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dc.contributor.authorDenton, Christopher P.en_US
dc.contributor.authorMerkel, Peter A.en_US
dc.contributor.authorFurst, Daniel E.en_US
dc.contributor.authorKhanna, Dineshen_US
dc.contributor.authorEmery, Paulen_US
dc.contributor.authorHsu, Vivien M.en_US
dc.contributor.authorSilliman, Nancyen_US
dc.contributor.authorStreisand, Jamesen_US
dc.contributor.authorPowell, Johnen_US
dc.contributor.authorÅkesson, Anitaen_US
dc.contributor.authorCoppock, Johnen_US
dc.contributor.authorHoogen, Frank van denen_US
dc.contributor.authorHerrick, Arianeen_US
dc.contributor.authorMayes, Maureen D.en_US
dc.contributor.authorVeale, Douglasen_US
dc.contributor.authorHaas, Joannaen_US
dc.contributor.authorLedbetter, Stephenen_US
dc.contributor.authorKorn, Joseph H.en_US
dc.contributor.authorBlack, Carol M.en_US
dc.contributor.authorSeibold, James R.en_US
dc.date.accessioned2007-09-20T18:07:00Z
dc.date.available2008-04-03T18:47:58Zen_US
dc.date.issued2007-01en_US
dc.identifier.citationDenton, Christopher P.; Merkel, Peter A.; Furst, Daniel E.; Khanna, Dinesh; Emery, Paul; Hsu, Vivien M.; Silliman, Nancy; Streisand, James; Powell, John; Åkesson, Anita; Coppock, John; Hoogen, Frank van den; Herrick, Ariane; Mayes, Maureen D.; Veale, Douglas; Haas, Joanna; Ledbetter, Stephen; Korn, Joseph H.; Black, Carol M.; Seibold, James R. (2007). "Recombinant human anti–transforming growth factor Β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192." Arthritis & Rheumatism 56(1): 323-333. <http://hdl.handle.net/2027.42/55924>en_US
dc.identifier.issn0004-3591en_US
dc.identifier.issn1529-0131en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/55924
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17195236&dopt=citationen_US
dc.description.abstractObjective To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor Β1 (TGFΒ1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). Methods Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFΒ1 and TGFΒ2. Results Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = −0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). Conclusion We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFΒ1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.en_US
dc.format.extent162817 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.titleRecombinant human anti–transforming growth factor Β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192en_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelGeriatricsen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumRoyal Free Hospital, London, UK ; Boston University School of Medicine, Boston, Massachusetts ; University of California, Los Angeles ; Leeds University, Leeds, UK ; University of Medicine and Dentistry of New Jersey, New Brunswick ; Genzyme, Boston, Massachusetts ; Cambridge Antibody Technology, Cambridge, UK ; Lund University Hospital, Lund, Sweden ; Walsgrave Hospital, Coventry, UK ; University Hospital, Nijmegen, The Netherlands ; Hope Hospital, Salford, UK ; University of Texas Health Science Center at Houston ; St. Vincent's Hospital, Dublin, Ireland ; University of Michigan, Ann Arbor ; Dr. Korn is deceased.en_US
dc.contributor.affiliationumUniversity of Michigan, Ann Arboren_US
dc.contributor.affiliationotherRoyal Free Hospital, London, UK ; Centre for Rheumatology, Royal Free and University College Medical School, Royal Free Hospital, Pond Street, London NW3 2QG, UKen_US
dc.contributor.affiliationotherBoston University School of Medicine, Boston, Massachusettsen_US
dc.contributor.affiliationotherUniversity of California, Los Angelesen_US
dc.contributor.affiliationotherUniversity of California, Los Angelesen_US
dc.contributor.affiliationotherLeeds University, Leeds, UKen_US
dc.contributor.affiliationotherUniversity of Medicine and Dentistry of New Jersey, New Brunswicken_US
dc.contributor.affiliationotherGenzyme, Boston, Massachusetts ; Drs. Silliman, Streisand, Haas, and Ledbetter own stock and/or hold stock options in Genzyme. Dr. Powell owns stock and/or holds stock options in Cambridge Antibody Technology. Dr. van den Hoogen has received consulting fees and/or honoraria (less than $10,000 each) from Abbott and Bristol-Myers Squibb. Dr. Mayes has received consulting fees or honoraria (less than $10,000 each) from Actelion, Encysive, and Novartis.en_US
dc.contributor.affiliationotherGenzyme, Boston, Massachusettsen_US
dc.contributor.affiliationotherCambridge Antibody Technology, Cambridge, UKen_US
dc.contributor.affiliationotherLund University Hospital, Lund, Swedenen_US
dc.contributor.affiliationotherWalsgrave Hospital, Coventry, UKen_US
dc.contributor.affiliationotherUniversity Hospital, Nijmegen, The Netherlandsen_US
dc.contributor.affiliationotherHope Hospital, Salford, UKen_US
dc.contributor.affiliationotherUniversity of Texas Health Science Center at Houstonen_US
dc.contributor.affiliationotherSt. Vincent's Hospital, Dublin, Irelanden_US
dc.contributor.affiliationotherGenzyme, Boston, Massachusettsen_US
dc.contributor.affiliationotherGenzyme, Boston, Massachusettsen_US
dc.contributor.affiliationotherRoyal Free Hospital, London, UKen_US
dc.identifier.pmid17195236en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/55924/1/22289_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/art.22289en_US
dc.identifier.sourceArthritis & Rheumatismen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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