Polypharmacy in Multiple Sclerosis: Prevalence, Risks, and Mitigation Strategies.

PURPOSE OF REVIEW: Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is common for symptom management in people with multiple sclerosis, but risks drug-drug interactions and additive side effects. Multiple sclerosis providers should therefore focus on the appropriateness and risks versus benefits of pharmacotherapy in each patient. This review describes the prevalence and risks associated with polypharmacy in people with multiple sclerosis and offers strategies to identify and mitigate inappropriate polypharmacy. RECENT FINDINGS: Research in people with multiple sclerosis has identified risk factors and negative outcomes associated with polypharmacy. Medication class-specific investigations highlight their contribution to potentially inappropriate polypharmacy in people with multiple sclerosis. People with multiple sclerosis are at risk for inappropriate polypharmacy. Multiple sclerosis providers should review medications and consider their appropriateness and potential for deprescribing within the context of each patient.

A randomized controlled trial for a peer-facilitated telemedicine hepatitis c treatment intervention for people who use drugs in rural communities: study protocol for the "peer tele-HCV" study.

BACKGROUND: Hepatitis C virus (HCV) transmission is primarily driven by injection drug use, and acute HCV infection rates are increased in rural communities with substantial barriers to care. Treatment of HCV in persons who use drugs (PWUD) is cost effective, decreases high risk behaviors and HCV transmission, and achieves high rates of treatment completion and sustained viral response. Adapting HCV care delivery to utilize peer support specialists, telemedicine technology, and streamlined testing and treatment strategies can better reach rural populations living with HCV. METHODS: This is an open label, two-arm, non-blinded, randomized controlled trial designed to test the superiority of peer-facilitated and streamlined telemedicine HCV care (peer tele-HCV) compared to enhanced usual care (EUC) among PWUD in rural Oregon. In the intervention arm, peers conduct HCV screening in the community, facilitate pretreatment evaluation and linkage to telemedicine hepatitis C treatment providers, and support participants in HCV medication adherence. For participants assigned to EUC, peers facilitate pretreatment evaluation and referral to community-based treatment providers. The primary outcome is sustained virologic response at 12 weeks post treatment (SVR12). Secondary outcomes include: (1) HCV treatment initiation, (2) HCV treatment completion, (3) engagement with harm reduction resources, (4) rates of substance use, and (5) engagement in addiction treatment resources. The primary and secondary outcomes are analyzed using intention-to-treat (ITT) comparisons between telemedicine and EUC. A qualitative analysis will assess patient, peer, and clinician experiences of peer-facilitated telemedicine hepatitis C treatment. DISCUSSION: This study uses a novel peer-based telemedicine delivery model with streamlined testing protocols to improve access to HCV treatment in rural communities with high rates of injection drug use and ongoing disease transmission. We hypothesize that the peer tele-HCV model will increase treatment initiation, treatment completion, SVR12 rates, and engagement with harm reduction services compared to EUC. Trial registration This trial has been registered with ClinicalTrials.gov (clinicaltrials.gov NCT04798521).

Adherence to Hepatitis C Treatment Among Underserved Patients With Substance Use Disorder in a Pharmacist-led Treatment Model.

BackgroundTreatment with medications for opioid use disorder (MOUD) may improve hepatitis C virus (HCV) treatment outcomes by providing additional contact with health care professionals to support patient engagement. Objective: We describe a pharmacist-led HCV treatment model and assessed the effect of MOUD on adherence to direct-acting antivirals (DAAs) in an underserved patient population. Methods: This was a retrospective cohort study of adults (age≥18 years) treated for HCV infection with DAAs at a Federally Qualified Health Center in Portland, Oregon, between March 1, 2019, and March 16, 2020. Patients were followed to 12 weeks to assess adherence to DAAs by MOUD status. Results: Among 59 eligible patients, 16 (27%) were prescribed MOUD. Baseline characteristics were similar between patients who did and did not receive MOUD. Adherence to DAAs was overall high and not significantly different between the groups (median: 98.5% vs median: 100%; P = .06). Five patients missed at least one dose due to an adverse drug effect and two of these patients discontinued HCV therapy due to these effects. Conclusion: Adherence to HCV therapy was nearly 100% among underserved patients in a pharmacist-led HCV treatment model and did not differ by MOUD engagement.

Frequency and clinical outcomes of pharmacist-driven switching from warfarin to direct oral anticoagulants in an underserved patient population: A retrospective cohort study.

PURPOSE: Direct oral anticoagulant (DOAC) medications have improved safety, efficacy, and laboratory monitoring requirements compared to warfarin. However, available data are limited on the frequency and clinical outcomes of pharmacist-driven warfarin-to-DOAC switches. We aimed to quantify the frequencies and rationale of warfarin-to-DOAC switches in an underserved population. We also assessed clinical outcomes and compliance with recommended laboratory monitoring after switches. METHODS: This retrospective cohort study included adult (age 18 years or older) patients on warfarin who were assessed by a clinical pharmacist for switch appropriateness to a DOAC. Study data were collected via manual chart review and included demographics, comorbid illnesses, switch status, the rationale for or against switching, incidence of thromboses and bleeds within 6 months of the switch assessment, and the time to the first complete blood count and renal and hepatic function tests after the switch. Statistical analysis utilized descriptive statistics, including the mean and SD, median and interquartile range, and frequencies and percentages. RESULTS: Among 189 eligible patients, 108 (57%) were switched from warfarin to a DOAC. The primary rationales for switching were less monitoring (64%) and labile international normalized ratio (32%). The main reason against switching was DOAC inappropriateness (53%), such as in morbid obesity (14%). Patient preference was commonly cited in both groups (54% and 36%, respectively). The overall incidence of thrombotic events (9%) and bleeds (15%) after switch assessment was low. Laboratory monitoring after switches was consistent with current recommendations. CONCLUSION: No increase in harm was observed 6 months after switch assessment when pharmacists at a family medicine clinic switched underserved patients from warfarin to DOACs.

Pharmacists' Knowledge and Perceptions of FDA Approval Standards and the Breakthrough Therapy Designation.

The "breakthrough therapy" designation (BTD) is a recent mechanism implemented by the United States Food and Drug Administration (FDA) to expedite access to drugs that address unmet needs. The purpose of this study is to describe pharmacists' knowledge of FDA drug-approval standards and knowledge and perceptions of the BTD. Pharmacists engaged in advanced clinical practice were identified through membership profiles of a professional pharmacy organization. Eligible participants were then sent a questionnaire to assess knowledge of FDA approval standards and the BTD. A total of 226 pharmacists responded. The majority of respondents were women (70.2%) and had completed post-graduate training (85.8%). Over half correctly answered at least two of three questions on FDA approval standards (58.1%) and the BTD (78.1%). Only 24.1% of respondents identified as being familiar with the BTD. The majority of pharmacists (62.8%) were certain that FDA-approved "breakthrough" drugs represented a major advance over currently approved therapies and most (88.5%) preferred the drug designated as "breakthrough" in a hypothetical scenario. In conclusion, pharmacists were able to correctly answer questions about FDA approval standards and the BTD. However, they were unfamiliar with the implications of a BTD and may overestimate the benefit demonstrated by these drugs. Future research should identify knowledge gaps in pharmacist understanding of regulatory mechanisms designed to expedite drug approval.

Launching an innovative educational model addressing substance use disorders and dental pain management (Project ECHO® in dentistry).

BACKGROUND: Uninformed opioid prescribing by dentists has contributed to the current opioid crisis. This report describes the development and implementation of an innovative, interactive, multidisciplinary, and participant-centric telementoring program "Pain Management and Substance Use Disorders Dental ECHO (Extension for Community Health Care Outcomes)". We disseminated information to dentists about appropriate opioid prescribing practices and engaged them with a focus on pain management and substance use disorders. The objective of this study was to assess the effectiveness of this program for self-reported: (1) change in knowledge and confidence related to clinical skills for dental pain management of patients with substance use disorders; (2) change in clinical behavior of dentists for safe opioids prescribing; and (3) change in clinic policies regarding safe opioids prescribing. METHODS: An interdisciplinary panel of experts in medicine, pharmacy, social work, and dentistry designed and led the "Pain Management and Substance Use Disorders Dental ECHO" for invited dental care providers and dental students. Six cohorts each consisting of six, 1-h-long sessions were conducted via the Zoom videoconference platform in years 2020 and 2021. Each session included a didactic expert presentation, a participant-presented patient case and discussion. Each participant completed pre- and post-program surveys to assess the program's influence on participant knowledge, clinical confidence and behavior change. RESULTS: The participants (N = 151) were dentists (n = 109), dental faculty (n = 15), dental residents (n = 6), dental hygienists/assistants (n = 13) and nurses and clinic administrators (n = 8). Self-reported perceived medication knowledge, confidence in identification, treatment and willingness to engage with substance use disorders patients, and reported compliance with Prescription Drug Monitoring Program (PDMP) checks increased significantly from before to after the sessions (p < 0.001). Overall, participants expressed high levels of satisfaction with the content and reported that the sessions provided high benefit. CONCLUSION: The Project ECHO model is effective in rapidly disseminating evidence-based information. Dentists viewed this model as having a high degree of benefit for the optimal management of dental pain and the recognition and treatment of substance use disorders.

Effect of relaxing hepatitis C treatment restrictions on direct-acting antiviral use in a Medicaid program: an interrupted time series analysis.

BACKGROUND: Although direct-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C virus (HCV), many state Medicaid programs have limited coverage because of their expense. In 2015, the Centers for Medicare & Medicaid Services (CMS) notified states about the legality of Medicaid coverage limitations, particularly within managed care programs. OBJECTIVES: To (1) examine how relaxation and alignment of hepatitis C policies within the Oregon Medicaid program affected DAA utilization and (2) describe changes in DAA coverage policies and patient characteristics of treated individuals over time. METHODS: We manually collected DAA Medicaid drug policies in the state of Oregon before and after the CMS notification was released. After categorizing DAA policies into 2 groups based on baseline prior authorization criteria (restrictive and permissive), we evaluated how changes in these DAA policies affected utilization over 3 time periods (pre-CMS period, post-CMS period, and fibrosis policy alignment). Immediate and gradual changes in trend were assessed using an interrupted time series regression model. Finally, we examined patient characteristics and liver disease complications over time as policy restrictions were removed and aligned with one another. RESULTS: From 2014 to 2018, Oregon's coordinated care organizations and fee-for-service drug policies relaxed liver fibrosis and substance abstinence coverage criteria leading to immediate increases in DAA use in 2016 (0.62 prescriptions per 10,000 enrollees per month; 95% CI = 0.17 to 1.08) and 2018 (1.07 prescriptions per 10,000 enrollees per month; 95% CI = 0.63 to 1.51) among more restrictive coordinated care organizations at baseline. This was followed by a decrease in trend after the 2016 and 2018 impact (-0.05; 95% CI = -0.11 to -0.001 and -0.07; 95% CI = -0.13 to -0.02, respectively). Over the 3 periods, there was a decrease in treated individuals with liver-related complications (P < 0.0001) and an increase in those with a substance use diagnosis (P = 0.0013). CONCLUSIONS: Reducing coverage limitations resulted in treatment of patients with fewer liver-related complications and more substance use disorders. Expanding access to treatment did not result in sustained increases in utilization, and additional interventions may be necessary to meet HCV elimination goals. DISCLOSURES: This study was funded in part by AbbVie Pharmaceuticals, which did not have any role in the study design, collection, analysis and interpretation of data, writing the report, or the decision to submit the report for publication. Hartung received support for his work on this study via a grant from AbbVie Pharmaceuticals. The other authors did not receive any financial support for their contributions to this study. The authors have no other financial disclosures to report. This study was presented at the Academy Health Annual Research Meeting in Washington, DC, on June 3, 2019.

Clinical Management of Pharmacokinetic Drug Interactions with Direct Oral Anticoagulants (DOACs).

Compared with warfarin, the direct-acting oral anticoagulants (DOAC) have fewer pharmacokinetic drug interactions. However, significant drug interactions do exist with documented changes in DOAC concentrations, which can exceed 100%. Unlike warfarin, DOACs have no validated surrogate test to monitor the intensity of anticoagulation. However, several analyses of major outcomes trials with DOACs have demonstrated that serum concentrations do affect both the thrombotic benefits and the hemorrhagic risks of these agents. This paper reviews the known significant pharmacokinetic interactions with DOACs and includes considerations for their use in the presence of interacting medications.

FDA Breakthrough Therapy Designation: Evaluating the Quality of the Evidence behind the Drug Approvals.

The United States Food and Drug Administration (FDA) has created approval pathways and designations to accelerate access to medications indicated for serious or life-threatening conditions with limited treatment options. Implemented in 2012, the most recent of these is the breakthrough therapy designation (BTD). The purpose of this article was to review the evidence surrounding approval of medications with nononcology indications approved with the BTD designation from 2012 to 2016. Fifteen medications were identified for eight conditions, ranging from conditions that are relatively common, such as chronic hepatitis C infection, to those that are extremely rare, such as lysosomal acid lipase deficiency. The quality of evidence behind these approvals was highly heterogeneous. Much remains unknown about the safety and efficacy of many agents approved through the BTD. Health care professionals should be aware of these limitations to better educate patients and other providers appropriately.

The safety and efficacy of vortioxetine for acute treatment of major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Vortioxetine is the first mixed serotonin agonist and antagonist antidepressant approved in the US. We sought to evaluate all published and unpublished data available to determine the efficacy and harms of vortioxetine in adults with major depressive disorder. METHODS: We used a predefined search strategy of MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Drugs@FDA to identify studies evaluating vortioxetine in the acute treatment of major depressive disorder. Only randomized controlled trials (RCTs) that provided results on relevant clinical efficacy and safety outcomes were included. Study quality was assessed and results were pooled using mixed effect meta-analyses where applicable. RESULTS: We identified 11 RCTs with 6,145 participants meeting inclusion criteria (eight were published and three were unpublished). The trials did not exceed 8 weeks in duration. The response rate with vortioxetine was significantly higher for 1-mg (relative risk (RR) = 1.91; 95% confidence interval (CI) 1.36 to 2.69), 5-mg (RR = 1.33; 95% CI 1.10 to 1.61), 10-mg (RR = 1.42; 95% CI 1.21 to 1.67), and 20-mg doses (RR = 1.58; 95% CI 1.19 to 2.08) compared to placebo. Remission rates were significantly higher for the 10-mg group (RR = 1.45; 95% CI 1.18 to 1.77) and the 20-mg group (RR = 1.68; 95% CI 1.19 to 2.37) compared to placebo. Meta-regression of dose on the log odds ratio of response was not statistically significant (ß = 0.01; P = 0.46). Vortioxetine response rates were lower than active serotonin and norepinephrine reuptake inhibitor (SNRI) comparators for the 5-mg (RR = 0.88; 95% CI 0.80 to 0.98), 15-mg (RR = 0.78; 95% CI 0.68 to 0.90), and 20-mg (RR = 0.82; 95% CI 0.72 to 0.94) doses. The most common adverse events were nausea and vomiting which increased in frequency with higher doses. CONCLUSIONS: Vortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD). Although treatment effect estimates varied substantially between studies, a dose effect was not observed. Vortioxetine does not appear to be more effective, and is potentially less effective, than an SNRI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013006198 .