Clinical Use of Tecovirimat (Tpoxx) for Treatment of Monkeypox Under an Investigational New Drug Protocol - United States, May-August 2022.

Currently, no Food and Drug Administration (FDA)-approved treatments for human monkeypox are available. Tecovirimat (Tpoxx), however, is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox. Use of tecovirimat for treatment of monkeypox in the United States is permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism. CDC holds a nonresearch EA-IND protocol that facilitates access to and use of tecovirimat for treatment of monkeypox.§ The protocol includes patient treatment and adverse event reporting forms to monitor safety and ensure intended clinical use in accordance with FDA EA-IND requirements. The current multinational monkeypox outbreak, first detected in a country where Monkeypox virus infection is not endemic in May 2022, has predominantly affected gay, bisexual, and other men who have sex with men (MSM) (1,2). To describe characteristics of persons treated with tecovirimat for Monkeypox virus infection, demographic and clinical data abstracted from available tecovirimat EA-IND treatment forms were analyzed. As of August 20, 2022, intake and outcome forms were available for 549 and 369 patients, respectively; 97.7% of patients were men, with a median age of 36.5 years. Among patients with available data, 38.8% were reported to be non-Hispanic White (White) persons, 99.8% were prescribed oral tecovirimat, and 93.1% were not hospitalized. Approximately one half of patients with Monkeypox virus infection who received tecovirimat were living with HIV infection. The median interval from initiation of tecovirimat to subjective improvement was 3 days and did not differ by HIV infection status. Adverse events were reported in 3.5% of patients; all but one adverse event were nonserious. These data support the continued access to and treatment with tecovirimat for patients with or at risk for severe disease in the ongoing monkeypox outbreak.

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon ß-1a or dimethyl fumarate: a real-world study.

OBJECTIVE: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) ß-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). METHODS: A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN ß-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN ß-1a or DMF, or (b) previously treated, switching to sc IFN ß-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. RESULTS: One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN ß-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN ß-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN ß-1a. No differences in relapse risk or ARR between sc IFN ß-1a- and DMF-treated patients were observed. CONCLUSIONS: sc IFN ß-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

The Economic Impact of Levothyroxine Dose Adjustments: the CONTROL HE Study.

BACKGROUND: In general, hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for levothyroxine dose adjustments is frequent in clinical practice. The extent to which levothyroxine dose adjustments increase the utilization of healthcare resources has not previously been described in the clinical literature. OBJECTIVE: The primary objective of our study was to measure the effect of levothyroxine dose adjustments in terms of their utilization of healthcare resources including direct and indirect costs. A secondary goal was to identify any differences in patient characteristics that may be responsible for levothyroxine dose adjustments. METHODS: A retrospective medical chart review was conducted among patients of selected healthcare providers in the USA. Patients who were recently started on levothyroxine therapy (<6 months) were excluded to avoid situations that were more likely attributable to treatment initiation than inadequate therapeutic effect. Trained nurses extracted data from patient charts and electronic medical record systems for review. We analyzed the cost of resources consumed by the frequency of levothyroxine dose changes over 24 months: 0 dose changes (no dose adjustment group); one dose change, two dose changes, three or more dose changes (≥1 dose adjustment group). RESULTS: The study included 454 patients. Overall estimated resource utilization was higher per patient in the ≥1 dose adjustment group (US$5824) vs. the no dose adjustment group (US$3166) during the 24-month study period. When direct and indirect costs were combined, overall costs of care were greatest in patients requiring three or more dose adjustments (US$8220/patient). Patients in this cohort incurred 2.5-fold greater total costs compared with patients requiring no dose adjustments (US$8220 vs. US$3166). Among the 58 patients in the group requiring three or more dose adjustments, mean direct medical costs were significantly higher than in the patients requiring no dose adjustments (US$6387 vs. US$2182). Patients with at least one dose adjustment experienced a 40.3% increase in lost productivity vs. patients who had no dose adjustments (US$1381 vs. US$984). Loss of productivity was highest among patients with three or more levothyroxine dose adjustments. Among this cohort, there was an 86.4% increase in lost productivity vs. patients who had no levothyroxine dose adjustments (US$1833 vs. US$984). CONCLUSIONS: Patients experiencing multiple levothyroxine dose adjustments were shown to consume more healthcare resources, resulting in higher costs than those who required no dose adjustments. Each care episode contributed to lost time and wages with total estimated lost productivity escalating with increasing levothyroxine dose adjustments over a 24-month period.

Retrospective Study of Patients Switched from Tablet Formulations to a Gel Cap Formulation of Levothyroxine: Results of the CONTROL Switch Study.

INTRODUCTION: Medication changes involving levothyroxine-either dose titrations or switching formulations-occur frequently in patients with erratic thyroid-stimulating hormone (TSH) levels and persistent hypothyroid symptoms. We investigated whether switching patients from levothyroxine tablets to a gel cap formulation of levothyroxine might reduce dose adjustments and improve tolerability and efficacy outcomes. OBJECTIVES: Primary study objectives included quantifying the percentage of patients achieving TSH levels within a pre-specified range, median dose changes experienced, and the percentage of patients with improved hypothyroid symptom control after switching from levothyroxine tablets to levothyroxine gel caps. METHODS: A retrospective medical chart review was conducted among 99 randomly selected hypothyroid patients who were switched from a tablet to a gel cap formulation of levothyroxine. Patients were required to have been on levothyroxine monotherapy for ≥1 year prior to the medication switch. Data was collected for 6 months pre-switch and up to 6 months post-switch. RESULTS: Of the 99 patients studied, the majority (51.5%) experienced no documented change in TSH status after the switch (P < 0.0001). However, there was a decrease in the mean number of dose changes experienced (1.61 ± 0.96 vs. 0.73 ± 0.96; P < 0.0001). Improved hypothyroid symptom control was reported among 61.6% of patients (61 of 99; P < 0.0001). CONCLUSION: The results of CONTROL Switch support a strategy of switching patients who may experience tolerability or efficacy problems with standard levothyroxine tablets to the levothyroxine gel cap formulation.