A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis: design and conduct of study and baseline characteristics of patients

Abstract

The design and conduct of a randomized, double-blinded, placebo-controlled, multicenter, phase III study of recombinant interferon beta-1a (IFN-beta-1a) as treatment for exacerbating-remitting MS are described, as are baseline characteristics of the study population. The purpose of the study was to determine if 6.0 x 10(6) IU (30 micrograms) of IFN-beta-1a, administered by weekly intramuscular (i.m.) injections, was effective in delaying the onset of sustained disability. The primary outcome measure was time to onset of treatment failure, defined as a worsening on the Kurtzke Expanded Disability Status Scale (EDSS) of greater than or equal to 1.0 point compared with baseline, persisting for at least 6 months. An intent-to-treat design was used. The primary outcome measure was analyzed using the Mantel-Cox log-rank statistic and Kaplan-Meier survival curves. Secondary outcomes included quantitative measures of upper and lower extremity function, neuropsychological test performance, functional and quality of life assessments and several measures derived from annual brain MRI studies. Entry criteria included prestudy exacerbation rates of at least 0.67 per year and EDSS scores of 1.0-3.5. A total of 301 MS patients were randomly assigned to receive weekly i.m. injections of IFN-beta-1a or placebo. The average age of the study population at entry was 37 years; 92% were Caucasian and 73% were women. The mean prestudy disease duration was 6.5 years, mean prestudy exacerbation rate was 1.2 per year and the mean EDSS score was 2.3. The randomization yielded well-balanced treatment arms. Various aspects of the study are discussed, including: (1) the decision to focus study design on sustained disability; (2) the rationale for the treatment regimen; (3) measures taken to assure the reliability of the primary outcome measure; and (4) a description of the secondary outcome measures.

Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS

“…We used a double-blind, placebo-controlled, randomized design. 12 A total of 301 patients were enrolled at four US sites. Patients had relapsing MS with mild disability (baseline Expanded Disability Status Scale scores (EDSS) 13 from 1.0 through 3.5), and at least two documented clinical relapses in the 3 years prior to study entry.…”

Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes

“…O surto de EM foi definido como o desenvolvimento de novos sinais neurológicos ou piora de sintomas neurológicos prévios, com duração de 48 horas em paciente que estava estável ou melhorando nos últimos 30 dias, ocorrendo na ausência de febre e/ou infecção 9,10 . Para caracterizar um surto o exame neurológico deveria mostrar sinais evidentes de alterações comparadas com exame prévio do paciente, e considerado como exacerbação quando detectava-se incremento de 0,5 ponto no EDSS ou de 1 ponto nas funções cerebelares, piramidais, de tronco cerebral ou visual.…”

“…Pacientes que apresentavam nevralgia de trigêmio e/ou distonia paroxística, com duração mínima de 48 horas, mesmo sem comprometer o escore do EDSS, eram considerados como em surto. Ao contrário não se consideram sintomas de surto alterações sensitivas, inclusive o sinal de Lhermitte, alterações esfincterianas, cognitivas, fadiga ou depressão, sem entretanto acarretar modificações do escore do EDSS, critério adotado por Jacobs e col. 9 . Ocorrendo surto, o paciente era medicado com metilprednisolona, sob a forma de pulsoterapia, seguida ou não de prednisona oral por 3 semanas, mantendo-se o interferon beta.…”

“…11 . Pacientes com mais de dois surtos na vigência do tratamento com interferon eram excluídos do protocolo 9 .…”

Μελέτη Πολυμορφισμών Των Γονιδίων Των Κυτταροκινών Σε Ασθενείς Με Σκλήρυνση Κατά Πλάκας

“…Τα φαρμακευτικά σκευάσματα αφορούν σε δύο ανασυνδυασμένες μορφές IFN-β, την ΙFN-β 1a (Avonex, Rebif) και την IFN-β 1b (Betaferon, Extavia), που έχουν εγκριθεί για την θεραπεία της ΣΚΠ. H IFN-β 1a έχει εγκριθεί για τη RR μορφή της νόσου, καθώς και για τη SP μορφή με συνοδές εξάρσεις ενώ η IFN-β 1b έχει εγκριθεί τόσο για τη RR όσο και για τη SP μορφή , The IFNB Multiple Sclerosis Study Group, 1993, The IFNB Multiple sclerosis Group, 1995, Jacobs LD, 1995, Jacobs LD, 1996, Alam J, 1997, European Study Group on interferon β-1b in secondary progressive MS, 1998, PRISMS Study Group, 1998, Gasperini C, 1998, Munafo A, 1998, Miller DH, 1999, Liu C, 1999, Zhao GJ, 2000. Το Avonex χορηγείται i.m.…”