Hypothesis /Aims: The American Urological Association (AUA) guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA , sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. 
There has not been a direct comparison of the three available treatments, and there has also been a lack of efficiency and safety comparisons between the three treatment options. The current study used network meta-analysis to compare the efficacy of these three modalities for managing adult overactive bladder (OAB) syndrome.

Materials and Methods: We performed systematic literature searches of several databases from January 1995 to September 2019 with language restricted to English. 
All randomized control trials that compared any dose of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) with each other or a placebo for the management of adult overactive bladder (OAB) were included in the study.

Results: The initial search identified 1940 and 5722 potential studies from PubMed and EMBASE, respectively. After the removal of duplicates the total number of articles was 7662. After screening, a total of 5738 articles were excluded based on their title and/or abstract, while another 185 articles were removed after a full-text assessment. A total of 20 articles met the qualitative inclusion criteria, while 17 trials, including 3038 participants, met the criteria for systematic review and network meta-analysis. These 17 randomized control trials, with a follow up of 3–6 months in the predominance of trials (range 1.5–24 months), were included for analysis. For each trial outcome, the results were reported as an average number of episodes of the outcome at baseline.

Pairwise meta-analysis revealed that all three modalities were more efficacious than a placebo with regard to the outcomes of interests, including urinary frequency, incontinence, and achieving ≥50% of symptoms improvement. SNM achieved the greatest reduction in urinary incontinence episodes and voiding frequency/day. OnabotulinumtoxinA was associated with the highest risk of urine retention and UTI episodes in the follow-up period. As none of the included studies used a unified or standard questionnaire to evaluate the QoL, the results regarding QoL were not pooled for the meta-analysis. We suggested that International Continence Society or International Urogynecology Association should unify the QoL questionnaire based on evidence and experts’ opinion for a better evaluation of post treatment result. Compared with OnabotulinumtoxinA and PTNS, SNM resulted in the greatest reduction in urinary incontinence episodes and voiding frequency.

Conclusion: The results revealed that all three modalities were efficacious in managing adult OAB syndrome, and all were better than a placebo on the specific symptoms reported to be the outcome of the study. This review shows that at 12 weeks follow-up, SNM yielded the greatest reduction in urinary incontinence episodes and urinary frequency/day. OnabotulinumtoxinA resulted in a higher incidence of complications, including urinary tract infection and urinary retention. However, comparison of their long-term efficacy was lacking. Further studies on the long-term effectiveness of the three treatment options, with standardized questionnaires and parameters are warranted.