Botulinum toxin type A versus oral anticholinergic medication cost-effectiveness for the treatment of neurogenic detrusor overactivity. Jose Carlos Truzzi1, Lessandro Curcio Gonçalves2, Romolo Guida Júnior3, Maira Libertad Soligo Takemoto4, Roberta Arinelli Fernandes4 Federal University of São Paulo1; Ipanema Hospital – Rio de Janeiro2; Hospital dos Servidores Públicos – Rio de Janeiro3; ANOVA4

Introduction/Aim of the study: Results: Detrusor overactivity and urinary incontinence figure as factors of significant Although Botulinum toxin type A was more costly, it was more effective when compared impairment of QOL in neurologic patients, besides can put them in risk of to oral anticholinergics within a ten-year period. (Figure 3 A and B) renal impairment. Oral anticholinergic (OA) medications are typically the fi rst line A 1.0000 approach with good subjective results.1 However persistence with oral anticholinergic 0.9000 therapy is low.2 Botulinum toxin injection into the detrusor muscle has been used for 0.8000 refractory cases, being its cost an important decision factor when deciding to change 0.7000 the former treatment. The aim of this study was to determine the cost-effectiveness of 0.6000 Botulinum Toxin type A (BT-A) vs. oral anticholinergic medications for the treatment 0.5000 0.4000 of neurogenic detrusor overactivity (NDO) from the public payer’s perspective. Probability 0.3000 0.2000 Material and Methods: 0.1000 0.0000 A Markov decision model was developed to compare the overall costs (in US dollars, 0 102030405060708090100110120 Months of follow-up USD) and effectiveness (persistent incontinence-free years) of oral anticholinergics BT-A OA and Botulinum Toxin type A injected into the detrusor. (Figure 1) B 120000000

100000000 W/BT-A WO/BT-A 1st line 2st line 80000000 anticholinergic BT-A anticholinergic 60000000

40000000

Annual cost (US$) Annual cost 20000000

0 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 st st st 1 line 2 line 3 line Figure 3 - A. Proportion of favorable outcome according to each treatment group. anticholinergic anticholinergic anticholinergic B. Annual cost follow-up of the neurogenic overactive bladder, Brazilian Public Health Care, 2011-2020 The persistent urinary incontinence-free period was estimated to be 7.3 and 3.0 years Figure 1 - Therapeutic sequences adopted in the Decision Model. for BT-A and oral medication, respectively. (Figure 4) Outcome BT-A OA The incremental cost-effectiveness ratio (ICER) was calculated as (Botulinum toxin type A cost – oral anticholinergic cost) / (Botulinum toxin type A incontinence-free Success years 9.2 3.3 years – oral anticholinergic incontinence-free years). A 10-year time frame with monthly cycle was designed based on data from a systematic review of clinical Incontinence-free years 9.9 3.9 and observational studies to simulate NDO patients’ long-term outcome. (Figure 2) Discounted success years 7.2 2.9 A one-way sensitivity analysis was performed. We applied a fi ve-percent annual discount to costs and benefi ts. Discounted Incontinence-free years 7.3 3.0 Figure 4 - Total of estimated outcome in each group.

The incremental cumulative cost in 10 years was 1,707 USD, which represents a discounted monthly cost of 61 USD for BT-A and 46 USD for oral anticholinergic Success w/o Success w/o Success w/ Success w/ AE medication. (Figure 5) To achieve an additional one incontinence-free year, an annual AE Non- investment of 397 USD in BT-A would be needed, when compared to oral medication. AE Adherent AE Adherent Non-Adherent Adherent 70

Switching 60 50

40

Failure w/o Failure w/ Failure w/o Failure w/ AE 30 AE Non- AE Adherent AE Adherent Non-Adherent 20 Adherent (US$) Mensal cost 10

0 Persistent BT-A OA Incontinence Figure 5 - Mensal cost of treatment according to the strategy in use.

Conclusion: Death Although BT-A is more costly, it was more effective than the oral anticholinergic treatment for NDO patients. Considering the high dropout rate with oral anticholinergics due to adverse events or the absence of an objective effective improvement, BT-A showed a higher projected effectiveness with an acceptable incremental cost-effectiveness ratio (ICER). Only oral anthicolinergic patients can transit to state. References: Indicates that patients switch treatments in the original health state, not a transition. 1- Chapple et al. The Effects of Antimuscarinic Treatments in Overactive Bladder: An Update of a Systematic Review and Meta-Analysis. Eur Urol. 2008; 54:543-562 2- Shaya FT et al. Persistence with overactive bladder pharmacotherapy in a Medicaid population. Am J Manag Figure 2 - Markov Model. Care. 2005; 11(4 Suppl):S121-9.