# Targeted innate immune inhibition therapy compared with antibiotics for recurrent acute cystitis: a randomized, open-label phase 2 trial

## TL;DR

A new immune therapy, anakinra, was found to be as effective as the antibiotic nitrofurantoin in treating recurrent bladder infections in women.

## Contribution

This study demonstrates that targeted innate immune inhibition is non-inferior to antibiotics for treating recurrent cystitis.

## Key findings

- Symptom scores decreased significantly in both anakinra and nitrofurantoin groups after 5 days and remained low for up to 6 months.
- Anakinra rapidly inhibited immune gene expression, unlike nitrofurantoin.
- Both treatments improved quality of life without adverse effects and reduced recurrence rates over 6 months.

## Abstract

Cystitis is a bacterial infection of the bladder that occurs in about half of women at least once in their lifetime. Antibiotics such as nitrofurantoin are used to treat cystitis, but antibiotic resistance is a concern, especially for recurrent infections. Here we report an open-label, randomized, single-centre, phase 2 study to analyse the acute and long-term safety and efficacy of the IL-1 receptor antagonist anakinra, compared with nitrofurantoin, in recurrent cystitis. A total of 30 adult female patients with a documented history of recurrent cystitis and a current acute cystitis episode were randomized in a 2:1 ratio to treatment with anakinra (n = 20) or nitrofurantoin (n = 10) for 5 days. Primary and secondary efficacy end-points were reached, defined as the reduction in typical symptoms, measured by the acute cystitis symptom score (day 5), longitudinal symptom scores, recurrence rates, quality of life, gene expression analysis and microbiology at follow-up on days 15 and 30 and at 6 months. Symptom scores were decreased in the anakinra (P < 0.001) and nitrofurantoin (P < 0.001) arms after 5 days and remained low after 15 days, 30 days and 6 months. Recurrences were less frequent after 6 months in both treatment groups compared with the 6-month pre-enrolment history (P < 0.001 for anakinra and P = 0.004 for nitrofurantoin), and the quality of life was increased, without adverse effects. Immune gene expression was rapidly inhibited in the anakinra-treated patients but not in the nitrofurantoin group. Targeted innate immune inhibition therapy shows non-inferiority to nitrofurantoin in patients with recurrent acute cystitis. German Clinical Trials Register ID: DRKS00025964.

An open-label, randomized, single-centre, phase 2 study shows that the IL-1 receptor antagonist anakinra shows non-inferiority to the antibiotic nitrofurantoin in patients with recurrent acute cystitis.