Introduction

Urinary tract infections (UTIs) are common in women and the prevalence of recurrent UTIs is significant. They impose significant health and economic burdens, worsened by rising antimicrobial resistance. While long-term low-dose antibiotics reduce recurrence, concerns over resistance drive interest in alternatives. Methenamine hippurate, a urinary antiseptic, shows promise, but evidence on its clinical and cost-effectiveness compared with antibiotics remains limited, prompting evaluation in the ALTAR trial.

Aim

To compare the cost-effectiveness of methenamine hippurate and antibiotic prophylaxis in the management of recurrent UTIs.

Method

Study Design

• Multicentre, open-label, randomised, non-inferiority trial

Treatment Strategy

• The study included women aged >18 years with recurrent UTIs, requiring prophylactic treatment
• The cohort was randomised to receive either once-daily antibiotic prophylaxis or twice-daily methenamine hippurate for 12 months
• The ALTAR trial economic evaluation assessed cost-effectiveness of methenamine hippurate versus antibiotics from an NHS perspective over 18 months
• Costs included medications, healthcare use, and antimicrobial resistance in sensitivity analysis
• Quality-adjusted life years (QALYs) was estimated using the responses to the EQ-5D-5L at baseline, 3,6,9,12 and 18 months
• Statistical models estimated cost and outcome differences, while uncertainty was explored using bootstrapping and cost-effectiveness acceptability curves to determine value for money

Endpoints

• Incremental cost per QALY gained at 18 months

Results

• The economic analysis included data of 205 participants
• On an average, the total costs for each healthcare resource in the methenamine hippurate arm were higher than the antibiotic prophylaxis arm; 931 vs 1013 £ respectively
• The antibiotic prophylaxis arm reported higher utilities and QALYs (1,182 vs 1,133) as compared to the methenamine hippurate arm
• As per the adjusted analysis, which estimated the incremental results, methenamine hippurate was less costly and more effective in terms of QALYs gained, concluding that methenamine hippurate was dominant as seen in Table 1.

  Table 1. Cost-utility results

  	Cost (£)	Incremental cost (£)	QALYs	Incremental QALYs
  Antibiotic prophylaxis	931		1.182
  Methenamine hippurate	1013	-40	1.133	0.014

• Methenamine hippurate showed a 51% probability of being cost-effective at zero willingness to pay per QALY, increasing with higher thresholds
• However, the probability never exceeded 67%, suggesting moderate but uncertain cost-effectiveness compared with antibiotic prophylaxis across different willingness-to-pay levels
• Participants on methenamine hippurate had slightly more UTIs but lower antimicrobial resistance costs than antibiotic prophylaxis
• When antimicrobial resistance (AMR) costs were included, methenamine hippurate was generally less costly and more effective
• It showed a 69–76% probability of being cost-effective across willingness-to-pay thresholds, supporting its potential as an alternative preventive strategy

Conclusion

• Primary analysis showed no clear economic advantage between treatments for recurrent urinary tract infections in women.
• However, including antimicrobial resistance costs favored methenamine hippurate, with a 76% probability of cost-effectiveness at £20,000 per QALY, highlighting AMR as an important factor.

BMJ Open. 2024 Apr 29;14(4):e074445. Doi: 10.1136/bmjopen-2023-074445.