Efficacy and safety of first-line therapies and first-line-based combination therapies for monosymptomatic nocturnal enuresis in children: a network meta-analysis.
Combining desmopressin with anticholinergic agents may improve treatment outcomes for nocturnal enuresis in children, but further research is needed to confirm these findings.
Where it sits
this study against the rest of the desmopressin corpusSummary and findings
This network meta-analysis evaluated the efficacy and safety of first-line and combination therapies for monosymptomatic nocturnal enuresis in children, including desmopressin. Desmopressin combined with anticholinergic agents showed improved complete response rates compared to monotherapy. No significant differences in adverse events were observed across treatments.
Abstract
<h4>Objective</h4>To systematically evaluate the efficacy and safety of first-line therapies and first-line-based combination therapies for treating monosymptomatic nocturnal enuresis (MNE) in children using a network meta-analysis.<h4>Methods</h4>PubMed, Embase, the Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov were comprehensively searched to identify randomized controlled trials (RCTs) comparing either different first-line therapies or combination regimens involving first-line treatments versus monotherapy for MNE. Two researchers independently screened studies, extracted data according to predefined criteria, and assessed the methodological quality of the included trials. Data were analyzed using R software, with relative risk (RR) used as the effect size for dichotomous outcomes. The certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) approach.<h4>Results</h4>A total of 23 RCTs involving 2424 children and eight interventions were included. The network meta-analysis showed that desmopressin combined with oxybutynin, propiverine, solifenacin, or tolterodine was significantly more effective in achieving complete response (CR) than desmopressin monotherapy. Additionally, combinations of desmopressin with oxybutynin or tolterodine were superior to alarm monotherapy. No statistically significant differences were found among interventions regarding partial response (PR). For relapse rate, alarm monotherapy, desmopressin plus alarm, and desmopressin plus solifenacin were significantly better than desmopressin monotherapy. No significant differences in adverse events (AEs) were found across the interventions. In terms of CR, the top three interventions were desmopressin plus oxybutynin, desmopressin plus tolterodine, and desmopressin plus solifenacin. For PR, the leading treatments were desmopressin plus oxybutynin, desmopressin monotherapy, and alarm therapy. Regarding relapse rate, desmopressin plus solifenacin, alarm therapy, and desmopressin plus tolterodine ranked highest. For AEs, alarm therapy, desmopressin plus propiverine, and desmopressin monotherapy had the lowest incidence. The certainty of evidence for the primary outcome ranged from moderate to low according to the CINeMA assessment.<h4>Conclusion</h4>Desmopressin combined with anticholinergic agents significantly improved CR versus desmopressin monotherapy and demonstrated partial significant superiority over alarm therapy alone. Among these, desmopressin plus oxybutynin demonstrated the best overall efficacy. Alarm therapy and desmopressin alone showed similar therapeutic effectiveness. Desmopressin monotherapy was associated with a higher relapse rate. Importantly, combination therapy did not significantly increase the risk of AEs compared to monotherapies. According to the CINeMA framework, the certainty of evidence was mostly low to moderate, highlighting the need for cautious interpretation and further high-quality trials.
Background
Monosymptomatic nocturnal enuresis (MNE) in children is a common condition that can impact quality of life. While desmopressin is a standard treatment, its efficacy can vary, and relapse rates are a concern. This study aims to compare the efficacy and safety of first-line therapies and combination regimens to optimize treatment strategies for MNE.
Methods
The study conducted a network meta-analysis of 23 randomized controlled trials involving 2424 children. Various first-line therapies and combinations were compared, including desmopressin, anticholinergic agents, and alarm therapy. The primary outcome was complete response (CR), with secondary outcomes including partial response (PR), relapse rate, and adverse events (AEs). The analysis used relative risk (RR) as the effect size for dichotomous outcomes.
Results
Desmopressin combined with oxybutynin, tolterodine, or solifenacin significantly improved complete response rates compared to desmopressin monotherapy. Combinations of desmopressin with oxybutynin or tolterodine were superior to alarm monotherapy for CR. No significant differences were found among interventions for partial response. Alarm monotherapy and combinations with solifenacin showed lower relapse rates than desmopressin monotherapy. Adverse events did not significantly differ across treatments.
Interpretation
The study suggests that combining desmopressin with anticholinergic agents may enhance treatment efficacy for MNE compared to monotherapy. However, the low to moderate certainty of evidence limits the robustness of these conclusions. The findings align with previous research indicating potential benefits of combination therapy, but further high-quality trials are needed to confirm these results and assess long-term outcomes.
Key findings
- 23 RCTs, n=2424 children, 8 interventions.
- Desmopressin plus oxybutynin, tolterodine, or solifenacin improved CR vs monotherapy.
- Desmopressin plus oxybutynin or tolterodine superior to alarm monotherapy for CR.
- No significant differences in AEs across interventions.
- Certainty of evidence ranged from moderate to low (CINeMA).
Limitations
- Certainty of evidence mostly low to moderate.
- Network meta-analysis relies on indirect comparisons.
- Potential variability in study quality and methodologies.
- Lack of long-term follow-up data.