Long-Term Discontinuation of Botulinum Toxin A Intradetrusor Injections for Neurogenic Detrusor Overactivity: A Multicenter Study

Baron, M.; Peyronnet, B.; Aublé, A.; Hascoët, J.; Castel-Lacanal, É.; Miget, Gabriel; Doze, Sabine Le; Prudhomme, Thomas; Manunta, A.; Cornu, Jean‐Nicolas; Gamé, X.

doi:10.1016/j.juro.2018.10.012

Cited by 35 publications

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“…Two main reasons might explain that these innovations did not translated into a reduced urological mortality in spina bifida patients. First, several studies have evidenced that spina bifida patients might be poorly responsive to some of these latest neurourological treatments, especially to intradetrusor botulinum toxin injections [19][20]. The other putative explanation could be the well-established difficulties of many spina bifida patients with medical adherence, heavily influenced by multifactorial issues such as cognitive dysfunctions, mental health issues and parenting behaviors [21][22].…”

Section: Discussionmentioning

confidence: 99%

Urologic Disorders are Still the Leading Cause of In-hospital Death in Patients With Spina Bifida

Peyronnet

Gao

Brochard

et al. 2020

Urology

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Objective To assess and analyze the contemporary causes of inhospital deaths of spina bifida patients. Methods It was a cross-sectional observational study of the longitudinal national cohort of all patients hospitalized in French public and private hospitals. We analyzed the data from the French hospital discharge database (Programme de Médicalisation des Systemes d'Information, PMSI) from 2009 to 2014. The number of inhospital deaths was extracted using the combination of the ICD-10 codes "Q05" or "Q760" and a discharge code=9. Results There were 138 inhospital deaths of spina bifida patients over the 6-year study period. The median age at death was 41 years (IQR: 25-52). The median age at death was significantly lower in patients with vs. without hydrocephalus (26.6 vs. 45.5 years; p<0.0001). The leading cause of inhospital death was urological disorders (n=24; 17.3%). Other main causes of death were pulmonary disorders (n=23; 16.7%), neurological disorders (n=19; 13.8%) and bowel disorders (n=15; 10.9%). Upper urinary tract damage accounted for most of the urological causes of death: eight patients died from urinary tract infections (33.3%), seven patients died from renal failure (29.2%), four died from bladder cancer (16.7%) and five from other urological causes. The only variable significantly associated with a death from urological causes was the absence of hydrocephalus (OR=0.26; p=0.009). Conclusion Urological disorders remain the leading cause of inhospital death in spina bifida patients in France. The present study highlights that efforts to improve the urological management of the spina bifida population are still greatly needed.

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Section: Discussionmentioning

confidence: 99%

Urologic Disorders are Still the Leading Cause of In-hospital Death in Patients With Spina Bifida

Peyronnet

Gao

Brochard

et al. 2020

Urology

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“…9,10 Urinary markers may also help to find therapeutic targets for NLUTD in this population in whom usual neurourological treatments such as intradetrusor botulinum toxin has been proven less effective. 11,12 The aim of the present study was to assess the predictive values of six urinary markers (NGF, BDNF, TIMP-2, MMP-2, TGF-B1, and PGE-2) for high-risk urodynamic features and upper urinary tract damage in adult patients with spina bifida.…”

Section: Introductionmentioning

confidence: 99%

Urinary TIMP‐2 and MMP‐2 are significantly associated with poor bladder compliance in adult patients with spina bifida

Peyronnet

Richard

Bendavid

et al. 2019

Neurourology and Urodynamics

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Aims To assess the predictive values of six urinary markers (nerve growth factor [NGF], brain‐derived neurotrophic factor [BDNF], matrix metalloproteinase 2 [MMP‐2], tissue inhibitor metalloproteinase 2 [TIMP‐2], transformation growth factor β‐1 [TGF‐B1], and prostaglandin 2 [PGE2]) for adverse urodynamic features and for upper urinary tract damage in adult patients with spina bifida. Materials and methods A single‐center prospective trial was conducted from March 2015 to March 2017 including all consecutive adult patients with spina bifida seen for urodynamic testing. The urine was collected and stored at −80°C. A urodynamic and an upper urinary tract were systematically performed. At the end of the inclusion period, urines were defrosted and urinary nerve growth factor, BDNF, TIMP‐2, and TGF‐B1 were assessed using validated ELISA kits. The urinary markers levels were adjusted on the urinary creatinine level. Urinary MMP‐2 levels were assessed by zymography. Results Fourty patients were included. Only TIMP‐2 and MMP‐2 were significantly associated with poor bladder compliance (P = .043 and P = .039, respectively). TIMP‐2 was also the only urinary marker significantly associated with upper urinary tract damage on imaging (OR = 19.81; P = .02). Of all urodynamic parameters, bladder compliance and maximum detrusor pressure were the only ones associated with upper urinary tract damage on imaging (P = .01 and P = .02), The diagnostic performances of urinary TIMP‐2 for upper urinary tract damage were slightly superior to PdetMax and bladder compliance with an area under the curve of 0.72. Conclusion Urinary TIMP‐2 and MMP‐2 were significantly associated with poor bladder compliance and urinary TIMP‐2 was significantly associated with upper urinary tract damage. These findings support a pathophysiological role of extracellular matrix remodeling in poor bladder compliance of adult patients with spina bifida.

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“…In a recent review [ 27 ], summarizing 18 studies with a total of 1533 patients, discontinuation rates between 12.1 and 45.2% were described. A 10-year observation period in 140 patients showed an estimated 10-year discontinuation-free survival rate of 49.1% [ 13 ] and a discontinuation rate of 40% [ 12 ]. In addition to personal decisions and technical problems, antibody formation or structural changes in the detrusor are considered the main cause of treatment discontinuation.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have investigated the long-term outcomes and reasons for the discontinuation of BoNT-A injections [ 11 , 12 ]. However, the detailed mechanisms of therapy failure are unclear; biochemical processes such as antibody formation and structural changes in the detrusor muscle have been discussed [ 13 ], as well as technical issues and catheterization-related difficulties [ 14 ]. If neutralizing antibodies (NAbs) against BoNT-A can be detected, they are considered the cause of treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Can clinical and urodynamic parameters predict the occurrence of neutralizing antibodies in therapy failure of intradetrusor onabotulinumtoxin A injections in patients with spinal cord injury?

et al. 2020

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Background The aim of the study was to clarify whether clinical and/or urodynamic parameters could be used to infer the probability of neutralizing antibody (NAb) formation as a possible cause of therapy failure (non-response, NR) in patients with neurogenic detrusor overactivity (NDO) due to acquired spinal cord injury/disease (SCI/D) treated with intradetrusor botulinum neurotoxin A (BoNT-A) injections. Methods A retrospective chart review was performed of all patients with SCI/D who underwent both intradetrusor onabotulinumtoxin A injections and the determination of neutralizing antibodies against BoNT-A between January 1, 2002, and December 31, 2018. NR was defined as urodynamically confirmed persistent or reappearing NDO. Results A total of 2700 BoNT-A injections in 414 patients were ascertained. In 69 patients with primary NR after the first BoNT-A injection ( n = 6) or with secondary NR after more than one BoNT-A injection ( n = 63), an antibody analysis was performed. Antibody examination showed 36 (52.2%) negative, 5 (7.2%) borderline and 14 (each 20.3%) each of positive and highly positive values. Subgroup analysis indicated a correlation between NAb formation and the duration of BoNT-A therapy ( p = 0.015), the mean number of BoNT-A injections ( p = 0.011) and the time interval between BoNT-A applications (< 7 months, p = 0.022). Urodynamic data analysis indicate significant differences with cut-off values of MCC (< 225 ml, p = 0.038) and MDP (> 45 cmH 2 O, p = 0.040). However, in the regression analysis models, the predictive value for the occurrence of NAb was too low (MCC: ROC AUC 0.62, MDP: ROC AUC 0.52) to distinguish with sufficient certainty between NAb-positive and NAb-negative NR patients. Conclusions Despite significant correlations, clinical and urodynamic parameters are only partially suitable for predicting antibody formation against BoNT-A.

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Long-Term Discontinuation of Botulinum Toxin A Intradetrusor Injections for Neurogenic Detrusor Overactivity: A Multicenter Study

Cited by 35 publications

References 0 publications

Urologic Disorders are Still the Leading Cause of In-hospital Death in Patients With Spina Bifida

Urologic Disorders are Still the Leading Cause of In-hospital Death in Patients With Spina Bifida

Urinary TIMP‐2 and MMP‐2 are significantly associated with poor bladder compliance in adult patients with spina bifida

Can clinical and urodynamic parameters predict the occurrence of neutralizing antibodies in therapy failure of intradetrusor onabotulinumtoxin A injections in patients with spinal cord injury?

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