Class Of Medications For Prevention Research Articles

Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis

IntroductionSubanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care.MethodsA retrospective study was conducted...

The migraine signature study: Methods and baseline results.

ObjectiveTo characterize patients who utilize services for migraine in a large integrated health care network, and describe patterns of care and utilization.BackgroundWithin health care systems, migraine is a common reason for seeking primary and neurology care, but relatively little is documented about who seeks care and the factors that explain variation in utilization.MethodsWe conducted a retrospective cohort study using electronic health record (EHR) data from Sutter Health primary care (PC) patients who had at least one office visit to a PC clinic between 2013 and 2017. Migraine status was ascertained from diagnosis codes and medication orders. Control status was assigned to those with no evidence of care for any type of headache. We divided the primary care migraine cohort into two groups: those who received all their care for migraine from PC (denoted PC‐M) and those who had ≥1 encounter with a neurologist for migraine (denoted N‐M). Migraine cases were also designated as having preexisting migraine if they had an encounter with a migraine diagnosis within (±) 6 months of their first study period PC visit and, otherwise, designated as first migraine consult. Two levels of contrasts included: patients with migraine and controls; and within the group of patients with migraine, PC‐M and N‐M groups. Comorbid conditions were determined from EHR encounter diagnosis codes.ResultsWe identified 94,149 patients with migraine (including 21,525 N‐M and 72,624 PC‐M) and 1,248,763 controls. Comorbidities: Proportions of psychiatric [29.8% (n = 28,054) vs. 11.8% (n = 147,043)], autoimmune [(4.4% (n = 4162) vs. 2.6% (n = 31,981)], pain [13.2% (n = 12,439) vs. 5.8% (n = 72,049)], respiratory [24.6% (n = 23,186) vs. 12.3% (n = 153,692)], neurologic [2.9% (n = 2688) vs. 0.9% (n = 11,321)], and cerebrovascular [1.0% (n = 945) vs. 0.6% (n = 7500)] conditions were higher in the migraine group compared to controls, all p < 0.001. Among patients with migraine, the N‐M group was similar to the PC‐M group in sex, age, ethnicity, and marital status, but were more likely to have preexisting migraine (49.9% (n = 10,734) vs. 36.2% (n = 26,317), p < 0.001). Proportions of comorbid conditions were higher among the N‐M group than the PC‐M group {psychiatric [38.5% (n = 8291) vs. 27.2% (n = 19,763)], autoimmune [6.3% (n = 1365) vs. 3.9% (n = 2797)], pain [19.6% (n = 4218) vs. 11.3% (n = 8211)], respiratory [30.3% (n = 6516) vs. 23.0% (n = 16,670)], neurologic [6.0% (n = 1288) vs. 1.9% (n = 1400)], cardiovascular [9.7% (n = 2091) vs. 7.0% (n = 5076)], and cerebrovascular [2.3% (n = 500) vs. 0.6% (n = 445)], all p < 0.001}. Medications: During the study period, 82.6% (n = 77,762) of patients with migraine received ≥1 prescription order for an acute migraine medication [89.4% (n = 19,250) of N‐M vs. 80.6% (n = 58,512) of PC]. Opioids were prescribed to 52.9% (n = 49,837) of patients with migraine [63.5% (n = 13,669) for N‐M and 49.8% (n = 36,168) for PC‐M patients). During the study period, 61.4% (n = 57,810) of patients received ≥1 prescription for a migraine preventive medication [81.4% (n = 17,521) of N‐M and 55.5% (n = 40,289) of PC‐M patients]. The most commonly prescribed classes of preventive medications were antidepressants.ConclusionsAmong patients with migraine in a large health system, those who were also cared for in neurology were more likely to receive both acute and preventive medication migraine orders than those patients who did not see a neurologist, with triptans and antidepressants the most commonly prescribed classes of acute and preventive pharmacotherapies, respectively. Opioids were prescribed to approximately half of the total sample and more common in the N‐M group. Adjusting for demographics, patients with migraine had higher rates of nearly every comorbidity we assessed and were more likely to utilize services compared to those without migraine. Overall, patients with migraine also cared for in neurology practices used more of all health care resource types under consideration and had more medical issues, which may be due in some part to a more severe, frequent and disabling disease state compared to those who sought care exclusively from PC practices.

Individual Patient Data from the Pivotal Randomized Controlled Trials of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (COMBINE AF): Design and Rationale: From the COMBINE AF (A Collaboration between Multiple institutions to Better Investigate Non-vitamin K antagonist oral anticoagulant use in Atrial Fibrillation) Investigators

Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date. COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771). In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.

Fremanezumab in the prevention of migraine: a profile of its use

Fremanezumab (fremanezumab-vfrm; Ajovy®), a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), is indicated for the prevention of migraine in adults in the EU and USA. Subcutaneous fremanezumab 225 mg once monthly or 675 mg once every 3 months was effective in reducing monthly migraine days or headache days in patients with episodic or chronic migraine in pivotal, 12-week clinical trials. Both regimens also reduce acute headache medication use and headache-related disability. Improvements were maintained through ≤ 52 weeks of additional treatment in a longer-term extension study. In a trial in treatment-resistant migraine, both fremanezumab regimens reduced monthly migraine days in patients who had failed 2–4 classes of preventive medications. Fremanezumab is generally well tolerated, with most adverse events (AEs) being injection site reactions of mild or moderate severity.

Fremanezumab impact on disability and MSQOL in patients with inadequate response to 2-4 classes of preventive medications who reverted from chronic to episodic migraine

Headache-related disability and migraine-specific quality of life (MSQoL) were exploratory endpoints of the FOCUS phase 3b study of fremanezumab, the first and largest study of preventive treatment in adults with episodic or chronic migraine (EM or CM) and documented inadequate response to 2-4 classes of migraine preventive medications. This post-hoc analysis evaluated disability and MSQoL in patients reverting from CM to EM during the study. After obtaining IRB approval, patients with CM were randomised (1:1:1) to double-blind treatment with quarterly fremanezumab (month 1: 675 mg; months 2/3: placebo), monthly fremanezumab (month 1: 675 mg; months 2/3: 225 mg), or matched monthly placebo for 12 weeks. Reversion rates were defined as: A) ≥15 headache days (HDs) at baseline but <15 HDs at all 3 months or B) ≥15 HDs at baseline but <15 HDs on average over 12 weeks. Of the CM patients, 18/167(11%) with placebo, 59/167(35%) with quarterly fremanezumab, and 59/172(34%) with monthly fremanezumab reverted to EM using definition A, and 50/167(30%), 81/167(49%), and 91/172(53%), respectively, reverted using definition B. Reductions from baseline in the 6-item Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) scores and improvements from baseline in all MSQoL domain scores were greater with fremanezumab versus placebo during the 4 weeks after the third dose of study drug (Table). Fremanezumab was associated with improvements in headache-related disability and all MSQoL domain scores versus placebo in patients with documented inadequate response to 2-4 classes of migraine preventive medications who reverted from CM to EM.

Safety and efficacy of alirocumab: A meta analysis of 12 randomized controlled trials.

Background and Objective:Hypercholesterolemia is one of the major risk factor for atherosclerotic coronary heart disease, especially coronary heart disease. Most effective class of medications for prevention of cardiovascular events and LDL-C reduction are the statins. Approximately only one fourth of these high risk patients had achieved LDL-C levels <70 mg/dL with statins. Monoclonal antibody targeting PCSK9 is a novel class of drug used in the treatment of Hypercholesterolemia. Alirocumab is one such human monoclonal antibody directed against PCSK9. Binding of PCSK9 to the LDL-R on the hepatocytes promotes LDL-R degradation. Inhibition of PCSK9 binding to LDL-R leads to increased number of LDL-Rs to clear LDL, thus decreasing LDL-C levels. The purpose of this systematic study is to assess the safety and efficacy of Alirocumab in adults with hypercholesterolemia and Familial hypercholesterolemia.Materials and Methods:We searched Medline, PubMed Central database, Google scholar, EBSCO, Wiley library, conference proceedings and Clinical trials.gov registry through March 2017. Phase 3 randomized, controlled trials (RCTs) using Alirocumab in adults with hypercholesterolemia and Familial Hypercholesterolemia were selected.Results:In twelve RCTs comprising of 6019 patients included in the meta-analysis, significant favorable changes in LDL-C and HDL-C were found.Limitations:Results were derived from study level data rather than patient level data.Conclusions:Alirocumab substantially reduced the LDL-C level by over 50 %, increased the HDL-C level, and resulted in favorable changes in other lipids.

Case-crossover Studies of Therapeutics

Self-controlled analysis methods implicitly adjust for time-invariant confounding within individuals. A person's prognosis often varies over time and affects both therapy choice and subsequent health outcomes. Current approaches may not be able to fully address this within-person confounding. We evaluated the potential impact of time-varying prognosis in self-controlled studies of treatment effects and the extent to which alternative adjustment strategies could mitigate these biases. We used Medicare data linked to prescription drug data from a pharmaceutical assistance program to conduct case-crossover studies of the relationship between intermittent use of five classes of preventive medications (statins, oral hypoglycemics, antihypertensives, osteoporosis, and glaucoma medications) and death-relationships that are strongly biased because of healthy-user and sick-stopper effects. We used the case-case time-control design to adjust for confounding from exposure trends related to prognosis. Each class of medications was evaluated separately, with the remaining four used as reference drugs to estimate prognosis-related exposure trends. The case-crossover odds ratios were 0.39, 0.38, 0.40, 0.39, and 0.45 for statin, antihypertensive, glaucoma, hypoglycemic, and osteoporosis drugs, respectively. After adjusting for the estimated noncausal prognosis-related trends in drug exposure among all eligible cases, odds ratios were clustered closer to null (0.99, 0.95, 1.02, 0.99, and 1.16, respectively). Consideration of the sociology of medication use leading to health outcomes is essential in designing and analyzing self-controlled studies of treatment effects. Although the case-case time-control design was able to reduce bias from prognosis-related exposure trends in our examples, the difficulty in identifying appropriate reference exposures could be prohibitive.