One‐year safety and efficacy of ustekinumab and results of dose adjustment after switching from inadequate methotrexate treatment: the TRANSIT randomized trial in moderate‐to‐severe plaque psoriasis. (18th February 2014)

• Record Type: Journal Article
• Authors: Reich, K.; Puig, L.; Paul, C.; Kragballe, K.; Luger, T.; Lambert, J.; Chimenti, S.; Girolomoni, G.; Nicolas, J.‐F.; Rizova, E.; Brunori, M.; Mistry, S.; Bergmans, P.; Barker, J.
• Other Names: Adamski Z. investigator.; Altomare G. investigator.; Aricò M. investigator.; Aste N. investigator.; Aubin F. investigator.; Augustin M. investigator.; Ayala F. investigator.; Bachelez H. investigator.; Baran E. investigator.; Barker J. investigator.; Belinchón I. investigator.; Berbis P. investigator.; Bernengo M.G. investigator.; Bessis D. investigator.; Beylot‐Barry M. investigator.; Bordas Orpinell F.J. investigator.; Burden D. investigator.; Bylaite M. investigator.; Cambazard F. investigator.; Carazo S. investigator.; Carrascosa J.M. investigator.; Carretero G. investigator.; Cerio R. investigator.; Chimenti S. investigator.; David M. investigator.; Duval‐Modeste A.B. investigator.; Eedy D. investigator.; Estebaranz L. investigator.; Filipe P. investigator.; Flytström I. investigator.; Fonseca E. investigator.; Gamanya R. investigator.; Ghislain P.‐D. investigator.; Giannetti A. investigator.; Girolomoni G. investigator.; Gospodinov D. investigator.; Griffiths C. investigator.; Grob J.‐J. investigator.; Guillet G. investigator.; Hernanz Hermosa J.M. investigator.; Hoffmann M. investigator.; Ioannidis D. investigator.; Jacobi A. investigator.; Jemec G. investigator.; Kadurina M. investigator.; Kaszuba K. investigator.; Katsambas A. investigator.; Kemeny L. investigator.; Kerkhof P. investigator.; Kragballe K. investigator.; Kuzmina N. investigator.; Lambert K. investigator.; Lázaro P. investigator.; Lotti T. investigator.; Luger T. investigator.; Matz H. investigator.; Modiano P. investigator.; Moessner R. investigator.; Moreno D. investigator.; Moreno Jímenez J.C. investigator.; Mørk N.J. investigator.; Mrowietz U. investigator.; Murphy R. investigator.; Nicolas J.‐F. investigator.; Nikkels A. investigator.; Oliveira H. investigator.; Ormerod A. investigator.; Ortonne J.‐P. investigator.; Parodi A. investigator.; Pasternack R. investigator.; Paul C. investigator.; Pec J. investigator.; Peserico A. investigator.; Philipp S. investigator.; Piquet L. investigator.; Plantin P. investigator.; Puig L. investigator.; Reich K. investigator.; Reményik E. investigator.; Riedl E. investigator.; Röcken M. investigator.; Rustin M. investigator.; Saari S. investigator.; Saiag P. investigator.; Salmhofer W. investigator.; Schadendorf D. investigator.; Sebastian M. investigator.; Simaljakova M. investigator.; Simon J.C. investigator.; Spirén A. investigator.; Stalder J.‐F. investigator.; Stavrianeas N. investigator.; Sticherling M. investigator.; Ternowitz T. investigator.; Thaci D. investigator.; Thio B. investigator.; Uhlig D. investigator.; Valiukeviciene S. investigator.; Vanaclocha Sebastián F.J. investigator.; Wozel G. investigator.;
• Is Part Of: British journal of dermatology. Volume 170:Number 2(2014:Feb.)
• Page Start: 435
• Page End: 444
• Publication Date: 2014-02-18
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.12643
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: There are limited long‐term, 'real‐world' data on ustekinumab, or the effect of dose adjustment in suboptimal responders. Objectives: We describe 52‐week data from TRANSIT, which initiated ustekinumab by licensed regimen and investigated exploratory dose adjustment. Methods: Patients with moderate‐to‐severe psoriasis and inadequate methotrexate response received ustekinumab, with immediate or gradual methotrexate withdrawal. Outcomes were similar between treatment arms at week 12 (primary endpoint), so week 52 data were pooled. Patients weighing ≤ 100 kg or > 100 kg were administered ustekinumab 45 or 90 mg, respectively. Patients weighing ≤ 100 kg without 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at weeks 28 or 40 received a dose adjustment to 90 mg. The primary analysis used observed data. Results: Overall, 391 and 98 patients received ustekinumab 45 and 90 mg, respectively. Forty‐four patients (9%) discontinued before week 52 (0·4% due to adverse events). At week 52 (in the overall population), 369 patients (83%) achieved a PASI score ≤ 5, and 341 patients (77%) achieved PASI 75; the median PASI score decreased from 15 at baseline to 1·8. At weeks 28 and 40, 84 and 31 patients, respectively, did not achieve PASI 75 and received a dose adjustment; by week 52, 35/82 (43%) and 15/31 (48%) of these patients, respectively, achieved PASI 75 (two discontinued between weeks 28 and 40). Conclusions: Ustekinumab showed sustained 1‐year efficacy and was well tolerated when initially administered according to label. Adjusting the ustekinumab dose to 90 mg may result in clinically meaningful improvement in response in patients weighing ≤ 100 kg with suboptimal initial response. Abstract : What's already known about this topic? The TRANSIT trial showed that ustekinumab was effective within 12 weeks in patients with an inadequate response to methotrexate. There was no difference in the safety profile irrespective of whether methotrexate was withdrawn abruptly or gradually. What does this study add? Ustekinumab showed sustained efficacy after 1 year of treatment according to European label in patients who had experienced inadequate response to methotrexate, and safety was consistent with the known profile of ustekinumab. A Psoriasis Area and Severity Index (PASI) 75 response was achieved at week 52 in 43–48% of patients weighing ≤ 100 kg who underwent dose adjustment from 45 to 90 mg at week 28 or 40 for lack of PASI 75 response at these time points.