Effectiveness of Wobenzym in combined therapy of chronic bacterial prostatitis. Results of systematic review and meta-analysis

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INTRODUCTION

Chronic prostatitis is very common among young and middle-aged men [1, 2]. The global incidence of chronic prostatitis is 2.2–9.7% [2, 3]. In recent years, the incidence has been steadily growing [4–6]. Chronic inflammation in the prostate is caused by a variety of pathological reactions, including anatomical and physiological characteristics of the prostate, the presence of a pathogen capable of adhesion and biofilm production, microcirculatory disorders, and fibrosis [7, 8].

Exacerbations of chronic bacterial prostatitis (CBP) are characterized by pain, sexual dysfunction, dysuria, and psycho-emotional disorders [9, 10]. Currently, CBP is treated using combination therapy. Antibiotics are first-choice drugs. In 2023, the European Association of Urology (EAU) advocated using fluoroquinolones, despite uropathogens being highly resistant to them. Fluoroquinolones are recommended as first-line drugs for empirical treatment of CBP because of their good pharmacokinetic properties, generally favorable safety profile, and activity against gram-negative bacteria [11]. Pathogenesis-oriented combination therapy with antibiotics, herbal extracts, and alternative therapy drugs is recommended [12, 13]. However, symptoms persist in many patients even after treatment is completed [14], which is frequently associated with the failure to eradicate the CBP pathogen [9], immune disorders, and local inflammation with connective tissue fibrosis in the prostate.

Thus, the prevalence of CPB, recurrent or persistent inflammation, and increasing resistance of uropathogenic flora necessitate the search for drugs that improve therapy outcomes, with the potential for long-term use in combination therapy and subsequent relapse prevention.

To successfully treat CBP patients, drugs targeting individual components or influencing several components of pathogenesis are used as adjuvant/alternative therapy. An example of such drugs is Wobenzym, a combination of highly active plant and animal enzymes. This combination includes pancreatin, papain, bromelain, trypsin, lipase, amylase, chymotrypsin, and rutoside trihydrate. According to the product information, Wobenzym has anti-inflammatory, immunomodulatory, fibrinolytic, antiplatelet, antiedemic, and secondary analgesic effects¹. Enzyme combinations enhance the effect of antibacterials [15]. Wobenzym has the ability to improve etiotropic drug delivery to the site of infection, increase the accessibility of the carrier cell and pathogen receptors, reduce acidity at the inflammation site, and change the properties of microbial biofilms [16]. Enzymes enhance the phagocytic and cytotoxic activity of immune cells (monocytes/macrophages, natural killer cells, and T cells). The therapeutic effect of Wobenzym stems from its effects on inflammation, immunity, and vascular platelet hemostasis² [17]. The efficacy of Wobenzym in the treatment of CBP requires further research.

BACKGROUND

So far, no meta-analyses of the efficacy of Wobenzym in CBP have been published. As a result, crucial questions remain. What impact does it have on pathogen eradication rates? What impact does it have on symptoms and quality of life in CBP patients? What effect does Wobenzym have on blood flow and urine flow rate when added to combination therapy for CBP?

The aim of this study was to assess the efficacy of Wobenzym in combination therapy for CBP.

The review included randomized and non-randomized controlled efficacy studies of Wobenzym in combination therapy for CBP. The study included CBP patients, regardless of age, race, or social class. The study compared combination therapy for CBP with and without Wobenzym. The endpoints were defined as follows.

Primary endpoint:

1. Pathogen eradication rate after treatment.

Secondary endpoints:

1. Changes in the Quality of Life (QoL) score after treatment.
2. Changes in prostate ultrasound findings (peak systolic velocity in arteries, linear blood flow velocity in veins) after treatment.
3. Changes in the maximum urine flow rate after treatment.
4. Changes in the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score after treatment (Pain and Quality of Life domains).
5. Changes in immunogram parameters after treatment.

Electronic database search

The search was performed in the following databases: PubMed (https://www.nlm.nih.gov), using the search terms “clinical trial”, “humans”, “Wobenzym”, and “prostatitis”; Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library (https://www.cochranelibrary.com/central), National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov), and World Health Organization International Clinical Trials Registry Platform (ICTRP) (https://www.who.int/ictrp/en/), using the search term “Wobenzym”; Google Scholar (https://scholar.google.ru/), using the search terms “clinical trial”, “Wobenzym”, “prostatitis”, “исследование” (clinical trial), “Вобэнзим” (Wobenzym), and “простатит” (prostatitis); eLibrary.ru (http://elibrary.ru), using the search terms “Вобэнзим” (Wobenzym), and “простатит” (prostatitis); CyberLeninka (http://cyberleninka.ru), using the search terms “clinical trial”, “Wobenzym”, “prostatitis”, “исследование” (clinical trial), “Вобэнзим” (Wobenzym), and “простатит” (prostatitis); Gray Zone (search engine results), using the search terms “clinical trial”, “Wobenzym”, and “prostatitis”, “исследование” (clinical trial), “Вобэнзим” (Wobenzym), and “простатит” (prostatitis).

Study heterogeneity assessment

The degree of heterogeneity was assessed visually, and forest plots were made. A quantitative assessment was also conducted by calculating the chi-square test (threshold: p < 0.10), I², and τ². The following heterogeneity classification for I² values was used: 0–25%, no heterogeneity; 25–50%, low; 50–75%, moderate; >75%, high.

Bias assessment

The risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins J., 2021) [18] for randomized and non-randomized studies. The assessment was performed according to the Cochrane Collaboration guidelines [19] using a validated questionnaire by O.Yu. Rebrova et al. (2015) [20]. The Robvis tool was used for data visualization [21]. We rated the risk of bias as “low,” “high,” or “unclear” for each study separately and for all studies together. Any disagreements that emerged at any point were settled through discussion.

Data synthesis

Data synthesis was based on a conservative assumption that all authors provided their findings as standard error (SE), which were then converted to standard deviation (SD) according to the formula $SD=SE \times \sqrt{n}$  where n is the number of patients in the group. The R language and RStudio platform (version R) were used for the analysis.

Data integration and analysis

We used the GRADE approach for data interpretation [22].

Search results

Following the search and screening of eligible studies, 9 of 712 identified articles were included in the analysis (Fig. 1).

 

Fig. 1. Block diagram PRISMA [23]

Рис. 1. Блок-схема PRISMA [23]

 

None of the studies had a high risk of bias in any domain (Fig. 2).

 

Fig. 2. Assessing the risk of bias across studies. D1 — confounding bias; D2 — selection bias, D3 — intervention classification bias; D4 — intervention bias; D5 — missing data bias; D6 — bias when measuring results; D7 — systematic error in selecting the reported result

Рис. 2. Оценка риска систематической ошибки по исследованиям. D1 — предвзятость из-за смешения; D2 — предвзятость в отборе участников исследования; D3 — предвзятость в классификации вмешательств; D4 — смещение из-за отклонений от запланированных вмешательств; D5 — систематическая ошибка из-за отсутствия данных; D6 — систематическая ошибка при измерении результатов; D7 — систематическая ошибка при выборе сообщаемого результата; Low — низкий; Moderate — умеренный; No information — нет информации

 

RESULTS

The review included 9 non-randomized studies in 1,292 CBP patients. The studies were published in the Russian language between 2004 and 2020. Their characteristics are presented in Table 1.

 

Table 1. Main characteristics of included studies Таблица 1. Основные характеристики включенных исследований
Author, year	Pathology	Randomization	Subjects, n	Mean age	Treatment group		Control group
					n	therapy	n	therapy
Dzhalilov H.N. (2020) [24]	CBP	no	84	67.5	44	Drugs improving prostate microcirculation and hemodynamics, antibiotics, polyoxidonium, Wobenzym	40	Drugs improving rostate microcirculation and hemodynamics, antibiotics
Dosta N.I. (2013) [15]	CBP	no	35	21.0±7.9	20	Antibiotics, Wobenzym	15	Antibiotics
Ershov E.V. (2007) [25]	CBP	no	239	25.6±3.5	66	Antibiotics, Wobenzym	40	Antibiotics
Kodiri T.R. (2013) [26]	CBP	no	68	–	28	Antibiotics, Wobenzym	40	Antibiotics
Noskov N.Yu. (2004) [27]	CBP	no	110	–	70	Antibiotics, Wobenzym	40	Antibiotics
Tkachuk V.N. (2015) [28]	CBP	no	250	28.6±4.5	210	Antibiotics, Wobenzym	40	Antibiotics
Tkachuk V.N. (2007) [29]	CBP	no	237	28.3±2.9	70	Antibiotics, Wobenzym	65	Antibiotics
Solihov D.N. (2009) [30]	CBP	no	135	33.5±4.6	70	Antibiotics, Wobenzym	65	Antibiotics
Dzhalilov H.N. (2019) [31]	CBP	no	134	–	67	Antibiotics, Wobenzym	67	Antibiotics

 

Pathogen eradication rate after treatment

This parameter was provided in the required format in the following articles: Dosta N.I. (2013) [15], Ershov E.V. (2007) [25], Noskov N.Yu. (2004) [27], Tkachuk V.N. (2015) [28], and Tkachuk V.N. (2007) [29] (Table 2).

 

Table 2. Results of studies on eradication of uropathogens Таблица 2. Результаты исследований по эрадикации уропатогенов
Author, year	Treatment group			Control group
	n	uropathogen isolation rate, %		n	uropathogen isolation rate, %
		before treatment	after treatment		before treatment	after treatment
Dosta N.I. (2013) [15]	20	100	47	15	100	73.0
Ershov E.V. (2007) [25]	66	100	4.5	40	100	37.5
Noskov N.Yu. (2004) [27]	70	100	4.3	40	100	35
Tkachuk V.N. (2015) [28]	210	100	3.8	40	100	44.5
Tkachuk V.N. (2007) [29]	70	100	4.3	65	100	35.3

 

Fig. 3. Meta-analysis of the frequency of eradication of pathogens after therapy including Wobenzym

Рис. 3. Метаанализ частоты эрадикации возбудителей после терапии, включающей Вобэнзим

 

There was no heterogeneity (I² = 0%), τ² = 0.18 and 0.005, p > 0.10. The 95% confidence interval (CI) of the pooled odds ratio (OR), calculated for both the fixed and random effects models, did not cross 1 (Table 3, ä).

 

Table 3. Eradication rates and eradication odds ratios of uropathogens for each study Таблица 3. Частота эрадикации и отношение шансов эрадикации уропатогенов по каждому исследованию
Study	Treatment group		Control group		OR	95% CI
						lower limit	upper limit
	n	events	n	events
Dosta N.I. (2013) [15]	20	11	15	4	3.36	0.79	14.25
Ershov E.V. (2007) [25]	66	63	40	25	12.60	3.35	47.32
Noskov N.Yu. (2004) [27]	70	67	40	26	12.03	3.19	45.32
Tkachuk V.N. (2015) [28]	210	202	40	23	18.66	7.26	48.00
Tkachuk V.N. (2007) [29]	70	67	65	42	12.23	3.46	43.27
Note. OR, odds ratio; CI, confidence interval.

 

Thus, therapy with Wobenzym in CBP patients significantly more often results in pathogen eradication compared to therapy without Wobenzym. The OR of the fixed effects model was 11.19 (95% CI 6.42, 19.50; p = 0.00); the OR of the random effects model was 11.22 (95% CI 5.75, 21.88; p = 0.00).

Changes in the QoL score after treatment with Wobenzym

This parameter was provided in the required format in the following articles: Dosta N.I. (2013) [15], Jalilov Kh.N. (2020) [24], and Jalilov Kh.N. (2019) [31] (Table 4).

 

Table 4. Quality of life indicators on the QoL scale according to research data Таблица 4. Показатели качества жизни по шкале QoL по данным исследований
Study	Treatment group			Control group			MD	95% CI
	n	M	SD	n	M	SD		lower limit	upper limit
Dzhalilov H.N. (2019) [31]	44	1.8	1.33	40	4.0	0.89	–2.2	–2.68	–1.72
Dzhalilov H.N. (2020) [24]	51	2.7	2.14	51	4.2	3.57	–1.5	–2.64	–0.36
Dosta N.I. (2013) [15]	20	1.0	3.13	15	2.0	1.55	–1.0	–2.58	0.58
Note. Here and in Tables 5–9: M, mean; SD, standard deviation; MD, mean difference; CI, confidence interval.

 

Heterogeneity was low (I² = 32%), τ² = 0.17, p > 0.10. The 95% CI of the pooled mean difference for a decrease in the QoL score, calculated for both the fixed and random effects models, did not cross 0, indicating a positive effect of the treatment on quality of life (Fig. 4).

 

Fig. 4. Meta-analysis of changes in QoL scores after treatment

Рис. 4. Метаанализ изменения баллов по шкале QoL после лечения

 

Thus, therapy with Wobenzym in CBP patients significantly decreases the QoL score compared to therapy without Wobenzym, indicating an improvement in quality of life. The mean difference (MD) was –2.02 (95% CI –2.44, –1.59; p = 0.00) in the fixed effects model and –1.82 (95% CI –2.54, –1.11; p = 0.00) in the random effects model.

Changes in the linear blood flow velocity in prostate veins after treatment

This parameter was provided in the required format in the following articles: Ershov E.V. (2007) [25] and Tkachuk V.N. (2015) [28] (Table 5).

 

Table 5. Indicators of linear blood flow velocity in the veins of the prostate gland according to research data, cm/s Таблица 5. Показатели линейной скорости кровотока в венах предстательной железы по данным исследований, см/с
Study	Treatment group			Control group			MD	95% CI
	n	M	SD	n	M	SD		lower limit	upper limit
Ershov E.V. (2007) [25]	66	4.92	1.54	40	3.98	1.01	0.94	0.45	1.43
Tkachuk V.N. (2015) [28]	210	4.91	4.49	40	3.12	3.23	1.79	0.62	2.96

 

Heterogeneity was low (I² = 42%), τ² = 0.17, p > 0.10. The 95% CI of the pooled mean difference, calculated for both the fixed and random effects models, did not cross 0 (Fig. 5).

 

Fig. 5. Meta-analysis of changes in the linear velocity of blood flow in the veins of the prostate gland after treatment

Рис. 5. Метаанализ изменения линейной скорости кровотока в венах предстательной железы после лечения

 

Thus, therapy with Wobenzym in CBP patients significantly increases the linear blood flow velocity in prostate veins by more than 1 cm/s compared to therapy without Wobenzym. The mean difference (MD) was 1.07 (95% CI 0.62, 1.51; p = 0.00) in the fixed effects model and 1.20 (95% CI 0.42, 1.68; p = 0.00) in the random effects model.

Changes in the peak systolic velocity in prostate arteries after treatment

This parameter was provided in the required format in the following articles: Ershov E.V. (2007) [25], Tkachuk V.N. (2007) [29], and Tkachuk V.N. (2015) [28] (Table 6).

 

Table 6. Indicators of peak systolic blood flow velocity in the arteries of the prostate gland according to research data, cm/s Таблица 6. Показатели пиковой систолической скорости кровотока в артериях предстательной железы по данным исследований, см/с
Study	Treatment group			Control group			MD	95% CI
	n	M	SD	n	M	SD		lower limit	upper limit
Ershov E.V. (2007) [25]	66	13.92	2.84	40	10.62	3.42	3.30	2.04	4.56
Tkachuk V.N. (2007) [29]	70	13.02	3.01	65	10.06	6.77	2.96	1.17	4.75
Tkachuk V.N. (2015) [28]	210	14.02	5.65	40	10.06	3.42	3.96	2.65	5.27

 

There was no heterogeneity (I² = 0%), τ² = 0.06, p > 0.10. The 95% CI of the pooled mean difference, calculated for both the fixed and random effects models, did not cross 0 (Fig. 6).

 

Fig. 6. Meta-analysis of changes in peak systolic blood flow velocity in the prostate arteries after treatment

Рис. 6. Метаанализ изменения пиковой систолической скорости кровотока в артериях предстательной железы после лечения

 

Thus, therapy with Wobenzym in CBP patients significantly increases the peak systolic velocity in prostate arteries compared to therapy without Wobenzym. The between-group difference was 3.5 cm/s; thus, the peak systolic velocity in patients receiving Wobenzym was approximately 30% higher compared to control. The mean difference (MD) was 3.48 (95% CI 2.67, 4.29; p = 0.00) in the fixed effects model and 3.48 (95% CI 2.62, 4.34; p = 0.00) in the random effects model.

Changes in the maximum urine flow rate after treatment

This parameter was provided in the required format in the following articles: Kodiri T.R. (2013) [28], Solikhov D.N. (2009) [30], and Jalilov Kh.N. (2019) [31] (Table 7).

 

Table 7. Indicators of maximum urine flow rate according to research data, mL/s Таблица 7. Показатели максимальной скорости потока мочи по данным исследований, мл/с
Study	Treatment group			Control group			MD	95% CI
	n	M	SD	n	M	SD		lower limit	upper limit
Dzhalilov H.N. (2019) [31]	44	19.0	8.62	40	13.1	7.59	5.9	2.43	9.37
Kodiri T.R. (2013) [28]	28	19.5	6.35	40	13.2	10.75	6.3	2.22	10.38
Solihov D.N. (2009) [30]	70	19.0	10.88	65	13.1	9.67	5.9	2.43	9.37

 

There was no heterogeneity (I² = 0%), τ² = 0.0005, p > 0.10. The 95% CI of the pooled mean difference, calculated for both the fixed and random effects models, did not cross 0 (Fig. 7).

 

Fig. 7. Meta-analysis of changes in maximum urine flow rate after treatment

Рис. 7. Метаанализ изменения максимальной скорости потока мочи после лечения

 

Thus, therapy with Wobenzym in CBP patients significantly increases the maximum urine flow rate compared to therapy without Wobenzym. The mean difference (MD) was 6.01 (95% CI 3.9, 8.11; p = 0.00) in the fixed effects model and 6.01 (95% CI 3.9, 8.11; p = 0.00) in the random effects model.

Changes in the NIH-CPSI Pain domain score after treatment

This parameter was provided in the required format in the following articles: Dosta N.I. (2013) [15] and Tkachuk V.N. (2015) [28] (Table 8).

 

Table 8. NIH-CPSI Pain Subscale Scores according to research data Таблица 8. Показатели баллов подшкалы «Боль» NIH-CPSI по данным исследований
Study	Treatment group			Control group			MD	95% CI
	n	M	SD	n	M	SD		lower limit	upper limit
Dosta N.I. (2013) [15]	20	5.9	8.50	15	8.1	3.49	–2.2	–6.32	1.92
Tkachuk V.N. (2015) [28]	210	2.1	7.25	40	8.4	7.59	–6.3	–8.85	–3.75

 

Heterogeneity was moderate (I² = 64%), τ² = 4.87, p = 0.10. The 95% CI of the pooled mean difference, calculated for both the fixed and random effects models, did not cross 0 (Fig. 8).

 

Fig. 8. Meta-analysis of changes in NIH-CPSI Pain subscale scores after treatment

Рис. 8. Метаанализ изменения баллов подшкалы «Боль» NIH-CPSI после лечения

 

Thus, therapy with Wobenzym in CBP patients significantly decreases the NIH-CPSI Pain domain score compared to therapy without Wobenzym. The between-group difference was 5 points. The mean difference (MD) was –5.17 (95% CI –7.33, –3.0; p = 0.00) in the fixed effects model and –4.60 (95% CI –8.45, –0.76; p = 0.02) in the random effects model.

Changes in the NIH-CPSI Quality of Life domain score after treatment

This parameter was provided in the required format in the following articles: Dosta N.I. (2013) [15] and Tkachuk V.N. (2015) [28] (Table 9).

 

Table 9. NIH-CPSI Quality of Life Subscale Scores according to research data Таблица 9. Показатели баллов подшкалы «Качество жизни» NIH-CPSI по данным исследований
Study	Treatment group			Control group			MD	95% CI
	n	M	SD	n	M	SD		lower limit	upper limit
Dosta N.I. (2013) [15]	20	2.0	4.02	15	3.0	1.94	–1.0	–3.02	1.02
Tkachuk V.N. (2015) [28]	210	3.1	5.80	40	6.5	3.79	–3.4	–4.81	–1.99

 

Heterogeneity was moderate (I² = 73%), τ² = 1.86, p < 0.10. The 95% CI of the pooled mean difference, calculated for both the fixed and random effects models, did not cross 0 (Fig. 9).

 

Fig. 9. Meta-analysis of change in NIH-CPSI Quality of Life subscale scores after treatment

Рис. 9. Метаанализ изменения баллов подшкалы «Качество жизни» NIH-CPSI после лечения

 

Thus, therapy with Wobenzym in CBP patients significantly decreases the NIH-CPSI Quality of Life domain score compared to therapy without Wobenzym. The between-group difference was 2 points. The mean difference (MD) was –2.61 (95% CI –3.77, –1.45; p = 0.00) in the fixed effects model and –2.32 (95% CI –4.57, –0.08; p = 0.04) in the random effects model.

Changes in immunogram parameters after treatment

This parameter was provided in the required format only in one article: Noskov N.Yu. (2004) [27] (Table 10).

 

Table 10. Immunogram parameters according to the study by N.Yu. Noskov (2004) [27] Таблица 10. Показатели иммунограммы у больных по данным исследования Н.Ю. Носкова (2004) [27]
Immunology parameters	Before treatment	After treatment
		Treatment group		Control group
		M±SD	р	M±SD	р
CD3+ T cells, %	82.9±9.4	69.4±8.8	<0.01	79.5±10.1	0.1
CD4+ T cells, %	24.1±3.8	41.6±8.8	<0.01	35.4±7.1	<0.05
CD8+ T cells, %	18.1±2.4	24.8±3.5	<0.01	20.5±1.7	<0.05
CD22+ T cells, %	14.3±0.9	23.6±2.4	<0.01	19.4±3.3	<0.05
PHA-induced lymphocyte activity, cpm	4310±106	7231±80	<0.01	4935±215	<0.05
CH 100, RU	98.5±5.3	169.8±8.4	<0.01	109.1±5.1	<0.05
Circulating immune complexes, RU	0.05±0.008	0.07±0.005	<0.05	0.06±0.009	<0.05
CD4/CD8, RU	1.33±0.3	1.68±0.5	<0.01	1.73±0.4	<0.01
IgM, g/L	0.5±0.1	0.9±0.3	<0.01	0.6±0.3	<0.05
IgG, g/L	6.0±0.4	10.3±0.4	<0.01	8.3±1.1	<0.05
IgA, g/L	2.2±0.6	3.4±0.7	<0.01	2.6±0.5	<0.05
Note. M, mean; SD, standard deviation; MD, mean difference; CI, confidence interval; PHA, phytohemagglutinin.

 

After the treatment, immunogram parameters significantly improved in both groups. However, there was a greater increase in CD4⁺ T cells, CD8⁺T cells, lymphocyte activity, СН100, and IgM, IgG, and IgA in the treatment group [29].

The study by Tkachuk V.N. et al. (2015) [28] also provides immunology examination findings. Patients in the treatment group who received combination therapy with Wobenzym showed an improvement in all immunology parameters significantly earlier. Before treatment, CBP patients had immunodeficiency with T-cell immunity disorders and decreased phagocytic activity. After treatment, the treatment group showed an increase in CD3⁺ T-cells from 35.6±2.9 to 49.3±2.7% (p < 0.01), CD4⁺ T-cells from 17.9±2.1 to 32.4±1.9% (p < 0.01), B-cells (CD22⁺) from 14.3±0.9 to 20.5±1.8% (p < 0.05), T-helper/ T-suppressor ratio from 1.1±0.1 to 1.7±0.3 (p < 0.05), and functional lymphocyte activity from 4,338±209 to 7,396±346 cpm (p < 0.001).

CONCLUSIONS

We found 9 non-randomized efficacy studies of combination therapy with Wobenzym in CBP patients vs. standard of care.

The meta-analysis revealed the following:

1. The majority of studies showed that therapy with Wobenzym in CBP patients significantly more often results in pathogen eradication compared to therapy without Wobenzym. The OR of the fixed effects model was 11.19 (95% CI 6.42, 19.50; p = 0.00); the OR of the random effects model was 11.22 (95.% CI 5.75, 21.88; p = 0.00).
2. Therapy with Wobenzym in CBP patients significantly decreases the QoL score compared to therapy without Wobenzym. The studies showed a significant between-group difference of 2 points. MD was –2.02 (95% CI –2.44, –1.59; p = 0.00) in the fixed effects model and –1.82 (95% CI –2.54, –1.11; p = 0.00) in the random effects model.
3. Therapy with Wobenzym in CBP patients significantly increases the linear blood flow velocity in prostate veins by more than 1 cm/s compared to therapy without Wobenzym. The studies showed a significant improvement in prostate blood flow. MD was 1.07 (95% CI 0.62, 1.51; p = 0.00) in the fixed effects model and 1.20 (95% CI 0.42, 1.68; p = 0.00) in the random effects model. The result was significant, with a significant between-group difference.
4. Therapy with Wobenzym in CBP patients significantly increases the peak systolic velocity in prostate arteries compared to therapy without Wobenzym. The between-group difference was 3.5 cm/s. MD was 3.48 (95% CI 2.67, 4.29; p = 0.00) in the fixed effects model and 3.48 (95% CI 2.62, 4.34; p = 0.00) in the random effects model.
5. Therapy with Wobenzym in CBP patients significantly increases the maximum urine flow rate compared to therapy without Wobenzym. MD was 6.01 (95% CI 3.9, 8.11; p = 0.00) in the fixed effects model and 6.01 (95% CI 3.9, 8.11; p = 0.00) in the random effects model.
6. Therapy with Wobenzym in CBP patients significantly decreases the NIH-CPSI Pain domain score compared to therapy without Wobenzym. The between-group difference was 5 points. MD was –5.17 (95% CI –7.33, –3.0; p = 0.00) in the fixed effects model and –4.60 (95% CI –8.45, –0.76; p = 0.02) in the random effects model.
7. Therapy with Wobenzym in CBP patients significantly decreases the NIH-CPSI Quality of Life domain score compared to therapy without Wobenzym. The result was significant; however, heterogeneity was high. The between-group difference was 2 points. High heterogeneity can be explained by a small number of included studies. MD was –2.61 (95% CI –3.77, –1.45; p = 0.00) in the fixed effects model and –2.32 (95% CI –4.57, –0.08; p = 0.04) in the random effects model.
8. Therapy with Wobenzym in CBP patients provides a greater increase in CD4⁺ T-cells, CD8⁺ T-cells, lymphocyte activity, СН100, and IgM, IgG, and IgA.

Overall completeness and applicability of evidence

In general, all studies used the same Wobenzym dosage regimen and treatment duration. The age of study subjects varied widely, from young to older patients; thus, study findings can be applied to the population receiving Wobenzym in real-world practice.

Quality of evidence

None of the studies had a high risk of bias in any domain. The majority of risk domains had an unclear risk of bias.

Risk of bias during the review

We extracted the data without any limitations.

Agreement and disagreement with other studies and reviews

We could not find any other systematic reviews of the efficacy of Wobenzym in combination therapy for CBP in open sources.

Commercial impact

None of the studies had a conflict of interest to declare.

CONCLUSION

The systematic review and meta-analysis confirmed the positive effect of Wobenzym when added to combination therapy for CBP. Combination therapy including Wobenzym provides an 11-fold increase in pathogen eradication rate compared to therapy without Wobenzym. This is essential for the treatment of prostate infection and inflammation, and is linked to pathogenesis-oriented anti-inflammatory and antibiofilm effects of the drug, as well as its influence on pathogen mobility and adhesion. Moreover, combination therapy with Wobenzym enhances blood flow to the prostate, as indicated by improved arterial and venous microcirculation in the prostate tissues. This appears to be attributable to the drug’s beneficial influence on the course of inflammation, as well as improvements in blood rheology and vascular platelet hemostasis.

When added to chronic prostatitis therapy, Wobenzym improves maximum urine flow rate and urination by reducing prostate tissue swelling. Therapy with Wobenzym decreases the severity of prostatitis symptoms, as indicated by a decrease in the NIH-CPSI score (Pain and Quality of Life domains) and the QoL score. These findings suggest reversal or reduction in symptoms and improvement in the quality of life of CBP patients in the study group.

When added to chronic prostatitis therapy, Wobenzym promotes immune defense, which is indicated by a greater increase in CD4⁺ T-cells, CD8⁺ T-cells, lymphocyte activity, СН100, and IgM, IgG, and IgA, compared to patients who did not receive Wobenzym.

Given the foregoing, the objective, significant positive effect of Wobenzym as part of combination therapy in CBP patients can be attributed to its pathogenetic action in this patient population.

To gather evidence and produce more reliable findings, randomized blinded studies with similar endpoints and follow-up periods should be conducted in CBP patients.

ADDITIONAL INFORMATION

Acknowledgements. The authors are grateful to a scientific agency Sciencefiles for assistance in the advanced statistical processing during the drafting of an article.

Authors’ contribution. All authors made a substantial contribution to the conception of the study, acquisition, analysis, interpretation of data for the work, drafting and revising the article, final approval of the version to be published and agree to be accountable for all aspects of the study.

Personal contribution of each author: Yu.A. Kupriyanov — data collection; A.V. Zaitsev — review of publications; A.N. Bernikov — data analysis; L.A. Khodyreva — writing the text of the manuscript; D.Yu. Pushkar — research concept, scientific editing, scientific guidance.

Funding source. This study was not supported by any external sources of funding.

Competing interests. The authors declare that they have no competing interests.

 

¹ Wobenzym Summary of Product Characteristics ЛП-№(002667)-(РГ-RU) dated June 30, 2023. https://grls.minzdrav.gov.ru/InstrImg/2023/07/13/1495064/c9c87bad-c031-41fb-b6eb-1fe76b5d97fd.pdf

² Wobenzym Summary of Product Characteristics ЛП-№(002667)-(РГ-RU) dated June 30, 2023. https://grls.minzdrav.gov.ru/InstrImg/2023/07/13/1495064/c9c87bad-c031-41fb-b6eb-1fe76b5d97fd.pdf

About the authors

Yuriy A. Kupriyanov

Russian University of Medicine; Research Institute of Health Care Organization and Medical Management of the Moscow City Health Department; S.P. Botkin City Clinical Hospital

Email: dr.kupriyanov@mail.ru
ORCID iD: 0000-0002-5807-7591
SPIN-code: 5203-9824

Cand. Sci. (Medicine), Associate Professor

Russian Federation, Moscow; Moscow; Moscow

Andrey V. Zaitsev

Russian University of Medicine

Email: zaitcevandrew@mail.ru
SPIN-code: 6223-5408
Scopus Author ID: 7201772210

Dr. Sci. (Medicicne), Professor

Russian Federation, Moscow

Alexander N. Bernikov

Russian University of Medicine

Email: bernikov@mac.com
ORCID iD: 0000-0001-8361-585X
SPIN-code: 9288-4518

Cand. Sci. (Medicine), Associate Professor

Russian Federation, Moscow

Lyubov A. Khodyreva

Research Institute of Health Care Organization and Medical Management of the Moscow City Health Department

Author for correspondence.
Email: Khodyreva60@mail.ru
ORCID iD: 0000-0002-0751-4982
SPIN-code: 3565-5366
Scopus Author ID: 6602548630

Dr. Sci. (Medicine)

Russian Federation, 9 Sharikopodshipnikovskaya st., Moscow, 115080

Dmitry Yu. Pushkar

Russian University of Medicine; S.P. Botkin City Clinical Hospital

Email: pushkardm@mail.ru
ORCID iD: 0000-0002-6096-5723
SPIN-code: 8221-8306
Scopus Author ID: 24171496100

Academician of the Russian Academy of Sciences, Dr. Sci. (Medicicne), Professor

Russian Federation, Moscow; Moscow

References

Supplementary files