Comparison of Effectiveness and Safety of Immunotherapy of Warts with Intralesional Versus Subcutaneous MMR Vaccine: An Open Label Randomized, Parallel Group, Clinical Trial.

Common wart, also known as verruca vulgaris is characterized by focal proliferation of keratinocytes caused by multiple strains of human papilloma virus (HPV). Conventional treatments like chemical cautery, cryotherapy, electro-cautery, etc often fail to cure verruca satisfactorily. The present work was a randomized, parallel-group, non-inferiority clinical trial with an objective of comparing the effectiveness and safety of subcutaneous MMR versus intralesional MMR vaccine in the treatment of multiple warts. Method: Consenting patients of both sexes of 18-65 years age, who have viral warts and did not receive anti-wart treatment in the last 4 weeks and devoid of any active bacterial or viral skin diseases were included in the study. Interventions: Eligible patients were randomized into either group A (receiving 0.3 ml of intralesional MMR) or group B (receiving 0.5 ml of subcutaneous MMR). A total of three injections were administered at two weeks interval. Outcome Measure: The response was considered complete if there was disappearance of the wart(s) and return of the normal skin markings, partial if the wart(s) was regression in size by 50-99% and no response if there was be 0-49% decrease in wart size.
Results: Thirty patients were recruited in each group; 5 of group A and 3 of group B were lost to follow up. Modified intention to treat analysis was performed, so, the last observation of such patients was carried forward and all 60 participants were analysed. Number of warts and size of the largest wart were declined significantly (P < 0.001 and P = 0.001 respectively) in both the treatment arms. No significant difference between two groups were seen. Complete clearance including distant lesions was achieved in 22 patients; 12 (48%) in group A and 10 (37.04%) in group B, but the final outcome at the end of the study showed no significant difference between the two t groups. (P = 0.64). Adverse Events: Only one patient had developed mild fever with tender, enlarged parotid gland after first injection of subcutaneous MMR which resolved within two weeks.
Conclusion: Efficacy and safety profile of Subcutaneous and intralesional MMR were almost same. Both can be considered as safe and cost effective treatment of warts while the subcutaneous route may be easier to administer. Copyright:

Introduction

Common warts or verruca vulgaris is characterized by focal proliferation of keratinocytes due to infection with the human papilloma virus (HPV) and can occur anywhere in the body.[12] Its persistence and recurrence affect the quality of life. About two-thirds of the warts resolve spontaneously but most patients seek treatment because of their unsightly appearance, rapidly increasing number or associated tenderness.[3] Treatment for the periungual and plantar wart, and extensive lesions often become frustrating for the dermatologist and the patient alike.[4] Though chemical cautery, cryotherapy, electro-cautery, excision, bleomycin sulphate injection, laser vaporization and photodynamic therapy are still considered as the primary treatment modalities, none of them can guarantee a cure and recurrence is common.[3] Cryotherapy or surgery can result in scarring, too.[2] Distant lesions are usually not resolved with these local approaches, resulting in repeated and long-drawn treatment sessions.

To cope up with this challenge, contact sensitizers like 2, 4 Dinitrochlorobenzene (DNCB) also, immune-modifiers like imiquimod, HPV, bacillus Calmette–Guérin (BCG), purified protein derivative (PPD), candida, trichophytin, mumps, measles, mumps and rubella (MMR) and Mycobacterium w vaccine are now in use which utilizes the delayed-type hypersensitivity response to achieve an HPV-targeted immune reaction and regarded as immunotherapy.[4]

The literature search revealed many studies using intralesional (IL) MMR vaccine in the treatment of common wart(s) and intradermal PPD in the treatment of anogenital warts,[56789] but studies using subcutaneous (SC) MMR vaccine for the treatment of wart are yet to be done and so no head-to-head data is available for comparison of subcutaneous MMR and intralesional MMR injections in the treatment of viral wart. Our study hypothesis was that subcutaneous MMR vaccine may also be effective for clearance of distal lesions of wart albeit with a more convenient route; where it can be given by health care professionals other than dermatologists.

Hence, this study is undertaken to evaluate the effectiveness of intralesional MMR vaccine versus subcutaneous MMR in the treatment of wart(s).

Specific objectives

The specific objective of this study is to compare the effectiveness and safety of intradermal MMR versus intralesional MMR vaccine in the treatment of multiple warts.

Methods

Trial design

This is an institution-based, randomized, open-label, parallel-group, non-inferiority trial with an allocation ratio of 1:1. The study was carried out in the dermatology outpatient department (OPD) of Medical College, Kolkata.

Non-inferiority trials are conducted to show that the new treatment is as effective but need not be superior when compared to the standard treatment. The corresponding null hypothesis is as follows: The new treatment is inferior to the control treatment by a clinically relevant amount.[10]

Participants

Consenting patients of 18–65 years, irrespective of gender, having ≥2 viral warts who did not receive anti-wart treatment in the previous 4 weeks and devoid of any active bacterial or viral skin diseases were included in the study. Immunosuppressed patients, pregnant and lactating women and patients suffering from chronic hepatic or renal disorders and who participated in a clinical trial in the last 3 months were excluded from the study.

Interventions

The MMR vaccine (TRESIVAC®; Serum Institute of India Pvt. Ltd., Pune, India) used was a freeze-dried preparation of live attenuated strains of measles, mumps and rubella viruses available in a single-dose vial of 0.5 ml. Patients were injected with the reconstituted MMR vaccine either 0.5 ml through subcutaneous route sterile syringe attached to a 23-gauge needle or 0.3 ml intradermally into the single largest wart using an insulin syringe, having a 31-gauge needle. A total of three injections were administered at 2 weeks intervals.

Outcomes

The response was considered complete if there was the disappearance of the wart(s) and return of the normal skin markings, partial if there was a regression in size/number of the wart(s) by 50–99% and no response if there was 0–49% decrease in wart size/number. Adverse events such as pain, swelling and flu-like symptoms were noted following the injection.

A 5-point Likert scale was used for patients’ global assessment of disease activity improvement and physicians’ global assessment of disease activity improvement where 0,1234 scores were given for no improvement, mild improvement, moderate improvement, marked improvement and excellent improvement, respectively.

Sample size

A sample size of 26 in each group was calculated considering complete clearance of warts of 80% with intralesional MMR vaccine[9] and assuming 60% with subcutaneous MMR with 80% power and 0.025 probability of type I error, and a non-inferiority margin of 15% (using WinPepi version 11.65 statistical software). Considering a possible 10% dropout rate, this translated to a recruitment target of approximately 30 subjects in each group or 60 subjects overall.

Randomization

Eligible patients were randomized into either group A (receiving 0.3 ml of intralesional MMR) or group B (receiving 0.5 ml of subcutaneous MMR) with an allocation ratio of 1:1 as per the randomization sequence (balanced unstratified randomization using WinPepi software ETCETERA version 2.32 which is a WinPepi (PEPI-for-Windows) programme generated by an independent coordinator (IC).

Statistical methods

Continuous efficacy variables were compared between groups by Mann–Whitney U test and within group by Friedman's analysis of variance (ANOVA) test as the data were not distributed normally. Mann–Whitney U test and Wilcoxon's test was carried out for unpaired and paired non-parametric data. Categorical data were compared between groups by Chi-squared test or Fisher's exact test, as appropriate. Friedman's ANOVA was carried out with non-parametric data for within group repeated measures comparisons. Data were entered in Microsoft Excel and analysis was done with the help of statistical software Medcalc® v 19.1. One sided p value was set at 0.025.

Modified intention to treat analysis was done for assessment of efficacy. For analysis of adverse effects, all the patients who had received at least one dose of the medication were considered. Ethics committee approval was obtained on 23.09.2017.

Results

Out of 108 patients with multiple (two or more) warts screened for this study, a total of 60 patients, 30 patients each in group A (receiving 0.3 ml of intralesional MMR) or group B (receiving 0.5 ml of subcutaneous MMR) with an allocation ratio 1:1 as per the randomization sequence, were enrolled for this study. Every patient was given treatment (subcutaneous or intralesional injection MMR) at a fortnightly interval for three injections and then followed up for another 3 months at 4-week intervals, total study duration being 4 months.

One patient each from group A and group B did not come for follow-up from the third visit; three patients from group A and one patient from group B lost to follow-up from the fourth visit and one patient from each group lost at the fifth visit. However, since we followed the modified intention to treat strategy, the last observation of such patients was carried forward and all 60 participants were analysed [Figure 1].

Figure 1

Flow chart showing recruitment of the study participants

Observations

Baseline demographic profile of study participants

All study subjects were recruited on an ambulatory (outpatient) basis. As seen in Table 1, males outnumbered females in both the groups: 20 males and 10 females in group A and 19 males and 11 females in group B. In both the groups, the majority of patients were young adults; 34 ± 10.63 years for group A and 33.36 ± 9.91 for group B. Study groups were comparable at baseline with respect to age and sex. It was predominantly an urban (66.7% and 76.7%), literate (80% and 90%, respectively) population.

Table 1

Demographic profile of study participants

Parameters	Group A=IL (n=30)	Group B=SC (n=30)	P-value (between groups)
Age (years)
Mean±SD	34±10.63	33.36±9.91	0.83
Median (IQR)	34.5 (24-45)	35 (26-40)
Gender			1.000
Male	20 (66.7%)	19 (63.3%)
Female	10 (33.3%)	11 (36.7%)
Income
APL	18 (60%)	24 (80%)	0.65
BPL	12 (40%)	6 (20%)
Residence
Urban	20 (66.7%)	23 (76.7%)	0.37
Rural	10 (33.3%)	7 (23.3%)
Education
Illiterate	6 (20%)	3 (10%)	P=0.53
Primary	13 (43.3%)	12 (40%)
Secondary	6 (20)	10 (33.33%)
Graduate	5 (16.7%)	5 (16.7%)
Occupation
Farmer	4 (13.3%)	4 (13.3%)	0.12
Labourer	2 (6.7%)	3 (10%)
Housewives	9 (30%)	9 (30%)
Businessman	3 (10%)	1 (3.3%)
Miscellaneous	12 (40%)	13 (43.3%)

Abbreviations: SD=Standard deviation, IQR=Interquartile range, IL=Intralesional, SC=Subcutaneous, APL=Above poverty line, BPL=Below poverty line, P value is from Student’s unpaired t-test for age; Fisher’s exact test for gender distribution, residence and income; and Chi-square test for occupation and education

In the baseline visit, morphological types of the wart, presence of koebnerization, total number and size of the largest wart at baseline were assessed; prior treatment history was asked for [Table 2].

Table 2

Baseline clinical profile of study participants

Parameters	Group A IL (n=30)	Group B Sc (n=30)	P-value (between groups)
Type of wart
Verruca Vulgaris	18 (60%)	20 (66.67%)	0.37 (chisquare )
Plantar wart	4 (13.33%)	1 (3.33%)
Others	8 (26.67%)	9 (30%)
History of previous treatment
No	11 (36.67%)	11 (36.67%)	P=1.000(Fisher’s exact test)
Yes	19 (63.33%)	19 (63.33%)
Koebnerisation	19 (63.33%)	10 (33.33%)	P=0.038(Fisher’s exact test)
Absent	11 (36.67%)	20 (66.67%)
Present
Number of warts at baseline
Mean±SD	18.4±20.69	26±23.89	P=0.082 (Mann whitney U test)
Median (IQR)	11.50 (6to21)	20.00 (12 to 30)
Size of largest wart at baseline (mm)
Mean±SD	4.86±2.97	5.3±3.64	P=0.887(Mann whitney U test)
Median (IQR)	4.5 (3to 6)	4.5 (3 to 6)

P-value was obtained from Mann–Whitney test for number and size of warts (as the distributions reject normality), Chi-square test for type of wart, Fisher’s exact test for previous treatment and koebnerization

The most common type of wart was verruca vulgaris (60% in group A and 66.6% in group B) in our study; the rest were plantar wart, verruca plana or combinations of two types. Both the groups were comparable (p = 0.37).

The baseline number of warts was statistically not different (p = 0.082) in the two groups. It varied between 2 and 100 (18.4 ± 20.69) in group A and 3 and 100 (26 ± 23.89) in group B.

The size of the largest wart at baseline was 4.86 ± 2.97 mm for group A and 5.3 ± 3.64 mm for group B which was also comparable (p = 0.89).

Koebnerization was present in 36.7% (n = 11) of group A and 63.3% (n = 19) in group B. Hence, a greater number of patients (p = 0.038) in the group B had koebnerization in the baseline.

In both the groups, the number of patients who were treated previously with homeopathy or ayurvedic medications or not treated at all were the same; 19 (63.3%) and 11 (36.7%), respectively (p = 1.000).

Changes in the number of warts

The changes in the number of warts during 1 month of active treatment and 3 months of post-treatment follow-up are depicted in Table 3 and the outcomes were evaluated as complete (100%), partial (≥50%) or no (<50% or stable) response according to decrease in the number of warts. It was evident that the number of warts significantly (p < 0.00001) declined in both the treatment arms over this time period [Figures 2 and 3].

Table 3

The changes in the number of warts during 1 month of active treatment and 3 months of post-treatment follow-up

Visit	IL	SC	P-value (between groups)
Baseline (Mean±SD)	18.4±20.89	26±23.89	P=0.082
Median (IQR)	11.50 (6, 21)	20.00 (12, 30)
First follow-up (Mean±SD)	16.5±20.03	23.96±23.95
Median (IQR)	8.5 (5, 19)	20 (5, 30)	0.10
Second follow-up (Mean±SD)	14.23±19.63	17.46±16.80
Median (IQR)	8 (4, 17)	14.5 (5, 22)	0.18
Third follow-up (Mean±SD)	11.23±19.94	13.56±16.55
Median (IQR)	4 (2,9)	9 (3, 20)	0.21
Fourth follow-up (Mean±SD)	9.1±19.55	10.93±13.52
Median (IQR)	2.5 (0,7)	5 (0, 18)	0.21
Fifth follow-up (Mean±SD)	8.8±19.64	9.7±12.42	0.29
Median (IQR)	2 (0, 7)	5 (0, 18)
P-value (within groups)	<0.00001	<0.00001

P value between groups determined by Mann–Whitney U test. P value within groups determined by Friedman’s ANOVA

Figure 2

Changes of warts following intralesional MMR: (a) baseline; (b) At first follow-up after 2 weeks; (c) At second follow-up after 4 weeks; (d) At third follow-up after 8 weeks; (e) At fourth follow-up after 12 weeks; (f) At fifth follow-up after 16 weeks

Figure 3

Changes of warts following subcutaneous MMR: (a) baseline; (b) At first follow-up after 2 weeks; (c) At second follow-up after 4 weeks; (d) At third follow-up after 8 weeks; (e) At fourth follow-up after 12 weeks; (f) At fifth follow-up after 16 weeks

In the first follow-up, the majority of the patients showed no response in both the study groups. The partial reduction was seen in only one (3.3%) patient of group B. In the subsequent visits, the proportions of therapeutic response were increased gradually. At the fifth follow-up, we found 40% patients in each group with no response, 20% of group A and 26.7% of group B with partial response and 40% of group A and 33.3% of group B patients with complete response [Table 5]. Intergroup comparison revealed no significant difference in any visits [Figure 4].

Table 5

Response pattern of wart with treatment in comparison to baseline number

Visit	Group A (IL) n=30				Group B (SC) n=30				P
	NR (0/<50%)		PR (<100%) <100%	CR (100%) 100%	NR (0/<50%)		PR (<100%) <100%	CR (100%) 100%
	NC	<50%			NC	<50%
First follow-up n=30	15 (50%)	15 (50%)	0	0	21 (70%)	8 (26.7%)	1 (3.3%)	0	0.13
Second follow-up n=30	9 (30%)	15 (50%)	5 (16.7%)	1 (3.3%)	9 (30%)	12 (40%)	9 (30%)	0	0.48
Third follow-up n=30	7 (23.3%)	8 (26.7%)	10 (33.3%)	5 16.7%)	8 (26.7%)	6 (20%)	12 (40%)	4 (13.3%)	0.89
Fourth follow-up n=30	7 (23.3%)	5 16.7%)	8 (26.7%)	10 (33.3%)	7 (23.3%)	6 (20%)	9 (30%)	8 (26.7%)	0.95
Fifth follow-up n=30	7 (23.3%)	5 (16.7%)	6 (20%)	12 (40%)	7 (23.3%)	5 (16.7%)	8 (26.7%)	10 (33.3%)	0.93

Abbreviations: NC=no change, NR=no response, PR=partial response, CR=complete response P-value was obtained by Chi-square test

Figure 4

Comparison of reduction of the wart number in the two treatment arms

Changes in the size of the largest wart

The dimension changes of the largest wart during the treatment period are depicted in Table 4. Similar to the number of warts, it was also assessed as complete (100%), partial (≥50%) or no response (<50% or stable) according to a decrease in the wart size. With treatment, 36.7% of group A and 33.3% of group B patients showed no response (0–49%), good response (50–99% reduction) was noted in 23.3% and 30% while complete resolution (100%) was seen in 40% (n = 12) and 36.7% (n = 11), respectively. The largest wart reduced significantly (p = 0.00001) from baseline in both the groups but it was not different (p = 0.62) between the two groups [Figure 5].

Table 4

Changes in the size of largest warts in the two treatment groups

Visit	IL	SC (n=30)	P-value (between groups)
Baseline
Mean±SD	4.86±2.97	5.3±3.64	P=0.89
Median (IQR)	4.5 (3, 6)	4.5 (3, 6)
First follow-up
Mean±SD	4.25±3.10	4.57±3.62	0.92
Median (IQR)	3 (2,5)	3 (2,5)
Second follow-up
Mean±SD	3.43±2.35	3.95±3.34	0.83
Median (IQR)	3 (2,4)	3 (2,5)
Third follow-up
Mean±SD	2.7±2.41	3.51±3.59	0.57
Median (IQR)	2 (1,3)	2 (1,5)
Fourth follow-up	2.16±2.4	3.08±3.76	0.61
Mean±SD	2 (0,3)	1.5 (0,5)
Median (IQR)
Fifth follow-up	2±2.49	2.85±3.84
Mean±SD	1.5 (0,3)	1 (0,4.5)	0.62
Median (IQR)
P-value (within groups)	<0.00001	<0.00001

P-value between groups determined by Mann–Whitney U test. P value within groups determined by Friedman’s ANOVA. No significant difference (P=0.62) in reduction (%) in the size of largest wart between two groups

Figure 5

Comparison of reduction in the size of the largest wart in the two treatment arms

Complete clearance

We compared the complete clearance of warts in terms of the total number and terms of size of the largest wart. The results were summarized in Tables 5 and 6, respectively.

Table 6

Reduction in the size of largest wart with treatment

	Group A (IL) n=30				Group B (SC) n=30				P
	NR (0/<50%)		PR (<100%)	CR (100%)	NR (0/<50%)		PR (<100%)	CR (100%)
	NC	<50%			NC	<50%
Visit
First follow-up n=30	19 (63.3%)	8 (26.7%)	3 (10%	0	18 (60%)	8 (26.7%)	4 (13.3%)	0	0.92
Second follow-up n=30	8 (26.7%)	14 (46.7%)	7 (23.3%)	1 (3.3%)	10 (33.3%)	10 (33.3%)	10 (33.3%)	0	0.49
Third follow-up n=30	4 (13.3%)	11 (36.7%)	10 (33.3%)	5 (16.7%)	8 (26.7%)	7 (23.3%)	11 (36.7%)	4 (13.3%)	0.50
Fourth follow-up n=30	4 (13.3%)	8 (26.7%)	9 (30%)	9 (30%)	6 (20%)	6 (20%)	9 (30%)	9 (30%)	0.88
Fifth follow-up n=30	4 (13.3%)	7 (23.3%	7 (23.3%	12 (40%)	5 (16.7%)	5 (16.7%)	9 (30%)	11 (36.7%)	0.86

Abbreviations: NR=no response, PR=partial response, CR=complete response. P-value was obtained by Chi-square test

Among 60 patients, 12 (40%) in group A and 10 (33.3%) in group B achieved complete clearance at the end of the study (p = 0.93).

Complete resolution (100%) of the largest wart was seen in 40% (n = 12) and 36.7% (n = 11) while good response (50–99% reduction) was noted in 23.3% (n = 7) and 30% (n = 9), respectively (p = 0.86); another 23.3% (n = 7) of group A and 16.7% (n = 5) patients of group B were lacking response (<50%) and no change in the largest wart was appreciated in 13.3% patients (n = 4) of group A and 16.7% (n = 5) of group B. Complete resolution of warts considering the size and the number were obtained from the third follow-up Table 5 onwards in group B and second follow-up onwards in the group A. The final outcome showed no difference between the two groups.

The end results showed significant improvement in both groups as per physician's global assessment of disease activity improvement (p < 0.001) and patient's global assessment of disease activity improvement (p-value < 0.001).

Harm

One patient had extensive verruca plana and developed mild fever with tender, enlarged parotid gland after the first injection of subcutaneous MMR. These resolved within 2 weeks, and the patient received the subsequent injections and ended up with a complete resolution of warts at the end of the study. Barring this case, neither the assessing physician detected any serious adverse events nor did the patients complain of the same in any visit.

Discussion

Conventional treatments for verruca like chemical cautery, cryotherapy, electro-cautery, etc., act through viral particles destruction; hence, inconsistent and incomplete removal resulting in persistent and recurrent verruca is quite frequent. To ameliorate this challenge, newer treating options with injections of various antigens like HPV, BCG, PPD, candida, trichophytin, mumps, MMR and Mycobacterium w vaccine are coming up.

Two doses of live attenuated MMR vaccine is usually given subcutaneously with an interval of 4 weeks as a part of routine immunization to immunocompetent children. Different studies had established intralesional MMR as an effective treatment in the treatment of wart(s).[45678]

The literature search was unable to find studies in the treatment of viral warts using subcutaneous MMR injections, so data are unavailable for comparison of subcutaneous MMR and IL MMR in the treatment of warts. We had tried to compare the effectiveness of intralesional MMR vaccine versus subcutaneous MMR vaccine in the treatment of warts and compared our results with the studies done with IL MMR previously.

The baseline demography showed that both the study groups were comparable at baseline with respect to age and sex; indicating that age and sex have not confounded the results of our study. It was predominantly an urban (group A 66.7%, group B 76.7%), literate (group A 80%, group B 90%) population as expected from the catchment area of a tertiary level hospital.

The majority of study patients were young adults; 34 ± 10.63 years for group A and 33.36 ± 9.91 for group B. Raju et al. (2015)[6] had found similar age distribution (30.98 ± 8.13.) but Zamanian et al. (2014)[5] showed a lower age range of 18.9 ± 12 years in the MMR group and 20.1 ± 10 years in the control group.

In our study, males outnumbered females in both the groups; 2:1 in group A and 1.73 in group B. Raju et al. (2015)[6] found 62.9% male and 37.03% female in his study. Another study reported 90% male and 10% female in the MMR group while 95% males and 5% females in the control arm.[11] Accidental prick or trauma in the outdoors may be a factor for male predominance.

The size of the largest wart diminished gradually with treatment. Complete resolution of the largest wart is seen in 40% (n = 12) of group A and 36.7% (n = 11) of group B patients, which is lower than a study from North India,[12] where complete resolution of the injected wart was reported in 68% patients with IL MMR. We presume that a lesser number of injections in our study may contribute to this discrepancy.

We found a significant (p < 0.0001) reduction in the total number of warts including distant warts in both the treatment arms over this time period because of systemic immunologic effects. Intergroup comparison however revealed no significant difference in any visits.

Dhope et al.[11] compared the grade of response in the MMR group with the normal saline control group at the end of the third week (first follow-up visit), and showed no change in 25%, poor response in 60% and good response in 15% patients of the MMR group. None of the patients showed complete cure at the first follow-up, which was similar to our study. At the end of 9 weeks (third visit), these responses changed to 5%, 20%, 10% and 65%, respectively.

A study in Iran (2019) for resistant palmoplantar warts showed that partial response was visible after the second injection in 10.3% of patients, which gradually changed to 45.8%, 34.8% and 13.0% with the third, fourth and fifth injection, respectively. Complete clearance was observed in 65.2% with IL MMR vs 23.85% in the placebo group.[13]

In our study, a complete cure was noted from the second follow-up visit in group A and the third follow-up visit in group B.

This gradual improvement in the therapeutic outcome with time in all studies can be related to the boosting effect of virus-targeted immune reaction.

We found 40% of patients of group A and more than 30% of patients of group B ended up with a complete resolution of warts at the fifth follow-up. Our study finding was not similar to other studies; Raju et al. (2015)[6] reported complete remission in 70.4%, which was more or less similar to studies done by Nofal et al. (80%),[14] Mohammad et al. (82%)[15] and Gamil et al. (87%).[16] Comparative findings of different immunotherapy studies with MMR antigen for viral wart are summarized in Table 7.

Table 7

Comparison of different studies showing variable response in immunotherapy with MMR for viral wart

Study (year)	Antigen	Response in the study group			Response in the control group
		Complete		No	Complete		No
Zamanian et al.[5] (2014)	MMR	75%		8.3%	27.3%		31.8%
Saini et al.[7] (2016)	MMR	46.5%		32.6%	No control group
Awal G et al.[12] (2018)	MMR	68%		6.9%	10%		60%
Nofal et al.[14] (2010)	MMR	81.4%		8.6%	27.5%		57.5%
Study	Antigen	Complete	Partial	No	Complete	Partial	No
Mohammad et al.[15] (2013)	MMR	82%	6%	12%	0%	30%	70%
Gamil H et al.[16] (2010)	MMR	87%	4.3%	8.7%	No control group
Present study (2020)	MMR	Intralesional route			Subcutaneous route
		Complete	Partial	No	Complete	Partial	No
Number of wart		40%	20%	40%	33.3%	26.7%	40%
Size of largest wart		40%	23.3%	36.7%	36.7%	30%	33.3%

Complete cure in our study was lower than the previous studies probably due to shorter follow-up period and lesser number of injections (5 versus 3).

Only one patient from our study group showed significant adverse effects with clinical features of mumps. The rest of the participants tolerated MMR very well in both groups in contrast to Dhope, et al.,[11] who reported minor side effects including pain (85%), erythema (25%), swelling (20%) and flulike symptoms (10%) in many patients with IL MMR.

Conclusion

From our study, it can be inferred that subcutaneous MMR also promises as an effective therapeutic modality in multiple warts, especially where intralesional vaccines are difficult to administer, like very small lesions of verruca plana or genital lesions. It is Sub cutaneous MMR is inferior to intralesional MMR for local and distal clearance of warts without producing much adverse effects. Hence, MMR can be considered a safe and costeffective treatment of warts through both IL and SC routes.

Limitations

The total study duration was for 4 months only. Hence, recurrence after this period was not assessed. HPV serotyping, cytokine profile and titre were also beyond the scope of this study due to logistic and financial constraints.

Support

IADVL WB branch.

Financial support and sponsorship

Funded by IADVL WB research grant.

Conflicts of interest

There are no conflicts of interest.