Sc Interferon Research Articles

Adherence to subcutaneous interferon beta-1a treatment among patients with relapsing multiple sclerosis: the MAIN-MS study

Introduction and backgroundAdherence is a critical factor for optimal clinical outcomes in multiple sclerosis (MS) treatment. This study investigated the adherence and clinical outcomes of MS patients treated with subcutaneous (sc) interferon (IFN) (β)-1a, an established immunomodulatory treatment for relapsing MS. The benefits of a patient support programme (PSP) were also studied.MethodsThis phase-IV prospective, observational multicentre study enrolled patients with relapsing MS who were treated with sc IFN β-1a for 24 months was conducted at 53 centres across 17 countries. The primary endpoint was adherence to sc IFN β-1a treatment, as assessed using Morisky Green Levine Medication Adherence Scale (MGLS) scores at 24 months. The MGLS is a self-reported diagnostic tool to address medication non-adherence, with a score ranging from 0 to 4, with 0 representing high adherence, 1–2 representing medium adherence, and 3–4 representing low adherence. Other endpoints included time to study and treatment discontinuation over 24 months, the proportion of relapse-free patients, and Expanded Disability Status Scale (EDSS) progression (defined as ≥1.0 point increase sustained for 3 months) at 24 months. A subgroup analysis was performed for endpoints based on patients assigned to PSP (yes/no—PSP versus non-PSP subgroup).ResultsOf the 577 patients enrolled, 408 had evaluable MGLS scores at 24 months. A total of 336 (58.2%; 95% confidence interval [CI]: 54.1–62.3%) patients reported high adherence, 57 (9.9%; 95% CIs: 7.6–12.7%) reported medium adherence, and 15 (2.6%; 95% CI: 1.5–4.3%) reported low adherence at 24 months. The PSP subgroup reported higher adherence (n = 206; 65.8%) than the non-PSP subgroup (n = 130; 56.5%). By 24 months, 52.2% of the patients were relapse-free and 17.2% patients experienced ≥1 relapse. Expanded Disability Status Scale progression was observed in 12.3% of patients. Over the 24-month period, 30.8% of the patients discontinued treatment, and the most common reasons for treatment discontinuation were adverse events (AEs, 10.4%), being lost to followup (7.1%), and a lack of efficacy (5.5%). Overall, 39.6% patients experienced ≥1 AE, which ranged from mild to moderate.ConclusionThe study demonstrated high adherence to sc IFN β-1a treatment with an added benefit of PSP participation. More than half of the patients remained relapse-free over a 24-month period. No new safety concerns to sc IFN β-1a treatment were observed.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT02921035, NCT02921035.

MAGNIMS score predicts long-term clinical disease activity-free status and confirmed disability progression in patients treated with subcutaneous interferon beta-1a

BackgroundSubcutaneous (sc) interferon (IFN) β-1a reduces relapse rates and delays disability progression in patients with MS. We examined the association of the year 1 Magnetic Resonance Imaging in MS (MAGNIMS) score with long-term clinical disease activity (CDA) -free status and confirmed disability progression in patients treated with sc IFN β-1a in PRISMS. MethodsPatients treated with sc IFN β-1a three-times-weekly (22 or 44 μg; pooled data) were classified by MAGNIMS score (0, n = 129; 1, n = 108; 2, n = 130) at year 1. Hazard ratios (HR; 95% confidence intervals [CI]) for risk of CDA and confirmed Expanded Disability Status Score (EDSS) progression were calculated by MAGNIMS score for up to 15 years of follow-up. ResultsThe risk of CDA was higher with a year 1 MAGNIMS score of 1 versus 0 (HR 1.82 [1.38–2.41]), 2 versus 0 (2.63 [2.01–3.45]) and 2 versus 1 (1.45 [1.11–1.89], all p < 0.0001). The same outcome was observed with the risk of confirmed EDSS progression (1 versus 0: 1.93 [1.23–3.02]; 2 versus 0: 2.95 [1.95–4.46]; 2 versus 1: 1.53 [1.05–2.23]; all p < 0.0001). ConclusionIn PRISMS, MAGNIMS score at Year 1 predicted risk of CDA and confirmed disability progression in sc IFN β-1a-treated patients over up to 15 years.PRISMS-15 clinicaltrial.gov identifier: NCT01034644

Cost-utility analysis of alemtuzumab in comparison with interferon beta, fingolimod, and natalizumab treatment for relapsing-remitting multiple sclerosis in Austria

Background: Multiple sclerosis (MS), a chronic progressive, demyelinating, inflammatory disease, affects 2.5 million people worldwide. Approximately 63% of cases are classified as relapsing–remitting MS (RRMS) at the time of diagnosis. The aim of this cost-utility analysis is to evaluate alemtuzumab vs interferon beta (intramuscular [IM] interferon beta-1a, subcutaneous [SC] interferon beta-1a, SC interferon beta-1b, and SC pegylated interferon beta-1a) in previously treated, and vs SC interferon beta-1a, fingolimod, and natalizumab in untreated RRMS patients to determine the incremental cost-effectiveness ratio among the treatment alternatives as prices, the route, and the frequency of administration of considered products vary significantly.Methods: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained). Markov modeling with a 10-year time horizon was carried out. During each 3-month cycle, patients maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS), or showed EDSS progression in SPMS; experienced relapses; suffered from an adverse event (AE); changed treatment; or died. A published network meta-analysis (NMA) was used for indirect comparison. The possibility of a therapy switch was considered. Clinical input data and resource utilization data were derived from the literature. Costs were extracted from price lists published in Austria and were calculated from the payer’s perspective.Results: In treatment naïve patients, alemtuzumab is associated with costs of €132,663 and 5.25 QALYs in a 10-year time horizon. Costs for SC interferon beta amount to €164,159 and generate 4.85 QALYs. Also, in the pre-treated patients, alemtuzumab dominated comparators by accumulating higher total QALYs (4.88) and lower total costs (€137.409) compared to interferon beta-1a (€200.133), fingolimod (€240.903), and natalizumab (€247.758).Conclusion: The analysis shows that alemtuzumab is a cost-saving alternative to treat RRMS in pre-treated and therapy naïve patients. From the patient perspective, alemtuzumab improves quality-of-life.

Matching-adjusted comparisons demonstrate better clinical outcomes with SC peginterferon beta-1a every two weeks than with SC interferon beta-1a three times per week

BackgroundSubcutaneous (SC) peginterferon beta-1a and SC interferon beta-1a (IFN beta-1a) have demonstrated efficacy in treating relapsing-remitting multiple sclerosis (RRMS) but have never been compared in direct head-to-head clinical trials, the gold-standard comparison. A well-balanced matching-adjusted comparison of weighted individual patient data on SC peginterferon beta-1a, and aggregate data from published phase 3 clinical trials of SC IFN beta-1a, was conducted to provide additional information on the comparative efficacy of these two agents. MethodsIndividual patient data from a study of SC peginterferon beta-1a 125 mcg every two weeks (ADVANCE) and pooled summary data from four published studies of SC IFN beta-1a 44 mcg three times per week (OPERA I and II, CARE-MS I and II) with similar populations were utilized. A comparison was conducted by weighting individual peginterferon beta-1a–treated patients, using estimated propensity of enrolling in SC IFN beta-1a treatment to match multiple key aggregate baseline characteristics of SC IFN beta-1a–treated patients. After matching, weighted annualized relapse rate (ARR), 24-week confirmed disability worsening (CDW), and clinical no evidence of disease activity (clinical-NEDA) were calculated and compared for peginterferon beta-1a and SC IFN beta-1a. ResultsAfter matching, baseline characteristics were well balanced across treatment groups. At 2 years, ARR after matching was 0.256 for patients receiving peginterferon beta-1a (effective n = 376) and 0.335 for those receiving SC IFN beta-1a (n = 1218) (P = 0.0901). The percentage of patients who were relapse free over 2 years was significantly higher with peginterferon beta-1a than with SC IFN beta-1a (75.1% vs. 57.4% [after matching], P < 0.0001). The peginterferon beta-1a treatment group had a significantly lower proportion of patients with 24-week CDW compared with SC IFN beta-1a (after matching 6.5% vs. 13.2%; P = 0.0007). Clinical-NEDA occurred in a significantly higher proportion of patients treated with SC peginterferon beta-1a versus SC IFN beta-1a (74.1% vs. 48.1%; P < 0.0001). ConclusionsThis matching-adjusted comparison using data from four phase 3 trials with SC IFN beta-1a formulations demonstrated that patients with RRMS treated with SC peginterferon beta-1a 125 mcg every two weeks achieved better clinical outcomes than patients who received SC IFN beta-1a 44 mcg three times per week.

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study

Objective: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS).Methods: A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years’ follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias.Results: One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007–5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350–3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed.Conclusions: sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

SC peginterferon beta-1a every 2 weeks demonstrated better clinical outcomes than SC interferon beta-1a TIW in patients with RMS, using a matching-adjusted comparison of 5 Phase 3 trials (P6.367)

SC peginterferon beta-1a every 2 weeks demonstrated better clinical outcomes than SC interferon beta-1a TIW in patients with RMS, using a matching-adjusted comparison of 5 Phase 3 trials (P6.367)

Reasons for discontinuation of subcutaneous interferon \u03b2-1a three times a week among patients with multiple sclerosis: a real-world cohort study

BackgroundContinuation of interferon (IFN) β-based therapies is important for maximum treatment effectiveness in patients with multiple sclerosis (MS); however, few real-world data are available on discontinuation from IFN β. The aim of this cohort analysis was to estimate real-world discontinuation rates up to 3 years among MS patients in the United States taking subcutaneous (sc) IFN β-1a three times a week (tiw) and to identify whether the factors associated with discontinuation change over time.MethodsPatient data were pooled from the MarketScan© Commercial and Medicare Supplemental healthcare claims databases. Patients with ≥1 multiple sclerosis diagnosis who were sc IFN β-1a tiw naïve, had ≥1 year of continuous eligibility before treatment, and ≥1 prescription were followed from first prescription (index date) until date of discontinuation, switch, or end of observation. Treatment status was analysed at exactly 1, 2 or 3 years after index. Multivariable models were used to identify drivers of discontinuation.ResultsData from 5956 patients were included; 2862 patients (48.1%) discontinued therapy. Discontinuation rates were 36.9% (1 year), 49.5% (2 years) and 55.8% (3 years). A greater proportion of discontinuing patients had poor adherence (<80% [94.0%] versus ≥80% [51.7%]) or were taking additional medication at follow-up versus the overall population. Factors independently associated with discontinuation irrespective of time on therapy were increasing number of magnetic resonance imaging scans (1 year adjusted odds ratio 1.45, 95% confidence interval 1.26–1.67; 2 years 1.18, 1.06–1.32; 3 years 1.20, 1.07–1.34) and adherence <80% versus ≥80% (1 year 180.95, 135.84–241.03; 2 years 135.80, 100.10–184.23; 3 years 174.89, 115.27–265.38). Factors associated only with early discontinuation (at 1 year) were ≥3 sets of laboratory investigations versus none (2.54, 1.20–5.38), and anxiolytic use at follow-up (1.40, 1.06–1.82). Factors associated only with later discontinuation (at 2 years and/or at 3 years) were antidepressant use at follow-up (2 years 1.46, 1.10–1.94) and greater number of relapses (2 years 1.60, 1.11–2.30; 3 years 2.31, 1.27–4.22).ConclusionsPotential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.

Cognition and fatigue in patients with relapsing multiple sclerosis treated by subcutaneous interferon β-1a: an observational study SKORE.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, which often causes progressive neurological disability. In addition to motor and sensory dysfunction, cognitive decline and fatigue are frequent manifestations of the disease. Fatigue is probably the most common symptom, with up to 90% of MS individuals reporting fatigue at some point. Cognitive impairment affects about 50% of patients and may be present at all MS stages. The aim of this observational study was to evaluate changes in cognition, fatigue, and disability status in 300 relapsing-remitting MS (RRMS) patients, treated with subcutaneous (sc) interferon (IFN) β-1a over 2 years. The study was designed as an observational, multicentre, prospective, single-arm, phase IV study carried out in 13 MS centres in the Czech Republic. Cognition status was assessed using the Paced Auditory Serial Addition Task (PASAT), fatigue using the Fatigue Descriptive Scale (FDS), and disability using the Expanded Disability Status Scale (EDSS), at baseline, and after 6, 12 and 24 months. The percentage of patients with changed versus stable cognition, fatigue status and disability was calculated at each time point and the changes in these scores were evaluated. The proportion of patients with cognitive improvement was higher compared with those with a stable or decreased PASAT scores at all time points, and the average cognitive performance improved during the follow-up period. Also the proportion of patients with stable or improved fatigue and EDSS scores was higher compared with those in which FDS or EDSS scores declined, this was found at all time points of the analysed sample. However, the direct effect of IFN β-1a on cognition and fatigue cannot be concluded from this study. The results of this observational study have demonstrated a stable or improved cognitive performance, fatigue status, and disability level in the majority of RRMS patients treated with sc IFN β-1a over a two-year follow-up period, in a real life setting, in the Czech Republic.

Effects of current treatments in progressive retinal nerve fiber layer loss in multiple sclerosis patients

PurposeTo evaluate progressive changes in the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS) to assess the possible neuroprotective role of different frequently used therapies in this disease.Methods104 patients with MS underwent a complete ophthalmic evaluation including structural assessment of the RNFL thickness using Spectral domain Optical coherence tomography (SD‐OCT). All subjects were re‐evaluated after 5 years to quantify structural changes. Changes were compared between treated and untreated patients, between different therapies and between intramuscular (IM) interferon (IFN) beta‐1a (Avonex) and other frequently prescribed treatments (subcutaneus IFN beta‐1a, IFN beta‐1b, glatiramer acetate, metoxantrone and natalizumab).ResultsSignificant thinning of the peripapillary RNFL thickness was observed at 5‐year follow‐up in all patients (p &lt; 0.001). A significant loss in the RNFL thickness (inferior sector, p = 0.002) was observed in the treated group compared to untreated patients. No significant differences were found between therapies when single groups of treatments were compared. Progressive RNFL loss was observed in the glatiramer acetate group over the IM IFN beta‐1a group (p = 0.002). A clear tendency towards a greater axonal loss was observed in the IFN beta‐1b, the glatiramer acetate and the SC IFN beta‐1a group compared to IM IFN beta‐1a treatment.ConclusionsIM IFN beta‐1a may have a neuroprotective effect over progressive axonal degeneration in MS patients compared to other current therapies. These patients present progressive axonal loss detected by the analysis of the RNFL using OCT which may be useful to evaluate disease progression and effectiveness of current MS therapies.

Long-Term Adherence to IFN Beta-1a Treatment when Using RebiSmart® Device in Patients with Relapsing-Remitting Multiple Sclerosis.

The effectiveness of disease-modifying drugs in the treatment of multiple sclerosis is associated with adherence. RebiSmart® electronic device provides useful information about adherence to the treatment with subcutaneous (sc) interferon (IFN) β-1a (Rebif®). The aim of the study was to determine long-term adherence to this treatment in patients with relapsing-remitting multiple sclerosis (RRMS). This retrospective multicentre observational study analysed 258 patients with RRMS who were receiving sc IFN β-1a (Rebif®) treatment by using RebiSmart® until replacement (36 months maximum lifetime) or treatment discontinuation. Adherence was calculated with data (injection dosage, time, and date) automatically recorded by RebiSmart®. Patients in the study had a mean age of 41 years with a female proportion of 68%. Mean EDSS score at start of treatment was 1.8 (95% CI, 1.6–1.9). Overall adherence was 92.6% (95% CI, 90.6–94.5%). A total of 30.2% of patients achieved an adherence rate of 100%, 80.6% at least 90%, and only 13.2% of patients showed a suboptimal adherence (<80%). A total of 59.9% of subjects were relapse-free after treatment initiation. Among 106 subjects (41.1%) who experienced, on average, 1.4 relapses, the majority were mild (40.6%) or moderate (47.2%). Having experienced relapses from the beginning of the treatment was the only variable significantly related to achieving an adherence of at least 80% (OR = 3.06, 1.28–7.31). Results of this study indicate that sc IFN β-1a administration facilitated by RebiSmart® could lead to high rates of adherence to a prescribed dose regimen over 36 months.

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.

Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy.

Factors influencing long-term outcomes in relapsing–remitting multiple sclerosis: PRISMS-15

AimAn exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing–remitting multiple sclerosis (RRMS).MethodsPatients...

Adherence to, and effectiveness of, subcutaneous interferon β-1a administered by RebiSmart® in patients with relapsing multiple sclerosis: results of the 1-year, observational SMART study

Background: Patients with multiple sclerosis who have poor adherence to treatment have a higher risk of relapse than adherent patients. This study assessed adherence to, and effectiveness and convenience of, treatment with subcutaneous (sc) interferon (IFN) β-1a (Rebif®, Merck Serono SA) 44 or 22 μg three times weekly in patients with relapsing multiple sclerosis (RMS) using the RebiSmart® electronic, multidose, autoinjector for 1 year.Study design: European, multicentre, observational study among neurologists: inclusion criteria included RMS, Expanded Disability Status Scale score ≤ 6, sc IFN β-1a administered by RebiSmart for ≤ 6 weeks. The primary endpoint was cumulative adherence recorded by RebiSmart.Results: The safety population included 912 patients, 77.4% (n = 823) of whom completed the Month-12 visit. Mean (± standard deviation) cumulative adherence was 97.1 ± 7.3% (n = 791). The most common reason for missed injection was ‘forgot to inject’ (37.0%). At Month 12/ED, 79.5% of patients were relapse-free. Of 353 patients who rated the convenience of the device, 68.3% found injecting ‘very easy’. No unknown safety issues were detected.Conclusions: Patients with RMS self-injecting sc IFN β-1a with RebiSmart had excellent adherence at Month 12/ED, which was associated with good clinical outcomes and no unexpected safety issues. Patients rated RebiSmart as convenient and easy to use.

P046 - Cumulative review of thrombotic microangiopathy, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome reports with SC interferon beta-1a

Background/objectives Rare cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome have been reported with interferon beta products. This was a cumulative review of thrombotic microangiopathy cases recorded in a Global Safety Database for subcutaneous interferon beta-1a. Methods Search criteria were all reported cases, serious and non-serious, from all sources (including non-healthcare professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or Company; data lock was 03 May 2014. Results Ninety one cases with 105 events were retrieved; 76.9% (70/91) patients were female, consistent with the underlying disease of multiple sclerosis. Time-to-onset varied from 2 months to 14 years; 31.9% events occurred within 2-years of treatment initiation. 7 patients had a fatal outcome (5 were secondary to other causes; 2 had insufficient information). 44 patients recovered, 32 had not recovered at the time of the report and in 8 cases the outcome was not reported/unknown. Treatment was discontinued in 84.6% (77/91). In 67.0% (61/91), a causal association between treatment and the occurrence of thrombotic microangiopathy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected. Risk factors and/or confounding factors were present in 41/91 cases (45.1%). Early prodromal syndrome or specific patterns were not detected although 55.0% (50/91) contained insufficient information. The overall reporting rate of thrombotic microangiopathy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was 7.2 per 100,000 patient-years. Reporting rates for human serum albumin-containing versus human serum albumin-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. Conclusions No new signal relating specifically to increased frequency of thrombotic microangiopathy, as thrombotic thrombocytopenic purpura and hemolytic uremic syndrome with the human serum albumin-free formulation was detected and no additional risk mitigation measures were required regarding the different formulations. The benefit-risk balance of subcutaneous interferon beta-1a remains positive and routine pharmacovigilance monitoring is appropriate.

A retrospective UK audit assessing the effect of the MySupport programme on patient persistence with MS treatment

Background: People with multiple sclerosis (MS) receiving disease-modifying therapy must persist with their treatment for the prescribed duration and adhere to the prescribed interval and dose to achieve the full benefits. Aim: This audit aimed to assess whether the MySupport programme for patients with MS could improve persistence with subcutaneous (sc) interferon (IFN) β-1a. Methods: Anonymised data was retrospectively supplied by homecare providers for patients registered to receive sc IFN β-1a in January 2010. The number of ‘active’ patients (those continuing to receive scheduled deliveries) was recorded monthly for 24 months for patients receiving NHS treatment alone and those receiving both NHS treatment and MySupport. Results: A greater proportion of patients receiving NHS treatment and MySupport than of patients receiving NHS support only were on treatment at 12 months (90.0% vs 79.3%) and 24 months (74.9% vs 61.8%). The odds of being on treatment were significantly greater in patients receiving NHS treatment and MySupport than NHS support only at all time points (P&lt;0.0001). Conclusion: A personalised support programme using one-to-one nursing support and additional support media can increase the likelihood of patients with MS remaining on sc IFN β-1a.

An observational, retrospective, UK and Ireland audit of patient adherence to subcutaneous interferon beta-1a injections using the RebiSmart(®) injection device.

BackgroundPoor adherence to disease-modifying drugs is associated with an increased risk of relapse in patients with multiple sclerosis. However, adherence is difficult to assess objectively. RebiSmart® (Merck Serono SA, Geneva, Switzerland), a device for subcutaneous (sc) injection of interferon (IFN) β-1a, features an electronic injection log that can assist in objective monitoring of adherence.ObjectiveTo assess adherence to sc IFN β-1a injections using data from RebiSmart®.MethodsThis was a single-group, observational, retrospective audit. Adherence data were collected from patients with relapsing multiple sclerosis in the United Kingdom and Ireland who had been prescribed sc IFN β-1a and had been using RebiSmart® for a minimum of 24 months.ResultsIn total, 225 patients were included in the full analysis set; 72% were in the United Kingdom, and 28% were in Ireland. Overall, the mean age was 44.1 years, and 73% were women. Patients received sc IFN β-1a 44 µg (68%) or 22 µg (32%) three times per week. Mean adherence over the course of 24 months was 95.0% (median, 99.4%), and similar values were observed across all periods. The proportion of patients with 80% or higher adherence was 92.0% at 12 months and 91.1% at 24 months.ConclusionHigh adherence to sc IFN β-1a was observed across all patient groups using RebiSmart®, according to 2-year treatment adherence data. This may be partly attributed to the expert support patients received, supplemented by routine and regular contact from the MySupport patient-support program, as well as the self-motivation of patients who persisted with treatment for 2 or more years.

Patient expectations and experiences of multiple sclerosis interferon &amp;szlig;-1a treatment: a longitudinal, observational study in routine UK clinical practice

BackgroundPremature discontinuation and poor treatment adherence are problems in chronic conditions, such as multiple sclerosis in which patients must take long-term treatment in order to receive maximum benefit from their medication. The Assessing needs In Multiple Sclerosis (AIMS) study explored factors related to premature treatment discontinuation and patients’ experiences of subcutaneous (sc) interferon (IFN) β-1a treatment in the UK.MethodsA questionnaire-based survey was integrated into the Bupa Home Healthcare patient-support program, which delivers sc IFN β-1a to patients in their home. Data were collected via patient questionnaires incorporated into routine clinical care and administered upon registration of a new patient by the coordinator, following initial delivery of treatment, prior to each delivery during therapy and at the end of treatment. Univariate and multivariate analyses were performed to identify factors associated with premature discontinuation.ResultsData were collected from 2,390 patients (1,267 new; 1,123 existing) from 59 UK prescribing centers (November 2006–April 2011). Following the first delivery of sc IFN β-1a, 94% (1,149/1,225) of patients had received training, and 73% (818/1,120) reported that they had no concerns. In total, 24% of new patients discontinued therapy by the end of the study. In the univariate model, none of the candidate variables tested were significant predictors of treatment discontinuation. The strongest predictors of discontinuation in multivariate analyses were lack of information prior to starting treatment and patients feeling unwell on treatment and geographic region (P<0.05 for each variable).ConclusionThis study suggests that patients feeling well on treatment and provision of high-quality information are the main determinants of persistence with sc IFN β-1a therapy. A package of care that targets these issues should therefore be considered when initiating sc IFN β-1a therapy.

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.

Subcutaneous Interferon β-1a May Protect against Cognitive Impairment in Patients with Relapsing–Remitting Multiple Sclerosis: 5-Year Follow-up of the COGIMUS Study

ObjectiveTo assess the effects of subcutaneous (sc) interferon (IFN) -1a on cognition over 5 years in mildly disabled patients with relapsing–remitting multiple sclerosis (RRMS).MethodsPatients aged 18–50 years with RRMS (Expanded Disability Status Scale score ≤4.0) who had completed the 3-year COGIMUS study underwent standardized magnetic resonance imaging, neurological examination, and neuropsychological testing at years 4 and 5. Predictors of cognitive impairment at year 5 were identified using multivariate analysis.ResultsOf 331 patients who completed the 3-year COGIMUS study, 265 participated in the 2-year extension study, 201 of whom (75.8%; sc IFN β-1a three times weekly: 44 µg, n = 108; 22 µg, n = 93) completed 5 years' follow-up. The proportion of patients with cognitive impairment in the study population overall remained stable between baseline (18.0%) and year 5 (22.6%). The proportion of patients with cognitive impairment also remained stable in both treatment groups between baseline and year 5, and between year 3 and year 5. However, a significantly higher proportion of men than women had cognitive impairment at year 5 (26.5% vs 14.4%, p = 0.046). Treatment with the 22 versus 44 µg dose was predictive of cognitive impairment at year 5 (hazard ratio 0.68; 95% confidence interval 0.48–0.97).ConclusionsThis study suggests that sc IFN β-1a dose-dependently stabilizes or delays cognitive impairment over a 5-year period in most patients with mild RRMS. Women seem to be more protected against developing cognitive impairment, which may indicate greater response to therapy or the inherently better prognosis associated with female sex in MS.

Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study

BackgroundAchieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN) β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsBRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge) was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg), subcutaneously (sc), three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET) for: physical examinations; diary card completion (baseline, Weeks 4, 8 only); neurological examinations (baseline, Week 12/ET only); MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12 only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial Addition Task (PASAT; baseline only). Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device.ResultsOverall, 88.2% (105/119; intent-to-treat population) of patients were adherent; 67.2% (80/119) administered all scheduled injections. Medical reasons accounted for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87). Adherence did not correlate with baseline Expanded Disability Status Scale (P = 0.821) or PASAT (P = 0.952) scores, or pre-study therapy (P = 0.303). No significant changes (baseline-Week 12) in mean HADS depression (P = 0.482) or anxiety (P = 0.156) scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly rated. Mean MSTCQ scores for 'flu-like' symptoms (P = 0.022) and global side effects (P = 0.002) significantly improved from Week 4-12. Mean MSTCQ scores for pain at injection site and injection pain increased from Week 4-12 (P < 0.001). Adverse events were mild/moderate. No new safety signals were identified.ConclusionConvenience and ease of use of the autoinjection device may improve adherence and, therefore, outcomes, in patients with RRMS receiving sc IFN β-1a.Trial registrationEU Clinical Trials Register (EU-CTR; http://www.clinicaltrialsregister.eu): 2009-013333-24