Neuropsychological effects of interferon β‐1a in relapsing multiple sclerosis (original) (raw)
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Neuropsychological effects of interferon ?-1a in relapsing multiple sclerosis
Annals of Neurology, 2000
Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon -1a (IFN-1a, 30 g administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFN-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFN-1a group. These results support and extend previous observations of significant beneficial effects of IFN-1a for relapsing MS.
Journal of the neurological sciences, 2014
Multiple sclerosis (MS) is a chronic autoimmune disease that can deteriorate cognitive function in at least 50% of patients even in the early stages. We conducted a three-arm parallel study with balanced randomization to evaluate the effect of various disease-modifying therapies (DMTs) on cognitive function in MS. Ninety newly diagnosed, definite MS subjects referred to Ghaem Medical Center, Mashhad, Iran, were enrolled into this study between 2006 and 2009. They were randomly categorized into three DMT groups; Avonex, Rebif and Betaferon. Cognition status was assessed in MS patients at baseline and 12 months after treatment with DMTs using the 5 tests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). The Symbol Digit Modalities Test scores improved in all groups at 12 month vs. baseline (Avonex: 34.50 vs. 38.95, p=0.011; Rebif: 35.30 vs. 40.13, p=0.001; Betaferon: 26.18 vs. 29.32, p=0.029). The Selective Reminding Test (SRT)-Total, the 10/36-Delay, and the Paced ...
Multiple Sclerosis Journal, 2012
Background: Cognitive dysfunction occurs at the earliest stages of multiple sclerosis (MS), including the stage of clinically isolated syndrome (CIS). Methods: We evaluated the impact of interferon beta-1b (IFNβ-1b) 250 µg on cognitive performance during the CIS stage in the BENEFITstudy. Cognition was assessed by Paced Auditory Serial Addition Test-3” (PASAT-3”) scores. Results: Improvement in PASAT-3” score from baseline to year two was greater for IFNβ-1b treatment than placebo in patients not reaching clinically definite MS (CDMS) by year two. The treatment effect was maintained at year five and was statistically significant. Conclusions: To conclude, early IFNβ-1b treatment had a sustained positive effect on PASAT-3” score over the 5-year BENEFIT study.
Therapeutic advances in neurological disorders, 2009
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 a...
PLoS ONE, 2013
Objective: To assess the effects of subcutaneous (sc) interferon (IFN)-1a on cognition over 5 years in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Patients aged 18-50 years with RRMS (Expanded Disability Status Scale score #4.0) who had completed the 3year COGIMUS study underwent standardized magnetic resonance imaging, neurological examination, and neuropsychological testing at years 4 and 5. Predictors of cognitive impairment at year 5 were identified using multivariate analysis. Results: Of 331 patients who completed the 3-year COGIMUS study, 265 participated in the 2-year extension study, 201 of whom (75.8%; sc IFN b-1a three times weekly: 44 mg, n = 108; 22 mg, n = 93) completed 5 years' follow-up. The proportion of patients with cognitive impairment in the study population overall remained stable between baseline (18.0%) and year 5 (22.6%). The proportion of patients with cognitive impairment also remained stable in both treatment groups between baseline and year 5, and between year 3 and year 5. However, a significantly higher proportion of men than women had cognitive impairment at year 5 (26.5% vs 14.4%, p = 0.046). Treatment with the 22 versus 44 mg dose was predictive of cognitive impairment at year 5 (hazard ratio 0.68; 95% confidence interval 0.48-0.97). Conclusions: This study suggests that sc IFN b-1a dose-dependently stabilizes or delays cognitive impairment over a 5-year period in most patients with mild RRMS. Women seem to be more protected against developing cognitive impairment, which may indicate greater response to therapy or the inherently better prognosis associated with female sex in MS.
Multiple Sclerosis Journal, 2010
The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNb-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score 4.0) were assigned IFNb therapy at the physician's discretion and underwent standardized magnetic resonance imaging, neurological examination and neuropsychological testing at the baseline and regular intervals for up to three years. This analysis included 459 patients who received sc IFNb-1a (44 mcg: n ¼ 236; 22 mcg: n ¼ 223; three-year follow up was available for 318 patients). The hazard ratio for cognitive impairment over three years (44 mcg versus 22 mcg) was 0.68 (95% confidence interval [CI]: 0.480-0.972), suggesting a 32% lower risk with the higher dose treatment. At year 3, the proportion of patients who were cognitively impaired increased slightly from 23.5% at the baseline to 24.8% in the IFNb-1a 22 mcg treatment group, but remained stable at 15.2% in the IFNb-1a 44 mcg treatment group. The proportion of patients with cognitive impairment at year 3 was significantly higher in the 22 mcg group than in the 44 mcg group (P ¼ 0.03), although a trend was also seen at the baseline (P ¼ 0.058). Multivariate logistic regression (corrected for baseline cognitive deficits) indicated that treatment with the higher dose of IFNb-1a was predictive of lower cognitive impairment at three years (odds ratio: 0.51, 95% CI: 0.26-0.99) compared with the lower dose of IFNb-1a. These findings suggest that sc IFNb-1a may have dose-dependent cognitive benefits in mildly disabled patients with RRMS, and may support early initiation of high-dose IFNb-1a treatment.
Cognitive dysfunction in multiple sclerosis: The effect of pharmacological interventions
International Review of Psychiatry, 2010
Research has recently focused on cognitive dysfunction in multiple sclerosis (MS). Cognitive deficits are frequently encountered in patients and account for important impairment in quality of life, therefore posing a major therapeutic challenge for the disease. We presently review studies on cognitive effects of pharmacological treatments in MS. There is evidence for a possible beneficial effect of immunomodulatory treatments, particularly of interferons, and also of acetylcholinesterase inhibitors on cognition in MS, which, however, requires evaluation in larger, multi-centre, longitudinal studies. Methodological issues and future prospects regarding the investigation of this issue are also discussed.
Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis
Neurology, 1997
Article abstract-Background and Objectiue: A phase I11 double-blind, placebo-controlled clinical trial demonstrated that interferon beta-la (IFNP-la) (Avonex, Biogen) significantly delayed progression of disability in relapsing MS patients. The primary clinical outcome was time from study entry until disability progression, defined as 21.0 point worsening from baseline Kurtzke Expanded Disability Status Scale (EDSS) score persisting for at least two consecutive scheduled visits separated by 6 months. The objective of this study was to examine the magnitude of benefit on EDSS and its clinical significance. Methods: Post hoc analyses related to disability outcomes using data collected during the double-blind, placebo-controlled phase I11 clinical trial. Results: (1) Clinical efficacy related to disability did not depend on the definition of disability progression. A significant benefit in favor of IFNP-la was observed when 22.0 point worsening from baseline EDSS was required or when worsening was required t o persist for 21.0 year. (2) Placebo recipients who reached the primary clinical outcome worsened by a larger amount from baseline EDSS than did IFNp-la recipients who reached the primary study outcome. (3) Significantly fewer IFNP-la recipients progressed to EDSS milestones of 4.0 (relatively severe impairment) or 6.0 (unilateral assistance needed to walk). (4) Cox proportional hazards models demonstrated that the only baseline characteristic strongly correlated with longer time to disability progression was IFNP-la treatment. Conclusions: The primary clinical outcome for the IFNP-la clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFNP-la treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.
Background: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. Objective: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. Methods: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsingremitting MS treated with subcutaneous interferon beta-1a. Results: In total, 331 patients completed the study (168 received interferon beta-1a, 44 mg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 mg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low (<30) at all time points. Conclusion: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found.