Treatment-Free Interval: A Novel Approach to Assessing Real-World Treatment Effectiveness and Economic Impact Among Patients with Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA. METHODS: Adult patients (18-64 years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics® Plus database (10/01/2015-12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30 consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences. RESULTS: There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1 years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30 days (76.2% vs. 66.7%), ≥ 60 days (67.0% vs. 47.0%), ≥ 90 days (61.0% vs. 38.7%), ≥ 180 days (51.7% vs. 31.0%), and ≥ 240 days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30 days, mean TFI durations were 8.3 and 6.0 months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437; p = 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250; p < 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1 million per year or $0.18 per-member-per-month. CONCLUSIONS: This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.

Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Long-term Patiromer Use and Outcomes Among US Veterans With Hyperkalemia and CKD: A Propensity-Matched Cohort Study.

Rationale & Objective: Patiromer is a potassium binder approved for the long-term management of hyperkalemia. Although patiromer use among patients with advanced chronic kidney disease (CKD) has been shown to reduce the discontinuation of renin-angiotensin-aldosterone system inhibition therapy, it remains unclear whether patiromer can improve clinical outcomes. The aim of this study was to examine the association of long-term patiromer use with clinical outcomes among hyperkalemic patients with CKD. Study Design: This was a longitudinal observational study. Setting & Participants: We evaluated a national cohort of 854,217 US Veterans who had at least 1 serum potassium measurement of ≥5.1 mEq/L and were treated at US Department of Veterans Affairs health care facilities between January 2016 and September 2019. Exposure: The exposure was long-term patiromer use. Outcomes: The outcomes were as follows: (1) composite endpoint of kidney failure with replacement therapy (KFRT) or all-cause death and (2) all-cause death including the post-KFRT period. Analytical Approach: Cox proportional Fine-Gray subdistribution hazard models were used in a propensity-matched cohort. Results: Among 2,004 patients who ever used patiromer during the study period (0.2% of the cohort), 666 met the criteria for long-term patiromer use. We matched 308 long-term patiromer users to 308 nonusers based on propensity scores. The median estimated glomerular filtration rate was 23.5 mL/min/1.73m2, and the median potassium level was 5.2 mEq/L. Approximately 45% were on renin-angiotensin system inhibitor(s) at baseline. During follow-up, 93 patients developed KFRT, and 134 patients died. Long-term patiromer users, when compared to nonusers, experienced a 26% lower risk of the composite outcome (HR, 0.74; 95% CI, 0.53-1.01; P = 0.06) and a 41% lower risk of all-cause mortality (HR, 0.59; 95% CI, 0.41-0.84; P = 0.003). Limitations: The study cohort included mostly male veterans with relatively short follow-up periods. Conclusions: Long-term patiromer use was associated with a lower risk of all-cause mortality among patients with CKD and hyperkalemia. Long-term potassium binder use for hyperkalemia may improve clinical outcomes in CKD. Plain-Language Summary: Hyperkalemia is a common complication of chronic kidney disease (CKD) and can result in the discontinuation of renin-angiotensin-aldosterone system inhibition therapy, a cornerstone of CKD management. Patiromer is a new potassium binder approved for the long-term management of hyperkalemia, but it remains unclear whether patiromer can improve clinical outcomes. We examined a cohort of US Veterans with hyperkalemia between January 2016 and September 2019 and found that patiromer use was uncommon for treating hyperkalemia during this study period. We then matched 308 long-term patiromer users and 308 nonusers based on propensity scores. Long-term patiromer users, when compared to nonusers, experienced a 26% lower risk of the composite outcome and a 41% lower risk of all-cause mortality. These findings indicate that long-term potassium binder use for hyperkalemia may improve clinical outcomes in CKD.