Sc Interferon Beta-1a Research Articles

Current and future trends in multiple sclerosis management: Near East perspective.

Multiple sclerosis (MS) prevalence is rising in the Middle East. Most MS medications are available in the region, but not all, possibly affecting neurologists' prescribing habits. To provide an overview of the current practices of Near East (NE) healthcare practitioners by probing their prescribing decisions, to report the COVID-19 impacts on neurologists' prescribing habits, and to explore the future relevance of current medication used in MS management among other newcomers. A cross-sectional study was carried out using an online survey from April 27, 2022, to July 5, 2022. The questionnaire was designed with the input of five neurologists representing five NE countries (Iran, Iraq, Lebanon, Jordan & Palestine). They identified several factors that play a crucial role in the optimal care of MS patients. The link was shared among neurologists using snowball sampling. The survey included 98 neurologists. Effectiveness and safety balance was the most important factor considered when selecting the MS treatment. Among patients with MS, the most challenging factor for the patients was thought to be related to family planning, followed by affordability and tolerability of side effects. In the treatment of mild to moderate relapsing remitting multiple sclerosis (RRMS) in men, Interferon beta 1a SC, Fingolimod, and Glatiramer acetate were the most commonly recommended treatments. Dimethyl fumarate substituted fingolimod in female patients. Interferon beta 1a SC was the safest treatment for mild to moderate RRMS. Interferon beta 1a SC was preferred over other treatments for patients with mild to moderate MS and planning for pregnancy (56.6%) or breastfeeding (60.2%). Fingolimod was not a choice for these patients. Neurologists seemed to discuss the top three treatments of Natalizumab, Ocrelizumab, and Cladribine with patients with highly active MS. When asked to position future disease-modifying therapies five years from today, more than 45% of physicians expressed a lack of information on Bruton's tyrosine kinase (BTK) inhibitors. Most neurologists in the NE region followed Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) recommendations for prescribing treatment. The treatment choice also depended on the availability of disease-modifying therapies (DMTs) in the region. Regarding the use of upcoming DMTs, there is a clear need for real-world data, long-term extension studies, and comparative studies to support their efficacy and safety profiles in treating patients with MS.

POSC22 Demographics and Clinical DATA of a Real World Cohort of Multiple Sclerosis Patients Being Treated with Interferon Beta-1A SC in Portugal

POSC22 Demographics and Clinical DATA of a Real World Cohort of Multiple Sclerosis Patients Being Treated with Interferon Beta-1A SC in Portugal

Patients’ preferences and willingness-to-pay for disease-modifying therapies

BackgroundWhile disease-modifying therapies (DMTs) for multiple sclerosis (MS) treatments are costly, patient valuation of DMTs has not been examined. The objective of this study was to examine patients' preferences and willingness-to-pay (WTP) for DMTs. MethodsSix attributes (i.e., number of relapses, percentage of disability progression, percentage of severe adverse events, route of administration, frequency of administration, and out-of-pocket cost) and their levels were used to develop a discrete choice experiment questionnaire. Each questionnaire comprised seven choice sets and each choice set contained two hypothetical DMTs and an opt-out alternative. A total of 1,200 U.S. patients with MS were asked to choose a DMT option or opt-out in each choice set. Multinomial logit model was used to determine relative preferences of each attribute. WTPs for all attributes and DMTs were calculated. ResultsA total of 508 patients were analyzed. Patients preferred DMTs with lower relapse rate, lower disability progression, lower severe adverse event, lower frequency of administration, and lower cost. In addition, they preferred oral DMTs. They were willing to pay $2,768, $289, $292, and $76 a month in exchange for every 1-time decrease in the number of relapses in two years, every 1% decrease in disability progression in two years, every 1% decrease in severe adverse events, and every 1-time decrease in the frequency of administration per month, respectively. The patients were willing to pay, in relation to market prices, between $7,020 and $134,934 per year for all DMTs, but interferon beta-1a SC. ConclusionsPatients with MS considered relapse rate, disability progression, severe adverse events, route of administration, frequency of administration, and out-of-pocket cost, when they chose DMTs. Their WTPs for DMTs varied widely.

002 Therapeutic lag in relapsing multiple sclerosis

IntroductionIn multiple sclerosis (MS), treatment start or switch is prompted disease activity, often represented by relapses. Immunomodulatory therapies have potent effects on relapse rates but the time required to attain maximal effect is unclear. We aim to develop a method that allows identification of the time to full clinically manifest effect of treatment on relapses.MethodsData from MSBase, a multinational MS registry, were used. Inclusion criteria consisted of patients with remitting relapsing MS or clinically isolated syndrome (CIS), minimum 3-year pre-treatment follow up, 1-year treatment persistence, yearly review and availability of the minimum dataset. Stratified by therapy, density curves representing relapses occurrence were created. The first local minimum of the first derivative after treatment start was identified, representing stabilisation of treatment effect. Similar method was utilised to calculate the last pre-treatment point of stabilisation. Annualised relapse rates (ARR) were compared in the pre-treatment pre stabilisation and post-treatment post stabilisation periods.Results4979 eligible patients with 6218 treatment epochs were identified for analysis. Time, in years, to treatment effect was shortest for interferon beta-1a sc (0.22, 0.19–0.22), interferon beta-1b (0.24, 0.21–0.24) and fingolimod (0.26, 0.23–0.26) and longest for dimethyl fumarate (0.54, 0.51–0.54) and glatiramer acetate (0.62, 0.60–0.62). Significant differences in pre vs post treatment ARR were present for patients on natalizumab, fingolimod and dimethyl fumarate. A sequential analysis confirmed outcome stability after approximately 1000 recorded number of events.ConclusionsWe have developed a method to objectively quantify time from commencing therapy to its full effect. Time to full effect varies among therapies.

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.

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)

Multiple immune disorders after natalizumab discontinuation: After the CIRIS, the SIRIS?

Natalizumab (NTZ) is an effective treatment for patients with highly active relapsing remitting multiple sclerosis (MS). However, when the therapy must be interrupted, it is important to anticipate the withdrawal to avoid reactivation or disease rebound. Described here is the case of a 35-year-old woman, with a past history of beta thalassemia, bulimia and asthma, who was diagnosed with MS at age 26. She was treated initially with first-line subcutaneous (sc) immunomodulatory treatments. However, due to liver toxicity, interferon beta-1a sc was interrupted and replaced by glatiramer acetate treatment, which was well tolerated and used for several years. Unfortunately, disease progression with numerous relapses and contrast enhancement on brain MRI led to initiation of NTZ treatment. After more than 2 years of treatment, NTZ was interrupted because of pregnancy, and the patient was again put on glatiramer acetate. Eight weeks after interruption of NTZ therapy, the first signs of diabetes were observed, together with an increase in blood levels of hepatic enzymes, skin reactions such as angioedema and giant urticaria, and hypothyroidism requiring hormone supplementation. The patient delivered her baby without complications, and NTZ was reintroduced several months later. At the present time, the patient's hypothyroidism, diabetes and increased blood levels of hepatic enzymes persist, although no new skin reactions have been observed. Withdrawal of NTZ can not only lead to reactivation of the disease or its rebound, but also to autoimmune manifestations within the framework of immune reconstitution inflammatory syndrome (IRIS). This risk needs to be considered when therapy has to be interrupted, especially when a personal and/or familial past history of autoimmune disease is present.

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.

Early Onset and Predictive Value of MRI Measures among Patients Receiving Interferon Beta-1a SC tiw for RRMS: Post Hoc Analyses of PRISMS-2 Data (P7.254)

Early Onset and Predictive Value of MRI Measures among Patients Receiving Interferon Beta-1a SC tiw for RRMS: Post Hoc Analyses of PRISMS-2 Data (P7.254)

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.

Efficacy and safety of subcutaneous interferon beta-1a in relapsing–remitting multiple sclerosis: Further outcomes from the IMPROVE study

Background The IMPROVE study demonstrated that the fetal bovine serum (FBS)- and human serum albumin (HSA)-free formulation of subcutaneous (sc) interferon (IFN) beta-1a had beneficial effects on the numbers of combined unique active magnetic resonance imaging (MRI) lesions in relapsing–remitting multiple sclerosis (RRMS). Here we report additional MRI endpoints (including post hoc analyses), and clinical efficacy, safety, and immunogenicity outcomes. Methods Patients with active RRMS were randomized (2:1) to IFN beta-1a, 44 mcg sc three times weekly (tiw) (n = 120), or placebo (n = 60), for 16 weeks (double-blind phase). All patients then received IFN beta-1a, 44 mcg sc tiw, for 24 weeks (rater-blind phase). Patients underwent MRI brain scans every 4 weeks. Results Compared with placebo, there was a 68% reduction in the mean cumulative number of new gadolinium-enhancing lesions with IFN beta-1a as early as week 4 ( p < 0.001), and a 53% reduction in the mean cumulative number of new T2 lesions as early as week 8 ( p = 0.025; post hoc analyses). During the 16-week double-blind phase, the relapse rate was 0.14 (95% confidence interval [CI] 0.09–0.23) with IFN beta-1a and 0.33 (95% CI 0.22–0.52) with placebo ( p = 0.010). Safety outcomes were consistent with those expected with IFN-beta treatment. Conclusions The FBS/HSA-free formulation of sc IFN beta-1a has a beneficial impact on MRI and efficacy outcomes as early as 4 weeks after treatment initiation in patients with RRMS and has a safety profile consistent with previous trials of sc IFN beta-1a.

Current Therapeutic Options in Pediatric Multiple Sclerosis

Therapies for relapsing-remitting pediatric multiple sclerosis (MS) are aimed at preventing relapses (disease modifying therapies), treating acute attacks, and managing disabling cognitive and physical symptoms. Initial disease modifying therapy to prevent relapses should use one of four first-line injectable therapies that are approved for adult relapsing-remitting MS: interferon beta 1a IM, interferon beta 1a SC, interferon beta 1b SC, or glatiramer acetate. If breakthrough disease occurs or the medication is poorly tolerated, the next step should be to try one of the other first-line therapies. If the first-line therapies have been exhausted, second-line therapies such as natalizumab, cyclophosphamide, or mitoxantrone may be considered. One must use caution when choosing these potent therapies, as secondary effects may include serious infection or malignancy. Phase III studies in adult MS have been published on two oral agents, fingolimod and cladribine, and fingolimod has received FDA approval for use in relapsing-remitting MS in adults. These drugs have not been evaluated in the pediatric MS population, nor have any of three other oral agents now in phase III development: laquinimod, BG-12, and teriflunomide. Acute relapses can be treated with pulse methylprednisolone at a dosage of 20 to 30mg/kg per day (maximum 1g per day) for 3 to 5days. If this is ineffective, intravenous immunoglobulin (2g/kg divided over 2-5days) or plasmapheresis may be considered. Neuropsychological, physical therapy, and occupational therapy screening should be performed on patients with pediatric MS. Interventions focusing on visual motor integration may be particularly useful in this group Spasticity may be treated with symptomatic therapies, but one must be aware of potential adverse effects of agents such as baclofen and diazepam. Headache, fatigue, anxiety, and depression are frequently seen, and patients may need a psychiatry consultation and counseling.

The risk of malignancy is not increased in patients with multiple sclerosis treated with subcutaneous interferon beta-1a: analysis of data from clinical trial and post-marketing surveillance settings

Background: Risks that are potentially associated with long-term therapies should be assessed. Objective: The present analyses were performed to determine the risk of malignancy in patients with multiple sclerosis (MS) receiving subcutaneous (sc) interferon (IFN) beta-1a, using pooled safety data from key clinical trials and data from the Merck Serono Global Drug Safety database. Methods: The standard Medical Dictionary for Regulatory Activities query “malignancies” was used to retrieve relevant cases from each data set. The incidence of malignancies per 1000 patient-years was calculated using the pooled safety data from clinical trials. The reporting rates of malignancy types were calculated for the post-marketing setting based on sales volume. Malignancies were grouped by organ localization and classified as medically confirmed or not medically confirmed according to the source of each report. The number of reported cases of each type was compared with the expected number in the general population. Results: Analysis of pooled safety data from 12 key clinical trials did not show an increased incidence of malignancy per 1000 patient-years with sc IFN beta-1a (4.0; 95% confidence interval (CI): 2.9–5.5) compared with placebo (6.4; 95% CI: 3.3–11.2). Analysis of the database shows that among the medically confirmed cases, reported to expected ratios ranged from 1 : 6 to 1 : 18 for solid tumours and from 1 : 2 to 1 : 9 for lymphohaematopoietic tumours. Conclusion: Safety data from both clinical trial and post-marketing settings suggest that treatment with sc IFN beta-1a does not increase the risk of malignancy in patients with MS.

Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing–remitting multiple sclerosis

Objective: To measure the effects of disease-modifying drugs (DMDs) on the development of cortical lesions (CL) and cortical atrophy in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: RRMS patients (n = 165) were randomized to subcutaneous (sc) interferon (IFN) beta-1a (44 mcg three times weekly), intramuscular (im) IFN beta-1a (30 mcg weekly) or glatiramer acetate (GA; 20 mg daily). The reference population comprised 50 untreated patients. Clinical and MRI examinations were performed at baseline, 12 months and 24 months. Results: One hundred and forty-one treated patients completed the study. After 12 months, 37/50 (74%) of untreated patients developed ≥1 new CL (mean 1.6), compared with 30/47 (64%) of im IFN beta-1a-treated patients (mean 1.2, p = 0.021), 24/48 (50%) of GA-treated patients (mean 0.8, p = 0.001) and 12/46 (26%) of sc IFN beta-1a-treated patients (mean 0.4, p < 0.001). After 24 months, ≥1 new CL was observed in 41/50 (82%) of untreated (mean 3.0), 34/47 (72%) of im IFN beta-1a-treated (mean 1.6, p < 0.001), 30/48 (62%) of GA-treated (mean 1.3, p < 0.001) and 24/46 (52%) of sc IFN beta-1a-treated patients (mean 0.8, p < 0.001). Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients (p = 0.023). Conclusions: Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients, with faster and more pronounced effects seen with sc IFN beta-1a than with im IFN beta-1a or GA.

Impact of exposure to interferon beta-1a on outcomes in patients with relapsing–remitting multiple sclerosis: exploratory analyses from the PRISMS long-term follow-up study

To explore the effects of exposure to subcutaneous (sc) interferon (IFN) beta-1a on efficacy in patients with relapsing-remitting multiple sclerosis (RRMS) enrolled in the PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study. Patients with RRMS received IFN beta-1a, 44 or 22 µg sc three times weekly (tiw), or placebo, for 2 years, at which point placebo recipients were re-randomized to IFN beta-1a, 44 or 22 µg sc tiw, for a further 2-4 years. Long-term follow-up visits occurred 7-8 years after enrolment and allowed participation of patients who had previously discontinued treatment. Post hoc descriptive analyses were conducted within the lower (MIN) and upper (MAX) quartiles of patients divided according to cumulative dose of IFN beta-1a and cumulative time on treatment. Outcomes were explored in patients initially randomized to IFN beta-1a, 44 µg sc tiw, who had received continuous or noncontinuous therapy during the study. For both cumulative dose and time analyses, the MIN and MAX groups comprised 96 and 95 patients, respectively. The continuous and noncontinuous groups included 45 and 91 patients, respectively. The MAX DOSE and MAX TIME groups had lower annualized relapse rates, lower rates of conversion to secondary progressive MS, lower percentages of patients with Expanded Disability Status Scale progression, higher percentages of relapse-free patients, and less T2 burden of disease than the MIN groups. The continuous therapy group had a lower annualized relapse rate and lower percentages of patients with Expanded Disability Status Scale progression or conversion to secondary progressive MS than the noncontinuous therapy group. The findings of these post hoc analyses suggest that high exposure to sc IFN beta-1a may be associated with better clinical outcomes than low exposure, and also highlight the importance of maximizing adherence. Additional prospective investigation is warranted to evaluate further the effects of treatment exposure on outcomes and to determine the benefits of interventions to improve adherence.

Patient satisfaction following transition from the original to the new formulation of subcutaneous interferon beta-1a in relapsing multiple sclerosis: a randomized, two-arm, open-label, Phase IIIb study

To assess satisfaction with the serum-free formulation of subcutaneous (sc) interferon (IFN) beta-1a among patients with relapsing multiple sclerosis (MS). Patients with relapsing MS who had been receiving sc IFN beta-1a for at least 6 months, were transitioned to the new formulation, 44 mug three times weekly. Patients were randomized to preventative ibuprofen (400 mg 30-60 minutes prior to injection) or ibuprofen as needed (PRN) for 4 weeks. The primary endpoint was the 'flu-like' symptom (FLS) domain score of the validated Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ). Of the 117 patients enrolled, 109 (93.2%) completed the study. Neither group's MSTCQ FLS score showed a clinically meaningful change from baseline to week 4: mean +/- SD changes were -1.1 +/- 4.4 in the preventative ibuprofen group and 0.8 +/- 3.6 in the ibuprofen PRN group. MSTCQ injection system satisfaction and global side-effect scores were unchanged; total and injection-site reaction scores improved moderately in both groups between baseline and week 4. Results showed continued or increased levels of satisfaction with the new formulation of sc IFN beta-1a. FLS occurring with the new formulation were generally mild and seldom sufficiently bothersome to require ibuprofen treatment.

Patient-rated suitability of a novel electronic device for self-injection of subcutaneous interferon beta-1a in relapsing multiple sclerosis: an international, single-arm, multicentre, Phase IIIb study

BackgroundMultiple sclerosis (MS) currently requires long-term treatment with disease-modifying drugs, administered parenterally up to once daily. The need for regular self-injection can be a barrier to treatment for many patients. Autoinjectors can help patients overcome problems or concerns with self-injection and could, therefore, improve treatment adherence. This study was performed to assess the suitability of a new electronic device for the subcutaneous (sc) administration of interferon (IFN) beta-1a, 44 mcg three times weekly, for relapsing MS.MethodsIn this Phase IIIb, multicentre, single-arm study, patients with relapsing MS who had been consistently self-injecting sc IFN beta-1a using an autoinjector for at least 6 weeks were taught to use the new device and self-administered treatment for 12 weeks thereafter. Patient-rated suitability of the device was assessed at the end of Week 12 using the Patient User Trial Questionnaire. Patient satisfaction with, and evaluation of, the injection process was assessed using the MS Treatment Concern Questionnaire. Trainers evaluated the device using the Trainer User Trial Questionnaire.ResultsAt Week 12, 71.6% (73/102) of patients considered the device 'very suitable' or 'suitable' for self-injection; 92.2% (94/102) reported some degree of suitability and only 7.8% (8/102) found the device 'not at all suitable'. At Weeks 4, 8 and 12, most patients reported that injection preparation and clean-up, performing injections and ease of device use in the previous 4 weeks compared favourably with, or was equivalent to, their previous experience of self-injection. Injection-related pain, injection reactions and 'flu-like' symptoms remained stable over the 12 weeks. Each device feature was rated 'very useful' or 'useful' by at least 80% of patients. All trainers and 95.2% (99/104) of patients found device functions 'very easy' or 'easy' to use. Overall convenience was considered the most important benefit of the device.ConclusionsMost patients considered the new electronic injection device suitable for the sc injection of IFN beta-1a. They found the device easy to use with useful features, and reported benefits such as overall convenience. The device may, therefore, increase treatment adherence in patients with MS, particularly those with injection-related issues.Trial registrationNCT00735007

Traitements de fond de la sclérose en plaques : enseignements des études randomisées comparatives directes

Several first-line immunomodulatory treatments are available to physicians for treating patients with relapsing-remitting multiple sclerosis, namely three interferon-beta preparations and glatiramer acetate. In order to enlighten their choice of treatment, physicians need data from good quality comparative clinical trials.This review outlines and compares the findings of the various randomized clinical trials that have assessed the efficacy and safety of immunomodulatory treatments for multiple sclerosis. Six such studies have been reported to date, a Danish study (interferon-beta 1a sc versus interferon-beta 1b sc), the EVIDENCE study (interferon-beta 1a sc versus interferon-beta 1a im), the INCOMIN study (interferon-beta 1b sc versus interferon-beta 1a im), the BECOME and BEYOND studies (interferon-beta 1b sc versus glatiramer acetate) and the REGARD study (interferon-beta 1a sc versus glatiramer acetate).These studies have demonstrated somewhat superior efficacy for interferon-beta preparations administered subcutaneously several times a week compared to preparations administered intramuscularly once a week. In contrast, no difference in efficacy has been demonstrated between the two subcutaneously administered interferon-beta preparations, or between either of these preparations and glatiramer acetate. Differences in the safety profile of the four immunomodulatory treatments were observed, in particular a more favorable skin tolerance with intramuscularly administered interferon-beta and a better systemic adverse event profile for glatiramer acetate.These various randomized comparative trials have provided objective criteria that can be used by physicians for choosing between immunomodulatory treatments.

Subcutaneous interferon beta-1a has a positive effect on cognitive performance in mildly disabled patients with relapsing—remitting multiple sclerosis: 2-year results from the COGIMUS study

The effect of interferon (IFN) beta-1a (44 and 22 μg subcutaneously [sc] three times weekly [tiw]) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (McDonald criteria; Expanded Disability Status Scale =4.0) was assessed by validated neuropsychological testing at baseline and at regular intervals for up to 2 years in this ongoing open-label, 3-year study. Year-2 data were available for 356 patients (22 μg, n = 175; 44μg, n = 181). The proportion of patients with impaired cognitive function was stable during the study: 21.4% at baseline and 21.6% at 2 years. At 2 years, the proportion of patients with =3 impaired cognitive tests was significantly lower in the 44 μg treatment group (17.0%) compared with the 22 μg group (26.5%; p = 0.034), although there was already a trend towards a higher proportion of patients with cognitive impairment in the 22 μg group at baseline. Factors associated with impairment in = three cognitive tests after 2 years were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.00-1.09), verbal intelligence quotient (OR: 0.95; 95% CI: 0.92-0.98), and having = three impaired cognitive tests at baseline (OR: 11.60; 95% CI: 5.94-22.64). These interim results show that IFN beta-1a sc tiw may have beneficial effects on cognitive function as early as 2 years after treatment initiation, but the final 3-year data of the study are required to confirm these results.