Poster Abstracts
`
`0493
`
`Pharmacokinetics of oval cladvibine (Miylinax®) after administration
`in patienis with multiple sclerosis
`
`Munafo, A’, Tran, D®, Marcus, $3, Ammoury, Ni. /Seronc
`International SA, Geneva, Switzerland; °Bourn Hall Clinic, Cambridge,
`UK; Ftvax Corp fac, Miami, USA
`Background: Intravenous (IV) cladribine produces clinical benefits in
`multiple selorosis OWS) patients. Since oral administration would havs
`advantages over the IV route, the bioavailabiliry and pharmacokinetics
`of an oral cladribine formulation were assessed.
`Method: Tn a. randomized. 2-way crossover manner, 26 confirmed MS
`patients (mean age 44.1] years, mean weight 72 kg) each received
`3 single fixed cladribine doscs separated by >5 days: 3mg and 10mz
`orally
`(Mylnax-Serono/Ivax),
`and 3mg
`by
`1-h
`IV infusion
`‘Leustatin®-Janssen-Cilag). Blood samples were obtained before
`administration and repeatedly over ] day thereafter. Masma concen-
`trations were measured by HPLC/MS.
`Results: Achieved 0.5—-0.6h after oral administration, peak concentra-
`tion (Cyax) averaged (geometric mean) 5608 pg/mL and 21242pg/mL.
`after 3mg and 10mg orally, respectively, compared with 21425pg/mL
`after 1-h TV infusion. Areas under the concentration-time curve (AUC)
`with 3mg and 10mg orally were 20159h-pg/mL and 76690h-pg/mL,
`respectively, and $852&h-pgymL following IV infusion. Mean absolute
`bioavailability was 35% and 34% followmg 3mg and 1Umg orally,
`respectively. Variability was well controlled, with a coefficient-of-
`variance of < 20% imtra-patient and 30-35%imter-patient, on AUC.
`There was uo evidence of clinically imporiau, pharnmacokineuc
`nonlinearity after oral cladribine at either dose. Tolerability was
`good: the only reported adverse events occurred alter 3mg orally: a
`mild headache in one patient, moderate headache and vomiting in a
`second; none were considered treatment-related.
`Conclusion: Oral cladiibine bas favourable pharmacokinetic aud salety
`profiles following administration of a single dose in MS patients: a
`Phase III tnal with oral cladnbine is underway.
`
`0494
`Influence of Immunomodulatory Therapies on Anti-Mlyelin-Antibodies
`in Multiple Sclerosis (MIS)
`
`Khalil, M’, Egg, R’, Reindl, M’, Lutterotti, A’, Ehling, R’, Geiss, C’,
`Kuenz, B', Deisenhammer, F', Berger, T’. ’Cfinical Denartment af
`Neurology, danstruck Medical University, Innsbruck, Ausiriu
`
`Background: Antimyclin antibodics scom to play a role in RRMS
`patients. Qwn previous data suggested an mfluence of mterferon-beta
`on those antibodies, measured at a single time point, in 261 MS
`patients.
`Objectives: This prospective study investigated the fluence of disease
`modifyimng-drugs (DMD) on the antibodyresponse against MOG and
`MBPafter ong year of treatment.
`Methods: We have analyzed IgG, IgM and IgA serum antibodies
`against MOG and MBP in 49 RRMSpatients recerving various DML
`(16 Betaferon, 11 Avonex, 6 Rebif, 7 glatiramer acetate, 9 Intravenous
`immunoglobulins) before and after one year of therapy. 14 RRMS
`patients withoul DMD served as controls. None ol the pauieuts had a
`relapse or received corticosteroids within one month before blood
`sampling. EDSS was assessed every three months for
`two years,
`relapses Lad io be confined. Antibodies were detected by seuuquan-
`titative Westernblet.
`Results: We found a signiticant mfluence of DMD on anti-MBP IgM
`antibodies after one year of treatment (p = 0.035). The change of the
`relapse rate after
`two years of treatment with DMD differed
`significantly im patients positive for anti-MBP [gM antibodies
`comparedto anti-MBP TgM negative parents measured at month 12
`of treatment fp = 0.002).
`Conclusion: MBP is quantitatively the major myelin protem. Antibody
`responses to this antigen might reflect the extent of inflammation and
`
`‘luesday, November 8, 2005
`
`$225
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`tissue destruction in MS patients. Although number of patients and
`the follow up period have ta be extended we suggest that anti MBP
`aulibodies may serve as a biomarker for moutloriug indirectly the
`effectiveness of DMD.
`
`0495
`The critical role of pro- and anti-apoptotic mediators in patients with
`muliiple sclerosis
`
`Fl Beshlawy, W.F', Abd Allah, M?, Hawas, S?, Ghoname, NF.
`Neuropsychiatry; “Clinical Pathology; *Microbiology Tanta University,
`and Medical Immunclogy Mansoura University, Egypt
`Background: Multiple sclerosis
`(MS)
`is a chrome neurological
`disorder characterized by myclin destruction and a variable degree of
`oligodendrocyte death. Programmedcall death (apoptosis) is critical
`for the normal development and homeostasis cf the immune system.
`Apoptosis of autoreactive T cells in the CINS is likely to be important
`in preventing the development of MS. CD95/CD95L interaction
`results in activation-induced apoptosis and their abnormal expression
`together with NI-kB and Bel-2 may be involved m the pathogenesis
`and the clinical course of MS.
`Aim: To study the role of pro- and anti-apoptotic mediators in MS
`patients.
`Methods: we studied the level and expression of Fas, Fa-L, NF-kB
`and Hol-2 using R1-PCR, morphological changes of apoptosis im
`peripheral blood mononuclearcells, DNA fragmentation in 16 patients
`with MS divided into 3 groups, relapsing, remitting and chronic cases.
`Tu addition, a group of 16 healtly cases served as controls.
`Results: we found that Fas & Fas-L were significantly decreased in
`patients with MS compared with healthy contrels. While NF-kB and
`Bel-2 were significantly mereased in patients compared with controls.
`Conclusion: Fas, Fas-L, Nf-kB and Bel-2 play an importantrole in the
`pathogenesis of MS.
`
`0496
`Cognitive dysfunctions and fatigue in newly diagnosed multiple
`sclerosis patients and in the eaxly stage of the disease
`
`Engel, C’, Greim, B’, Zettl, UK". /University of Rostock, Department
`of Newology, Germany
`Backeround: Cognitive dysfunctions and fatigue are frequent symp-
`toms in the course of multiple sclerosis (MS). There are some long-
`term studies which showstability or slow progression at any time of
`the course. No study investigated cognitive dysfunctions a3 well as
`fatigue at the ime of diagnosis.
`Method: The cognitive performance of 50 patients with newly
`diagnosed multiple sclerosis was compared with that of 33 control
`subjects, matched for sex, age and education. The test-battery included
`tests of reasoning, verbal and nonverbal memory, alertness, divided
`and focused attention. Tests were applied at diagnosis, a half, one and
`three years later. Fatigue was measured subjectively by the Modified
`Fatigus Lmpact Scale and objectively by a test of vigilance. Physical
`disability (EDSS) and depression (BDI) were controlled.
`Results: Patients had an average age of 35 years, a mean EDSS-score of
`1.5. 92%sullered (tom a relapsing-renutiug MS. Al baseline 50% of
`the patients were cognitively unimpaired, 38% showed mild and 12%
`moderate cognitive deterioration. Patients performed significantly
`poorer
`than controls in uouverbal memory aud reactiou-lume.
`Wo differences were found in reasoning and verbal memory. Three
`years later no improvement m cogmtive performance was found.
`Fatigue was reported im 63%at baseline and one year later. After three
`years only 47%suffered from it. Throughout testing the BDI-score
`was significantly correlated with subjective fatigue.
`frequent.
`Concinsion: Cognitive dysfunctions
`and
`fatigues were
`symptoms already in newly diagnosed MS patients. After three years
`the cognitive performance as well as the reported fangue did not
`imcrease.
`
`Hopewell EX1072
`Hopewell v. Merck
`IPR2023-00481
`
`Hopewell EX1072
`Hopewell v. Merck
`IPR2023-00481
`
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