Disease-modifying Drugs In Patients Research Articles

Repurposing multiples sclerosis disease-modifying drugs for Parkinson's disease

Parkinson’s disease (PD) is an age-related neurodegenerative disease mainly affecting the elderly population. Despite recent progresses in pharmacologic therapies and surgical interventions such as deep brain stimulation, current PD therapies are limited to relieving disease symptoms rather than stopping disease progression, highlighting an urgent yet unmet need for disease-modifying interventions. Neuroinflammation has been proposed as a pivotal contributing factor that drives the initiation and progression of PD pathology. Owing to the revolution in disease-modifying drugs (DMDs) that successfully change the course of multiple sclerosis (MS), a central nervous system inflammatory autoimmune disease, it has become tempting to repurpose MS DMDs as new treatment options for PD. This review summarizes the ongoing and completed studies of MS DMDs in PD as a potential opportunity to address this unmet need. Future clinical trials are warranted to further evaluate the efficacy of DMDs in patients with PD.

Use of disease-modifying drugs in diabetic patients with heart failure with reduced ejection fraction.

Type 2 diabetes mellitus and heart failure are closely related, patients with type 2 diabetes mellitus have a higher risk of developing heart failure, and those with heart failure are at increased risk of developing type 2 diabetes. Although no specific randomized clinical trials have been conducted to test the effect of cardiovascular therapies (drugs and/or devices) in diabetic patients with heart failure, a lot of evidence shows that all interventions effective in improving prognosis in patients with heart failure reduced ejection fraction are equally beneficial in patients with and without diabetes. However, the use of disease-modifying drugs in patients with diabetes and heart failure reduced ejection fraction is a clinical challenge due to the increased risk of adverse effects. For example, β-blockers are underutilized in diabetic patients due to the theoretical unfavorable effects on glucose metabolism as well as the use of drugs that interact with the renin-angiotensin system can be challenged in patients with diabetic nephropathy because of the risk of hyperkalemia. This review outlines the current use of disease-modifying drugs in diabetic patients with heart failure reduced ejection fraction. In addition, the role of novel pharmacologic agents as type 2 sodium-glucose co-transporter inhibitors (SGLT2ii) is discussed.

Limitations of the Unified Multiple System Atrophy Rating Scale as outcome measure for clinical trials and a roadmap for improvement.

PurposeThe unified multiple system atrophy (MSA) rating scale (UMSARS) was developed almost 20 years ago as a clinical rating scale to capture multiple aspects of the disease. With its widespread use, the shortcomings of the UMSARS as a clinical outcome assessment (COA) have become increasingly apparent. We here summarize the shortcomings of the scale, confirm some of its limitations with data from the Natural History Study of the Synucleinopathies (NHSS), and suggest a framework to develop and validate an improved COA to be used in future clinical trials of disease-modifying drugs in patients with MSA.MethodsExpert consensus assessment of the limitations of the UMSARS and recommendations for the development and validation of a novel COA for MSA. We used UMSARS data from the ongoing NHSS (ClinicalTrials.gov: NCT01799915) to showcase some of these limitations.ResultsThe UMSARS in general, and specific items in particular, have limitations to detect change resulting in a ceiling effect. Some items have specific limitations including unclear anchoring descriptions, lack of correlation with disease severity, susceptibility to improve with symptomatic therapies (e.g., orthostatic hypotension, constipation, and bladder dysfunction), and redundancy, among others.ConclusionsBecause of the limitations of the UMSARS, developing and validating an improved COA is a priority. The time is right for academic MSA clinicians together with industry, professional societies, and patient advocacy groups to develop and validate a new COA.

Real-world adherence to, and persistence with, once- and twice-daily oral disease-modifying drugs in patients with multiple sclerosis: a systematic review and meta-analysis

BackgroundNonadherence to disease-modifying drugs (DMDs) for multiple sclerosis (MS) is associated with poorer clinical outcomes, including higher rates of relapse and disease progression, and higher medical resource use. A systematic review and quantification of adherence and persistence with oral DMDs would help clarify the extent of nonadherence and nonpersistence in patients with MS to help prescribers make informed treatment plans and optimize patient care.The objectives were to: 1) conduct a systematic literature review to assess the availability and variability of oral DMD adherence and/or persistence rates across ‘real-world’ data sources; and 2) conduct meta-analyses of the rates of adherence and persistence for once- and twice-daily oral DMDs in patients with MS using real-world data.MethodsA systematic review of studies published between January 2010 and April 2018 in the PubMed database was performed. Only studies assessing once- and twice-daily oral DMDs were available for inclusion in the analysis. Study quality was evaluated using a modified version of the Newcastle-Ottawa Scale, a tool for assessing quality of observational studies. The random effects model evaluated pooled summary estimates of nonadherence.ResultsFrom 510 abstracts, 31 studies comprising 16,398 patients with MS treated with daily oral DMDs were included. Overall 1-year mean medication possession ratio (MPR; n = 4 studies) was 83.3% (95% confidence interval [CI] 74.5–92.1%) and proportion of days covered (PDC; n = 4 studies) was 76.5% (95% CI 72.0–81.1%). Pooled 1-year MPR ≥80% adherence (n = 6) was 78.5% (95% CI 63.5–88.5%) and PDC ≥80% (n = 5 studies) was 71.8% (95% CI 59.1–81.9%). Pooled 1-year discontinuation (n = 20) was 25.4% (95% CI 21.6–29.7%).ConclusionsApproximately one in five patients with MS do not adhere to, and one in four discontinue, daily oral DMDs before 1 year. Opportunities to improve adherence and ultimately patient outcomes, such as patient education, medication support/reminders, simplified dosing regimens, and reducing administration or monitoring requirements, remain. Implementation of efforts to improve adherence are essential to improving care of patients with MS.

Drug-use patterns and severe adverse events with disease-modifying drugs in patients with multiple sclerosis: a cohort study based on German claims data.

Purpose: To describe drug-use patterns in patients with multiple sclerosis (MS) using disease-modifying drugs (DMDs) and to estimate the incidence of severe adverse events (SAEs) of treatment.Methods: We conducted a cohort study within the German Pharmacoepidemiological Research Database between January 1, 2006 and December 31, 2013. MS patients on DMDs were described in terms of clinical characteristics and drug-use patterns. Next, we assessed the incidence of AEs in new users of fingolimod, natalizumab, glatiramer acetate, and IFNβ1a.Results: Among approximately 11 million insured members of German Statutory Health Insurance, the DMD-user cohort comprised 15,377 patients with MS, with a mean age of 39.6 years and 68% females. Nearly half of all DMD users had a diagnosis of depression, with prevalence ranging from 40.1% for IFNβ1a to 62.3% for immunoglobulins. The overall rate of MS relapses per patient and year was 0.34 (95% CI 0.33–0.34). During an average follow-up of 1,650 days, the majority (42.4%) of MS patients were adherent to DMD treatment (“continuous single users”), followed by patients interrupting treatment (39.5%, “interrupters”). Switch of DMD treatment (11.9%) was less frequent, and only 5.6% discontinued treatment. Treatment discontinuation was most common in users of natalizumab (7.5%) and IFNβ1b (7.0%). The most frequent SAE was hospitalization for depression, followed by any infectious disease and any malignancy. The incidence rate of all adverse events did not significantly differ across different DMDs.Conclusion: Treatment discontinuation with DMDs and treatment switch were rare. Causes of rather frequent DMD-treatment interruption have to be evaluated in further studies based on primary data collection. Active safety monitoring of new DMDs based on claims data requires large data sets to detect rare AEs and availability of up-to-date data.

Assessment of the adherence to disease-modifying drugs in patients with chronic inflammatory rheumatic diseases: Results of a survey of 1594 patients.

a) to describe the self-reported adherence to disease modifying drugs (DMARDs) (methotrexate and biological DMARDs) among patients with chronic inflammatory rheumatic diseases (CIRDs); b) to assess factors associated with non-adherence. An observational, cross-sectional, nationwide study was conducted through the use of an electronic survey, which was released via patient organizations in France to rheumatic patients. The main outcome was the rate of non-adherence to DMARDs, which was evaluated with the following question "Have you ever tried to stop or space out your treatment in contrast to what was planned with your doctor?" A positive answer was considered "low adherent". Sociodemographic variables, type of CIRD and treatment information were also collected. Factors associated with low adherence to methotrexate and bDMARDs were explored by univariate and multivariate logistic regressions. Among the 1594 participants who completed the survey, 795 (49.9%) were receiving methotrexate and 709 (44.5%) bDMARDs. A total of 159 (20.0%) were identified as low adherents to methotrexate, and being a woman was independently associated with low adherence (OR 1.90 [95% CI 1.07 - 3.36)] to this drug. Regarding bDMARDs, 177 (25.0%) were identified as low adherent, and the factors independently associated with low adherence were being employed (OR 1.47 [95% CI 1.04 - 2.09]) and no concomitant use of methotrexate (OR 0.51 [95% CI 0.36 - 0.73]). This study suggests that more than 20% of CIRDs patients are low adherent to their DMARDs, and this is more frequent when bDMARDs are administered as a monotherapy.

Recommendations for the assessment and optimization of adherence to disease-modifying drugs in chronic inflammatory rheumatic diseases: A process based on literature reviews and expert consensus.

Adherence to treatment is a key issue in chronic inflammatory rheumatic diseases (CIRDs). To develop recommendations to facilitate in daily practice, the management of non-adherence to disease-modifying drugs in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, connective tissue diseases or other CIRDs. The process comprised (a) systematic literature reviews of methods (including questionnaires) to measure non-adherence, risk factors for non-adherence and efficacy of targeted interventions; (b) development of recommendations through consensus of 104 rheumatologist and nurse experts; (c) assessment of agreement and ease of applicability (1-5 where 5 is highest) by the 104 experts. (a) Overall, 274 publications were analysed. (b) The consensus process led to 5 overarching principles and 10 recommendations regarding adherence. Key points include that adherence should be assessed at each outpatient visit, at least using an open question; questionnaires and hydroxychloroquine blood level assessments may also be useful. Risk factors associated to non-adherence were listed. Patient information and education, and patient/physician shared decision, are key to optimize adherence. Other techniques such as formalized education sessions, motivational interviewing and cognitive behavioral therapy may be useful. All health professionals can get involved and e-health may be a support. (c) The agreement with the recommendations was high (range of means, 3.9-4.5) but ease of applicability was lower (2.7-4.4). Using an evidence-based approach followed by expert consensus, this initiative should improve the assessment and optimization of adherence in chronic inflammatory rheumatic disorders.

Medication possession ratio: implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis

BackgroundThe purpose of this study was to compare two methods of adherence calculation using administrative data for patients with multiple sclerosis (MS) who are prescribed disease-modifying drugs.MethodsPharmacy-billed disease-modifying drug prescription claims were selected from the 2007–2008 LifeLink™ Health Plan Claims Database. The index date was the first disease-modifying drug prescription claim. Two cohorts were created: all patients with a disease-modifying drug claim in 2007 and a subset with continuous eligibility for 12 months post-index. Adherence was calculated across all disease-modifying drugs for 12 months post-index. Medication possession ratios (MPRs) with variable (start to end of therapy) and fixed (365 days) duration denominators were calculated. Variable MPR was calculated by summing days supply from the first to the last prescription (inclusive) divided by time between the last prescription date plus days supply and the first prescription date. Variable MPR was evaluated for all patients and the continuously eligible cohort. Fixed MPR used the same numerator but divided by 365 days of follow-up and evaluated only for the continuously eligible cohort.ResultsThere were 3405 patients with MS and a disease-modifying drug claim in 2007 and 2145 in the continuously eligible cohort. Means for variable MPR ranged from 87.5% ± 16.6% for the continuously eligible cohort to 90.5% ± 16.0% for the 2007 cohort. The comparable value for fixed MPR was 78.0% ± 28.2% for the continuously eligible cohort. Fixed MPR gave a consistently lower rate of adherence than variable MPR at an 80% adherence threshold.ConclusionDifferent adherence measures can yield different outcomes, especially when using different eligibility criteria. These results demonstrate the importance of full disclosure of methods used for calculations and specification of the study population.

Adherence to Disease-Modifying Drugs in Patients with Multiple Sclerosis: A Consensus Statement from the Middle East MS Advisory Group

ABSTRACTAdherence to therapy is a key issue in chronic illnesses. In addition, several features of multiple sclerosis (MS) and its treatment may increase the likelihood of patient nonadherence and discontinuation of treatment. Nonadherence will obviously compromise the efficacy of disease-modifying drugs in patients with MS. This subject was discussed by a group of local MS specialists from the Middle East. The group debated several key questions about the features and causes of patient nonadherence and its management. Further, they made recommendations for optimizing treatment adherence in this area.

The Case for Early Diagnosis and Treatment In Relapsing Remitting Multiple Sclerosis

Abstract The emergence of partially effective disease-modifying drugs for patients with relapsing remitting multiple sclerosis (RR-MS) has raised important questions. Which patients with RR-MS should be started on disease-modifying drugs? Can some patients be observed without treatment? Treatment decisions are difficult in part because currently available drugs must be administered by injections, and the drugs are expensive. Emerging research findings support the view that most people diagnosed with RR-MS are at risk for irreversible brain tissue injury and resultant neurologic disability. Importantly, the pathologic process is active during the early stages in many RR-MS patients who appear clinically stable. These findings provide a rationale for proactively treating patients with RR-MS early in their disease course with disease-modifying drugs in order to suppress disease activity, minimize tissue injury, and prevent disability at a later stage. Evidence in support of this approach is reviewed in this report, as are practical issues related to the use of disease-modifying drugs in RR-MS patients.