Introduction
Historically, for patients with myelomeningocele, once they become refractory to oral therapy and clean intermittent catheterization, the primary option for renal preservation or symptom management was enterocystoplasty and/or urinary diversion. Although it is the gold standard for refractory neurogenic bladder, enterocystoplasty is associated with long term morbidity1. As a result, there has been increased use of intravesical Botulinum toxin (IVB) injection in the myelomeningocele population to reduce urinary incontinence and improve urodynamic parameters. Hascoet et al. found that IVB resulted in complete resolution of incontinence in 32 to 100% of patients with an average 28–180% increase in compliance after the first injection.2 IVB gained FDA approval for detrusor overactivity in the adult neurogenic bladder population in 2011,3 and recently gained approval for this same indication in pediatric patients in February 2021 based on reduction in daily incontinence episodes.4 Due to its efficacy, IVB could delay or diminish indications to initiate enterocystoplasty in some patients.5 There remain however questions regarding its long-term durability.2
Population-level data has not been used to evaluate the use of IVB and its effect on the use of enterocystoplasty. Moreover, while complications secondary to enterocystoplasty have been evaluated, there has not been a comparison of outcomes between enterocystoplasty and IVB. Thus, the objectives of this study were to compare utilization trends of IVB and enterocystoplasty in the pediatric compared to the adult myelomeningocele population, and to compare healthcare utilization and outcomes post-treatment. We hypothesize that IVB use has increased over time since 2011 in the spina bifida patient population, and that there has been a corresponding decrease in enterocystoplasty.
Methods
The Truven Analytics MarketScan database of Commercial Claims Encounters (MSCCE) was queried from January 1, 2008 to December 31, 2017 for all patients with a diagnosis of myelomeningocele (ie. spina bifida) identified using International Classification of Diseases 9th edition (ICD9) and 10th edition (ICD10 codes (Supplementary Table 1). The MSCCE contains information from adjudicated and paid insurance claims filed for employment insured individuals. We collected demographic data on patient age at the time of enrollement in the database, sex, region, rurality, and insurance benificiary relationship. We also identified myelomeningocele location based on ICD9/10 coding (Supplementary Table 1), other relevant comorbidities using ICD9/10 codes (Supplementary Table 1), and the number of unique anticholinergic drugs based on the generic identifier (Supplementary Table 1), and unique prescription drugs the patients received prior to their index procedure.
All patients were followed through their enrollment period. Peditric patients were categorized as such until age 21 years. We identified those who received either IVB or enterocystoplasty. IVB was identified using Current Procedural Terminology (CPT) codes for chemodenervation of the bladder (CPT 52287), or a combination of a cystoscopy (CPT 52000 or 53899) and an Healthcare Common Procedure Coding System code for Onabotulinum (J0585) or AbobotulinumtoxinA (J0586). Enterocystoplasty was identified using a CPT code for enterocystoplasty with intestinal anastomosis (CPT 51960), ICD-9 Clinical Modification (CM) for augmentation of bladder (ICD-9CM 57.87), or a record with a procedure code for repair of the bladder (CPT 51800) with a concurrent diagnostic code for neurogenic bladder (ICD9: 596.5x; ICD10: N31.0, N31.1, N31.8, N31.9, N32.81, N39.41, N39.46)6. Patients were categorized by their index procedure and they were assigned the date of the procedure as the index date. If they received both procedures (IVB and enterocystoplasty), they were categorized by whichever came first.
Patients were followed up to 10 years post-index procedure to identify days of hospitalization, emergency department (ED) visits, urinary tract infections (UTIs) (Supplemental), or urologic procedures (Supplemental). We included a 1-day black-out period between the index procedure and the first eligible date for any outcome. For hospitalizations, we did not count hospitalizations beginning on the same day as the index procedure.
The annual rates of index procedures were compared using linear regressions of the proportion of people in each subsample (adult and pediatric patients). We performed breakpoint analysis using the R package ‘segmented’7 for the proportion of people receiving IVB to identify a possible inflection at which the rate of IVB administration changed significantly. Trends were visually inspected prior to breakpoint analysis to estimate a starting value. To evaluate the association between index procedure and outcomes, we modeled days of hospitalization, ED visits, UTIs, and urologic procedures using a Poisson distribution. In all models sex, age group (pediatric or adult), procedure type (enterocystoplasty or IVB), population density (urban or rural), and comorbidity (pressure ulcers, renal disease, hydrocephalus, and mobility restraints) were included as independent variables. We also included years of follow up post-procedure as an ordinal variable to account for differences in follow up time. All statistical analyses were performed using R (R Core Team, Version 4.0.3, Vienna, Austria). Statistical hypothesis tests were two sided, and significant p-values were set at <0.05.
Results
We identified 60,983 patients with myelomeningocele in the MSCCE database between 2008 and 2017. The sample was stratified into pediatric (≤21 years old; n=25,015) and adult (>21 years old, n=35,934) patients based on age at the time of index procedure. Baseline demographics and comorbidities are listed in Table 1. Among the pediatric population, nearly twice as many patients had an enterocystoplasty compared to IVB (n=317 versus n=138). Among the adult population, very few patients underwent enterocystoplasty (n=25) compared to IVB (n=116). Overall, the majority of patients were female (n=38,112), with a higher proportion of females among the adult (69.2%) compared to the pediatric group (52.9%). Patients received IVB at a mean age of 13.4 years (SD 6.6) and enterocystoplasty at 11.5 years (SD 4.7). Among the adults, mean age at which patients received IVB was 39.6 years (SD 13.5) and enterocystoplasty was 32.1 years (SD 7.7). Most of the sample were in an urban setting (pediatric 84.0%; adult 84.8%). Among treated patients, there was a higher proportion of comorbidities compared to the overall myelomeningocele population. Among pediatric patients treated with IVB or enterocystoplasty, 40.4% (n=184) received an anticholinergic in the year prior to the index procedure, and they had been prescribed a median of one drug. Among adult patients treated, 31.3% (n=52) received an anticholinergic in the year prior to the index procedure, and they received a median of two unique anticholinergic drugs prior to index procedure.
Table 1.
Baseline demographics and comorbidities of the myelomeningocele population in the Truven MarketScan Database stratified by age at index procedure
| ≤21 years old (n = 25,015) | >21 years old (n = 35,934) | |||||
|---|---|---|---|---|---|---|
|
|
||||||
| Characteristic | IVB | Augment | Total | IVB | Augment | Total |
| Total (N)* | 138 (0.6%) | 317 (1.3%) | 25015 | 116 (0.3%) | 25 (0.07%) | 35934 (100%) |
| Sex (female) (N)† | 71 (51.5%) | 157 (49.5%) | 13236 (52.9%) | 85 (73.3%) | 13 (52.0%) | 24876 (69.2%) |
| Mean age of first recordCy(SD)) | 10.1 (6.4) | 9.4 (4.9) | 10.0 (6.6) | 36.6 (12.7) | 30.4 (7.4) | 41.3 (13.3) |
| Mean age at time of index procedure (y (SD)) | 13.4 (6.6) | 11.5 (4.7) | 12.1 (5.4) | 39.6 (13.5) | 32.1 (7.7) | 38.2 (12.9) |
| Mean enrollment time (d (SD)) | 2029(1113) | 1880 (1032) | 1453 (1017) | 1872 (1137) | 1828 (1094) | 1528 (1011) |
| Mean follow up (d (SD)) | 698 (563) | 981 (858) | 895 (791) | 631 (501) | 1016 (858) | 699 (596) |
| Region | ||||||
| Northeast | 21 (15.2%) | 41 (12.9%) | 4113 (16.4%) | 26 (22.4%) | 5 (20.0%) | 6933 (19.3%) |
| Midwest | 50 (36.2%) | 90 (28.4%) | 6468 (25.9%) | 20 (17.2%) | 10 (40.0%) | 8273 (23.0%) |
| South | 43 (31.2%) | 121 (38.2%) | 9614 (38.4%) | 49 (42.2%) | 6 (24.0%) | 14563 (40.5%) |
| West | 22 (15.9%) | 55 (17.4%) | 3927 (15.7%) | 18 (15.5%) | 4 (16.0%) | 5133 (14.3%) |
| Other | 2 (1.5%) | 10 (3.1%) | 893 (3.6%) | 3 (2.6%) | 0 (0%) | 1032 (2.9%) |
| Population density (urban) | 114 (82.6%) | 257 (81.1%) | 21020 (84.0%) | 97 (83.6%) | 23 (92.0%) | 30486 (84.8%) |
| Beneficiary relationship | ||||||
| Employee | 1 (0.7%) | 2 (0.6%) | 945 (3.8%) | 62 (53.5%) | 7 (28.0%) | 21712 (60.4%) |
| Spouse | 0 (0%) | 0 (0%) | 65 (0.3%) | 25 (21.6%) | 2 (8.0%) | 11006 (30.6%) |
| Child/other | 137 (99.3%) | 315 (99.4%) | 24005 (96.0%) | 29 (25.0%) | 16 (64.0%) | 3216 (8.9%) |
| Myelomeningocele location | ||||||
| Cervical | 19 (13.8%) | 65 (20.5%) | 2274 (9.1%) | 14 (12.1%) | 2 (8.0%) | 3605 (10.0%) |
| Thoracic | 25 (18.1%) | 60 (18.9%) | 1511 (6.0%) | 12 (10.3%) | 0 (0%) | 1085 (3.0%) |
| Lumbar | 105 (76.1%) | 271 (85.5%) | 8655 (34.6%) | 59 (50.9%) | 16 (64.0%) | 6694 (18.6%) |
| Sacral | 40 (29.0%) | 55 (17.4%) | 1127 (4.5%) | 24 (20.7%) | 2 (8.0%) | 673 (1.9%) |
| Unspecified | 28 (20.3%) | 40 (12.6%) | 14301 (57.2%) | 43 (37.1%) | 6 (24.0%) | 24819 (69.1%) |
| Comorbidities | ||||||
| Pressure ulcers | 8 (5.8%) | 17 (5.4%) | 403 (1.6%) | 11 (9.5%) | 4 (16.0%) | 916 (2.6%) |
| Renal disease | 17 (12.3%) | 46 (14.5%) | 542 (2.2%) | 12 (10.3%) | 7 (28.0%) | 1853 (5.2%) |
| Hydrocephalus | 81 (58.7%) | 184 (58.0%) | 5421 (21.7%) | 37 (31.9%) | 12 (48.0%) | 3061 (8.5%) |
| Ventriculoperitoneal shunt | 71 (51.5%) | 158 (49.8%) | 4344 (17.4%) | 29 (25.0%) | 10 (40.0%) | 2142 (5.9%) |
| Mobility restraint | 25 (18.1%) | 29 (9.2%) | 625 (2.5%) | 15 (12.9%) | 5 (20.0%) | 501 (1.4%) |
| Drugs | ||||||
| Anticholinergic 1 y prior to procedure (N) | 71 (51.0%) | 113 (35.6%) | 184 (40.4%)* | 46 (39.6%) | 6 (24.0%) | 52 (31.3%)* |
| Median no. of anticholinergic drugs (SD) | 1 (0.99) | 1 (0.8) | 1 (0.9) | 2 (1.3) | 1.5 (0.9) | 2 (1.2) |
| Median no. of all drugs (SD) | 15 (13.6) | 10 (10.2) | 12 (11.7) | 20 (18.4) | 17 (8.9) | 19 (17.4) |
Percentages in ‘Total’ row denote total of overall myelomeningocele cohort. Total in this row is calculated among those who received either IVB or enterocystoplasty.
Percentages in other rows denote percentage of column group.
We evaluated the annual trend of the proportion of patients who received IVB or enterocystoplasty. Among children, there was a significant increase in IVB use (p=0.0015) and a non-significant decrease in enterocystoplasty rate (p=0.147) over the 10 years in the study. Using breakpoint analysis, we identified an inflection point at year 3.5 (i.e. Mid 2010) (SE=1.46) at which the year-to-year rate of IVB use significantly increased. Among adults, there was also a significant increase in IVB use (p<0.001) and a non-significant decrease in enterocystoplasty rate (p=0.48). An inflection point was identified at year 2.60 (i.e. Mid 2009, SE = 1.05) at which the year-to-year rate of IVB use increased significantly.
Among the pediatric population, the average number of IVB treatments received was 1.77 (SD=1.40) over an average of 698 days follow up (SD = 563 days), and this was higher among adults, with an average of 2.08 (SD = 1.61) IVB treatments over an average of 631 days follow up (SD = 501 days). In the year following IVB, 63 pediatric patients (45.7%) and 34 adult patients (29.3%) received prescriptions for anticholinergics (Supplementary Table 2) which was reduced from pre-operative rates of anticholinergic use (pediatric 51.0%, adult 39.6%; Table 1). Of the 254 patients (both age groups) who received IVB, 12 pediatric patients and 5 adult patients went on to receive an enterocystoplasty. Figure 2 shows the time to enterocystoplasty for patients who initially received IVB stratified by age group. The median time from IVB to enterocystoplasty was 364.5 days (95% CI 121–1010 days) among pediatric patients and 487 days (95% CI 299–764 days) among adult patients.
Figure 2.
Kaplan-Meier survival analysis of receipt of enterocystoplasty among patients who initially received IVB among patients a) ≤ 21 years old (n=141), and b)> 21 years old (n=116). Dashed lines are 95% confidence intervals
Post-procedure outcomes in the first year are summarized in Supplementary Table 2. In the first year post procedure, 24% of patients receiving IVB were hospitalized (n=61). This proportion did not differ among ≤21 year or >21 year old patients. A higher proportion of patients receiving enterocystoplasty were hospitalized (n=139; 40.6%), with a higher proportion among >21 compared to ≤21year olds (60.0% versus 39.1%). A similar difference was seen with ED visits, with a higher proportion of ED visits among those who had received enterocystoplasty compared to IVB (58.8% versus 39.3%). The opposite was seen with respect to urinary tract infections, with a higher proportion among those receiving IVB (24.0% versus 9.1%). The proportion of patients requiring urologic procedures in the first year were similar between the two treatment groups (IVB 61.4% versus enterocystoplasty 58.8%).
In multivariable poisson regression analysis we identified outcomes in patients who recived either IVB or enterocystoplasty up to 10 years post procedure (Table 2). Compared to those who received enterocystoplasty, those who received IVB experienced significantly lower number of hospitalization days (RR 0.64; 95% CI 0.53–0.78), rate of ED visits (RR 0.72; 95% CI 0.63–0.82), and increased rate of urologic procedures (RR 1.44; 95% CI 1.28–1.62). The index procedure type did not have a significant effect on the relative rate of UTIs (RR 1.10; 95% CI 0.96–1.27). Compared to pediatric patients, adults experienced increased rates of UTIs (RR 1.28; 95% CI 1.10–1.49) and urologic procedures (RR 1.34; 95% CI 1.18–1.52), however no significant effect on the rate of ED visits or hospitalization days (Table 2). The presence of any comorbidities besides mobility restraints was associated with increased relative rates of hospitalizations, ED visits, and UTIs (Table 2). Renal disease was the only comorbidity which was associated with an increased rate of urologic procedures (RR 1.30; 95% CI 1.13–1.50). Generally, the relative rate of all the outcomes measured increased with each year post procedure (Table 2).
Table 2.
Multivariable Poisson regression of outcomes following intravesical Botulinum toxin or enterocystoplasty among patients who received treatment (n=557). RR – relative rate, 95% CI – 95% confidence intervals, LCL – lower confidence limit, UCL – upper confidence limit, IVB – intravesical botulinum toxin, ED – Emergency Department, UTI – urinary tract infections,
| Hospitalization days | ED Visits | UTIs | Urologic Procedures | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 95% CI | 95% CI | 95% CI | 95% CI | |||||||||||||
| RR | LCL | UCL | p | RR | LCL | UCL | p | RR | LCL | UCL | p | RR | LCL | UCL | p | |
| Sex (Female) | 0.88 | 0.76 | 1.03 | 0.10 | 0.78 | 0.70 | 0.86 | <.0001 | 0.77 | 0.69 | 0.87 | <.0001 | 0.82 | 0.74 | 0.91 | <.001 |
| Procedure | ||||||||||||||||
| enterocystoplasty | Reference | |||||||||||||||
| IVB | 0.64 | 0.53 | 0.78 | <.0001 | 0.72 | 0.63 | 0.82 | <.0001 | 1.10 | 0.96 | 1.27 | 0.17 | 1.44 | 1.28 | 1.62 | <.0001 |
| Age group | ||||||||||||||||
| ≤ 21 years old | Reference | |||||||||||||||
| >21 years old | 0.99 | 0.80 | 1.23 | 0.94 | 1.14 | 0.99 | 1.32 | 0.06 | 1.28 | 1.10 | 1.49 | <.01 | 1.34 | 1.18 | 1.52 | <.0001 |
| Residence | ||||||||||||||||
| Rural | Reference | |||||||||||||||
| Urban | 1.33 | 1.09 | 1.64 | <.001 | 1.35 | 1.17 | 1.56 | <.0001 | 1.64 | 1.38 | 1.95 | <.0001 | 1.05 | 0.93 | 1.20 | 0.43 |
| Comorbidities | ||||||||||||||||
| Pressure ulcers | 1.71 | 1.36 | 2.13 | <.0001 | 1.89 | 1.61 | 2.19 | <.0001 | 1.44 | 1.18 | 1.74 | <.001 | 1.13 | 0.95 | 1.34 | 0.16 |
| Renal disease | 1.71 | 1.43 | 2.03 | <.0001 | 1.18 | 1.03 | 1.35 | 0.02 | 2.65 | 2.32 | 3.02 | <.0001 | 1.37 | 1.20 | 1.56 | <.0001 |
| Hydrocephalus | 1.37 | 1.17 | 1.61 | <.001 | 1.39 | 1.24 | 1.56 | <.0001 | 2.04 | 1.79 | 2.33 | <.0001 | 1.04 | 0.94 | 1.16 | 0.43 |
| Mobility Restraints | 1.14 | 0.92 | 1.40 | 0.22 | 1.17 | 1.01 | 1.35 | 0.04 | 1.00 | 0.85 | 1.17 | 0.99 | 1.13 | 0.98 | 1.29 | 0.09 |
| Post-procedure year | ||||||||||||||||
| 1 | Reference | |||||||||||||||
| 2 | 2.75 | 2.01 | 3.79 | <.0001 | 2.12 | 1.72 | 2.63 | <.0001 | 3.19 | 2.43 | 4.23 | <.0001 | 2.73 | 2.24 | 3.34 | <.0001 |
| 3 | 4.54 | 3.40 | 6.12 | <.0001 | 3.43 | 2.82 | 4.19 | <.0001 | 9.65 | 7.61 | 12.38 | <.0001 | 4.53 | 3.77 | 5.47 | <.0001 |
| 4 | 4.17 | 3.04 | 5.74 | <.0001 | 3.55 | 2.88 | 4.38 | <.0001 | 4.64 | 3.52 | 6.15 | <.0001 | 5.46 | 4.50 | 6.65 | <.0001 |
| 5 | 6.04 | 4.44 | 8.30 | <.0001 | 5.15 | 4.19 | 6.34 | <.0001 | 4.24 | 3.15 | 5.73 | <.0001 | 6.34 | 5.18 | 7.78 | <.0001 |
| 6 | 4.56 | 3.19 | 6.52 | <.0001 | 4.34 | 3.41 | 5.52 | <.0001 | 3.98 | 2.86 | 5.53 | <.0001 | 3.46 | 2.60 | 4.55 | <.0001 |
| 7 | 8.73 | 6.14 | 12.42 | <.0001 | 7.91 | 6.28 | 9.96 | <.0001 | 11.59 | 8.52 | 15.82 | <.0001 | 4.64 | 3.36 | 6.30 | <.0001 |
| 8 | 13.53 | 9.26 | 19.71 | <.0001 | 8.24 | 6.17 | 10.91 | <.0001 | 9.68 | 6.50 | 14.21 | <.0001 | 6.37 | 4.31 | 9.18 | <.0001 |
| 9 | 4.88 | 2.72 | 8.28 | <.0001 | 9.04 | 6.79 | 11.93 | <.0001 | 4.81 | 2.74 | 7.96 | <.0001 | 8.05 | 5.75 | 11.08 | <.0001 |
| 10 | 9.83 | 5.97 | 15.69 | <.0001 | 7.81 | 5.48 | 10.91 | <.0001 | 11.88 | 7.62 | 18.07 | <.0001 | 5.35 | 3.20 | 8.47 | <.0001 |
Discussion
In this population based study of a commercial insurance claims database we identified patients with myelomeningocele who underwent either IVB or enterocystoplasty. Among the pediatric population (≤21 years old), there were approximately twice as many patients undergoing enterocystoplasty compared to IVB, while most adults (>21 years old) receiving treatment underwent IVB, with very few patients receiving enterocystoplasty. There was an increasing annual rate of IVB in both age groups, with a significant increase in the annual rate of IVB use around mid-2009 to mid-2010. Patients received an average of approximately two IVB treatments. IVB use was associated with a decreased rate of hospitalization days, ED visits and an increased rate of urologic procedures compared to patients receiving enterocystoplasty. Adults experienced increased rates of UTIs and urologic procedures compared to pediatric patients.
To our knowledge, this is the first population-based sample to compare trends in the use of IVB and enterocystoplasty among the myelomeningocele population. It is also the first study to examine enterocystoplasty rates in the privately insured myelomeningocele population. We found that the rates of enterocystoplasty in this population (1.3% of adults and 0.7% of pediatric patients) were significantly lower than previously reported large studies. The enterocystoplasty rate among pediatric patients with Spina Bifida in the Pediatric Health Information System database (PHIS) is estimated around 5.3–5.5% (2000–2003)8, and more recently (2009–2014), 12.1% in the National Spina Bifida Patient Registry (NSBPR)9. One reason for this difference might be that patients received enterocystoplasty prior to enrollment in the MSCCE, which we would expect to affect the adult population more than the pediatric population, since patients may gain new insurance coverage after age 26. Another possibility is that patients who have commercial insurance coverage have different patterns of care. The trends in enterocystoplasty reported in the literature have been somewhat conflicting, depending on the database and time. A previous study of the Pediatric Health Information System database in the USA from 1999 to 2004, found that there was a stable rate of enterocystoplasties being performed8. More recently, Rehfuss et al. also examined the Pediatric Health Information System database from 2009–2018, and found that the annual incidence rate ratio of enterocystoplasty was stable (1.01, 95% CI 0.96–1.05; p=0.75)10. Conversely, Schlomer et al. investigated the Kids’ Inpatient Database from 2000 to 2009 and found a decrease in the annual volume of enterocystoplasties across the USA, with 792 enterocystoplasties in 2000, which decreased to 595 in 2009 (p=0.02).11 Wang et al. examined the Nationwide Inpatient Sample in the USA (representing a 20% stratified sample of US hospital admissions) and found that between 1998 and 2011 all surgical interventions (enterocystoplasty, IVB, vesicostomy, sphincterotomy, ileal conduit, and Mitrofanoff) for patients with myelomeningocele decreased from 2.0% to 1.8% and chronic renal insufficiency rates doubled from 6% to 12%.12 Concurrently, in the United Kingdom, Biers et al noted a 38% decrease in number of enterocystoplasties performed between 2000 and 201013. Shreck et al. used the United Kingdom Hospital episode statistics and found that the number of IVB treatments increased from 50 episodes in 2000 to 4088 in 2010.14
We found that patients who initiated IVB received a mean of approximately two injections/patient. However, few went on to receive enterocystoplasty with a median time of nearly 1 year in children and 1.5 years in adults between initial IVB and enterocystoplasty. Moreover, 39% received a prescription for anticholinergics in the year following IVB. This agrees with previous findings. Figuero et al. conducted a prospective study of 17 patients with congenital neurogenic bladder and found that 14 did not proceed to enterocystoplasty, with an average of 2.5 injections/patient (six patients had ≥3 injections).5 Similarly, in a series of 20 patients with neurogenic bladder dysfunction, 7 failed IVB (persistent urinary incontinence) and went on to receive enterocystoplasty, with the remaining 13 went back to a full dose of anticholinergics before the second IVB injection15. There are several reasons for patients to discontinue IVB but not proceed to enterocystoplasty. Persistent incontinence, decreased compliance or capacity managed with other medications, and recurrent urinary tract infections may all be reasons to consider IVB failure that may not warrant enterocystoplasty. Mechanisms including formation of neutralizing antibodies16 and fibrosis of the bladder have been hypothesized to explain initial17 and long-term ineffectiveness of repeat IVB injections.18 There are also alternative treatments to enterocystoplasty that we did not document, such as proceeding to ileal conduit, suprapubic tube or sphincterotomy among many possible options. In a retrospective multicenter cohort study of 142 patients with neurogenic bladder, the most common reason for discontinuation of IVB was failure defined as absent efficacy.19 Failure developed in 43.7% of cases and occurred after the first injection in 17.2% and after at least one successful initial injection in 26.5% of patients. Of the patients discontinuing IVB, 35.9% switched back to anticholinergics, 28.1% went on receive enterocystoplasty, 10.9% received an ileal conduit, 6.2% received a suprapubic tube, 3.1% received a sphincterotomy, and 12% received no further treatment.
We found that IVB was associated with a reduction in the relative rate of hospitalizations and ED visits (irrespective of diagnosis) following index treatment, even when we adjusted for other baseline characteristics including comorbidity. This is somewhat expected in the early period post-treatment, as enterocystoplasty has been associated with a significant rate of post-operative adverse events. In a national pediatric sample, McNamara et al. found that following enterocystoplasty and/or appendicovesicostomy, 30% of the patients experienced a complication within 30 days.20 Although we include a 30-day blackout period post index procedure in this study, we also observe a high rate of hospitalizations (35%) and ED visits (44%) within the first year post-enterocystoplasty. In a similar cohort, Du et al found that following enterocystoplasty, the reoperation rate and readmission rate were 9.6% and 13.2%, respectively.21
The strengths of this study include the use of a large national insurance claims database and nearly 61,000 patients with myelomeningocele. In addition, we have longitudinal data for patients in the database from their index event with an average of two to three years follow up.
There are also important limitations in this study. This sample is taken from an employment‐based insured population, and our study population may not be representative of patients covered by Medicaid and Medicare. Reports from the NSBPR indicate 47% of patients ages 0–22 with Spina Bifida have private insurance coverage.22 This sample is likely healthier and has better access to medical care than the Medicaid and Medicare population, and therefore may not require IVB or enterocystoplasty23. It is possible that children lose private insurance coverage when they reach age 26, and therefore myelomeningocele is relatively underrepresented among adults in this database. A general limitation of all studies using administrative data is the potential for misclassification. Patients were identified with spina bifida diagnosis codes, which are specific for this disorder and have been used in previous reports24. The administrative prevalence of spina bifida from our study is 3.79 per 10,000 enrollees, which is similar to recently published national prevalence estimates, 3.86 per 10,000 live births25. We are therefore confident that we have captured a large proportion of the entire population of patients in this database with myelomeningocele. Index procedures (IVB and enterocystoplasty) were identified using CPT codes, ICD codes, and concurrent diagnostic codes. Intravesical botox specific coding (CPT 52287) did not come into effect until 2013. Prior to this combinations of codes for cystoscopy and injection of drug were used. This inconsistency may introduce misclassification of IVB spanning over the time period of this study. We completed a thorough review of all possible procedural and J-codes that could be used for IVB to avoid this problem. There are several ways these procedures may be coded, and our approach is likely to over-capture enterocystoplasty, so it seems unlikely to explain lower rates of enterocystoplasty seen in this cohort. We are also unable to capture patients who underwent enterocystoplasty prior to study inclusion, which could disproportionately affect the adult sub-sample in this study, and could in more events post enrollement. These patients however would only be included in the study if they were undergoing repeat enterocystoplasty or IVB after enterocystoplasty, both rare events. We were also unable define the degree of disability, which can affect post-operative outcomes. Alabi et al. found that participants in the National Myelomeningocele Registry with nonmyelomeningocele spina bifida (including meningocele, lipomyelomeningocele, and fatty filum) had fewer complications after surgery compared to those with myelomeningocele.26 Another limitation is that we cannot identify the indications for which patients pursue either IVB or enterocystoplasty. This introduces potential residual confounding whereby patients undergoing treatment for certain indications (hostile bladder) may experience more adverse outcomes compared to those with more benign indication (detrusor overactivity incontinence).
In conclusion, there has been a significant increase in the rate of IVB use among patients with myelomeningocele. There was a significant rise in the use of IVB noted around mid-2009 to mid-2010, just before FDA approval in adult patients. Few patients who initiated treatment with IVB went on to receive enterocystoplasty, although 39%continued to receive anticholinergic prescriptions in the year following their initial treatment. Patients who receive IVB experience lower rates of hospitalization, ED visits, and higher rates of urologic procedures compared to patients who receive enterocystoplasty. It is evident, that IVB plays an important role in the care of patients with myelomeningocele and future work should focus on identifying patients suited for IVB, as well alternate management for those who discontinue IVB and do not proceed to enterocystoplasty.
Supplementary Material
Figure 1.
Annual trends of the proportion of the myelomeningocele population receiving botulinum toxin (solid line) and augmentation (dotted line) among patients (A) ≤ 21 years old (n = 25,015), and (B)> 21 years old (n = 35,934). (Color version available online.)
Key of Definitions for Abbreviations
- RR
Relative Rate
- SD
Standard deviation
- SE
Standard error
- CI
Confidence interval
- LCL
lower confidence limit
- UCL
upper confidence limit
- IVB
intravesical Botulinum toxin injection
- MSCCE
MarketScan database of Commercial Claims Encounters
- ICD9
International Classification of Diseases 9th edition
- ICD10
International Classification of Diseases 10th edition
- CPT
Current Procedural Terminology
- ED
Emergency department
- UTI
Urinary tract infection
References
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