Botulinum toxin A (BTX-A) injections have been shown to be effective and well tolerated in the treatment of idiopathic overactive bladder (OAB) refractory to oral pharmacotherapies. However, some patients exhibit little or no response to BTX-A and/or experience adverse events such as voiding dysfunction necessitating clean intermittent self-catheterisation (CISC) and urinary tract infections (UTI). Although BTX-A is well established in managing refractory OAB, little is know on those patients who fail treatment. Identifying factors that could predict failure or adverse events would be helpful in further improving outcomes for patients. The objective of this study was to systematically evaluate the published literature to assess whether any patient demographic, clinical or urodynamic factors were predictors for poor response and adverse events to BTX-A injections in patients with idiopathic OAB.

We performed an electronic search of the MEDLINE®, Embase® and Google Scholar databases in January 2018 according to the PRISMA guidelines. All studies reporting on predictive factors for poor response or adverse events to BTX-A injections in patients with idiopathic OAB were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, performed the data extraction and calculated the risk of bias for all included studies before the data was tabulated. The risk of bias was assessed using the Cochrane risk of bias assessment tool.

The search yielded 1441 articles, of which 12 were eligible for inclusion. Included studies were all cohort studies with level 2-3 evidence according to the Oxford Centre for Evidence-based Medicine levels of evidence. The majority of studies were level 3. Factors such as high pre-treatment maximum detrusor pressure (MDP), frailty, increasing age, smoking, poor bladder compliance and number of baseline leakage episodes have all been proposed as potential predictors of non-response. In predicting voiding dysfunction requiring CISC, factors such as voiding efficiency, bladder capacity, male gender, comorbidity, increasing age, detrusor contractility variables - PIP1, BCI and number of vaginal deliveries have all been implicated. Female gender and males with their prostates in situ have been suggested to increase the incidence of UTIs after BTX-A. The risk of bias assessment tool suggested a moderate to high risk of bias across all studies.

Significant detrusor pressures during filling cystometry may lead to severe OAB symptoms. Urge urinary incontinence severity may impact on efficacy due to the burden of symptoms especially if toxin doses were 100-200 U. Some studies would suggest higher toxin doses than what is currently licensed would be beneficial in such cases. Increasing age may effect outcomes as with age comes more co-morbidity and the potential for reduced detrusor contractility. In men one must also consider the role of benign prostatic enlargement and the possibility of secondary overactive bladder. Outcomes in this group maybe poorer as a result but also impact on voiding dysfunction post BTX-A and the need for CISC. It seems logical that those patients with poor detrusor contractility pre-treatment would be at an increased risk of voiding dysfunction post BTX-A. Studies included in the review lacked standardisation of definitions for a poor response and different toxin doses were utilised in different studies. Included studies were typically level 2-3 and therefore need confirming in larger better designed and better defined studies.

This review has identified a number of potential factors which may predict poor response and adverse events and thus help counsel patients prior to BTX-A treatment. However, current findings stem from small cohort studies, lacking standardised methodology, design and definition of poor response. Further large-scale trials are required to help better understand which patients will benefit most from this treatment. Patients who are likely to fail treatment or who don't accept the adverse events can then be channeled into alternative treatment options.