EVIDENCE Study Group. Evidence of Interferon Dose-response: Europian North American Compartative Efficacy
Panitch H, Goodin DS, Francis G, Chang P, Coyle PK, O'Connor P, Monaghan E, Li D, Weinshenker B
Neurology 2002 Nov 26;59(10):1496-506
University of British Columbia MS/MRI Research Group; University of Vermont College of Medicine, Burlington, VT 05401, USA
Interferon-beta (IFN-ß) reduces relapses and MRI activity in Relapsing/Remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial.
This randomized, controlled, multicenter trial compared the efficacy and safety of IFN-ß-1a (Rebif) 44 micro g subcutaneously three times weekly (tiw), and IFN-ß-1a (Avonex) 30 micro g IM once weekly (qw) in 677 patients with RRMS.
Assessors blinded to treatment performed Neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks.
After 24 weeks, 74.9% (254/339) of patients receiving IFN-ß-1a 44 micro g tiw remained relapse free compared with 63.3% (214/338) of those given 30 micro g qw.
The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 micro g tiw.
Patients receiving 44 micro g tiw (Rebif) had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 micro g qw (Avonex).
Injection-site reactions were more frequent with 44 micro g tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of Liver Enzymes (18% vs 9%, p = 0.002) and altered Leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 micro g qw dosage.
Neutralizing AntiBodies developed in 25% of 44 micro g tiw patients and in 2% of patients receiving 30 micro g qw.
Rebif (44 micro g subcutaneously tiw) was more effective than Avonex (30 micro g qw) on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.
Interferon-ß And Multiple Sclerosis: Look At The Evidence
Patti F, Reggio A
Int J Clin Pract Suppl 2002 Sep;(131):23-32
Universita di Catania, Centro Sclerosis Multipla, Dipartmento di NeuroScienze, Italy
Recent advances in therapy for Multiple Sclerosis (MS) have centred on the use of the disease-modifying drugs Glatiramer Acetate (GA) and Interferon-beta (Interferon-ß).
Several large-scale clinical trials have been carried out on the use of these compounds, but there have been few studies that have directly compared their efficacy in MS.
Furthermore, there has been controversy and confusion over the IFN-ß therapy regimen that will achieve the best possible clinical outcome for MS patients.
This review focuses principally on clinical trials of IFN-ß-1a, where data that allow direct comparison of different treatment regimens are now available.
Current data indicate that IFN-ß, and in particular IFN-ß-1a, has important advantages over GA in the treatment of Relapsing/Remitting MS (RRMS).
Additionally, IFN-ß-1a (Rebif, Serono), 44 microg administered subcutaneously (s.c.) three times weekly (t.i.w.), is significantly more effective than IFN-ß-1a (Avonex, Biogen), 30 microg administered intramuscularly once weekly.
For optimal management of RRMS, treatment with (Rebif) IFN-ß-1a, 44 microg s.c. t.i.w., should begin as early as possible after diagnosis.
Multiple Sclerosis, Interferon-ß-1b And Depression: A Prospective Investigation
Feinstein A, O'Connor P, Feinstein K
J Neurol 2002 Jul;249(7):815-20
University of Toronto and Sunnybrook and Women's College Health Sciences Centre, Department of Psychiatry, Room FG38, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
PMID# 12140662; UI# 22135904
The objectives were twofold to:
- Explore a possible association between Major Depression and treatment with Interferon-ß-1b in patients with Multiple Sclerosis; and
- Investigate whether putative antecedent risk factors such as a previous Psychiatric history and a family history of affective illness influence the prevalence of Major Depression post-treatment with Interferon-ß-1b.
Forty-two patients with Relapsing/Remitting MS underwent Neurological Examination and were interviewed with the Structured Clinical Interview for Axis 1 DSM-IV Disorders prior to starting Interferon-ß-1b and thereafter at 3, 6 and 12 months.
Ethical considerations dictated that patients diagnosed with Major Depression received anti-depressant medication.
At index assessment, 21.4 % of the sample were diagnosed with a Major Depression, the figures falling to 17.5 %, 11.4 % and 6.3 % at 3, 6 and 12 months respectively. The majority of subjects with a Major Depression had a history of Psychiatric illness prior to treatment with Interferon-ß-1b.
A family history of Affective Disorder was not associated with a significantly increased rate of major depression either before or after treatment with Interferon-ß-1b.
While the study's methodology did not address causality, the data demonstrate that Major Depression post-treatment with Interferon-ß-1b is linked to a history of Psychiatric illness prior to starting treatment.
The threefold decline in prevalence rates for Major Depression over the course of a year demonstrates a good response to AntiDepressant medication and possible beneficial effects of Interferon-ß-1b on mood.
Interferon-ß-1a For Early Multiple Sclerosis: CHAMPS Trial Subgroup Analyzes
Beck RW, Chandler DL, Cole SR, Simon JH, Jacobs LD, Kinkel RP, Selhorst JB, Rose JW, Cooper JA, Rice G, Murray TJ, Sandrock AW
Ann Neurol 2002 Apr;51(4):481-90
CHAMPS Analysis Center, Jaeb Center for Health Research, Tampa, FL 33613, USA
The objective of this work was to assess the effect of Interferon-beta-1a (Avonex) on the rate of development of Clinically Definite Multiple Sclerosis and Brain Magnetic Resonance Imaging changes in subgroups.
Based on type of presenting event, baseline Brain Magnetic Resonance Imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial.
After the onset of a first DeMyelinating event, 383 patients with Brain Magnetic Resonance Imaging evidence of SubClinical DeMyelination were treated with CorticoSteroids and randomly assigned to receive weekly intramuscular injections of 30 microg Interferon-ß-1a or placebo.
The treatment effect within subgroups was assessed in proportional hazards models both for the development of Clinically Definite Multiple Sclerosis and for a combined outcome of development of Clinically Definite Multiple Sclerosis or >1 new or enlarging T2 lesions on Brain Magnetic Resonance Imaging.
A beneficial effect of treatment was noted in all subgroups evaluated.
Adjusted rate ratios for the development of Clinically Definite Multiple Sclerosis in the Optic Neuritis, BrainStem-Cerebellar, and Spinal Cord Syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01).
And, for the development of the combined Clinically Definite Multiple Sclerosis/Magnetic Resonance Imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively.
A treatment benefit on both outcome measures also was seen in subgroups based on baseline Brain Magnetic Resonance Imaging parameters, gender, and age.
Interferon-ß-1a is beneficial when initiated at the first clinical DeMyelinating event (CIS) in patients with Brain Magnetic Resonance Imaging evidence of SubClinical DeMyelination.
The beneficial effect is present for Optic Neuritis, BrainStem-Cerebellar Syndromes, and Spinal Cord Syndromes.