Market Access Analysis of Biologics and Small-Molecule Inhibitors for Inflammatory Bowel Disease Among US Health Insurance Policies.

BACKGROUND AND AIMS:Treatment pathways for ulcerative colitis (UC) and Crohn's disease (CD) are shifting to a more individualized, risk-stratified approach. The perception is that insurance policies may not have implemented this paradigm shift, particularly regarding access to newer agents. We evaluated patient access to advanced therapies by analyzing policy information from the Managed Markets Insight and Technology database. METHODS:Coverage status as of December 2018 for all US lives was queried for adalimumab, infliximab, infliximab-dyyb, tofacitinib, ustekinumab, and vedolizumab by indication (UC and/or CD) and medical or pharmacy coverage benefit. Coverage status was classified by the number of biologic steps before access to specified drug as "No Biologic," "1 Prior Biologic," "2+ Prior Biologics," "Not Covered." Unknown lives were excluded from the analyses. RESULTS:Coverage analysis was available for approximately 302 million lives under each medical and pharmacy benefit. Our analysis indicates that approximately half of covered lives had access to all agents (except tofacitinib) as first-line therapy; two-thirds had access after one biologic exposure. Among newer agents, vedolizumab had the widest coverage. For indications of UC and CD, 81% of known lives had access to vedolizumab with no prior biologic exposure required ("No Biologic"), 95% after "No Biologic" + "1 prior Biologic." Geographic variations were identified for coverage patterns. CONCLUSIONS:This US-based healthcare policy analysis points to an increased access to advanced therapies for UC and CD. An individualized, risk-stratified treatment approach integrating advanced therapies, including those recently approved, into treatment pathways for UC and CD is feasible

Development of Inflammatory Bowel Disease in HIV Patients:A Danish Cohort Study (1983-2018) With American Validation (1999-2018)

BACKGROUND AND AIMS: Human immunodeficiency virus (HIV) infection is associated with several immune-mediated disorders. However, the risk of inflammatory bowel disease (IBD) in people living with HIV (PLWH) remains unclear. We aimed to assess the risk of IBD among PLWH using a nationwide, population-based Danish cohort and to validate findings in a large American insurance-based database. METHODS: Using Danish registries (1983–2018), we identified 8995 PLWH and age- and sex-matched them to 449,750 HIV-negative individuals. Cox regression analysis was undertaken to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for IBD diagnosis. Results were stratified by sex, age, and year of HIV diagnosis. Using an American insurance-based cohort, Explorys (1999–2018), we assessed the prevalence odds ratio (OR) and 95% CI of IBD diagnosis in PLWH compared with HIV-negative individuals. RESULTS: IBD diagnosis among PLWH in Denmark was increased (HR: 2.25, 95% CI: 1.78–2.83) compared with matched HIV-negative individuals. This was seen for both Crohn’s disease (HR: 2.25, 95% CI: 1.47–3.44) and ulcerative colitis (HR: 2.24, 95% CI: 1.70–2.96) and in male (HR: 2.75, 95% CI: 2.15–3.52) but not female (HR: 0.93, 95% CI: 0.48–1.79) PLWH. Explorys analysis also showed an increased odds of IBD diagnoses among PLWH (OR: 1.41; 95% CI: 1.35–1.49). CONCLUSION: This study finds an increased risk of IBD diagnosis among PLWH in both a Danish and US cohort, highlighting a need to consider IBD in PLWH with new-onset gastrointestinal symptoms. Further research into the role of antiretroviral therapy in this relationship is required

Isotopic constraints on the genesis and evolution of basanitic lavas at Haleakala, Island of Maui, Hawaii

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Geochimica et Cosmochimica Acta 195 (2016): 201-225, doi:10.1016/j.gca.2016.08.017.To understand the dynamics of solid mantle upwelling and melting in the Hawaiian plume, we present new major and trace element data, Nd, Sr, Hf, and Pb isotopic compositions, and 238U-230Th-226Ra and 235U-231Pa-227Ac activities for 13 Haleakala Crater nepheline normative basanites with ages ranging from ~900 to 4100 yr B.P.. These basanites of the Hana Volcanics exhibit an enrichment in incompatible trace elements and a more depleted isotopic signature than similarly aged Hawaiian shield lavas from Kilauea and Mauna Loa. Here we posit that as the Pacific lithosphere beneath the active shield volcanoes moves away from the center of the Hawaiian plume, increased incorporation of an intrinsic depleted component with relatively low 206Pb/204Pb produces the source of the basanites of the Hana Volcanics. Haleakala Crater basanites have average (230Th/238U) of 1.23 (n=13), average age-corrected (226Ra/230Th) of 1.25 (n=13), and average (231Pa/235U) of 1.67 (n=4), significantly higher than Kilauea and Mauna Loa tholeiites. U-series modeling shows that solid mantle upwelling velocity for Haleakala Crater basanites ranges from ~0.7 to 1.0 cm/yr, compared to ~10 to 20 cm/yr for tholeiites and ~1 to 2 cm/yr for alkali basalts. These modeling results indicate that solid mantle upwelling rates and porosity of the melting zone are lower for Hana Volcanics basanites than for shield-stage tholeiites from Kilauea and Mauna Loa and alkali basalts from Hualalai. The melting rate, which is directly proportional to both the solid mantle upwelling rate and the degree of melting, is therefore greatest in the center of the Hawaiian plume and lower on its periphery. Our results indicate that solid mantle upwelling velocity is at least 10 times higher at the center of the plume than at its periphery under Haleakala.Funding for this project was provided by NSF grants EAR-0001924 and EAR-9909473 to KWWS.2018-08-2

Long Term outcomes of percutaneous atrial fibrillation ablation in patients with continuous monitoring

INTRODUCTION: There is limited data using continuous monitoring to assess outcomes of atrial fibrillation (AF) ablation. This study assessed long-term outcomes of AF ablation in patients with implantable cardiac devices. METHODS: 207 patients (mean age 68.1 ± 9.5, 50.3% men) undergoing ablation for symptomatic AF were followed up for a mean period of 924.5 ± 636.7 days. Techniques included The Pulmonary Vein Ablation Catheter (PVAC) (59.4%), cryoablation (17.4%), point by point (14.0%) and The Novel Irrigated Multipolar Radiofrequency Ablation Catheter (nMARQ) (9.2%). RESULTS: 130 (62.8%) patients had paroxysmal AF (PAF) and 77 (37.2%) persistent AF. First ablation and repeat ablation reduced AF burden significantly (relative risk 0.91, [95% CI 0.89 to 0.94]; P <0.0001 and 0.90, [95% CI, 0.86-0.94]; P <0.0001). Median AF burden in PAF patients reduced from 1.05% (interquartile range [IQR], 0.1%-8.70%) to 0.10% ([IQR], 0%-2.28%) at one year and this was maintained out to four-years. Persistent AF burden reduced from 99.9% ([IQR], 51.53%-100%) to 0.30% ([IQR], 0%-77.25%) at one year increasing to 87.3% ([IQR], 4.25%-100%) after four years. If a second ablation was required, point-by-point ablation achieved greater reduction in AF burden (relative risk, 0.77 [95% CI, 0.65-0.91]; P <0.01). CONCLUSION: Ablation reduces AF burden both acutely and in the long-term. If a second ablation was required the point-by-point technique achieved greater reductions in AF burden than "single-shot" technologies. Persistent AF burden increased to near pre ablation levels by year 4 suggesting a different mechanism from PAF patients where this increase did not occur

A randomized sham-controlled study of pulmonary vein isolation in symptomatic atrial fibrillation (The SHAM-PVI study): Study design and rationale

INTRODUCTION: Pulmonary vein (PV) isolation has been shown to reduce atrial fibrillation (AF) burden and symptoms in patients. However, to date previous studies have been unblinded raising the possibility of a placebo effect to account for differences in outcomes. HYPOTHESIS & METHODS: The objective of this study is to compare PV isolation to a sham procedure in patients with symptomatic AF. The SHAM-PVI study is a double blind randomized controlled clinical trial. 140 patients with symptomatic paroxysmal or persistent AF will be randomized to either PV isolation (with cryoballoon ablation) or a sham procedure (with phrenic nerve pacing). All patients will receive an implantable loop recorder. The primary outcome is total AF burden at 6 months postrandomisation (excluding the 3 month blanking period). Key secondary outcomes include (1) time to symptomatic and asymptomatic atrial tachyarrhythmia (2) total atrial tachyarrhythmia episodes and (3) patient reported outcome measures. RESULTS: Enrollment was initiated in January 2020. Through April 2023 119 patients have been recruited. Results are expected to be disseminated in 2024. CONCLUSION: This study compares PV isolation using cryoablation to a sham procedure. The study will estimate the effect of PV isolation on AF burden

Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). METHODS: We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. RESULTS: Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P \u3c .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. CONCLUSIONS: We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718