A randomized double-blind trial of comparative efficacy and safety of Avonex and CinnoVex for treatment of relapsing-remitting multiple sclerosis

Background and aim

Interferon beta is currently the first line treatment of relapsing-remitting multiple sclerosis (RRMS). Different formulations of interferon beta are available. Avonex and CinnoVex are two interferon beta-1a being prescribed by neurologists in Iran. The aim of this study was to compare the four and half year outcome of Avonex and CinnoVex in patients with RRMS.

Methods

A total 186 of patients with definite RRMS diagnosis were followed for four and half years. Patients were randomly assigned to receive either Avonex or CinnoVex. Patients were subsequently visited every 6 months, and MRI was also undertaken prior each visit. The efficacy end points were to compare mean scores of expanded disability status scale (EDSS) and the proportion of patients with MRI and clinical activity in follow-up visits between Avonex and CinnoVex. Safety end point was to compare the percentage of adverse events between two groups.

Results

One hundred and eighty-two patients completed the study. The population of study experienced a steady increase in EDSS during follow-up with a mean increase of 1.03. Repeated measures ANOVA revealed no statistically significant difference between Avonex and CinnoVex (p?=?0.78). The most common adverse events were headache, myalgia, fatigue, fever, flu symptoms, injection site pain, and depression. Direct comparison of each adverse events revealed no meaningful difference between two groups except for only a few adverse events. There was no statistically significant difference in MRI activity and clinical activity between two groups.

Conclusion

Avonex and CinnoVex showed similar efficacy and safety outcome in patients with RRMS.

     

Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: a prospective, 6-month observational study

In this study, the tolerability and safety of treatment with pulsed steroids and glatiramer acetate and the occurrence of clinical and radiological activity after natalizumab (NTZ) cessation in multiple sclerosis (MS) patients were assessed. MS patients with NTZ were discontinued after 2 years of treatment, or if adverse events or disease progressed during NTZ. They were offered as alternative treatment 1 g methylprednisolone per month during 3 months followed by daily 20 mcg glatiramer acetate and were prospectively studied. Adverse events, occurrence of immune reconstitution inflammatory syndrome, clinical exacerbations, and gadolinium-enhancing lesions in MRI performed at 3 and 6 months after NTZ cessation were recorded. EDSS change during follow-up was also recorded. A total of 18 MS patients entered the study and were followed up for a mean of 10 months (range 6–18 months). There were no significant adverse events. At month 3, no patient had clinical or radiological disease activity. At month 6, 16.6% of patients had had a relapse and 55.5% of patients showed gadolinium-enhancing lesions in the MRI. After 6 months, 33.3% of patients had a further relapse. There was no IRIS, severe relapses, or significant difference between EDSS at NTZ discontinuation and after follow-up. The alternative treatment with monthly prednisolone followed by GA prevents the development of IRIS, but not the return to previous inflammatory activity, which occurs between 5 and 6 months after NTZ withdrawal.     

Efficacy and safety of intravenous thiamylal in pediatric procedural sedation for magnetic resonance imaging

ObjectiveTo evaluate the efficacy and safety of intravenous (i.v.) thiamylal in pediatric magnetic resonance imaging (MRI) sedation.MethodsInfants and children from 1 month up to 8 years of age who underwent MRI in our hospital between April 2017 and March 2019 were included in this prospective observational study. Initial dose of 2 mg/kg thiamylal was given intravenously; however, additional doses were administered as needed. MRI was performed after adequate sedation was achieved. The primary endpoint was the success rate of MRI, while secondary endpoints were adverse events related to sedation, time to sedate, recovery time, and the dose of thiamylal.ResultsA total of 118 patients were included in the analysis with median age and weight of 31.5 months (14.0–56.8 months) and 12.6 kg (9.5–15.7 kg), respectively. The success rate of MRI was 96.6% (114/118), and the median dose of thiamylal per body weight was 3.6 (2.8–4.0) mg/kg. The median time from the first dose of thiamylal to MRI was 7 min (4–10 min) and that from the end of MRI scanning to the confirmation of emergence was 8 min (5–25 min). Adverse events encountered included respiratory arrests (n = 3) and reduction in oxygen saturation (SpO₂; n = 9). There were no significant differences in the age, dose of thiamylal, sex, body weight, the American Society of Anesthesiologists physical status, and neurological abnormalities between the groups with and without respiratory complications.ConclusionThis study demonstrated an adequate efficacy and safety of i.v. thiamylal, with rapid sedation and patient recovery.     

Type I interferons and the quality of life of multiple sclerosis patients. Results from a clinical trial on interferon alfa-2a.

The objective of the study was to examine whether the beneficial effect of treatment of interferon alfa-2a on multiple sclerosis seen by magnetic resonance imaging is reflected in a corresponding improvement in the quality of life (QoL) and to address the impact of adverse events related to this treatment on the QoL. The study was a randomised double-blinded placebo-controlled treatment trial including 97 relapsing-remitting multiple sclerosis patients. Thirty-two patients received 4.5 MIU recombinant interferon alfa-2a, 32 patients received 9.0 MIU recombinant interferon alfa-2a and 33 patients received placebo treatment for 6 months. All patients were followed up 6 months after end of treatment. QoL was assessed according to the eight scales of the SF-36 Health Survey and measured at baseline, month 3, 6 and 12. The effect found on MRI was not reflected in a corresponding change in the QoL. We found a relationship between the presence of new enhancing lesions and reduced QoL among the placebo patients, whereas this was not found among the patients treated with interferon. The presence of the adverse events fatigue, myalgia, headache and weakness were significantly negatively correlated to several of the QoL dimensions. Conclusively, the treatment with interferon alfa-2a does not seem to improve the patients' QoL after 6 months of treatment, in spite of a marked effect measured by MRI. The treatment is followed by adverse events that negatively affected the QoL.     

Non-vision adverse events with vigabatrin therapy

Vigabatrin is an effective antiepileptic drug (AED) for the treatment of refractory complex partial seizures (rCPS) and infantile spasms (IS). In clinical trials, vigabatrin was generally well-tolerated with an adverse event profile similar to that of other AEDs. The most common treatment-related adverse events were central nervous system effects, including drowsiness, dizziness, headache, and fatigue, with adjunctive vigabatrin in adults with rCPS, and sedation, somnolence, and irritability with vigabatrin monotherapy in infants with IS. Vigabatrin had little effect on cognitive function, mood, or behavior in a battery of neuropsychologic tests for rCPS. In placebo-controlled clinical trials, the incidence of depression and psychosis, but not other psychiatric adverse events, was greater with vigabatrin than placebo. Intramyelinic edema (IME) was initially identified in rats and dogs and led to a temporary suspension of clinical trials in the United States. IME was subsequently correlated with delays in evoked potential (EP) and increased T(2) -weighted signals on magnetic resonance imaging (MRI). Clinical trials of vigabatrin were allowed to resume after IME was not detected by neuropathologic assessments of autopsy and neurosurgical specimens or by serial EP or MRI assessments in older children and adults receiving vigabatrin. Subsequently, MRI abnormalities characterized by increased T(2) intensity and restricted diffusion were identified in infants treated with vigabatrin for IS. These abnormalities generally resolved with discontinuation of vigabatrin and, in some cases, during continued therapy. The benefit of improved seizure control must be balanced against the potential risks associated with vigabatrin, including abnormal MRI changes and other vigabatrin-related safety issues.     

The role of hippocampal sclerosis in antiepileptic drug-related depression in patients with epilepsy: a study on levetiracetam.

OBJECTIVE: Hippocampal sclerosis (HS) has been described as a relevant factor for the development of topiramate-related depression and cognitive deficits. The aim of our study was to clarify whether patients with temporal lobe epilepsy (TLE) and HS were also at risk during therapy with levetiracetam (LEV). METHODS: Data of 156 patients was analysed: 78 with TLE and HS and 78 with TLE and normal MRI matched for age, starting dose and titration schedule of LEV. Patients were selected from a population of consecutive patients started on LEV between 2000 and 2002. RESULTS: No differences were observed in prevalence of cognitive adverse events and depression between the two groups. CONCLUSIONS: LEV treatment is not associated with cognitive adverse events and depression in patients with hippocampal sclerosis.     

曲唑酮与地西泮治疗焦虑性神经症的疗效对照研究

目的 评价曲唑酮治疗焦虑性神经症的疗效和副反应。方法 对５６例焦虑性神经症患者,采用曲唑酮（２８例）地西泮（２８例）进行对照治疗（疗程４例）。采用副反应量表（ＴＥＳＳ）和焦虑自评量表（ＳＡＳ）、焦虑量表（ＨＡＤＭ）评定疗效和副反应。结果 曲唑酮与地西泮的疗效相近（Ｐ〉０．０５）。治疗第４周末ＳＡＳ、ＨＡＭＡ及ＨＡＭＡ因子分的减分率两组差异有非常显著性（Ｐ〈０．０１）。副反应两药相似。曲唑酮的主要副反应为困倦和嗜睡。结论 曲唑酮治疗焦虑性神经症有效,副反应轻微。     

Misidentification of vagus nerve stimulator for intravenous access and other major adverse events

The vagus nerve stimulator has become a standard modality for intractable pediatric epilepsy. We reviewed our experience with major adverse events, after accidental puncture of a stimulator wire by an emergency room physician seeking intravenous access to treat status epilepticus. The Children's National Medical Center database was reviewed for patients undergoing vagus nerve stimulator placement between January 1988 and June 2006. Patient characteristics, duration of therapy, and treatment-limiting adverse events were noted. Of 62 patients implanted over 8 years, 22 (35%) had adverse events which led to a change in therapy. Adverse events included prominent drooling, coughing, throat discomfort, dysphagia, wound infection, difficulty breathing, vomiting, vocal-cord weakness, lead failure, and iatrogenic (piercing of wire; surgical clipping of wire during revision). Eight patients required nonroutine surgical intervention (13%). There were two unusual case presentations. In a 13-year-old boy with status epilepticus at an outlying emergency department, the stimulator line was pierced in search of intravenous access. In a 25-year-old housepainter, neck paresthesias upon right lateral neck turning were attributed to insufficient strain relief. Treatment-limiting adverse events occurred in approximately one-third of patients. Unanticipated adverse events included misidentification of the wire for intravenous access, clipping of the wire during surgical dissection, and cervical dysesthesias associated with head-turning.     

Ingested IFN-alpha: results of a pilot study in relapsing-remitting MS

OBJECTIVE: To investigate whether ingested human recombinant interferon-alpha2a (IFN-alpha2a) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS (RRMS). METHODS: Entry criteria included clinically definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI. RESULTS: Of 80 patients screened, 33 were eligible and 30 patients were enrolled for treatment. Patients were randomized (10 per group) to placebo, 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months. They were examined clinically and with monthly cerebral MRI. Sample size projections were based on the assumption of a parenteral IFN-like effect, a 90% reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable. RESULTS: There was no significant effect on enhancing lesions. However, post hoc analysis suggested a possible treatment effect in the 10,000 IU group. By direct monthly comparison of placebo and 10,000 IU group in treatment month 5, there were 73% (p < 0.05) fewer enhancements in the 10,000 IU group than in the placebo group. There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies. CONCLUSIONS: This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.     

Moclobemide and fluoxetine for panic disorder

An international, multicentre, double blind parallel group study compared the tolerability and efficacy of moclobemide with the selective serotonin reuptake inhibitor (SSRI) fluoxetine for panic disorder. SSRIs have been shown effective for panic. The target dose of moclobemide was 450 mg and of fluoxetine was 20 mg. There were two consecutive studies. An eight week study of acute adverse events, tolerability and efficacy was followed by a long-term extension study to 1 year. The efficacy data showed no significant difference between moclobemide and fluoxetine. Both had acute efficacy, with 63 % moclobemide and 70 % fluoxetine patients (ns) panic free at 8 weeks. Both agents were well tolerated to 8 weeks, but noclobemide had fewer severe adverse events (5) that fluoxetine (9). There were no severe adverse events in the extension phase with either drug, and almost all patients completing 1 year extension treatment (moclobemide 61 patients, fluoxetine 65) were much or very much improved. These data suggest moclobemide and fluoxetine are tolerated and effective for both acute panic treatment and maintenance therapy.     

锁骨下动脉闭塞血管内开通评估量表初步应用研究

目的研究锁骨下动脉闭塞血管内开通评估量表(Accept量表)在临床上的应用价值。方法将本院经全脑血管造影确诊的锁骨下动脉闭塞患者59例,基于Accept量表分为Ⅰ级患者、Ⅱ级患者和Ⅲ级患者。比较各组患者手术成功率和手术不良事件发生率。结果本研究中手术成功43例(72.9%)。根据Accept量表评分,所有患者分为三组:Ⅰ级17例,Ⅱ级30例,Ⅲ级12例。Ⅰ级患者手术成功率(100%)明显高于Ⅱ级患者(76.7%)和Ⅲ级患者(25%),且Ⅱ级患者手术成功率亦明显高于Ⅲ级患者(均P0.05)。Ⅰ级患者中15例顺向开通,2例双向开通;Ⅱ级患者中5例顺向开通,18例双向开通;Ⅲ级患者3例双向开通。59例患者总共发生15次(25.4%)手术不良事件;其中Ⅰ级患者不良事件发生率为5.9%;Ⅱ级患者不良事件发生率为23.3%;Ⅲ级患者手术不良事件发生率为58.3%,显著高于Ⅰ级患者(P0.05)。结论应用Accept量表评估锁骨下动脉闭塞血管内开通术证明具有可行性和可靠性,有助于临床医师快速做出临床决策,具有一定的临床应用价值。     

Disease-modifying effects of edasalonexent,an NF-κB inhibitor,in young boys with Duchenne muscular dystrophy: Results of the MoveDMD phase 2 and open label extension trial

Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy. Edasalonexent (CAT-1004) is an orally-administered novel small molecule that covalently links two bioactive compounds (salicylic acid and docosahexaenoic acid) that inhibit NF-κB. This placebo-controlled, proof-of-concept phase 2 study with open-label extension in boys ≥4-<8 years old with any dystrophin mutation examined the effect of edasalonexent (67 or 100 mg/kg/day) compared to placebo or off-treatment control. Endpoints were safety/tolerability, change from baseline in MRI T₂ relaxation time of lower leg muscles and functional assessment, as well as pharmacodynamics and biomarkers. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly of the gastrointestinal system (primarily diarrhea). There were no serious adverse events in the edasalonexent groups. Edasalonexent 100 mg/kg was associated with slowing of disease progression and preservation of muscle function compared to an off-treatment control period, with decrease in levels of NF-κB-regulated genes and improvements in biomarkers of muscle health and inflammation. These results support investigating edasalonexent in future trials and have informed the design of the edasalonexent phase 3 clinical trial in boys with Duchenne.     

A pilot trial of combination therapy with mitoxantrone and interferon beta-1b using monthly gadolinium-enhanced magnetic resonance imaging

OBJECTIVE: To examine the safety of combination therapy with mitoxantrone (MITX) and interferon beta-1b (IFNbeta-1b) in patients with multiple sclerosis (MS) and a high on-therapy relapse rate and enhancing lesions on baseline magnetic resonance imaging (MRI) scan. METHODS: Ten patients with worsening relapsing remitting or secondary progressive MS were studied using monthly MRI with triple-dose gadolinium contrast. All patients must have been on IFNbeta-1b for at least six months, have at least one enhancing lesion on a screening MRI, at least one relapse on IFNbeta-1b in the six months prior to study entry and be neutralizing antibody negative. Monthly MRI scans using triple dose contrast and a 30-minute delay between contrast administration and scanning were carried out three times over two months to obtain baseline numbers of enhancing lesions each month. At the end of the baseline phase, MITX was administered at 12 mg/m2 (month 3), and 5 mg/m2 at months 4 and 5. Dosing was continued at 5 mg/m2 every third month. Monthly MRI scanning was continued throughout the duration of MITX dosing. The primary outcome measure was the frequency of new enhancing lesions. Secondary outcome measures included relapse rate, and T1 hypointense and T2 lesion burden. RESULTS: Following the addition of MITX to IFNbeta-1b mean enhancing lesion frequency decreased 90% at month 7 (P = 0.008) and enhancing lesion volume decreased by 96% (P = 0.01). Relapse rates decreased 64% (P = 0.004). T2 lesion burden and T1 hypointense lesion burden increased slightly during the baseline phase and decreased following MITX but the difference did not reach statistical significance. There were no serious adverse events on combination therapy and no drop-outs due to toxicity. Total white blood cell count was reduced at 14 days post-MITX infusion but returned to normal levels by day 21. There were no neutropenic fevers and there was no clinically significant elevation of liver function tests. CONCLUSIONS: While the number of patients in this study was small, the results suggest that the combination is safe and well tolerated. Disease activity was substantially reduced following the addition of MITX to IFNbeta-1b.     

Natalizumab in aggressive multiple sclerosis after haematopoietic stem cell transplantation

High-dose cyclophosphamide followed by autologous haematopoietic stem cell transplantation (HDC-AHSCT) is a treatment option for aggressive and refractory multiple sclerosis (MS). Natalizumab is a monoclonal antibody approved for relapsing-remitting (RR) MS unresponsive to immunomodulating drugs. Nothing is known about the use of natalizumab in patients after HDC-AHSCT. We describe five female RR-MS patients with incomplete response to HDC-AHSCT. Natalizumab was then administered with abolition of both MRI and clinical activity. No severe adverse events, in particular opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML), were observed. Our results suggest that the use of natalizumab in aggressive RR-MS after HDC-AHSCT could be effective and safe. The very long-term risk of adverse events due to sequential aggressive immunosuppression has to be established.     

Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials.

OBJECTIVE: Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease (AD) and other dementia. Several clinical trials have not shown efficacy, and there have been concerns about adverse events. The objective of this study was to assess the evidence for efficacy and adverse events of atypicals for people with dementia. METHODS: MEDLINE, the Cochrane Register of Controlled Trials, meetings, presentations, and information obtained from sponsors were used in this study. Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States were studied. Clinical and trials characteristics, outcomes, and adverse events were extracted. Data were checked by a second reviewer. Fifteen trials including 16 contrasts of atypical antipsychotics with placebo met selection criteria: aripiprazole (k = 3), olanzapine (k = 5), quetiapine (k = 3), and risperidone (k = 5). A total of 3,353 patients were randomized to drug and 1,757 to placebo. Standard meta-analysis methods were used to summarize outcomes. RESULTS: Quality of the reporting of trials varied. Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine. Response rates were frequently not reported. There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis. Approximately one-third dropped out without overall differences between drug and placebo. Adverse events were mainly somnolence and urinary tract infection or incontinence across drugs, and extrapyramidal symptoms or abnormal gait with risperidone or olanzapine. Cognitive test scores worsened with drugs. There was no evidence for increased injury, falls, or syncope. There was a significant risk for cerebrovascular events, especially with risperidone; increased risk for death overall was reported elsewhere. CONCLUSIONS: Small statistical effect sizes on symptom rating scales support the evidence for the efficacy of aripiprazole and risperidone. Incomplete reporting restricts estimates of response rates and clinical significance. Dropouts and adverse events further limit effectiveness. Atypicals should be considered within the context of medical need and the efficacy and safety of alternatives. Individual patient meta-analyses are needed to better assess clinical significance and effectiveness.     

Adjunctive therapy of uncontrolled partial seizures with levetiracetam in Australian patients

OBJECTIVE: The goal of the work described here was to explore the efficacy, safety, and tolerability of adjunctive therapy with levetiracetam and associated changes in health-related quality of life in Australian patients with uncontrolled partial seizures. METHODS: A phase IV open-label 16-week clinical trial was undertaken. Patients received adjunctive levetiracetam, adjusted according to clinical response to a final daily dose of 1000-3000 mg. Seizure frequency and adverse events were recorded. A quality-of-life questionnaire (QOLIE-10-P) was administered at the start and end of therapy. RESULTS: The intention-to-treat population (N=152) experienced a median reduction in total seizure frequency of 57.7%. The 50% responder rate was 56.6%, and 12.5% of patients were free of seizures throughout the trial. Adverse events were mostly mild or moderate, leading to discontinuation in 9.9%. The most common adverse events were somnolence, fatigue, headache, and dizziness. Behavioral adverse events occurred in approximately one-quarter of patients, including two-thirds of those who withdrew because of adverse events. There was an improvement in the QOLIE-10-P score. CONCLUSION: Levetiracetam is effective and well tolerated when added to existing therapy in patients with uncontrolled partial seizures.     

Psychological stress and the subsequent appearance of new brain MRI lesions in MS

OBJECTIVE: To examine the relationship between stressful life events and psychological distress, and the subsequent development of gadolinium-enhancing (Gd+) brain lesions. BACKGROUND: It has long been speculated that stressful life events and psychological distress are associated with disease exacerbation in MS. This is the first prospective longitudinal study of the relationship between stressful life events, psychological distress, and disease activity as measured by Gd+ brain MRI. METHODS: Thirty-six patients (mean age, 44.4 years; 22 women, 14 men) with relapsing forms of MS were assessed once every 4 weeks for 28 to 100 weeks. Assessments included Gd+ MRI, the Social Readjustment Rating Scale (SRRS), the Hassles Scale, and the Profile of Mood States. The SRRS was altered in the following manner: 1) three items that confounded with MS were eliminated, 2) endorsed items were rated for intensity, and 3) the scale was divided into three subscales: major negative events, conflict and disruption in routine, and positive life events. Data were analyzed using mixed-effects logistic regression to account for intrasubject correlations. Stress and distress measures were used to predict concurrent and future MRI activity. RESULTS: For the total sample of patients, increased conflict and disruption in routine was followed by increased odds of developing new Gd+ brain lesions 8 weeks later (odds ratio, 1.64; p = 0.00083). There was no strong evidence of a relationship between psychological stress or distress and clinical exacerbation. CONCLUSIONS: These data provide support for the notion that conflict and disruption in routine are related to subsequent disease activity in MS. However, this relationship is not sufficiently robust to predict clinical exacerbations reliably in individual patients.     

Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei.

BACKGROUND: Early life stress (ELS) is linked to adult psychopathology and may contribute to long-term brain alterations, as suggested by studies of women who suffered childhood sexual abuse. We examine whether reported adverse ELS defined as stressful and/or traumatic adverse childhood events (ACEs) is associated with smaller limbic and basal ganglia volumes. METHOD: 265 healthy Australian men and women without psychopathology or brain disorders were studied. ACEs were assessed by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1-weighted MRI. Analyses examined ROI volumetric associations with reported ACEs and DASS scores. RESULTS: Participants with greater than two ACEs had smaller ACC and caudate nuclei than those without ACEs. A significant association between total ACEs and ROI volumes for these structures was observed. Regression analysis also revealed that ELS was more strongly associated than current emotional state (DASS) with these ROI volumes. CONCLUSIONS: Reported ELS is associated with smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The reasons for these brain effects are not entirely clear, but may reflect the influence of early stress and traumatic events on the developing brain.     

Benefits of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: final comparative results of the EVIDENCE trial

The EVIDENCE trial demonstrated that interferon (IFN) beta-1a, 44 mcg subcutaneously (sc) three times weekly (tiw) (Rebif), was significantly more effective than IFN beta-1a, 30 mcg intramuscularly (im) once weekly (qw) (Avonex), in reducing relapses and magnetic resonance imaging (MRI) activity in patients with relapsing-remitting multiple sclerosis at both 24 and 48 weeks of therapy. We now present final comparative data on these patients, showing that the superior efficacy of IFN beta-1a, 44mcg sc tiw, for relapse measures and MRI activity, compared with IFN beta-1a, 30mcg im qw, was sustained for at least 16 months. The development of antibodies to IFN was associated with reduced efficacy on MRI measures and fewer IFN-related adverse events, but did not have an impact on relapse outcomes.