EXPIRES
`
`3-SE 1998 BSDS
`mr_ TIPl.E SCLEROSIS
`
`BOSTON SPA
`L 23 780
`
`• C
`
`ART 4
`
`
`
`
`
`
`
`Sawai (IPR2019-00789), Ex. 1044, p. 001
`
`

`

`Multiple
`Sclerosis
`
`Editor-in-Chief:
`Ingrid V Allen Belfast, UK
`
`Co-Editor' for lhe Americas:
`Donald H Silberberg Philadelphia, USA
`
`Co-Etlilor for Asia-Pacific:
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`
`Editorial Board:
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`
`1DP.puty ndilur. Europn
`
`2 Dopuly oclilor. the Americas
`
`~
`STOCKTON
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`Sawai (IPR2019-00789), Ex. 1044, p. 002
`
`

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`Journals now publi hed
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`Sawai (IPR2019-00789), Ex. 1044, p. 003
`
`

`

`98
`E C T R
`MS
`
`I •
`
`: , p c:
`L._ . - ----... -. .... llllllliiill_•_._-__ -
`
`I
`... ,
`
`14th Congress of the European
`Committee for Treatment and Research in Multiple Sclerosis
`Stockholm, Sweden, September 9-12, 1998
`
`Local Organising Committee
`
`ECTRIMS Executive Committee
`
`Hans Link (Chairman)
`Jan Hillert (Scientific Secretary)
`Magnus Andersson
`Moiz Bakhiet
`Sten Fredrikson
`Kristina Gottberg
`Tomas Olsson
`Anders Svenningsson
`
`Ji.irg Kesselring (President)
`Christian Confavreux
`(V ice-President)
`Alan Thompson (Secretary)
`Luigi Amaducci
`Reinhard Hohlfeld
`Chris Pol.man
`Per Soelberg-Sorensen
`
`Congress Secretariat
`
`Congrex Sweden AB
`Attn: ECTRIMS '98
`PO Box 5619
`SE-114 86 Stockholm, Sweden
`Tel: +46-8-459 66 oo
`Fax: +46-8-661 91 25
`E-mail: ms@congrex.se
`
`Congress Home Page
`
`http ://v-.rww.congrex.com/ ectrims98/
`
`Sawai (IPR2019-00789), Ex. 1044, p. 004
`
`

`

`~ CKIDN
`
`Multiple Sclerosis is published by Stockton Press, a division of
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`Slalcmr.nL Whilst Hvery c~fnrl is _modi: to Hnsure Iha! drug dns~.s ,mil ollmr quanl!lics are pri:sentcd accurnlr.ly. renders Arc advisArl lhal new
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`
`Sawai (IPR2019-00789), Ex. 1044, p. 005
`
`

`

`c eros1s
`
`CLINICAL AND LABORATORY RESEARCH
`
`Volume 4 • Number 4 • August 1998
`
`9 September 1998
`DB
`MS Database
`
`10 September 1998
`OR I
`Pathology and Genetics
`Management and euroimaging
`lmmunology
`Neuropathology and Biochemistry of MS
`SI
`New Trends in MS Rehabilitation
`WI
`Update on Neuroimaging
`S2
`Animal models - their Usefulness in MS
`W2
`Poster Se.~ion !
`PI
`ARTI Regulation and Execution of Apoptotic Cell Death
`
`11 September 1998
`OR2
`Immunology
`Treatments
`CSF, other
`The New Immunology of MS
`The MS Clinic: Organisation and Clinical
`Man_agement
`Genetic Susceptibility: How to Proceed?
`CSF in MS
`Poster Session 2
`
`S4
`W4
`P2
`
`S3
`W3
`
`12 September 1998
`S5
`New/Improved MS Treatments
`P3
`Poster Session 3
`S6
`European MS Research al the Tum of the Millennium:
`Strenglhs and Weaknesses
`Author Index
`
`Ab tracl Numbers
`
`Page Numbers
`
`DB1 - DB3
`
`ORIOI-ORI06
`ORI07-0RI 12
`OR I 13-0RI 18
`SIOI-Sl03
`W\OI - Wl05
`S20l-S203
`W201- W203
`PI OOI-PI 142
`ARTIOI
`
`OR201-0R206
`OR207-0R2 I 2
`OR213-0R2 I 7
`S301-S302
`W301-W304
`
`S401
`W401-W403
`P2001 - P2149
`
`S501-S502
`P3001-P3069
`S601-S603
`
`271
`
`272
`274
`276
`278
`279
`281
`282
`284
`322
`
`323
`325
`327
`329
`330
`
`331
`332
`333
`
`373
`374
`393
`
`394
`
`DB - MS Databasees
`OR - Oral Presentation
`S - Major Symposium
`
`W - Educational Workshop
`P - Poster
`ART - State of Che Art Lecture
`
`~
`STOC KTON
`
`TI1e contents page of this journal is now a,·ailable on the
`Internet at: http://www.stockton-press.co.uk
`
`Sawai (IPR2019-00789), Ex. 1044, p. 006
`
`

`

`384
`
`Ectrims 98
`
`P3037
`Monitoring rrcalmffll •ffiriacy with magortic resonance
`imaging (MRI) in an open phase II study with oral fumaric(cid:173)
`acid e.,lers (l"umaderm") in poti.cnu wil.b rtl:ipsing-rcmilliag
`MS(RRMS)
`Meier D. Schimrigk S. Brune N. Hollinann V, Pohlau D, Pr7.untcl
`II, Oepanmcnl
`of Neurology,
`Josef-Hospital
`St.
`Unive!Sil~tskfinilc Bochum. Germany
`Background: MRI has become a powerful in.strurnenl for
`Multiple Sclerosis {MS) trial moni1oring as a surrog,,lc parameter
`of di.scase activity. In this S1udy we pcrfonn multiple MRI in 8
`paticnls with def: KRMS under oral fumaric-acid esters therapy
`ro, a period of 18 week.~
`1aterlab and Mc!hods: For study evnluolion we carry out
`immediate before
`baseline MRI scans 6 ww:eks before and
`1rca1men1. Also in 1he treatment period 12 and 18 weeks after firs!
`dose of study mcdiculion. Each time we perform conventiolllil T, ·
`weighted {TR~)300 ms. 'fl!"'90 ms). triple dose gadolinium(cid:173)
`DTI'/\ enhanced T,-wcighted CTR=800 n~<, TEcl7 m<) and nati,,.,
`T,-wcighlL-d MRI (44 contiguous intc:rlcavcd. 3 mm slices eacli.
`spatial resolut ion less 1han I mm). MRI are aequin:d on a 2 Tc:sb
`Bruker Tomikon scaMer. Image data arc direelly carried over into
`the image processing software. We use cu,,tom-made Image Toor"
`scripts for scrni-outomalcd image data utilisation. Main outcome is
`in
`rhc reduction of the number or ac1ivc
`lesions detected
`gadolinium enhanced T,-wcightcd MRI under 1rea1nienl compaml
`10 b:lreline. In additiorl the 101al lesion loll.d will be measured from
`Tr weigh1ed MRI.
`Results: So Car not all p3.ticn1s hnve finished the study. Our fim
`f\'Suhs urc very ,;n~Quraging, showing a dclinirivc decline of 1h<
`g:,Jolinium enhancing fc:sion number under treatment in each of
`the fir~t four study patients with RRMS indicating a possible
`1n,auncn1 ~rr-.ciacy or oral rumaric-acid esters in rhc rherapy or
`MS.
`
`P3039
`Inhibition ofTNF-« in relapsing MS increases clinical relapses
`
`The Lcncrccp1 MS Study Group, presented by G.S. Francis'
`1Montrc•I Neurological Institute, Montreal, Canada
`
`theoretical concepts and animal
`Background: Based on
`expcrimcnral evidence, there exists support for a role for pro(cid:173)
`infiammarory cytokincs in multiple sclerosis (MS) lesion
`pathogenesis. Administration of compounds 10 counteract pro(cid:173)
`inflammatory cytokines holds promise as tllcrapy in MS. We
`rq>ort the r~llS of blocking TN Fa in relapsing MS.
`
`Methods: 168 definite relapsing MS patients were treated in a 4
`anm {3 doses, I placebo) double-blind study of a recombinant
`rusion protein {TNF receptor JgG fusion protein). Patients
`received monthlydosing(IO mg, SO mg, JOO mg or placebo) for
`up to 48 weeks. Clinical assessments occurred every mon1h
`wltilc MRJ scans with and without gadolinium were perfonned
`al -4, 0, 4. 8, 12, 16, 20 and 24 weeks.
`
`Results: Relapse rate increased in patients taking TNFa inhibitor
`as compared to placebo: annualized relapse rate placebo = .98,
`10 mg = 1.00, SO mg "' 1.64, 100 mg"' 1.47 ()V'.009). A trend
`was also seen for prolonged relapse duration, increased relapse
`severity and incre:is<d MRJ activity wirh lrcatmenL Non(cid:173)
`neutralizing antibodies were seen in almost all trc:itcd patients
`but did not affect relapse frequency.
`
`~onclusion: Although cytokine manipulation holds promise, the
`!mpact of any manipulation may vary depending on the state or
`immune activation being targeted.
`
`P3038
`Dcledion ofalltnd ialracellularTH,· ~nd TH2-typc cytoklae
`produdion or peripheral blood 111ononucle1r cells (PBMCs) in
`palienu wirb relapsiug-remittlag Multiple Sckro,i, (RR :tS)
`oadergoiog •o oral fumaric-acld utu tbenpy
`Brune N, Schimrigk S, Meier D, Jocks M, Hoftin.'.lnn V, POhlau
`D, Przwnek H, Department or Neurology, Sl. Josef-HospitaJ,
`Universitllsldinik Bocbum, Germany
`inflanunatory
`is an
`Background: Multiple Sclerosis {MS)
`dcmyclinating autoimmwic-diSt:asc of the central nervous system.
`Relapses in MS arc assumed to be mediated by a TH,-type
`e)'lokinc proftlc whereas remissions are correlated with a TH2·
`type cytolcine pallem. We investigate the influence of oral
`fumaric..ecid cS1ers (Fun,pdenn•) as a possi'ble treatment for
`patients with RRMS during an open phase 11 prospective study.
`Materials 1111d Mtlhods: We C)(amincd 8 palienlS with defrnitivc
`RRMS. The investigation over 2ll wetk$ is divided into a baseline
`section (6 weeks), a treatment period (18 weeks) and a poSl·sludy
`section (4 weeks). Sevcml times ""' detect intracellular cytokioe
`production of PBMCs by flow c)'lomcuy. Using this technique,
`we measure the percentage of TH, 01.-2, TNF-a, INF-y)-and TH2
`(IL-4, 11..-10, TGF-ll)·lypc cytokines and their modification under
`drug therapy. Additionally we analyze the serum levels or soluble
`intracellular adhesion molecule I (slCAM l) by ELISA.
`RosuJL,: Until now, nol all paticnls finished the complete study.
`find a significant
`Under oral funwic-ac id esters lhctapy Wte
`inercase of TH,-!~ cytokincs regarding 11.-4. IL-IO ond TGF·P
`compan:d lo ba.sclinc. The findings persist during the trClllment
`period and decline nearly to the mscline data at the post study
`KC!iQn, Tiff-a. in,ri:= under lhcfUl)y which is propnbly related
`to the rise orJL-10. The main influence offumaric-acid esters on
`TH,·t)PC cytokines in patients with RRMS give this substance the
`porcncy 10 be n new oral drug therapy rhat could influence disease
`activity in MS.
`
`P3040
`Expanded Di.sability Status Scale (EDSS) dependend course of
`Multiple Sclerosis (MS): influence for clinical trials?
`
`Merke!bach S, Kohler A, MOiier M. Kolmel C, Scbimrigk K
`Department of Neurology, Homburg/Saar, Germany
`
`Background: Clinical trials proofed the efficiacy of modem
`drugs in the treatment of relapsing-remitting MS. Howeyer,
`nearly all trials used different inclusion criteria especially with
`· regard to EDSS limits.
`Patients and methods; We studied the long-term courses of300
`unselected patients (67% women, 33% men; mixed ambulatory
`and hospital series) retrospectively assessing the EDSS and
`calculated lht changes from visit to visit. Mean variation for
`relapsing-remitting patients with EDSS from O to 3.5 (group I)
`was compared 10 patients with EDSS &om O to 6.0 (group ff).
`Results: S6% of the patients were categorized as relapsing·
`remiuing MS (mean age at onset 2&.5 years, mean duration of
`disease 10.1 ys), 25% were secondary progressive (age 30.4 ys.
`duration 17.S ys), 19"/o were prirruuy progrcssive(age 36.6 ys,
`duration 12.8 ys). ln group I patients, the mean EDSS increase
`between consecutive visits was 0.24± 1.21 (mean intuvaU of
`visits I. 74 ys) and was significantly higher as compared to
`group U p1ticn1s with EDSS increase of0.11:1.26 (mean
`intervall 1.S8 ys; p < O.OS for EDSS change).
`Conclusion: Our data confirm the evidence, that results of
`clinical trials such as went of improvement, stability or
`worsening depend on the selection of patients with spccilll
`respect to non-linear EDSS-steps. Thus, for comparison or
`therapeutical efficiency between different trials uniform EDSS
`inclusion criteria arc needed. at least for relapsing-remining MS.
`
`Sawai (IPR2019-00789), Ex. 1044, p. 007
`
`