A Prospective, Observational, Multicenter Study Assessing Adherence to Interferon Beta-1b Therapy and Patient Satisfaction Using the BETACONNECT Auto-Injector.

INTRODUCTION: It is important to achieve good persistence and adherence to disease-modifying therapies (DMTs) to achieve the best outcomes in chronic diseases such as multiple sclerosis (MS). The BETACONNECT device is an electronic auto-injector for the DMT interferon beta-1b (Betaseron), designed to improve patients' injection experience and to monitor adherence. This observational study aimed to assess patient adherence to and persistence with interferon beta-1b therapy as well as patient-reported satisfaction in a US population. METHODS: A prospective, observational, multicenter study was conducted in 146 adult patients with relapsing-remitting MS or clinically isolated syndrome, newly prescribed or currently established on interferon beta-1b therapy and naïve to the BETACONNECT device, and followed up during a 6-month observation period. RESULTS: Among the 91 patients who completed the study, the overall mean adherence rate was 82.5%, with 65.9% of patients adherent for at least 80% for the duration of the 6-month period. At 6 months, 98.9% of patients had less than a 60-day gap in therapy. Of the 115 patients who provided satisfaction data, 90.5% of patients were either very satisfied or satisfied with the BETACONNECT device. CONCLUSION: This study shows that the BETACONNECT device was associated with high adherence to interferon beta-1b therapy in patients with MS. Patients also reported high degrees of satisfaction with the device. Therefore, this may be a viable delivery option to help with adherence and persistence, potentially leading to improved clinical outcomes.

Real-World Assessment of Interferon-ß-1b and Interferon-ß-1a Adherence Before and After the Introduction of the BETACONNECT® Autoinjector: A Retrospective Cohort Study.

BACKGROUND: Both interferon beta-1b (IFN-ß-1b) and interferon beta-1a (IFN-ß-1a) are immunomodulators that require regular subcutaneous self-administration by patients with multiple sclerosis (MS). However, no electronic autoinjector is available for IFN-ß-1a in the US. OBJECTIVE: This retrospective cohort study investigated adherence to two subcutaneous disease-modifying therapies, IFN-ß-1b and IFN-ß-1a, during two periods (before and after the introduction of the BETACONNECT® autoinjector for IFN-ß-1b). PATIENTS AND METHODS: Data were evaluated from the MarketScan database for adults in the US with an MS diagnosis and a medical claim for subcutaneous IFN-ß-1b or IFN-ß-1a, either before (October 2013-September 2015) or after the introduction of BETACONNECT (October 2016-September 2018). Patient populations were propensity-score matched by demographic and clinical characteristics. Persistence was recorded, and adherence was evaluated by medication possession ratio (MPR). RESULTS: The study included 196 IFN-ß-1b and 365 IFN-ß-1a people with MS (PwMS) (pre-BETACONNECT period), and 126 IFN-ß-1b and 223 IFN-ß-1a PwMS (post-BETACONNECT period). In the pre-BETACONNECT period, the proportion with at least 80% MPR was higher for IFN-ß-1a (90%) than for IFN-ß-1b (83%), but in the post-BETACONNECT period the proportion with ≥ 80% MPR was higher for IFN-ß-1b (92%) than for IFN-ß-1a (86%). In the pre-BETACONNECT period, median persistence (in days) was higher for IFN-ß-1a (199) than for IFN-ß-1b (152), while in post-BETACONNECT period persistence was higher for IFN-ß-1b (327) than for IFN-ß-1a (229). CONCLUSIONS: Following the introduction of BETACONNECT, this exploratory study suggested that PwMS taking IFN-ß-1b were more adherent compared with those taking IFN-ß-1a, with higher persistence, and more than 90% reached 80% MPR, a threshold commonly used to define good adherence.

Sentiment of Media Coverage and Reputation of the Pharmaceutical Industry.

BACKGROUND: Patients and health care professionals receive information about pharmaceutical companies through various sources, including but not limited to print media, social media, and electronic media. The objective of this research was to benchmark the sentiment of electronic newspaper media coverage between 2014 and 2016 and investigate the potential relationship to the public perception of the select pharmaceutical companies. METHODS: Reputation Institute's RepTrak System report was used for selection of 5 highly rated pharmaceutical companies (A-E). Electronic newspapers were selected based on US circulation within the selected time period. Lexalytics sentiment analysis software was used for analysis of relevant articles appearing in the selected newspapers. RESULTS: A total of 797 articles were analyzed; 63% were assessed as neutral, 24% as negative, and 14% as positive. The overall median sentiment scores (scale ranging from -2 through [Formula: see text]2) for companies A through E across all newspapers were determined to be [Formula: see text]0.026, [Formula: see text]0.03, [Formula: see text]0.028, [Formula: see text]0.034, and [Formula: see text]0.033, respectively. The most frequent topics were merger/acquisition/ re-structuring, finances/stocks/profits, and other, which included topics such as transparency of pharmaceutical industry data, lack of drug efficacy, and innovation. CONCLUSION: Overall, pharmaceutical companies were represented similarly across newspapers and most articles were assessed as neutral. However, on analysis of all nonneutral articles, all categories were assessed as negative with the exception of finances/stocks/profits.

Vitamin D and Multiple Sclerosis: A Comprehensive Review.

Numerous observational studies have suggested that there is a correlation between the level of serum vitamin D and MS risk and disease activity. To explore this hypothesis, a literature search of large, prospective, observation studies, epidemiological studies, and studies using new approaches such as Mendelian randomization was conducted. Available data and ongoing research included in this review suggest that the level of serum vitamin D affects the risk of developing MS and also modifies disease activity in MS patients. Newer Mendelian randomization analyses suggest there is a causal relationship between low vitamin D level and the risk of MS. Post-hoc evaluations from two phase 3 studies, BENEFIT and BEYOND, support the findings of observational trials. Study limitations identified in this review recognize the need for larger controlled clinical trials to establish vitamin D supplementation as the standard of care for MS patients. Though there is increasing evidence indicating that lower vitamin D levels are associated with increased risk of MS and with greater clinical and brain MRI activity in established MS, the impact of vitamin D supplementation on MS activity remains inadequately investigated.

Survey of US Patients with Multiple Sclerosis: Comparison of the New Electronic Interferon Beta-1b Autoinjector (BETACONNECT™) With Mechanical Autoinjectors.

INTRODUCTION: Patients with multiple sclerosis (MS) generally undergo long-term treatment with disease-modifying therapies (DMTs). In the US, patients taking glatiramer acetate, interferon beta-1a, or interferon beta-1b, typically use a mechanical autoinjector. Recent survey results have shown that using an electronic autoinjector, such as BETACONNECT™ (Bayer Pharma AG) for interferon beta-1b/Betaseron® (Bayer Pharma AG) may reduce injection discomfort and increase patient satisfaction with treatment. The aim of the current survey was to assess patient perceptions of BETACONNECT compared with mechanical autoinjectors using a survey integrated with demonstrations and simulated injections with BETACONNECT. METHODS: Patients with MS currently using mechanical autoinjectors for glatiramer acetate/Copaxone® (Teva Pharmaceuticals USA, Inc.), interferon beta-1a/Rebif® (EMD Serono Inc.), or interferon beta-1b/Extavia® (Novartis Pharmaceuticals Corp.), participated in a 60-min in-person interview. Patients rated the importance of 18 ideal autoinjector attributes, and the performance of their current autoinjectors across these attributes. BETACONNECT was demonstrated and patients performed simulated injections with BETACONNECT before rating it across the same attributes. Patient overall autoinjector preference was assessed. RESULTS: Ninety patients completed the survey: 63 were using autoinjectors for Copaxone, 25 for Rebif, and 2 for Extavia. BETACONNECT scored higher than mechanical autoinjectors across all 18 attributes. The top attributes of an ideal autoinjector were the injection process is easy overall, easy to push the button to start the injection, and autoinjector is comfortable to hold during injections. Unique BETACONNECT features most valued by patients were the built-in dwell time, self-check function, greater ability to customize injections, adjustment of injection speed, low injection noise, and automatic needle retraction. Overall, 75 out of 90 patients (83%) expressed a preference for BETACONNECT over their current autoinjector. CONCLUSION: BETACONNECT attributes and features were highly rated by patients, compared with both an ideal autoinjector and their current mechanical autoinjectors. These findings suggest that the use of BETACONNECT may increase patient satisfaction and potentially increase overall medication adherence. FUNDING: Bayer HealthCare Pharmaceuticals.

Patient Satisfaction with the New Interferon Beta-1b Autoinjector (BETACONNECT™).

INTRODUCTION: Multiple sclerosis (MS) typically requires life-long management with disease-modifying therapies (DMTs). Many DMTs require regular self-injection, and can be associated with injection site reactions, pain, and needle/injection phobia-but these can be addressed by improvements in autoinjector design. The aim of this study was to investigate patient satisfaction and preference for BETACONNECT™ (Bayer Pharma AG), a novel interferon beta-1b autoinjector. METHODS: Patients in Germany performing self-injections using BETACONNECT took part in the study. Data were collected through an online 15-min structured survey. Participants rated their experience with BETACONNECT on a 6-point scale and those satisfied with BETACONNECT were asked to describe the reason using a free-text box. RESULTS: One-hundred and eighteen patients with MS completed the survey. Ninety percent preferred BETACONNECT to their previous injection method (only 4% previously used manual injections, so most had previously used other autoinjectors). Ninety-two percent were very confident/confident in their ability to perform an injection using BETACONNECT. The most common free-text responses to "Why are you satisfied with the BETACONNECT™ autoinjector?" were ease of use (46%), less irritation/pain at the injection site (33%), and smoother injections (24%). Features considered most useful were automated injections (98%), adjustable injection speed (98%), and adjustable injection depth (98%). Ninety-seven percent thought it was easy to know when an injection was complete and 95% agreed/strongly agreed it was easy to learn to use the autoinjector. Seventy-three percent agreed that the quietness and effortlessness of the BETACONNECT reduced their level of injection anxiety, 92% that its size and shape makes it easy to handle during injections, and 67% that it decreases injection site pain. Eighty percent of those using the reminder function thought they were less likely to miss an injection. CONCLUSION: Patients with MS self-injecting interferon beta-1b expressed a high level of satisfaction and preference for BETACONNECT. Thus, BETACONNECT represents a valid option to improve patients' overall injection experience. FUNDING: Bayer HealthCare Pharmaceuticals.

Short-term and long-term safety and tolerability of interferon ß-1b in multiple sclerosis.

Clinical trials have generated a wealth of data on the safety profile of interferon ß-1b for patients with multiple sclerosis (MS). In general, interferon ß-1b has not been associated with serious or life-threatening side effects during long-term treatment. Flu-like symptoms, injection site reactions, depression, and elevated liver transaminases were the most common adverse events in clinical trials. This review will discuss the rates of these and other common adverse events observed in 3 clinical trials of interferon ß-1b: BENEFIT, BEYOND, and the 16-year Long-Term Follow-up (LTF) of the pivotal interferon ß-1b trial in MS, as well as how these adverse events may influence patient and physician decision making when selecting a disease-modifying therapy. In addition, we will discuss the effects of interferon ß-1b on mortality in the 16-year and 21-year LTF studies.

Causes of death among commercially insured multiple sclerosis patients in the United States.

BACKGROUND: Information on causes of death (CODs) for patients with multiple sclerosis (MS) in the United States is sparse and limited by standard categorizations of underlying and immediate CODs on death certificates. Prior research indicated that excess mortality among MS patients was largely due to greater mortality from infectious, cardiovascular, or pulmonary causes. OBJECTIVE: To analyze disease categories in order to gain insight to pathways, which lead directly to death in MS patients. METHODS: Commercially insured MS patients enrolled in the OptumInsight Research database between 1996 and 2009 were matched to non-MS comparators on age/residence at index year and sex. The cause most-directly leading to death from the death certificate, referred to as the "principal" COD, was determined using an algorithm to minimize the selection of either MS or cardiac/pulmonary arrest as the COD. Principal CODs were categorized into MS, cancer, cardiovascular, infectious, suicide, accidental, pulmonary, other, or unknown. Infectious, cardiovascular, and pulmonary CODs were further subcategorized. RESULTS: 30,402 MS patients were matched to 89,818 controls, with mortality rates of 899 and 446 deaths/100,000 person-years, respectively. Excluding MS, differences in mortality rate between MS patients and non-MS comparators were largely attributable to infections, cardiovascular causes, and pulmonary problems. Of the 95 excessive deaths (per 100,000 person-years) related to infectious causes, 41 (43.2%) were due to pulmonary infections and 45 (47.4%) were attributed to sepsis. Of the 46 excessive deaths (per 100,000 person-years) related to pulmonary causes, 27 (58.7%) were due to aspiration. No single diagnostic entity predominated for the 60 excessive deaths (per 100,000 person-years) attributable to cardiac CODs. CONCLUSIONS: The principal COD algorithm improved on other methods of determining COD in MS patients from death certificates. A greater awareness of the common CODs in MS patients will allow physicians to anticipate potential problems and, thereby, improve the care that they provide.

Immune response during interferon beta-1b treatment in patients with multiple sclerosis who experienced relapses and those who were relapse-free in the START study.

We measured immune markers in subjects with multiple sclerosis (MS) treated with IFNß-1b for 12 months. IL-17 levels were significantly higher at Month 6 (p=0.036) in relapsing subjects while BDNF levels were significantly higher at Month 3 (p=0.028) in relapse-free subjects. Change from baseline in IL-4 levels inversely correlated with disability score whereas change from baseline in IL-10/IFN-gamma ratio inversely correlated with occurrence of relapses. CXCR3+CD8+ T-cells tended to be higher but declined with treatment in relapse-free compared with relapsing subjects. Findings show the potential of cytokine and neurotrophic factors as biomarkers of clinical response to IFNß-1b.

The Combined Effect of Nursing Support and Adverse Event Mitigation on Adherence to Interferon Beta-1b Therapy in Early Multiple Sclerosis: The START Study.

There is limited clinical evidence on the impact of nurse support and adverse event (AE) mitigation techniques on adherence to interferon beta-1b (IFNß-1b) therapy in multiple sclerosis (MS) in a real-world setting. The aim of the Success of Titration, analgesics, and BETA nurse support on Acceptance Rates in MS Treatment (START) trial was to assess the combined effect of titration, analgesics, and BETA (Betaseron Education, Training, Assistance) nurse support on adherence to IFNß-1b therapy in patients with early-onset MS and to evaluate safety. Participants were instructed to titrate IFNß-1b and use analgesics to minimize flu-like symptoms. All received BETA nurse follow-up at frequent intervals: live training, two telephone calls during the first month of therapy, and monthly calls thereafter. Participants were considered adherent if they took at least 75% of the total prescribed doses over 12 months (≥75% compliance). Safety was monitored via reported AEs and laboratory test results. Participants who took at least one IFNß-1b dose over 12 months were analyzed (N = 104); 73.8% of participants completed the study. The mean age of participants was 37.2 years; 72.1% were women and 78.8% were white. Ninety participants had relapsing-remitting MS and 14 had clinically isolated syndrome. The mean compliance rate, reported for 96 participants with complete dose interruption records, was 84.4%. At 12 months, 78.1% of participants were considered adherent. The serious adverse event rate was 9.6%; most events were unrelated to therapy. Thus in the START study, in which participants received nursing support combined with dose titration and use of analgesics, the majority of participants were adherent to therapy.

Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNß-1b study.

OBJECTIVES: Compared with controls, multiple sclerosis (MS) patients die, on average, 7-14 years prematurely. Previously, we reported that, 21 years after their participation in the pivotal randomised, controlled trial (RCT) of interferon ß-1b, mortality was reduced by 46-47% in the two groups who received active therapy during the RCT. To determine whether the excessive deaths observed in placebo-treated patients was due to MS-related causes, we analysed the causes-of-death (CODs) in these three, randomised, patient cohorts. DESIGN: Long-term follow-up (LTF) of the pivotal RCT of interferon ß-1b. SETTING: Eleven North American MS-centres participated. PARTICIPANTS: In the original RCT, 372 patients participated, of whom 366 (98.4%) were identified after a median of 21.1 years from RCT enrolment. INTERVENTIONS: Using multiple information sources, we attempted to establish COD and its relationship to MS in deceased patients. PRIMARY OUTCOME: An independent adjudication committee, masked to treatment assignment and using prespecified criteria, determined the likely CODs and their MS relationships. RESULTS: Among the 366 MS patients included in this LTF study, 81 deaths were recorded. Mean age-at-death was 51.7 (±8.7) years. COD, MS relationship, or both were determined for 88% of deaths (71/81). Patients were assigned to one of nine COD categories: cardiovascular disease/stroke; cancer; pulmonary infections; sepsis; accidents; suicide; death due to MS; other known CODs; and unknown COD. Of the 69 patients for whom information on the relationship of death to MS was available, 78.3% (54/69) were adjudicated to be MS related. Patients randomised to receive placebo during the RCT (compared with patients receiving active treatment) experienced an excessive number of MS-related deaths. CONCLUSIONS: In this long-term, randomised, cohort study, MS patients receiving placebo during the RCT experienced greater all-cause mortality compared to those on active treatment. The excessive mortality in the original placebo group was largely from MS-related causes, especially, MS-related pulmonary infections.