PracticeUpdate Dermatology Best of 2018

EDITOR’S PICKS 10

Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-Analysis Journal of the American Academy of Dermatology Take-home message

COMMENT By Thomas Horn MD T his article describes ameta-analysis of reports on the use of intralesional immunotherapy to treat warts, con- cluding that the treatment works, with PPD and MMR being the most effec- tive immune stimulants. Good to know. I have often wondered about the wisdom of using therapeutically employed anti- gens in this setting, fearing that repeated administration over short periods of time may alter their immunogenicity later on. Still, any single antigen or mix of antigens stimulating the immune system in thewart milieu ought to have benefit. In countries using BCG as a tuberculosis-prevention strategy, I would predict good success in treating warts with it – some evidence exists already. The idea for this came to me during the darkest days of the HIV epidemic, before HAART. The explosion of HPV-induced disease across its entire spectrum as T-cell counts fell was insur- mountable. At the time, studies were being published exploring the value of injecting patients with skin test antigens to stimulate T-cell proliferation, postu- lating that any T-cell was a good T-cell, under the circumstances. Although that didn’t pan out, the notion of draw- ing T-cells into HPV-infected tissue to generate HPV-reactive effector cells in immunocompetent patients seems to have found its place in our (incredibly varied) treatment toolbox.

• These authors performed a review andmeta-analysis of 17 randomized controlled trials investigating various intralesional immunotherapeutic treatments for warts. Compared with placebo, purified protein derivative (PPD), measles, mumps, and rubella (MMR), and INF-β were most effective in terms of complete recovery at the primary site (OR, 39.56, 17.46, and 15.55, respectively). Compared with placebo, autoinoculation, PPD, and MMR were significantly superior to placebo at the distant site (OR, 79.95, 42.95, and 15.39, respectively). MMR was most effective in reducing same-site recurrence. • Intralesional injections, in particular PPD and MMR, may be effective for wart clearance at primary and distant sites, as well as for local recurrence reduction. Immunotherapeutic injections may enhance host cell–mediated immunity against the virus and thus have efficacy beyond the local injection site. InYoung Kim MD, PhD

Dr. Horn is Vice Chair of the Department of Dermatology at Massachusetts General Hospital in Boston, Massachusetts.

Abstract BACKGROUND Without clear evidence, selecting among the existing immunotherapeutic options for warts remains challenging. OBJECTIVE Through network meta-analyses, we aimed to evaluate the comparative efficacy of different intralesional immunotherapeutic modalities. METHODS We included randomized controlled trials (RCTs) comparing intralesional immuno- therapeutic modalities to cryotherapy, placebo or imiquimod. All outcomes were presented as odds ratio (OR) with 95% confidence-interval. Both conventional and network meta-analyses (with a frequentist approach) were conducted on R software. The P-score was used to rank different treatments.

RESULTS Network meta-analysis of 17 RCTs (1676 patients) showed that PPD (OR=39.56), MMR (OR=17.46) and INF-β (OR=15.55) had the high- est efficacy in terms of complete recovery at the primary site, compared to placebo. Regarding complete recovery at the distant site, autoinoc- ulation (OR=79.95), PPD (OR=42.95) and MMR (OR=15.39) were all statistically superior to pla- cebo. According to the P-score, MMR was more effective than other modalities in reducing recur- rence rate at the same site. LIMITATIONS Relatively-small sample size in some comparisons and variability in baseline characteristics. CONCLUSION PPD and MMR were the most effec- tive in achieving complete primary and distant

recovery (along with autoinoculation for distant recovery) and reducing the recurrence rate at the same site, compared to cryotherapy and other immunotherapeutic modalities. Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-Analysis. J Am Acad Dermatol 2018 Jul 09;[EPub Ahead of Print], S Salman, MS Ahmed, AM Ibrahim, et al. www.practiceupdate.com/c/70845

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