A Randomized, Double-blind, Placebo-controlled Trial of Certolizumab Pegol in Women with Refractory Interstitial Cystitis/Bladder Pain Syndrome

Abstract

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, disabling bladder disease, with an uncertain pathophysiology and no universally effective treatment.

Objective: To evaluate the efficacy and safety of certolizumab pegol compared with placebo in women with refractory IC/BPS.

Design, setting, and participants: Eligible women, aged 18-65 yr with moderate to severe IC/BPS, were enrolled in this randomized, double-blind, placebo-controlled pilot study.

Intervention: Study patients were randomized at a 2:1 ratio to receive either certolizumab pegol or placebo.

Outcome measurements and statistical analysis: The primary outcome measure was a patient-reported global response assessment (GRA). Secondary endpoints included Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), and a numeric rating scale for pain and urgency.

Results and limitations: The primary endpoint of GRA improvement at week 2 was not met. However, by week 18, there was significant improvement in GRA for certolizumab pegol compared with placebo in pain (odds ratio [OR]=17.3, p=0.002), urgency (OR=9.92, p=0.02), and overall symptoms (OR=15.0, p=0.006). At week 18, there was a statistically significant improvement for certolizumab pegol compared with placebo in change from baseline for ICSI of -3.6 (95% confidence interval [CI]: -6.9 to -0.29, p=0.03), ICPI of -3.0 (95% CI: -6.1 to 0.12, p=0.042), pain scale of -2.0 (95% CI: -3.9 to -0.15, p=0.02), and urgency scale of -1.7 (95% CI: -3.5 to 0.06, p=0.03). There was a significant difference in greater than 30% reduction in pain from baseline comparing certolizumab pegol with placebo at week 18 (OR=13.0, p=0.02). Limitations include a larger, longer, multicenter trial is warranted with phenotypic categorization of patients.

Conclusions: Women with moderate to severe refractory IC/BPS were more likely to experience significant improvement in symptoms with certolizumab pegol compared with placebo therapy. Further investigation of certolizumab pegol for the treatment of IC/BPS is warranted with a larger, longer, multicenter, randomized, placebo-controlled trial.

Patient summary: Women with moderate to severe interstitial cystitis/bladder pain syndrome were helped with a medication used to treat autoimmune diseases.

Keywords: Adalimumab; Autoimmune diseases; Bladder pain syndrome; Certolizumab pegol; Interstitial cystitis; Placebo effect; Tumor necrosis factor-alpha.