Drug Whisperer (Nov-Dec 2023)

1. This Topical Combo Gel May Be Another Viable Option for Managing Acne in Adolescents

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne.

METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability.

RESULTS: At Week 12, treatment success rates were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%-33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity.

CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne.

Eichenfield LF, et al. Triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel for moderate-to-severe acne in children and adolescents: Randomized phase 2 study. Pediatr Dermatol. 2023 May-Jun;40(3):452-459doi: 10.1111/pde.15283. Epub 2023 Mar 22.

2. Could Colchicine Be Used for Liver Cancer Prevention in High-Risk Patients?

BACKGROUND: Liver cancer and notably hepatocellular carcinoma (HCC), results in significantly high mortality rates worldwide. Chronic hepatitis and fatty liver, recognized precursors, underscore the imperative need for effective preventive strategies. This study explores colchicine, traditionally acknowledged for its anti-inflammatory properties and investigates its potential in liver cancer prevention. 

METHODS: Utilizing the iHi Data Platform of China Medical University Hospital, Taiwan, this study analyzed two decades of medical data, incorporating 10,353 patients each in the Colchicine and Non-Colchicine cohorts, to investigate the association between colchicine use and liver cancer risk. 

RESULTS: The study identified that colchicine users exhibited a 19% reduction in liver cancer risk, with a multivariable-adjusted odds ratio of 0.81 after accounting for confounding variables. Additionally, the influence of gender and comorbidities like diabetes mellitus on liver cancer risk was identified, corroborating the existing literature. A notable finding was that the prolonged use of colchicine was associated with improved outcomes, indicating a potential dose–response relationship. 

CONCLUSIONS: This study proposes a potential new role for colchicine in liver cancer prevention, extending beyond its established anti-inflammatory applications. While the findings are promising, further research is essential to validate these results. This research may serve as a foundation for future studies, aiming to further explore colchicine’s role via clinical trials and in-depth investigations, potentially impacting preventive strategies for liver cancer.

Lin JJ, et al. Unlocking Colchicine’s Untapped Potential: A Paradigm Shift in Hepatocellular Carcinoma Prevention.  Cancers 2023, 15(20), 5031; https://doi.org/10.3390/cancers15205031

3. Vaginal Estrogen Application Might be Safe Even in Women Diagnosed with Breast Cancer  

IMPORTANCE: Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer.

OBJECTIVE: To determine whether the risk of breast cancer-specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT).

DESIGN, SETTING AND PARTICIPANTS: This cohort study analyzed 2 large cohorts, one each in Scotland and Wales, of females aged 40 to 79 years with newly diagnosed breast cancer. These population-based cohorts were identified from national cancer registry records from 2010 to 2017 in Scotland and from 2000 to 2016 in Wales and were followed up for breast cancer-specific mortality until 2020. Females were excluded if they had a previous cancer diagnosis (except nonmelanoma skin cancer). Data analysis was performed between August 2022 and August 2023.

EXPOSURE: Use of vaginal estrogen therapy, including vaginal tablets and creams, was ascertained from pharmacy dispensing records of the Prescribing Information System for the Scotland cohort and from general practice prescription records for the Wales cohort.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to breast cancer-specific mortality, which was obtained from national mortality records. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for breast cancer-specific mortality, comparing vaginal estrogen therapy users with HRT nonusers and adjusting for confounders, including cancer stage and grade.

RESULTS: The 2 cohorts comprised 49 237 females with breast cancer (between 40 and 79 years of age) and 5795 breast cancer-specific deaths. Five percent of patients with breast cancer used vaginal estrogen therapy after breast cancer diagnosis. In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer-specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94).

CONCLUSIONS AND RELEVANCE: Results of this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT. This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.

McVicker L, et al. Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer.  JAMA Oncol. 2023 Nov 2:e234508. doi: 10.1001/jamaoncol.2023.4508. Online ahead of print.