Women with recurrent urinary tract infections (rUTI) who are managed with antibiotics, suffer from personal morbidity. Furthermore, this management favors antibiotic resitance development and widespread, and also burdens the society with significant direct and indirect costs. MV140 (Uromune®) is a polybacterial sublingual vaccine consisting of whole inactivated bacteria (E. coli 25%, K. pneumoniae 25%, E. faecalis 25% and P. vulgaris 25%) that has proven an excellent clinical benefit in observational studies over 1,000 individuals. 
We aimed to evaluate the effect of MV140 on UTI-associated healthcare burden, as well as its efficacy and safety, in a randomized placebo-controlled trial.

A phase III multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group trial enrolled 240 women aged 18-75 years with rUTI (≥ 5 uncomplicated cystitis during the previous year) from Spain and United Kingdom. Patients were excluded if they could not offer cooperation and/or had severe psychiatric disorders or presented with a pathologic post-void residual urine, moderate to severe incontinence, genital and/or urinary tract’s tumours, urinary lithiasis, alterations in the immune system, or complicated UTIs.

The study lasted 12 months per subject. In the first 6 months, each subject received the treatment (active, placebo, or active and placebo) through the sublingual route as follows, applying two sprays daily. The last 6 months correspond to the follow-up period. Patients were randomly allocated to receive placebo for 6 months or MV140 for 3 or 6 months, in a 1:1:1 ratio. 

MV140 (trial medication) was a polyvalent bacterial vaccine containing a mixture of four inactivated non-lysated bacterial concentrates (Escherichia coli 25%, Klebsiella pneumoniae 25%, Enterococcus faecalis 25%, Proteus vulgaris 25%) as active substance.

Primary endpoint: mean number of episodes of UTI. Major secondary endpoints: UTI-free rate in the 9th month of the study period following 3 months of intervention.  Other secondary analyses: number of consultations due to rUTI needed, consumption of antibiotics, and expenses of the healthcare resources.

The number of subjects who received treatment (excluded screening failures) were 230 and those who finished were 195.
As primary outcome of the study, the number of UTI episodes were significantly reduced in the 9-month efficacy period (i.e. following 3 months of intervention) in subjects receiving MV140 compared to placebo. The median of UTI episodes was 3.0 in placebo group [IQR, 0.5-6.0] compared to 0.0 [IQR, 0.0-1.0] in both groups receiving MV140 (P<0.001).

A significant increase in the UTI-free rate (major secondary outcome) was found in subjects receiving active treatment compared to placebo (25.0% in placebo, 55.7% in MV140 3M and 58.0% in MV140 6M groups; P<0.001). The median time until the appearance of the first UTI was significantly delayed in MV140-receiving individuals. The results were similar when the 6-month efficacy period (i.e. following 6 months of intervention) and the whole study period (12 months after initiation of intervention) were evaluated. 

The median number of antibiotic prescriptions was 4.5 [Interquartile range, IQR, 1.0-8.5] for placebo group compared to 1.0 [IQR, 0.0-3.0] in both groups receiving MV140 (P<0.001) during the whole study period. A significant reduction (75.0-100.0% decrease) in the need for healthcare resources was observed in the subjects that received the bacterial vaccine when compared to placebo mainly due to non-programmed visits to the urologists, as well as the complementary tests carried out. No significant differences between active treatments (different schedules) were found, with subjects treated with 3 or 6 months active dosing schedules showing very similar results. The median quantity of the healthcare expenses per subject was 464.7 € [IQR, 0.0-929.4] for placebo group, compared to 132.8 € [IQR, 0.0-265.5] and 0.0 € [IQR, 0.0-132.8] in groups receiving MV140 for 3 and 6 months, respectively (both P<0.001).

Only 5 subjects (2.2%) reported non-serious adverse reactions, 2 from placebo (urticaria and thickened mucus) and 3 from MV140 3-month group (itchy mouth, sore mouth, gastric discomfort and general malaise and itching).

This is the first time to show in a randomized placebo-controlled trial that the administration of MV140 (Uromune®) reduced UTI-associated healthcare burden in women with rUTI, accompanying a strong clinical efficacy. No differences between 3- or 6-month administration schedules were noticed. Although the immunomodulating vaccine is more expensive than the antibiotics commonly used for the treatment of UTI, the savings for the healthcare system are worth it.

MV140 is an effective non-antimicrobial option to prevent recurrent UTI in adult women, while positively contributing to reduce healthcare use. Reduction of antibiotics may indirectly help to combat the uncontrolled rise of antimicrobial resistance.