OAB is a chronic syndrome that is not life-threatening and does not progress to uncontrollable functional impairment, but has serious impacts on the patient's quality of life. Therefore, current research is increasingly focused on the impact of interventions on the quality of life of patients with OAB. For OAB treatment, improving patients' symptoms and reducing the incidence of adverse events are equally important for improving patients' quality of life and treatment compliance. his study aims to compare the therapeutic effects of different interventions in terms of efficacy and safety, and to identify the advantages and disadvantages of different drugs in the process of clinical application, so as to provide more direct data support for the individualized treatment and drug use of different patients in the clinic.
Ten OAB therapeutic agents were included in this study, involving a total of 19 interventions grouped by different doses administered, and the NMA results show that solifenacin had a relatively good overall efficacy and a significant advantage in improving patients' symptoms as in the previous study[6]. Solifenacin 10mg was the most effective in reducing the number of voiding and incontinence; solifenacin 5/10mg was the most effective in reducing urinary urgency and nocturia; solifenacin 10mg ranked second in both urgency incontinence and voided volume. In contrast, oxybutynin 5mg did not show the same efficacy and vibegron showed significant efficacy in incontinence compared with the previous study[6]. Besides FES4/8mg-QD and oxybutynin 5mg showed a better efficacy in urgency incontinence and voided volume per micturition, respectively. In terms of safety, the incidence of dry mouth events with solifenacin 5mg was not significantly different from placebo and was significantly lower than other anticholinergic drugs. Solifenacin is a competitive antagonist of M3 receptors and is highly specific and selective for bladder M3 receptors. The results of past studies have shown that solifenacin has a weaker blocking effect on salivary secretion than other anticholinergic drugs and that it inhibits salivary secretion at 3.6–6.5 times the effective concentration at which it produces an effect in the bladder[71, 72], which is consistent with the results of the present study. However, in the case of constipation, the results of this study showed that even a small dose of solifenacin (5mg) increased the incidence of constipation. Constipation has the greatest effect on patient satisfaction[73]. Therefore, the results suggest that solifenacin is not recommended for the clinical treatment of patients with OAB who are prone to constipation.
Different interventions have different pharmacological characteristics, and different doses may affect the efficacy of treatment, in addition to their safety. Therefore, it is necessary to select the appropriate medication and dose according to the individual patient's condition so that the patient's quality of life can be maximized.This NMA analyzed the incidence of dry mouth, constipation, nasopharyngitis, headache, hypertension, and urinary tract infection in the included studies and showed that anticholinergic drugs may increase the incidence of dry mouth and constipation, while imidafenacin may increase the risk of hypertension, and FES4/8mg-QD and CR-DAR15mg-QD increase the incidence of headache compared to placebo. SOL10mg-QD may increase the risk of urinary tract infections.
Before choosing a treatment plan, the benefits of the treatment plan for the patient and the possible risks and complications should be fully considered, and decisions should be made after weighing the pros and cons. In terms of efficacy, Vibegron and Mirabegron are superior to placebo and comparable to anticholinergics; although they do not show an efficacy advantage over anticholinergic drugs, their greatest advantage is in terms of safety, with both drugs showing good tolerability. In particular, vibegron and mirabegron have a significant advantage over cholinergic receptor antagonists with respect to dry mouth. As potent β3 agonists, vibegron and mirabegron relax the detrusor muscle by activating β3 receptors, thereby increasing bladder capacity and prolonging the interval between voiding without affecting bladder voiding activity. The selectivity for β3 receptors over other β receptor subtypes also suggests that both drugs are effective and well-tolerated novel drugs for OAB patients[74,75].
In the voided volume per micturition outcome indicator, there was inconsistency between the direct and indirect comparison results of SOL10mg-QD and PRO20mg-QD (p-value 0.017). Although the direct and indirect comparisons were significantly different, the results of the two interventions compared pointed towards the same direction, suggesting that SOL10 mg-QD was superior to PRO20 mg-QD, varying only in the degree of their difference, so the results were considered to be somewhat reliable.
Because of the overall inconsistency in this NMA study in terms of decreasing micturition/d and increasing voided volume/micturition, a subgroup regression analysis was performed. Despite the differences between male and female in the anatomy and physiology of the lower urinary tract system and the potential mechanisms of action that may lead to OAB-like symptoms[76], none of the clinical studies included "gender" as an analyzable data in detail, but simply expressed whether the proportion of women was ≥ 50%, so only subgroups of women ≥ and < 50% were analyzed in this study. The results of the subgroup analysis suggest that the results of Imidafenacin are opposite in the subgroups with greater than and less than 50% women, so it is speculated that the efficacy of imidafenacin in men and women may vary, which would need to be confirmed by the results of more single-sex studies.
To control for homogeneity in the included studies, strict entry row criteria were established and all 12-week efficacy indicators were used as the endpoints examined in this study, which avoided the introduction of clinical heterogeneity due to different study periods. Some limitations still exist in this study: 1. Because the quality of life measurements used in different studies are not uniform, this indicator of quality of life has not been analyzed and compared. Clinical endpoints can assess the effectiveness of symptom treatment from an objective perspective, but further research is needed to determine whether these symptom changes are relevant to the improvement of patients' quality of life. 2. No subgroup analysis of age was performed in this study. Existing studies have shown differences in the effectiveness of solifenacin versus mirabegron in elderly and non-differentiated age groups[77]. However, only 2 of the studies included in this study enrolled elderly subjects, so subgroup analysis could not be performed. requires long-term medication treatment, and the data from the 12-week study used in this study are not representative of its true efficacy and safety.