Predictive Value of Inflammatory Biomarkers for Mirabegron Response in Women With Overactive Bladder

BACKGROUND AND RATIONALE: Overactive bladder (OAB) is a chronic lower urinary tract condition characterized by urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence. Beta-3 adrenoceptor agonists such as mirabegron are an established first-line pharmacological option, yet the individual treatment response varies considerably. Emerging evidence links systemic low-grade inflammation to OAB pathophysiology. Baseline hematological indices derived from the routine complete blood count, such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII), may therefore carry predictive information at no additional cost.

STUDY OBJECTIVES: This prospective observational cohort study evaluates whether baseline NLR predicts the clinical response to standard mirabegron therapy (50 mg/day) at 3 months in treatment-naive women with OAB. The discriminative ability of baseline PLR and SII and the adjusted association of NLR with response are evaluated as secondary objectives.

METHODS: Consecutive eligible treatment-naive women in whom mirabegron 50 mg is initiated within routine clinical care are enrolled. Baseline evaluation includes clinical assessment, a 3-day voiding diary, a validated symptom questionnaire, routine urodynamic parameters, and a standardized complete blood count. Inflammatory indices are calculated with standard formulas. Response is assessed at 3 months. Data are collected on standardized case report forms and verified against electronic medical records.

STATISTICAL CONSIDERATIONS: The enrollment target is 115 patients to reach 80 evaluable patients. The discriminative ability of baseline inflammatory indices will be evaluated with ROC curve analysis; multivariable modeling will be used to assess adjusted associations. Details are prespecified in the study protocol.

Inclusion criteria

• Female patients aged 18 years or older
• Overactive bladder symptoms for at least 3 months
• Mirabegron 50 mg planned by physician decision within routine care
• Ability to provide written informed consent

Exclusion criteria

• Any previous OAB-specific treatment other than behavioral therapy (oral antimuscarinic or beta-3 agonist, intravesical botulinum toxin, sacral neuromodulation, or posterior tibial nerve stimulation)
• Acute infection within the last 4 weeks, including culture-confirmed urinary tract infection
• Chronic inflammatory disease (rheumatologic or autoimmune disease, or inflammatory bowel disease)
• Active malignancy or cancer treatment within the last 5 years
• Use of systemic glucocorticoids within the last 4 weeks, or chronic NSAID or immunosuppressive use
• Conditions affecting lower urinary tract function other than OAB (neurogenic bladder, urinary tract stones, history of pelvic radiotherapy or bladder surgery, pelvic organ prolapse stage 3 or higher, or stress-predominant mixed urinary incontinence)
• Known diagnosis of hematologic disease, anemia (Hb<9), or platelet disorder (PLT<100.000 or >600.000)
• Significant renal or hepatic impairment (eGFR below 30 mL/min/1.73 m2, or Child-Pugh class B or C)
• Uncontrolled hypertension (180/110 mmHg or higher) or any other contraindication to mirabegron
• Pregnancy or lactation
• Major surgery or trauma within the last 3 months
• Cognitive or functional inability to complete the voiding diary