Concurrent H1 antihistamines associated with better survival in BCG-treated bladder cancer

Use of H1 antihistamines (H1-AH) during intravesical bacillus Calmette-Guérin (BCG) immunotherapy is associated with better overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) in patients with non–muscle-invasive bladder cancer (NMIBC), according to a territory-wide retrospective observational study by researchers from the Chinese University of Hong Kong.

Concomitant H1-AH administration is associated with better survival outcomes for patients with metastatic urothelial carcinoma receiving immunotherapy. [Urol Oncol 2025;43:188.e9-188.e17] However, the role of H1-AH in NMIBC treated with adjuvant BCG immunotherapy has not been explored. “Our aim was to investigate the impact of H1-AH use on survival outcomes for patients with BCG-treated NMIBC,” wrote the researchers. [Eur Urol Open Sci 2025:83:23-29]

The analysis included 2,028 patients with NMIBC who received intravesical BCG immunotherapy in Hong Kong between 2001 and 2020. Of these, 1,539 patients had an H1-AH prescription at baseline (H1-AH group) and 489 did not receive an H1-AH prescription during the study period (control group).

Kaplan–Meier analysis revealed that compared with the control group, the H1-AH group had significantly better CSS (p=0.017) and PFS (p=0.001), but not OS (p=0.11) or RFS (p=0.2). However, there were some notable differences in the baseline characteristics of the two groups, such as greater median age (74 vs 70 years; p<0.001) and lower proportion of patients without comorbidities (47 vs 68 percent; p<0.001) in the H1-AH group. Multivariable Cox regression analysis showed that H1-AH use was associated with better OS (hazard ratio [HR], 0.76; 95 percent confidence interval [CI], 0.64–0.90), CSS (HR, 0.52; 95 percent CI, 0.36–0.74), and PFS (HR, 0.62; 95 percent CI, 0.45–0.87).

Of the 1,539 patients who had been prescribed H1-AH agents before BCG treatment, 473 patients stopped H1-AH before they started BCG therapy and did not take any H1-AH during BCG treatment (prior H1-AH subgroup). The remaining 1,066 patients started H1-AH before BCG therapy and continued H1-AH during the BCG course, receiving both treatments concurrently (H1-AH + BCG subgroup).

Multivariable Cox regression showed that concomitant H1-AH use during BCG treatment was associated with better OS (HR, 0.69; 95 percent CI, 0.58–0.82), CSS (HR, 0.44; 95 percent CI, 0.30–0.65), RFS (HR, 0.81; 95 percent CI, 0.67–0.98), and PFS (HR, 0.64; 95 percent CI, 0.45–0.91), while survival outcomes did not significantly differ between the prior H1-AH subgroup and the control group. “On one hand, this difference may be attributable to a much shorter median duration in the prior H1-AH subgroup [18 days] vs H1-AH + BCG subgroup [122 days]. On the other hand, it may reflect a synergistic effect between H1-AH agents and BCG immunotherapy,” remarked the researchers.

Among the limitations of the study, the researchers noted that H1-AH agents are available as both prescription and over-the-counter (OTC) medications in Hong Kong, making it possible that some patients in the control group used OTC H1-AH agents. Furthermore, the study lacked data on actual drug intake, adherence, dosage, and treatment duration, making dose–response analysis impossible.

“Our findings suggest that concurrent H1-AH use during BCG treatment for NMIBC was associated with better OS, CSS, RFS, and PFS, but they should be interpreted with caution and need to be confirmed in larger prospective studies,” concluded the researchers.