Poster Abstracts
`
`0493
`Pharmacokinetics of oval ladvibine (Mlylinax®) after administration
`in patients with multiple sclerosis
`
`Munafo, A}, Tran, D?, Marcus, Ss, Ammoury, N1. ?Serono
`International SA, Geneva, Switzerland: “Bourn Hall Clinic, Cambridge,
`UK; hax Corp dnc, Miami, USA
`Background: Intravenous (IV) cladnbine produces clinical benefits m
`multiple sclerosis (MS) patients. Since oral administration would have
`advantages over the IV route, the bioavailability and pharmacokinetics
`of an oral cladribine formulation were assessed.
`Method: In a randomized 3-way crossover manner, 26 confirmed MS
`paticnts (mean age 44.1 years, moan weight 72 kg) cach reecived
`3 single fixed cladribine doses separated by >5 days: 3mg and 10mg
`orally
`(Mylnax-Serono/Ivax),
`and 3mg
`by
`1-h
`ITV
`infusion
`(Leustatin®-Janssen-Cilag). Blood samples were obtained before
`administration and repeatedly over 1 day thereatter. Plasma concen-
`trations were measured by HPLC/MS.
`Results: Achieved ().5-U.¢h after oral administration, peak concentra-
`tion (Cmax) 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-pgjmL and 76690h-pg/mL,
`respectively, and 58528h-pgfwL following TVinfusion. Mean absolure
`hinavailability was 35% and 39% following 3mg and 10mg orally,
`respectively. Vanabilty was well controlled, with a coefficient-of-
`variance of <20% intraspatient and 30-35% inter-patient, on ATIC.
`There was no evidence of chmiecally important pharmacokinetic
`noulinearity afler cual cladribine at emher dose. Tolerabilily was
`good: the only reported adverse events occurred after 3mg orally: a
`mild headache m one patient, moderate headache and vomitmg m a
`second; none were considered. treatmenr-related.
`Conclusion: Oral cladnbine has favourable pharmacckinetic and safety
`profiles following adimiuisiralion of a single dose in MS patients: a
`Phase ITI trial with oral cladnbme is underway.
`0.494
`Influence of Immunomodulatory Therapies on Anti-Myelin-Antibodies
`in Multiple Sclerosis (MIS)
`Khalil, M}, Egg, R', Reindl, M?, Lutterotti, A’, Elling, R!, Gueiss, C’,
`Kuenz, B’, Deisenhammer, F’, Berger, T’. Clinical Department of
`Neurvloyy, Inasbeuck Medical University, Innsbruck, Austria
`Background: Antimyelin antibodies seem to play a role m KKMS
`paticnts. Own previous data suggested an influcnee of interfcoron-beta
`on those antibodies, measured at a single time poimt, in 26] MS
`patients.
`Objectives: This prospective study investigated the influence of disease
`moditying-drugs (DMD) on the antibody response against MOG and
`MBPafter onc year of trcatment.
`Methods: We have analyzed IgG, lgM and |zA serum antibodies
`against MOG and MBP in 49 RRMSpatients receiving various DMT
`(16 Betaferon, 11 Avonex, 6 Rebif, 7 glatiramer acetate, 9 mtravencus
`Inununegobulins) belore aud aller oue year of therapy. 14 RRMS
`patients without DMDserved as controls. None ef the patients had a
`relapse or recerved corticosteroids withm one month before bload
`sampling. FDSS was assessed every three months for
`twa vears,
`relapses had to be confirmed. Anubodies were detected by semiquan-
`lilalive Westerublov.
`Results: We found a significant mfluence of DMD on ant-MBP IgM
`antibodies after one year of treatment (p = 0.035). The change of the
`elapse rate after
`twa years of
`treatment with DMD differed
`significantly im patients posinve for anti-MBP IgM antibodies
`compared to anti-MRP TgM negative patients measured at month 12
`af treatment (p = 0.002).
`Couclusion: MBP is quantitatively the major myelin proteim. Antibody
`responses to this antigen might reflect the extent of mflammation and
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`Tuesday, November 8, 2005
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`$225
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`tissue destruction in MS patients. Although number of patients and
`the follow mp periad have to he extended we suggest that anri MRP
`antibodies may serve as a biomarker for momtermg mdirectly the
`effecliveness of DMD.
`
`0495
`The cyitical vole of pro- and anti-apoptotic mediators in patients with
`multiple sclerosis
`Fl Beshlawy, W.F', Abd Allah, M’, [lawas, $°, Ghoname, N.F.
`!Newropsychiatry; “Clinical Pathulogy; *Micrubiology Tanta University,
`and Medical Fnmunology Mansoura University, Egypt
`Background: Multiple sclerosis
`(MS)
`is a chronic neurological
`disorder characterized by myelin destruction and a variable degree of
`oligodendrocyte death. Programmed ccll death (apoptosis) is critical
`for the normal development and homeostasis of the immune system.
`Apoptosis of autoreactive T cells in the CNS is likely to be important
`in preventing the development of MS. CD95/CD9SL imteraction
`results m activation-mduced apoptosis and their abnormal expression
`together with NF-kB and Bel-2 may be involved im the pathogencsis
`and the climcal course of MS.
`Aim: To study the role of pro- and anti-apoptotic mediators in MS
`patients.
`Methods: we studied the level aud expression of Fas, Fa-L, NF-kB
`and Rel-2 using RT-PCR, morphological changes of apoptosis in
`peripheral blood mononuclearcells, DNA fragmentation m 14 patients
`
`with MS divided into 3 groups, relapsing, remitting and chron
`as
`In addition, a group cf 16 healthy cases served as controls.
`Resulis: we [ound that Fas & Fas-L were siguificautly decreased in
`patients with MS compared with healthy controls. While NF-kB and
`Bel-2 were significantly moreased in patients compared with controls.
`Conclusion: Fas, Fas-1,, “f-kR and. Rel-2 play an importantrele in the
`pathogenesis of MS.
`0496
`Cognitive dysfunctions and fatigue in newly diagnosed multiple
`sclerosis patients and in the early stage of the disease
`Engel, C’, Greim, B', Zettl, UK". ‘University of Rostock, Department
`of Neuralogy, Germany
`Background: Cognitive dysfunctions and fatigue are frequent symp-
`toms im the course of multiple sclerosis (MS). There are some long-
`term studies which show stability or slow progression at any time of
`the course. No study mvestigated cogninve dysfunctions as well as
`fatigue at the time 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. Thetest-battery included
`tests of reasommg, verbal and nonverbal memory, alertness, divided
`and focused attcntion. Tests were applied at diagnosis, a half, onc and
`three years later. l'atizue was measured subjectively by the Modified
`Fatiguc Impact Seale and abjectively by a test of vigilance. Physical
`disability (EDSS) and depression (BDI) were controlled.
`Resulis: Paticuis had au average age of33 years, a mean EDSS-score of
`1.8. 92% suffered from a relapsing-remitting MS. At baseline 50% of
`the patients were cognitively unimpaired, 38% showed mild and 12%
`moderate cognitive deterioration. Patients performed. significantly
`poorer
`than contrals m nonverbal memory and reaction-time.
`Ne differences were found in reasouing aud verbal memory. Three
`years later no improvement m cognitive performance was found.
`Tatigue was reported in 63%at baseline and oneyear later. After three
`years only 47% suffered from it. Throaghont testing the BDT-score
`was significantly correlated with subjective fatigue.
`frequent
`Condusion: Cognitive dysfunctions
`and.
`fatigue were
`symptoms already m newly diagnosed MS patients. After three years
`the coguilive performance as well as the reported fatigue did uot
`increase.
`
`Hopewell EX1072
`Hopewell v. Merck
`IPR2023-00480
`
`Hopewell EX1072
`Hopewell v. Merck
`IPR2023-00480
`
`1
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