Efficacy and safety of glucosaminylmuramyl dipeptide in treatment of human papillomavirus-associated diseases: a systematic review

Abstract

Introduction. Human papillomavirus infection (HPV-infection) remains one of the most important health problems as it significantly reduces the quality of life and stigmatizes the patients. Also, the prevalence of cervical cancer – the most severe outcome of the HPV-infection is 5 % of the global burden of cancer. Although vaccination against human papillomavirus has been proved efficient, its availability in Russia continues to be limited. Therefore, it is important to review other methods of HPV-infection control. A number of studies have confirmed the efficacy of glucosaminylmuramyl dipeptide (GMDP) in the treatment of diseases associated with HPV-infection, but no systematic evaluation of these studies has been published in the available literature.Aim: to analyze the data on the efficacy and safety of GMDP in the treatment of diseases and conditions associated with HPVinfection.Materials and methods. We used the PRISMA approach. The search for the relevant publications was conducted in international scientific databases: the Scientific Electronic Library, the Google Scholar, the ScienceDirect, the Cochrane Community Library, the Pubmed/MEDLINE, and clinical research registries. For this systematic analysis, only full-text publications were used. We evaluated the reliability of evidence and the methodological quality of the studies.Results. We used the following search queries: "glucosaminyl-muramyl dipeptide", "glucosamine L'muramyl dipeptide", "H-acetylglucosaminyl-H-acetylmuramyl dipeptide", "GMDP", "Licopid" (both in Russian and English transcriptions). Based on the results of the screening, 14 full-text publications were selected. At the final stage, review articles with secondary data were excluded; also excluded were original articles published in doubtful resources and those with an unclear status of peer reviewing. This systematic analysis includes 7 publications of acceptable methodological quality. Here, we summarize the consistent conclusions derived from these reports: the addition of therapy with GMDP to local (surgical) methods increases the efficacy of treatment and the duration of remission; destruction of condylomas is more effective when combined with the course of GMDP as compared to using the local destruction alone; GMDP enhances the production of cytokines that have a direct antiviral and antiproliferative effect in HPV-infection (interleukin-1, tumor necrosis factor alpha, gamma-interferon); GMDP causes normalization of cellular and humoral immunity (T-lymphocytes, T-cytotoxic lymphocytes, B-lymphocytes, CD3+, CD4+, CD8+, CD16+, and CD72+ lymphocytes, as well as the production of serum immunoglobulins IgA, IgG, and IgM). A high safety profile of GMDP is evidenced from the absence of reports on adverse events.Discussion. The recommendation for the inclusion of GMDP into a comprehensive treatment for HPV-infection in addition to local interventions is a strong recommendation. The differences between the Russian and international approaches can be explained by the difference in the available resources and funding. We propose to test whether using GMDP for reducing the risk of recurrent HPV-infection is beneficial in terms of pharmacoeconomics. Conclusion. The high efficacy and safety of GMDP in the combined therapy of HPV-infection has been confirmed. Further carefully designed studies on GMDP are needed.

Results of Complex Immunopharmacological Analysis of the Mechanisms of Action of Bioregulation Agents

“…In light of this, identification of pharmacological agents capable of modulating activity of mediator-producing immune cells and showing no drug-drug interactions with NSAIDs, without strict restriction of the duration of application and with a wide spectrum of indication seems important [7][8][9]. Such immunomodulatory drugs are suggested to act synergistically with NSAIDs and improve their effectiveness [10,11].…”

Muramyldipeptide - based compounds in current medicine: focus on glucosaminylmuramyl dipeptide

“…Преимуществами ГМДП перед другими иммуномодуляторами являются: известный механизм действия и предсказуемость фармакологического эффекта, максимально приближенного к естественной иммунорегуляции, хорошая изученность в отечественных и зарубежных экспериментальных и клинических исследованиях, а также высокая безопасность [52]. Авторы систематического обзора, посвященного оценке эффективности ГМДП при лечении заболеваний, ассоциированных с вирусом папилломы человека, идентифицировали 283 литературных первоисточника, по-священных изучению ГМДП в различных областях медицины, включая 58 публикаций, содержащихся в базе данных Pubmed/MEDLINE [26].…”

“…Включение ГМДП в комплексную терапию оказывало благоприятный эффект у женщин с различной урогенитальной патологией -воспалительными заболеваниями органов малого таза, бактериальным вагинозом, инфекциями, передающимися половым путем, и папилломовирусной инфекцией [19,26,67,68]. В недавно опубликованном систематическом обзоре, в который вошли 7 проспективных исследований, в том числе два плацебо-контролируемых и одно двойное слепое плацебо-контролируемое исследование, а также два исследования с участием детей в возрасте 9-12 и 14-15 лет, показано, что включение ГМДП в комплексную терапию заболеваний, ассоциированных с вирусом папилломы человека, приводит к повышению ее эффективности и увеличению продолжительности клинической ремиссии, а также к нормализации показателей клеточного и гуморального иммунитета.…”

“…При этом ни в одном исследовании, включенном в систематичесий обзор, при применении ГМДП не зарегистрировано ни одного нежелательного явления. Авторы обзора пришли к выводу, что рекомендацию по включению ГМДП дополнительно к деструктивным методам лечения в комплексную схему терапии заболеваний, ассоциированных с вирусом папилломы человека, можно отнести к категории А [26].…”