A comparative study of the relative bioavailability of different interferon beta preparations

Deisenhammer, Florian; Mayringer, Irmgard; Harvey, Jack; Dilitz, Erika; Gasse, T.; Stadlbauer, Daniel; Reindl, Markus; Berger, Thomas

doi:10.1212/wnl.54.11.2055

Cited by 80 publications

(40 citation statements)

References 18 publications

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“…These markers have been used as indicators of the biologic activity of IFN␤. The relative dose of the different preparations also can be assessed from another recent publication 38 in which antiviral protein (MxA) stimulation was studied in the untreated blood from 10 healthy volunteer subjects. In this study, in vitro stimulation of peripheral blood with all three agents (Avonex, Betaseron, and Rebif) resulted in a dose-dependant increase in MxA levels that was roughly equivalent for each agent on a MIU for MIU basis using the published MIU values.…”

Section: Analysis Of the Evidence Immunomodulatory Treatments Intermentioning

confidence: 99%

Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]

et al. 2002

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Overview. Clinical types of MS.MS is a chronic recurrent inflammatory disorder of the CNS. The disease results in injury to the myelin sheaths, the oligodendrocytes, and, to a lesser extent, the axons and nerve cells themselves. [1][2][3][4][5] The symptoms of MS vary, depending in part on the location of plaques within the CNS. Common symptoms include sensory disturbances in the limbs, optic nerve dysfunction, pyramidal tract dysfunction, bladder or bowel dysfunction, sexual dysfunction, ataxia, and diplopia. 5Four different clinical courses of MS have been defined. 6 The first, relapsing-remitting MS (RRMS), is characterized by self-limited attacks of neurologic dysfunction. These attacks develop acutely, evolving over days to weeks. Over the next several weeks to months, most patients experience a recovery of function that is often (but not always) complete. Between attacks the patient is neurologically and symptomatically stable. The second clinical course, secondary progressive MS (SPMS), begins as RRMS, but at some point the attack rate is reduced and the course becomes characterized by a steady deterioration in function unrelated to acute attacks. The third clinical type, primary progressive MS (PPMS), is characterized by a steady decline in function from the beginning without acute attacks. The fourth type, progressive-relapsing MS (PRMS), also begins with a progressive course although these patients also experience occasional attacks. Outcome measures in MS clinical trials.Evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy. Clearly, the most important therapeutic aim of any disease-modifying treatment of MS is to prevent or postpone long-term disability. However, long-term disability in MS often evolves slowly over many years.1-3 Clinical trials, by contrast, study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy. As a result, it is important to validate any short-term measure by its correlation with the actual patient outcome many years later. For a discussion of these issues, interested readers should consult the full-length assessment on the Neurology Web site at www.neurology.org.Scope of this guideline. The purpose of this assessment is to consider the clinical utility of these disease-modifying agents including the anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are currently available.

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Section: Analysis Of the Evidence Immunomodulatory Treatments Intermentioning

confidence: 99%

Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]

et al. 2002

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“…Of particular concern are Abs that may render the drugs less effective; examples include the development of Abs against factor VIII in hemophiliacs (1,2), calcitonin in patients treated for osteoporosis (3,4), erythropoietin (Epo) 2 in patients undergoing therapy for chronic renal failure (5,6), and IFN-␤ in individuals undergoing treatment for multiple sclerosis (7).…”

mentioning

confidence: 99%

“…However, exceptionally immunogenic products are known to exist, such as IFN-␤ and factor VIII, where as much as 30 -40% of patients develop neutralizing Abs (1,7). Unwanted immune responses against protein drugs can pose safety risks to patients in addition to simply reducing drug potency.…”

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confidence: 99%

Rationally Engineered Therapeutic Proteins with Reduced Immunogenicity

Tangri¹,

Mothé

Eisenbraun³

et al. 2005

The Journal of Immunology

160

169

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Chronic administration of protein therapeutics may elicit unacceptable immune responses to the specific protein. Our hypothesis is that the immunogenicity of protein drugs can be ascribed to a few immunodominant helper T lymphocyte (HTL) epitopes, and that reducing the MHC binding affinity of these HTL epitopes contained within these proteins can generate drugs with lower immunogenicity. To test this hypothesis, we studied the protein therapeutic erythropoietin (Epo). Two regions within Epo, designated Epo 91–120 and Epo 126–155, contained HTL epitopes that were recognized by individuals with numerous HLA-DR types, a property common to immunodominant HTL epitopes. We then engineered analog epitopes with reduced HLA binding affinity. These analog epitopes were associated with reduced in vitro immunogenicity. Two modified forms of Epo containing these substitutions were shown to be bioactive and nonimmunogenic in vitro. These findings support our hypothesis and demonstrate that immunogenicity of protein drugs can be reduced in a systematic and predictable manner.

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“…Diversi studi hanno confrontato l'attività biologica delle preparazioni di INF-β utilizzando marcatori indiretti della sua azione farmacodinamica [20][21][22][23][24]. Si tratta tuttavia di studi che, avendo utilizzato differenti approcci metodologici e standard di riferimento, risultano non sempre comparabili.…”

Section: Discussioneunclassified

“…la proteina antivirale MxA) e di un marcatore aspecifico apparentemente coinvolto nella fisiopatologia della SM (i.e., l'sVCAM: soluble vascular cell adhesion molecule-1) [24]. Tale studio prevedeva, inoltre, il confronto di Rebif ® 22 versus Avonex ® versus Betaferon ® sia dopo stimolazione in vitro di MxA in cellule ematiche di soggetti non trattati, sia tra i livelli plasmatici dei due marcatori dopo somministrazioni ripetute in una coorte di pazienti con SM.…”

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Analisi Costo Minimizzazione delle preparazioni di Interferon Beta per il trattamento della Sclerosi Multipla

Macchia¹,

Russo²,

Caprino³

2004

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SIFEIT, Società italiana per studi di economia ed etica sul farmaco e sugli interventi terapeutici INTRODUZIONELa Sclerosi Multipla (SM) è una patologia neurologica cronico-degenerativa che si caratterizza per la presenza di una progressiva demielinizzazione della sostanza bianca del sistema nervoso centrale [1]. La SM presenta frequentemente un esordio in età giovanile (tra i 20 e i 45 anni), con una maggiore prevalenza tra le donne (2:1) e può assumere diverse modalità di decorso: la forma più comune è quella detta Relasping-Remitting, nella quale a periodi di recrudescenza della malattia (con comparsa di sintomi di deficit neurologico) seguono periodi di totale remissione; tale decorso è presente nel 70% dei pazienti all'esordio della malattia. In circa il 50% dei casi, al decorso relasping-remitting ne segue uno secondariamente progressivo, che si caratterizza per lo sviluppo nel tempo di un progressivo danno neurologico associato a crescenti livelli di ABSTRACTThe multiple sclerosis (MS) is a neurologic disease that is characterized by a progressive demielinization of the white matter of the central nervous system. In the lasts decades, several therapies have been introduced after randomized, double-blind, placebo controlled trials. These trials supported the efficacy of Interferon-beta (INF-β) in reducing relapsing frequency and slowing the progressive disability, mainly in cases affected by relapsing-remitting MS course. In Italy four different preparations of INF-β are available for MS treatment having different INF-β types (i.e., INF-β1a e INF-β1b), different administration schemes, different INF-β doses and ways of administration. Recently, the biological activity of these preparations have been compared using the same assay system against the same INF-β standard. The aim of this study was to carry out a cost-minimization analysis, on the MS treatments in Italy comparing of the available preparations in terms of cost per microgram standardized by the level of biological activity. The economic evaluation has been conducted adopting the hospital perspective. Health resources have been valued considering euro currency during 2004. According to registered treatment protocol, the results showed that the micrograms per week of INF-β standardized by the level of biological activity ranged from 30µg of Avonex ® to 132µg of Rebif44 ® . Under the same levels of biological activity, Rebif44® resulted the INF-β preparation with the lower cost per micrograms (1.95 euro), followed by Rebif ® 22 and Betaferon ® that had a similar cost (2.90 e 2.97 respectively). Avonex ® resulted the INF-β preparation with the highest cost per micrograms (6,37 euro), about three times higher than that of the preparation with the lowest cost. ANALISI ECONOMICAdisabilità. Inoltre in circa il 10% dei casi, soprattutto quando l'esordio avviene in età più avanzata, la malattia può assumere un decorso primariamente progressivo. Solo in una residua percentuale di casi, infine, la malattia può assumere un decorso benigno, che si caratterizz...

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A comparative study of the relative bioavailability of different interferon beta preparations

Abstract: IFNbeta-1b induces higher levels of the above markers of IFNbeta bioactivity than either of the two IFNbeta-1a preparations. Moreover, there is a less striking difference between the two IFNbeta-1a preparations in favor of subcutaneous IFNbeta-1a.

Cited by 80 publications

References 18 publications

Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]

Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]

Rationally Engineered Therapeutic Proteins with Reduced Immunogenicity

Analisi Costo Minimizzazione delle preparazioni di Interferon Beta per il trattamento della Sclerosi Multipla

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