Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial.

BACKGROUND: Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. CLINICAL TRIALS REGISTRATION: NCT04647695.

Tratamiento farmacológico de la covid-19: revisión narrativa de los grupo de trabajo de enfermedades infecciosas y sepsis (gteis) y del grupo de trabajo de transfusiones y hemoderivados (gtth) / Pharmacological treatment of covid-19: narrative review of the working group in infectious diseases and sepsis (gteis) and the working groups in transfusions and blood products(gtth)

La infección por el virus SARS-CoV-2, denominada COVID-19 (COronaVIrus Disease 19), fue detectada inicialmente en China en diciembre 2019, y posteriormente se ha diseminado rápidamente por todo el mundo, hasta el punto de que el 11 de marzo la OMS declaró que el brote podría definirse como pandemia. La COVID-19 presenta un cuadro que oscila desde episodios leves pseudogripales a otros graves e incluso potencialmente mortales debido, sobre todo, a insuficiencia respiratoria aguda. Es frecuente el ingreso de estos pacientes en nuestros Servicios de Medicina Intensiva en relación con un Síndrome de Distrés Respiratorio Agudo (SDRA). La falta de un tratamiento con evidencia científica ha llevado al empleo de diferentes pautas terapéuticas, en muchas ocasiones, con modificaciones rápidas de los protocolos. Recientes revisiones en revistas de prestigio han destacado la falta de terapias probadas y la necesidad de ensayo clínicos que permitan establecer pautas de tratamiento claras y objetivas. Este documento tiene por objeto ofrecer una actualización de la terapia que se está aplicando en la actualidad, y una ayuda en la asistencia diaria, sin pretender sustituir los protocolos adoptados en cada centro

Infection by the SARS-CoV-2 virus, known as COVID-19 (Corona VIrus Disease-19) was initially detected in China in December 2019, and has subsequently spread rapidly throughout the world, to the point that on March 11 the World Health Organization (WHO) reported that the outbreak could be defined as a pandemic. COVID-19 disease ranges from mild flu-like episodes to other serious and even life-threatening conditions, mainly due to acute respiratory failure. These patients are frequently admitted to our Intensive Care Units in relation to acute respiratory distress syndrome (ARDS). The lack of a treatment based on scientific evidence has led to the use of different management guidelines, in many cases with rapid changes in the applied protocols. Recent reviews in reputed journals have unders cored the lack of proven therapies and the need for clinical trials to establish clear and objective treatment guidelines. The present study provides an update on the currently applied treatment, and intends to offer help in relation to daily care, without seeking to replace the protocols adopted in each individual center

Paediatric viral myocarditis successfully treated with interferon beta-1b and corticoids.

WHAT IS KNOWN AND OBJECTIVE: In paediatrics, evidence regarding the treatment of viral myocarditis using interferon beta-1B is restricted to four children older than two years and there are no reported cases of infants. The objective was to describe the efficacy and safety of interferon beta-1B in two infants under one year of age with viral myocarditis. CASE SUMMARY: Two infants were admitted to the hospital presenting with respiratory symptoms. Echocardiogram showed myocardial damage. Parvovirus-B19 was detected using a PCR assay, and treatment with interferon beta-1B was initiated. Six months later, the cardiac function had recovered in both cases. WHAT IS NEW AND CONCLUSION: This is the first published series of cases of infants less than 1 year of age with viral myocarditis treated with interferon beta-1B.

Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia.

OBJECTIVE: To evaluate the therapeutic effectiveness of favipiravir combined with inhaled interferon beta-1b in adult patients hospitalized with moderate to severe COVID-19 pneumonia. METHODS: A randomized, open-label controlled trial of oral favipiravir in adults hospitalized with moderate to severe COVID-19 pneumonia from June 22nd 2020 to August 13th 2020 was conducted. Patients were randomly assigned to receive either a combination of favipiravir with interferon beta-1b by inhalation aerosol or hydroxychloroquine (HCQ). The outcome endpoints included improvement in inflammatory markers, lower length of hospital stay (LOS), discharges and lower overall 14-day mortality. RESULTS: A total of 89 patients underwent randomization with 49% (n = 44) assigned to favipiravir and 51% (n = 45) assigned HCQ. The overall mean age was 55 ± 14 years and 58% (n = 52) were males. There were no significant differences in the inflammatory biomarkers at hospital discharge between the two groups; C-reactive protein (p = 0.413), ferritin (p = 0.968), lactate dehydrogenase (p = 0.259) and interleukin 6 (p = 0.410). There were also no significant differences between the two groups with regards to the overall LOS (7 vs 7 days; p = 0.948), transfers to the ICU (18.2% vs 17.8%; p = 0.960), discharges (65.9% vs 68.9%; p = 0.764) and overall mortality (11.4% vs 13.3%; p = 0.778). CONCLUSIONS: No differences in clinical outcomes were found between favipiravir plus inhaled interferon beta-1b and hydroxychloroquine in adults hospitalized with moderate to severe COVID-19 pneumonia.

Interferon ß-1b in treatment of severe COVID-19: A randomized clinical trial.

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.

Active Pulmonary Tuberculosis Triggered by Interferon Beta-1b Therapy of Multiple Sclerosis: Four Case Reports and a Literature Review.

In this paper, we reported on four cases of severe pulmonary active tuberculosis in patients with multiple sclerosis (MS) undergoing interferon beta-1b (IFNß-1b) therapy. Disease-modifying therapies (DMTs) in MS may increase the risk of developing active tuberculosis (TB) due to their impact on cellular immunity. Screening for latent infection with Mycobacterium tuberculosis (LTBI) should be performed, not only for the newer DMTs (alemtuzumab, ocrelizumab) but also for IFNß-1b, alongside better supervision of these patients.

Cutaneous necrotic lesion: A wonderful delay adverse effect of interferon beta-1b injection for multiple sclerosis treatment.

Multiple sclerosis (MS) is a chronic and inflammatory autoimmune disease. These patients may manifest severe inflammatory cutaneous reactions after using interferon beta-1b. This article describes a 55-year-old man with severe injection site reactions after 10 years administration of interferon beta-1b. The biopsy specimens revealed skin and subcutaneous tissue necrosis. Histologic evaluation revealed nonspecific inflammatory reactions with no evidence of vasculitis or granulomatous reactions. Based on clinical and pathological findings, the diagnosis of skin and soft tissue necrosis due to interferon injection was given. The injection of interferon beta-1b in the affected areas was stopped, and the patient's clinical condition improved by wound care. This report is aimed to increase awareness about severe adverse skin reactions, which may infrequently occur with subcutaneous interferon beta-1b injection after several years. Early diagnosis of this reaction can help to prevent associated complications.

Morphea secondary to interferon beta1b injection: a case and review of the literature.

Interferon beta (IFNß) is a drug used successfully in the treatment of multiple sclerosis (MS). Although IFNß is a safe and well-tolerated drug, dermatological side effects are common. The most common dermatological adverse effect is a local reaction at the injection site. It may also cause inflammatory and immune-mediated dermatological side effects. However, morphea induced by IFNß1b injection is very rare.

Cost-effectiveness of Teriflunomide Compared to Interferon Beta-1b for Relapsing Multiple Sclerosis Patients in China.

BACKGROUND AND OBJECTIVE: Teriflunomide is a once-daily oral immunomodulatory agent approved in 80 countries for the treatment of patients with relapsing multiple sclerosis (RMS). The study objective was to estimate the cost effectiveness of teriflunomide (14 mg tablet, daily) versus interferon beta-1b (250 mcg subcutaneous injection, every other day) among RMS patients from the Chinese healthcare system perspective. METHODS: A Markov model with annual cycles and a lifetime horizon was utilized to assess cost-effectiveness of teriflunomide in comparison with interferon beta-1b in RMS patients. Treatment effects, including 3-month confirmed disability worsening and annualized relapse rate, were derived from a network meta-analysis. Cost inputs included costs related to treatment acquisition, administration, monitoring, natural disease management through Expanded Disability Status Scale states, relapse treatment, and adverse event management. These costs were calculated as the product between unit costs from published sources and healthcare resource utilization patterns identified in a survey conducted among 11 neurologists across different areas in China. Health effects were expressed as quality-adjusted life years (QALYs) with costs in local currency (¥) and US dollars (US$), 2018. RESULTS: Teriflunomide dominated interferon beta-1b and was associated with lower total costs (teriflunomide ¥1,887,144 vs interferon beta-1b ¥2,061,393) and higher QALYs (teriflunomide 9.60 QALYs vs interferon beta-1b 8.88 QALYs). In probabilistic sensitivity analysis, teriflunomide was dominant in 62.2% of model runs. CONCLUSION: Teriflunomide is a cost-effective therapy over a lifetime time horizon compared to interferon beta-1b in the treatment of RMS patients in China. Results should be interpreted with caution as head-to-head comparisons are not available.

Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials.

BACKGROUND: Treatment of multiple sclerosis (MS) with interferon ß can lead to the development of antibodies directed against interferon ß that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon ß. OBJECTIVE: To validate the proposed genetic markers and to identify new markers. METHODS: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon ß-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon ß-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. RESULTS: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10-4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10-3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10-15). CONCLUSION: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon ß was confirmed in the combined analysis of two multi-national, multi-center studies.

Adherence, satisfaction and functional health status among patients with multiple sclerosis using the BETACONNECT® autoinjector: a prospective observational cohort study.

BACKGROUND: Maintaining patient adherence to disease modifying drugs in multiple sclerosis is a challenge, which can be improved by autoinjectors. The BETACONNECT® is a fully electronic autoinjector for the injection of interferon beta-1b (IFN beta-1b) automatically recording injections. METHODS: The BETAEVAL study was a prospective, observational, cohort study over 24 weeks among patients with relapsing remitting multiple sclerosis or clinically isolated syndrome treated with IFN beta-1b in Germany using the BETACONNECT®. The primary aim was to investigate treatment adherence, secondary aims included assessing satisfaction and functional health status. Adherence was evaluated from injection data recorded by the device. Patient-related data were obtained from clinical examinations and patient questionnaires. RESULTS: Of the 151 patients enrolled, 143 were available for analysis. Thirty-four patients discontinued the study prematurely. 107/143 (74.8%) patients still used the BETACONNECT® at the end of the study. Injection data from the device at any visit was available for 107 patients. Among those, the percentage of adherent patients injecting ≥80% of doses and still participating in the study was 57.9% at week 24. 29% of patients prematurely stopped the study, 13.1% injected <80%. Among patients with BETACONNECT® data at the respective visit, the proportion of adherent patients was high over the entire study period (week 4: 81.1% [N = 95], week 12: 86.7% [N = 83], week 24: 80.5% [N = 77]). Participants (N = 143) indicated high satisfaction with the BETACONNECT®. At week 24, 98.0% of patients who completed the corresponding questionnaire (strongly) agreed that it was user-friendly, 81.2% felt confident in using it compared to their previous way and 85.5% preferred it to their previous way of injection. Injection-related pain was rated as mild to moderate at all follow-up visits. Whereas 17.2% of patients with corresponding questionnaire indicated using analgesics prior to injection at week 4, only 9.1% did at week 24. Outcomes from questionnaires assessing functional health status, depression, fatigue and cognitive function were very similar throughout the study course. CONCLUSIONS: The majority of patients continued using the BETACONNECT® for IFN beta-1b treatment during the 24-week study period. Adherence was high among participants still using the BETACONNECT® and patients were highly satisfied with the device. Ongoing studies will evaluate long-term adherence and treatment outcomes in patients using the BETACONNECT®. TRIAL REGISTRATION: clinicaltrails.gov NCT02121444 (registered April 22, 2014).

Depression, anxiety and stress severities in multiple sclerosis patients using injectable versus oral treatments.

AIM: Studies on multiple sclerosis in Saudi Arabia remain scant, particularly studies on the psychological aspects. This study measures severities of depression, anxiety and stress, and compares them to the used disease-modifying treatment. MATERIALS & METHODS: Cross-sectional study using a phone questionnaire targeting 452 Saudi patients with relapsing-remitting multiple sclerosis following in King Khalid University Hospital, King Fahad Medical City or Security Forces Hospital. RESULTS: From 235 patients, 149 used interferons, 58 used fingolimod and 28 used natalizumab. Depression scores were similar among all demographic and drug groups. Interferons versus fingolimod anxiety scores were significantly different (p = 0.035). Stress scores were within normal limits. CONCLUSION: Mild anxiety was higher among interferon users, which could be due to injection anxiety reasons.

Cognitive dysfunction in patients with multiple sclerosis treated with first-line disease-modifying therapy: a multi-center, controlled study using the BICAMS battery.

Multiple sclerosis (MS) can impair cognitive functions even in the early stages. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery is very short and highly sensitive and can be used to evaluate cognitive status in the disease. Several clinical trials have shown beneficial effects of disease-modifying drugs (DMDs) on long-term cognitive measures which may even reduce cognitive deficits in MS patients. Relapsing remitting MS patients using DMDs were enrolled in the study and monitored for 12 months. BICAMS and the Expanded Disability Status Scale were applied to the study group. We evaluated and monitored 161 newly diagnosed cases of definite MS by the end of the trial. 110 patients (68.2%) were female. One hundred and two healthy subjects (female to male ratio 68:34) were enrolled into the study. MS patients were categorized into three DMT groups: IFNB1-a SC, IFNB1-b, and GA. Mean scores of all three cognitive tests (SDMT, BVMT-R, and CVLT-II) were significantly higher in the control group than in the MS patients. The number of cognitively impaired patients decreased from 31.7 to 21.7% on the basis of CVLT (p = 0.024), and 42 (26.1%) to 30 (18.6%) on the basis of BVMT-R at month 12. A significant difference was determined in terms of cognitive status between MS patients using both IFNB and GA and the healthy control group. Ours is the first study to compare IFNB and GA in terms of evaluating cognitive involvement and to use the BICAMS battery in monitoring treatment.

The 11-year long-term follow-up study from the randomized BENEFIT CIS trial.

OBJECTIVE: To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. METHODS: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Eleven years after randomization, patients were reassessed. RESULTS: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p = 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p = 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p = 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores (p = 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups. CONCLUSIONS: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS. CLINICALTRIALSGOV IDENTIFIER: NCT01795872. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years.

[Experience of application of Russian biosimilar of interferon beta-1b for treatment of pediatric multiple sclerosis]. / Opyt primeneniya rossiiskogo bioanaloga interferona beta-1b v lechenii detskogo rasseyannogo skleroza.

AIM: To evaluate efficacy and safety of biosimilars of interferon beta-1b (Infibeta) in patients aged 14 to 17 years. MATERIAL AND METHODS: Interferon beta 1b (Infibeta) was appointed 9 children and adolescents (4 boys and 5 girls) between the ages of 14 to 17 years (mean age of onset of therapy 16.22±1.09). RESULTS: In the course of therapy there was a significant decrease in the annualrelapse rate (ARR) to 0.33±0.5 (from 0 to 1, r≤0,0001) and the of regression of neurological deficit on the EDSS scale up to ±1.94±0.68 (1.5 to 3, p≤0.05). No cases of cancellation was not recorded due to poor tolerability or inefficiency. CONCLUSION: Although numerically small so far, but quite successful results on the use of Russian interferon beta-1b biosimilar (Infibeta) in children, we can recommend this treatment as sufficiently safe and effective.

Análisis de coste-efectividad del interferón beta-1b en el tratamiento de pacientes con síndrome desmielinizante aislado indicativo de esclerosis múltiple en España / Cost-effectiveness analysis of interferon beta-1b as treatment for patients with clinically isolated syndrome suggestive of multiple sclerosis in Spain

INTRODUCCIÓN: El estudio BENEFIT ha mostrado los beneficios del uso precoz del interferón beta 1 b (IFNβ-1b). El objetivo del trabajo fue estimar la eficiencia del tratamiento precoz vs. diferido del IFNβ-1b en pacientes con un síndrome desmielinizante aislado (SDA) indicativo de esclerosis múltiple (EM) en España. MÉTODOS: Se desarrolló un modelo de Markov desde la perspectiva social, con un horizonte temporal de 2 años hasta toda la vida. Una cohorte de 1.000 pacientes con SDA y estados de salud definidos por la Expanded Disability Syndrome Scale (EDSS) fue tratada o no con IFNβ-1b al inicio. Los datos del BENEFIT se usaron para la progresión en la EDSS y las transiciones a EM. Los costes se estimaron de la literatura. Las utilidades derivaron del EQ-5D y publicaciones y la mortalidad de tablas de mortalidad y de la EDSS. Costes (€ de 2013) y resultados se descontaron al 3% anual. Se realizó un análisis de sensibilidad probabilístico. RESULTADOS: En el caso base, tanto la razón de coste utilidad incremental (RCUI) como la razón de coste efectividad incremental (RCEI) del IFNβ-1b vs. no tratamiento fueron dominantes (más eficaz y menos costoso) bajo la perspectiva social. Bajo la perspectiva del SNS, la RCUI fue de 40.702 €/AVAC y la RCEI de 13 €/recaída evitada. CONCLUSIÓN: El tratamiento precoz con IFNβ-1b después de un SDA frente al tratamiento diferido es eficiente desde la perspectiva social, pero puede no ser eficiente desde la perspectiva del SNS al no tener en cuenta los costes no sanitarios

INTRODUCTION: The BENEFIT study has demonstrated the benefits of early treatment with interferon beta 1 b (IFNβ-1b). The objective of this study was to estimate the efficiency of early vs delayed IFNβ-1b treatment in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in Spain. METHODS: A Markov model reflecting the social perspective was developed with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients with CIS, whose health status had been measured on the Expanded Disability Symptom Scale (EDSS), included patients who received early IFNβ-1b treatment and those who did not. Data from the BENEFIT study were used to model EDSS progression and transitions to MS. Costs were estimated from published literature. Patient utilities were derived from EQ-5D data and published data. Mortality was estimated using life tables and EDSS data. Costs (€ at 2013 rates) and outcomes were discounted at 3% per annum. A probabilistic sensitivity analysis was performed. RESULTS: In the base case, both the incremental cost utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of IFNβ-1b versus no treatment were dominant (more effective and less costly) from a social perspective. From the perspective of the Spanish Health System, the ICUR was € 40,702/QALY and the ICER was € 13/relapse avoided. CONCLUSION: Early treatment with IFNβ-1b after a CIS versus delayed treatment is efficient from a social perspective, but it may not be efficient from the perspective of the NHS which does not take non health-related costs into account

Adherence to Long-Term Interferon Beta-1b Injection Therapy in Patients with Multiple Sclerosis Using an Electronic Diary.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring long-term treatment, which is often hampered by non-adherence to self-applicable therapies, provoking continued disease activity and health care system burdens. This study assessed the influence of a personal digital assistant (PDA) with diary function (n = 339 patients) on persistence and adherence to an interferon beta treatment regimen in comparison to a paper patient diary (n = 330 patients). METHODS: Patients who recently started with subcutaneous injections of interferon beta-1b were recruited in this prospective, non-interventional, national cohort study for an observational period of 2 years after successful completion of the initial dose escalation. RESULTS: Therapy persistence as assessed by the drop-out rate within 104 weeks was about 50% in both study cohorts. In male patients, the drop-out rate was 10% lower when using a PDA compared to the non-PDA group. Use of a PDA with an injection reminder function increased adherence to the injection schedule (every other day) by a mean of 24.5 injections over 24 months in comparison to use of a PDA without injection reminder function. CONCLUSION: Persistence in this study was in the published range of observational MS studies. Furthermore, in male patients continuation of therapy might be positively influenced by use of a PDA, and both female and male patients might benefit from an integrated reminder function. In conclusion, electronic diaries reminding patients of upcoming injections can promote an improved adherence to MS therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00902135. FUNDING: Bayer Vital GmbH.

Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches.

The role of nitric oxide and its reactive derivatives (NO x ) is well known in the pathogenesis of multiple sclerosis, which is an inflammatory disease while NO x seems to be important in coordinating inflammatory response. The purpose of the present study was to assess serum NO x as one of the nitrogen species and inflammatory parameters in relapsing-remitting multiple sclerosis patients and to compare the effectiveness of various types of disease-modifying therapies that reduce nitric oxide and inflammatory biomarkers. Elevated NO x level was observed in patients who received the first-line disease-modifying therapy (interferons beta-1a and beta-1b) in comparison with the subjects treated with the second-line disease-modifying therapy (natalizumab; fingolimod) and healthy controls without significant differences in C-reactive protein and interleukin-1 beta. A negative correlation was observed between serum NO x level and the duration of multiple sclerosis confirmed in the whole study population and in subjects treated with the first-line agents. Only serum NO x , concentration could reveal a potential efficacy of disease-modifying therapy with a better reduction in NO x level due to the second-line agents of disease-modifying therapy.

Treatment withdrawal in relapsing-remitting multiple sclerosis: a retrospective cohort study.

BACKGROUND: To investigate the effect of drug withdrawal on the course of relapsing-remitting multiple sclerosis (RR-MS). METHODS: An observational cohort retrospective study was performed to compare the time to relapse of patients who discontinued disease-modifying therapy (1a or 1b beta-interferons or glatiramer acetate) with the patients who did not. One hundred and twenty-eight RR-MS patients were investigated using a time-dependent approach. RESULTS: Over a median follow-up of 108 months, 60 patients discontinued treatment and 89 relapses were observed. The time to relapse was shorter in patients who discontinued treatment compared with those who did not (P < 0.001), median times being 31.1 months (95% confidence interval 10.4-50.8) and 85.8 months (95% confidence interval 58.6-106.3), respectively, whilst the baseline covariates (gender, Expanded Disability Status Scale at diagnosis) did not significantly affect the prognosis. CONCLUSIONS: It was found that stopping treatment strongly reduces the time to relapse and this information may be useful in patient management.