Using an expanded algorithm to estimate prevalence of amyotrophic lateral sclerosis in U.S. and UK.

BACKGROUND: There is an increasing need to better understand the burden of amyotrophic lateral sclerosis (ALS) using real-world data (RWD). However, identifying ALS cases using RWD presents several challenges due to the rarity of ALS and the differences in database coding systems. METHODS: MarketScan claims, and the UK Clinical Practice Research Datalink (CPRD) databases were searched for diagnosis codes of ALS or MND, the only drugs approved for treating ALS (riluzole and edaravone) and clinical visits with 12-month enrolment prior to 1 January 2011. The main algorithm required ≥ 1 ALS diagnosis code together with prescriptions or clinical visits. We expanded the existing algorithm to identify unspecific (possible) ALS group that had codes for motor neuron disease (MND) and the ALS drugs. The study period was from 1 January 2011 until 31 December 2020. RESULTS: We identified 16,246 patients with ≥ 1 ALS code in Marketscan (denominator n = 85,279,619), yet only 184 were found in the UK CPRD (denominator n = 21,318,589). Using the main algorithm 9,433 ALS patients were included in MarketScan, with a prevalence ranged between 4.5 per 100,000 in 2019 and 6.2 in 2015. In MarketScan, 3,658 (4.3 per 100,000) had ≥ 1 MND code and the ALS drug codes (possible cases). In CPRD, 47.9% of 2,785 patients with ≥ 1 MND code had a prescription for riluzole (6.3 per 100,000), regarded as possible ALS cases. CONCLUSIONS: The expanded algorithm enabled the identification of a large population with ALS, or possible ALS, and the estimation of ALS prevalence in MarketScan and CPRD.

Hybrid Controlled Clinical Trials Using Concurrent Registries in Amyotrophic Lateral Sclerosis: A Feasibility Study.

Hybrid designs with both randomized arms and an external control cohort preserve key features of randomization and utilize external information to augment clinical trials. In this study, we propose to leverage high-quality, patient-level concurrent registries to enhance clinical trials and illustrate the impact on trial design for amyotrophic lateral sclerosis. The proposed methodology was evaluated in a randomized, placebo-controlled clinical trial. We used patient-level information from a well-defined, population-based registry, that was running parallel to the randomized clinical trial, to identify concurrently nonparticipating, eligible patients who could be matched with trial participants, and integrate them into the statistical analysis. We assessed the impact of the addition of the external controls on the treatment effect estimate, precision, and time to reach a conclusion. During the runtime of the trial, a total of 1,141 registry patients were alive; 473 (41.5%) of them fulfilled the eligibility criteria and 133 (11.7%) were enrolled in the study. A matched control population could be identified among the nonparticipating patients. Augmenting the randomized controls with matched external controls could have avoided unnecessary randomization of 17 patients (-12.8%) as well as reducing the study duration from 30.1 months to 22.6 months (-25.0%). Matching eligible external controls from a different calendar period led to bias in the treatment effect estimate. Hybrid trial designs utilizing a concurrent registry with rigorous matching can minimize bias due to a mismatch in calendar time and differences in standard of care, and may accelerate the development of new treatments.

Physician- and patient-reported perspectives on myasthenia gravis in Europe: a real-world survey.

BACKGROUND: Myasthenia gravis (MG) is a rare, chronic, debilitating, unpredictable, and potentially life-threatening neuromuscular disease. There is a lack of real-world data on disease management that could be used to further understand and address unmet patient needs and burden. We aimed to provide comprehensive real-world insights in the management of MG in five European countries. METHODS: Data were collected using the Adelphi Real World Disease Specific Programme™ in MG, a point-in-time survey of physicians and their patients with MG in France, Germany, Italy, Spain, and the United Kingdom (UK). Physician- and patient-reported clinical data were collected, including demographics, comorbidities, symptoms, disease history, treatments, healthcare resource utilization (HCRU), and quality of life outcomes. RESULTS: In total, 144 physicians completed 778 patient record forms from March to July 2020 in the UK, and from June to September 2020 in France, Germany, Italy and Spain. Mean patient age at symptom onset was 47.7 years, with a mean time from symptom onset to diagnosis of 332.4 days (10.97 months). At diagnosis, 65.3% of patients were classified as Myasthenia Gravis Foundation of America Class II or above. Mean number of symptoms reported at diagnosis per patient was five, with ocular myasthenia reported in at least 50% of patients. At time of survey completion, the mean number of symptoms reported per patient was five and ocular myasthenia and ptosis were each still present in more than 50% of patients. Acetylcholinesterase inhibitors were the most commonly prescribed chronic treatments in all countries. Of 657 patients treated with chronic treatment at the time of the survey, 62% continued to experience moderate-to-severe symptoms. On average, 3.1 healthcare professionals (HCPs) were involved in patient management, 6.2 consultations were made per patient with any HCP over the last 12 months, and 178 (22.9%) patients were hospitalized in the last 12 months. Overall, HCRU and disease management were similar across all countries. CONCLUSIONS: Our findings demonstrated the high burden of MG despite current treatment options for patients with MG.

Treatment patterns in myasthenia gravis: A United States health claims analysis.

INTRODUCTION/AIMS: Limited knowledge exists on treatment patterns in clinical practice in patients with myasthenia gravis (MG). In this study we examined MG treatment patterns in the United States. METHODS: Adult patients newly diagnosed with MG were identified from the IBM MarketScan insurance claims database. Patients with ≥2 MG International Classification of Disease diagnosis codes ≥3 months apart were retrospectively followed from the date of their first MG diagnosis record or start of treatment with acetylcholinesterase inhibitors (AChEI), intravenous (IV) or subcutaneous (SC) immunoglobulin (Ig), or plasma exchange (PLEx) therapy. Based on treatment received at any time during the follow-up period, patients were segmented into six main treatment cohorts. Exacerbations and use of IVIg, SCIg, or PLEx after the index date were identified. RESULTS: During 2010 to 2019, 7,194 patients were followed for up to 10 (median, 2.3) years. Of 6,539 treated patients, 6,462 (99%) were ever treated with AChEI and/or corticosteroids (CS); 95% were first treated with AChEI and/or CS only; 33% received ≥1 nonsteroid immunosuppressive treatment (IST) and 2% received a biologic. During treatment with first IST (n = 2,166), patients experienced 42% and 94% higher incidence rates of exacerbations and IVIg, respectively, compared with AChEI and/or CS (n = 6,242), and 33% and 23% higher, respectively, compared with a second IST (n = 353). DISCUSSION: Many patients experienced exacerbations and received rescue therapy despite treatment, suggesting current treatments may not provide adequate disease control for some patients and that additional treatment options should be explored.

Healthcare resource use in myasthenia gravis: a US health claims analysis.

Background: There are limited data on the impact of myasthenia gravis (MG) on real-world healthcare resource use (HCRU) and patient burden in the United States. Objectives: This study aims to assess HCRU in patients with MG using data from a US health claims database. Design: A retrospective, database study of adult patients newly diagnosed with MG, using the IBM® MarketScan® Commercial Claims and Encounters and Medicare supplemental health insurance claims database. Methods: Patients with ⩾2 MG International Classification of Disease diagnosis codes ⩾3 months apart were followed from the date of their first MG diagnosis record or start of treatment. HCRU and use of immunoglobulins and plasma exchange during follow-up was assessed, as well as comorbidities, hospitalizations, emergency room (ER) visits, intensive care unit (ICU) admissions, and specialist visits per year after diagnosis, and compared with age- and sex-matched non-MG controls. Results: During 2010-2019, 7194 patients were followed for up to 10 years (median = 2.3 years). During follow-up, patients with MG were 2.6-fold more likely than controls to be hospitalized, and 4.5-fold more likely to be admitted to an ICU. Risk and numbers of ER admission, hospitalization, and ICU visits were the highest in the 12 months post-diagnosis of MG and were consistently higher than controls during follow-up. MG was the main cause for most hospitalizations. Conclusion: Patients with MG have higher HCRU, compared with the age- and sex-matched non-MG controls. The early years after MG diagnosis are a period of particularly high healthcare burden, with many patients requiring hospitalization and ICU care to manage serious exacerbations.

Physician-Reported Perspectives on Myasthenia Gravis in the United States: A Real-World Survey.

INTRODUCTION: Myasthenia gravis (MG) is a rare, debilitating, chronic disorder caused by the production of pathogenic immunoglobulin G autoantibodies against the neuromuscular junction. A lack of real-world studies in rare diseases reflects a relatively limited understanding of the significant unmet needs and burden of disease for patients. We aimed to provide comprehensive real-world insights into the management and burden of MG from treating physicians in the United States (US). METHODS: Data were collected using the Adelphi Real World MG Disease Specific Programme™, a point-in-time survey of physicians and their patients with MG, in the US between March and July 2020. Physician-reported clinical data, including demographics, comorbidities, symptoms, disease history, treatments, and healthcare resource utilization, were collected. RESULTS: In total, 456 patient record forms were completed by 78 physicians based in the US. At time of survey completion, patient mean age was 54.5 years. Mean time from symptom onset to diagnosis was 9.0 months (n = 357). Ocular symptoms were reported in 71.7% of patients. General fatigue affected 47.1% of patients and over half of those reported the severity as moderate or severe (59.5%, n = 128). Acetylcholinesterase inhibitors and/or steroids were the most frequently prescribed first-line treatment type among patients receiving treatment at time of survey completion and with moderate-to-severe symptoms (77.9%, n = 159/204). High-dose steroids (n = 14) and intravenous immunoglobulin (n = 13) were the most prescribed acute treatments among those receiving an acute treatment at time of survey completion (n = 36), with symptom exacerbations or myasthenic crises being the most common reasons for acute treatment. On average, 2.5 healthcare professionals were involved in patient management and 5.0 consultations were made per patient over the last 12 months. CONCLUSIONS: Our findings indicated that, despite treatment, there is a proportion of patients with MG in the US who had a significant need for improved disease management.

The Burden of Progressive Supranuclear Palsy on Patients, Caregivers, and Healthcare Systems by PSP Phenotype: A Cross-Sectional Study.

Progressive supranuclear palsy (PSP) is a rare, relentlessly progressive, ultimately fatal neurodegenerative brain disease. The objective of this study was to assess the burden of PSP on patients, caregivers, and healthcare systems by PSP phenotype. Data were drawn from the Adelphi PSP Disease Specific Programme™, a cross-sectional study of neurologists and people living with PSP in the United States of America, France, Germany, Italy, Spain, and the United Kingdom. All people living with PSP with a reported phenotype were included. PSP phenotype was reported for 242 patients (mean age: 70.2 years, 58% male): PSP-Richardson's syndrome, n = 96; PSP-predominant Parkinsonism, n = 88; PSP-predominant corticobasal syndrome, n = 28; PSP-predominant speech/language disorder, n = 12; PSP-progressive gait freezing, n = 9; PSP-predominant frontal presentation, n = 9. Most patients reported impaired cognitive, motor, behavioral and ocular functionality; 67-100% of patients (across phenotypes) had moderate-to-severe disease at the time of data collection. Post-diagnosis, the majority were provided with a visual and/or mobility aid (55-100%, across phenotypes), and/or required home modification to facilitate their needs (55-78%, across phenotypes). Patients required multiple types of healthcare professionals for disease management (mean 3.6-4.4, across phenotypes), and the majority reported receiving care from at least one caregiver (mean 1.3-1.8, across phenotypes). There is a high burden on patients, caregivers, and healthcare systems across all PSP phenotypes. Although phenotypes manifest different symptoms and are associated with different diagnostic pathways, once diagnosed with PSP, patients typically receive similar care.

Author Correction: The impact of poor asthma control among asthma patients treated with inhaled corticosteroids plus long-acting ß2-agonists in the United Kingdom: a cross-sectional analysis.

A correction to this article has been published and is linked from the HTML version of this article.

The impact of poor asthma control among asthma patients treated with inhaled corticosteroids plus long-acting ß2-agonists in the United Kingdom: a cross-sectional analysis.

There are several new treatment options for patients whose asthma remains uncontrolled on free-dose and fixed-dose combinations of inhaled corticosteroids plus long-acting ß2-agonists (ICS+LABA). In order to evaluate the likely impact of these treatments, we assessed the effect of uncontrolled asthma on healthcare and patient burden within the UK among adult patients treated with ICS+LABA. Data obtained from 2010-2011 UK National Health and Wellness Surveys identified 701 patients treated with ICS+LABA. Patients with not well-controlled asthma (Asthma Control Test™ score <20) were compared with well-controlled asthma (score ≥ 20) patients on multiple measures. Cost burden was calculated using healthcare resource utilisation models and work productivity and impairment questionnaire. Overall, 452 and 249 patients reported not well-controlled and well-controlled asthma, respectively. A greater proportion of not well-controlled patients visited the accident & emergency department (21 vs. 14%, P = 0.016), were hospitalised (13 vs. 8%, P = 0.022) and had lower mental and physical health-related quality of life (P < 0.001) and impaired work productivity and activity scores: presenteeism (23 vs. 11%, P < 0.001), work impairment (29 vs. 17%, P < 0.001) and activity impairment (46 vs. 24%, P < 0.001). Calculated direct and indirect yearly costs/person doubled among not well-controlled compared to well-controlled asthma patients (£6592 vs. £3220). Total cost to society was estimated at £6172 million/year (direct costs, £1307 million; indirect costs, £4865 million). In conclusion, not well-controlled asthma is common among UK adults treated with ICS+LABA, resulting in impairments across a number of important health outcomes and represents a significant unmet need and resource burden. ASTHMA: DRUG COMBO LEAVES MANY WITH UNCONTROLLED DISEASE: Many people who take inhaled steroids combined with long-acting ß2-agonist drugs still have poorly controlled asthma. A team led by Ian Pavord from the University of Oxford, UK, identified 701 people from the 2010-2011 UK National Health and Wellness Surveys who were taking this drug combination for their asthma. The researchers found that nearly two-thirds of these individuals had poorly controlled asthma associated with more visits to the emergency room, worse quality of life (both mentally and physically), impaired productivity and other health problems. The calculated direct and indirect costs per person with poorly controlled asthma were about double that for someone whose asthma was under control. The authors conclude that better treatment and management is needed to reduce costs and address the unmet medical need for people with persistent uncontrolled asthma.

The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK.

BACKGROUND: This study characterized a cohort of chronic obstructive pulmonary disease (COPD) patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization. METHODS: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting ß2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013) or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients' rate of face-to-face interactions with a health care professional (HCP), COPD-related exacerbations, hospitalizations, and referrals. RESULTS: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B) on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on maintenance bronchodilator monotherapy was 2 years. The median number of prescriptions was 14. On average, patients had 15 HCP interactions per year, and one in ten patients experienced a COPD exacerbation (N=8,811). One in 50 patients were hospitalized for COPD per year (n=4,848). CONCLUSION: The average monotherapy-treated patient had a higher than average HCP interaction rate. We also identified a large cohort of patients who were stepped up to triple therapy despite a low rate of exacerbations. The use of the new class of long-acting muscarinic antagonist/long-acting ß2-adrenergic agonist fixed-dose combinations may provide a useful step-up treatment option in such monotherapy patients, before the use of inhaled corticosteroids.

Demographic and Clinical Characteristics of Patients With Type 2 Diabetes Mellitus Initiating Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Study of UK General Practice.

PURPOSE: The majority of people with type 2 diabetes mellitus (T2DM) will develop chronic kidney disease in their lifetime. Because most dipeptidyl peptidase (DPP)-4 inhibitors require dose adjustment in patients with T2DM and renal impairment, we aimed to understand how these treatments are prescribed in UK clinical practice, and to determine whether recommended dose adjustments are being made at initial prescription. METHODS: This retrospective, descriptive cohort study analyzed data from the Clinical Practice Research Datalink (CPRD). Patients of interest were those with T2DM and renal impairment initiated on a DPP-4 inhibitor between 2014 and 2015. Patients under 40 years of age and with type 1 diabetes were excluded. Descriptive statistics were calculated for baseline demographic and clinical characteristics, and the study protocol was approved by the Independent Scientific Advisory Committee for Medicines and Healthcare products Regulatory Agency database research. FINDINGS: A total of 3425 patients diagnosed with T2DM and renal impairment and initiated on a DPP-4 inhibitor were identified. The percentages of patients prescribed the high dose of saxagliptin, alogliptin,sitagliptin, and vildagliptin were 48%, 43%, 41%, and 27%, respectively, which is not recommended given their renal dysfunction. These are conservative estimates, as they do not include patients with severe renal impairment on sitagliptin and alogliptin, whose doses should be further reduced. No patients were prescribed an inappropriately high dose of linagliptin, as there is no requirement for dose adjustment in patients with renal impairment. IMPLICATIONS: In this study, a considerable number of patients with T2DM and renal impairment were prescribed an inappropriately high dose of saxagliptin, alogliptin, sitagliptin, or vildagliptin for their level of renal impairment at treatment initiation. This prescribing could have been due to the complexity of different dosing requirements, or a lack of awareness of the need for dose adjustment of most DPP-4 inhibitors in patients with renal impairment. Linagliptin may be used in patients with moderate or severe renal impairment without dose adjustment.

Determinants of oral anticoagulation control in new warfarin patients: analysis using data from Clinical Practice Research Datalink.

BACKGROUND: The safety and effectiveness of warfarin therapy depends critically on the quality of anticoagulation control, often assessed using the percentage time in therapeutic International Normalised Ratio (INR) range (TTR). We aimed to identify patient characteristics related to anticoagulation control with warfarin, measured by TTR. METHOD: We carried out a population-based study using the Clinical Practice Research Datalink, including two cohorts of patients starting warfarin after a first diagnosis of atrial fibrillation (AF) or venous thromboembolism (VTE) between 2000 and 2013. We used multivariate mixed regression and logistic regression models to predict the fully-adjusted effect of each predictor variable upon TTR. RESULTS: The study population comprised 29,717 incident AF and 19,113 incident VTE patients who initiated warfarin. In real world clinical practice a minority of patients achieve good anticoagulation control with warfarin (44% AF and 36% VTE patients had TTR≥70%). Poor anticoagulation control driven by subtherapeutic INRs was observed in younger patients (<45years) and in AF patients with increased number of hospitalisations. Poor anticoagulation control driven by sub and/or supratherapeutic INRs was seen in AF and VTE patients current smokers, in patients using medications for pain and in VTE patients with active cancer. CONCLUSION: In a real world clinical practice there is a high amount of unpredictable inter-individual TTR variability and in some patients good anticoagulation control is more challenging than in others. These findings may help to identify patients who will require closer monitoring or innovative strategies to optimise the outcomes of oral anticoagulant therapy.

Thromboprophylaxis of elderly patients with AF in the UK: an analysis using the General Practice Research Database (GPRD) 2000-2009.

OBJECTIVE: To assess use of thromboprophylaxis in UK general practise among patients with atrial fibrillation (AF); to investigate whether elderly patients are less likely to receive anticoagulation therapy than younger patients. DESIGN: Retrospective cohort study SETTING: UK General Practice Research Database (GPRD) PATIENTS: Aged ≥60 years with a new diagnosis of AF (2000-2009). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The main outcome measure was initiation of warfarin in the first year following diagnosis. Patients were categorised by stroke risk (CHADS(2) score) and bleeding risk (HAS-BLED score). RESULTS: 81 381 patients were identified (21% aged 60-69 years, 37% aged 70-79 years, 42% aged 80+ years). Patients aged 80+ years were significantly less likely to be initiated on warfarin than younger patients, adjusted for gender, practice and comorbidities; 32% of patients aged 80+ years received warfarin compared with 57% aged 60-69 years (p<0.0001), and 55% aged 70-79 years (p<0.0001). For all strata of CHADS(2)/HASBLED scores, patients aged 80+ years were significantly less likely to be treated with warfarin than younger patients. Logistic regression showed that female sex, low Basal Metabolic Index (BMI), age over 80 years, increasing HAS-BLED score and dementia were independently associated with reduced use of warfarin. Stroke/Transient Ischaemic Attack (TIA), hypertension, heart failure and left ventricular systolic dysfunction were associated with increased use. Patients with HAS-BLED>CHADS(2) were less likely to be initiated on warfarin. Higher CHADS(2) scores were associated with increased anticoagulation use. CONCLUSIONS: Anticoagulation is being under-used in patients with AF aged 80+ years, even after taking into account increased bleeding risk in this age group.