11.2 12.0 12.6 1.3
(0-36) (0-35) (0-55) (0-11)
4.6 5.3 4.8 13.6
(0-25) (0-24) (0-28) (0-57)
.218 .321 .063 .216
37.1 9.6 6.6 5.3 3.6
(11-90) (0-42) (0-42) (0-41) (0-32)
28.2 20.9 17.9 12.6 7.7
(7-85) (6-55) (2-48) (0-26) (0-25)
.205 .03 .022 .022 .035
0 0 1 3
(0.0) (0.0) (11.1) (33.3)
.526 .054 .01 .017
2.6 (2.0-4.0)
.045
1 4 7 9
y
y
(10.0) (40.0) (70.0) (90.0)
1.1 (0.7-2.0)
y
y
y
y
6.8 (2.0-12.0) 10.8 (8.0-12.0) \.001
*Continuous data are presented as the mean (range) and categorical data as number (%). y Bold P values are statistically significant (P \ .05). z Mann-Whitney test was done. x Fisher exact test was done.
imiquimod group (3 of 9, P ¼ .017); however, the rate of other local and systemic adverse events, including pain (10.0% for ingenol mebutate group and 11.1% for imiquimod group) and pruritus (50% for ingenol mebutate group and 44.4% for imiquimod group) were similar between the groups and were tolerable in all patients. The major limitations of this study were that it was an unblinded study with a small sample size and lack of an explicit placebo group or active comparator group; however, imiquimod could be considered a placebo arm in this study, because it has recently been demonstrated not to be effective for MC.4 In summary, our findings suggest that ingenol mebutate could shorten the period of autoinoculation and transmission by rapid clearance of MC n 2019 1
J AM ACAD DERMATOL
2 Letter
n 2019
Fig 1. Serial changes of molluscum contagiosum lesions after 0.015% ingenol mebutate gel application in a 4-year-old girl at (A) baseline and after (B) 1 week, (C) 3 weeks, and (D) 12 weeks.
lesions. Destructive treatments, such as cryotherapy or curettage, are also rapid but may cause pain or not be well tolerated by children. Larger, controlled studies of ingenol mebutate for MC are warranted.
Correspondence to: Hyun-Chang Ko, MD, PhD, Department of Dermatology, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan, 50612, Korea
Kihyuk Shin, MD, PhD,a,b,c,d Kyung-Nam Bae, MD,a Hoon-Soo Kim, MD,a Byung-Soo Kim, MD, PhD,a Moon-Bum Kim, MD, PhD,a and Hyun-Chang Ko, MD, PhDa,b,c
E-mail: [email protected]
From the Department of Dermatology, School of Medicine, Pusan National University, Busana; the Department of Dermatology, Pusan National University Yangsan Hospital, Yangsanb; the Research Institute for Convergence of Biomedical Science and Technology, Yangsanc; and the Biomedical Research Institute, Pusan National University Hospital,d Korea
REFERENCES 1. Jahnke MN, Hwang S, Griffith JL, Shwayder T. Cantharidin for treatment of facial molluscum contagiosum: a retrospective review. J Am Acad Dermatol. 2018;78:198-200. 2. Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012;366:1010-1019. 3. Javed S, Tyring SK. Treatment of molluscum contagiosum with ingenol mebutate. J Am Acad Dermatol. 2014;70: e105. 4. Katz KA, Swetman GL. Imiquimod, molluscum, and the need for a better ‘‘best pharmaceuticals for children’’ act. Pediatrics. 2013;132:1-3.
Funding sources: None. Conflicts of interest: None disclosed. Reprints not available from the authors.
https://doi.org/10.1016/j.jaad.2019.08.081
LETTER Table I. Demographics and treatment outcomes of the patients
Characteristics*
To the Editor: Molluscum contagiosum (MC) is a common contagious cutaneous viral disease caused by the MC virus. Although MC resolves spontaneously, the demand exists for a rapid, less painful, and safe treatment due to its contagious nature, pruritus, cosmesis, and pain.1 Ingenol mebutate gel has recently been approved for the treatment of actinic keratosis by inducing direct and rapid cell death and immune responses.2 Although ingenol mebutate has the potential for the treatment of other cutaneous diseases, there has been a single case report of MC treated with ingenol mebutate in English literature.3 Our aim was to perform a pilot study of ingenol mebutate gel for patients with MC lesions. The Pusan National University Hospital Ethics Committee (H1902-005-076) approved the study. From 2015 to 2017, 19 patients with MC lesions were enrolled in the Dermatology Departments of Pusan National University Hospitals (Busan and Yangsan); of these, 10 patients were randomly assigned to the ingenol mebutate group and 9 to the imiquimod group. In the ingenol mebutate group, 0.015% ingenol mebutate gel was applied to the top of the lesion once daily for 3 consecutive days per week. In the imiquimod group, 5% imiquimod cream was applied directly on the lesion once daily 5 times per week. They were applied until the lesions disappeared completely. We observed significantly reduced MC lesions all throughout the follow-up period in the ingenol mebutate group, but at week 2, there was no significant decrease of lesions in the imiquimod group (Table I). Compared with the imiquimod group, the ingenol mebutate group showed significantly fewer lesions at weeks 2, 4, 8, and 12. The complete clearance rate of 90% in the ingenol mebutate group was higher than the 33.3% rate of the imiquimod group at week 12. Furthermore, significantly less time was needed to complete clearance and perilesional erythema in the ingenol mebutate group than in the imiquimod group. Representative clinical course of MC after ingenol mebutate application is presented in Fig 1. Crusts on the MC lesions were more frequently observed in the ingenol mebutate group (9 of 10) than in the J AM ACAD DERMATOL
Age, yz Malex Duration, moz Locationz Face Trunk Extremities Groin Number of lesions Week 0 Week 2 Week 4 Week 8 Week 12 Complete clearancex Week 2 Week 4 Week 8 Week 12 Time to Perilesional erythema, wk Complete clearance, wkz
Ingenol mebutate (n = 10)
Imiquimod (n = 9)
5.6 (1.7-8.0)y 4.3 (1.7-8.0)y 4 (40.0)y 5 (55.6)y y 8.5 (2.0-24.0) 6.4 (2.0-24.0)y y
y
P valuey
.173y .414y .453y y
11.2 12.0 12.6 1.3
(0-36) (0-35) (0-55) (0-11)
4.6 5.3 4.8 13.6
(0-25) (0-24) (0-28) (0-57)
.218 .321 .063 .216
37.1 9.6 6.6 5.3 3.6
(11-90) (0-42) (0-42) (0-41) (0-32)
28.2 20.9 17.9 12.6 7.7
(7-85) (6-55) (2-48) (0-26) (0-25)
.205 .03 .022 .022 .035
0 0 1 3
(0.0) (0.0) (11.1) (33.3)
.526 .054 .01 .017
2.6 (2.0-4.0)
.045
1 4 7 9
y
y
(10.0) (40.0) (70.0) (90.0)
1.1 (0.7-2.0)
y
y
y
y
6.8 (2.0-12.0) 10.8 (8.0-12.0) \.001
*Continuous data are presented as the mean (range) and categorical data as number (%). y Bold P values are statistically significant (P \ .05). z Mann-Whitney test was done. x Fisher exact test was done.
imiquimod group (3 of 9, P ¼ .017); however, the rate of other local and systemic adverse events, including pain (10.0% for ingenol mebutate group and 11.1% for imiquimod group) and pruritus (50% for ingenol mebutate group and 44.4% for imiquimod group) were similar between the groups and were tolerable in all patients. The major limitations of this study were that it was an unblinded study with a small sample size and lack of an explicit placebo group or active comparator group; however, imiquimod could be considered a placebo arm in this study, because it has recently been demonstrated not to be effective for MC.4 In summary, our findings suggest that ingenol mebutate could shorten the period of autoinoculation and transmission by rapid clearance of MC n 2019 1
J AM ACAD DERMATOL
2 Letter
n 2019
Fig 1. Serial changes of molluscum contagiosum lesions after 0.015% ingenol mebutate gel application in a 4-year-old girl at (A) baseline and after (B) 1 week, (C) 3 weeks, and (D) 12 weeks.
lesions. Destructive treatments, such as cryotherapy or curettage, are also rapid but may cause pain or not be well tolerated by children. Larger, controlled studies of ingenol mebutate for MC are warranted.
Correspondence to: Hyun-Chang Ko, MD, PhD, Department of Dermatology, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan, 50612, Korea
Kihyuk Shin, MD, PhD,a,b,c,d Kyung-Nam Bae, MD,a Hoon-Soo Kim, MD,a Byung-Soo Kim, MD, PhD,a Moon-Bum Kim, MD, PhD,a and Hyun-Chang Ko, MD, PhDa,b,c
E-mail: [email protected]
From the Department of Dermatology, School of Medicine, Pusan National University, Busana; the Department of Dermatology, Pusan National University Yangsan Hospital, Yangsanb; the Research Institute for Convergence of Biomedical Science and Technology, Yangsanc; and the Biomedical Research Institute, Pusan National University Hospital,d Korea
REFERENCES 1. Jahnke MN, Hwang S, Griffith JL, Shwayder T. Cantharidin for treatment of facial molluscum contagiosum: a retrospective review. J Am Acad Dermatol. 2018;78:198-200. 2. Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012;366:1010-1019. 3. Javed S, Tyring SK. Treatment of molluscum contagiosum with ingenol mebutate. J Am Acad Dermatol. 2014;70: e105. 4. Katz KA, Swetman GL. Imiquimod, molluscum, and the need for a better ‘‘best pharmaceuticals for children’’ act. Pediatrics. 2013;132:1-3.
Funding sources: None. Conflicts of interest: None disclosed. Reprints not available from the authors.
https://doi.org/10.1016/j.jaad.2019.08.081