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Tocilizumab in systemic sclerosis:a randomised, double-blind, placebo-controlled, phase 3 trial
- Source :
- Khanna , D , Lin , C J F , Furst , D E , Goldin , J , Kim , G , Kuwana , M , Allanore , Y , Matucci-Cerinic , M , Distler , O , Shima , Y , van Laar , J M , Spotswood , H , Wagner , B , Siegel , J , Jahreis , A , Denton , C P , Lucero , E , Pons-Estel , B , Rivero , M , Tate , G , Smith , V , De Langhe , E , Rashkov , R , Batalov , A , Goranov , I , Stoilov , R , Dunne , J , Johnson , S R , Pope , J E , Martinović Kaliterna , D , Mogensen , M , Olesen , A B , Henes , J C , Müller-Ladner , U , Riemekasten , G , Skapenko , A , Vlachoyiannopoulos , P , Kiss , E , Minier , T , Beretta , L , Gremese , E , Valentini , G , Asano , Y , Atsumi , T , Ihn , H , Ishii , T , Ishikawa , O , Takahashi , H , Takehara , K , Tanaka , Y , Yamasaki , Y , Bukauskiene , L , Butrimiene , I , Medrano Ramirez , G , Ramos-Remus , C , Sofia Rodriguez Reyna , T , de Vries-Bouwstra , J , van Laar , J M , Batko , B , Jeka , S , Kucharz , E , Majdan , M , Olesinska , M , Smolenska , Z , Alves , J , Santos , M , Mihai , C M , Rednic , S , Castellvi Barranco , I , Lopez Longo , F J , Simeon Aznar , C , Carreira , P , Walker , U A , Derrett-Smith , E , Griffiths , B , McKay , N , Denton , C P , Aelion , J , Borofsky , M , Fleischmann , R , Forstot , J Z , Furst , D E , Kafaja , S , Khan , M F , Kohen , M D , Martin , R W , Mendoza-Ballesteros , F , Nami , A , Pang , S , Rios , G , Simms , R , Sullivan , K M & Steen , V D 2020 , ' Tocilizumab in systemic sclerosis : a randomised, double-blind, placebo-controlled, phase 3 trial ' , The Lancet Respiratory Medicine , vol. 8 , no. 10 , pp. 963-974 .
- Publication Year :
- 2020
-
Abstract
- Background: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis. Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10–35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual. Findings: Between Nov 20, 2015, and Feb 14, 2017, 210 individuals were randomly assigned to receive tocilizumab (n=104) or placebo (n=106). In the intention-to-treat population, least squares mean [LSM] change from baseline to week 48 in mRSS was −6·14 for tocilizumab and −4·41 for placebo (adjusted difference −1·73 [95% CI −3·78 to 0·32]; p=0·10). The shift in distribution of change from baseline in FVC% predicted at week 48 favoured tocilizumab (van Elteren nominal p=0·002 vs placebo), with a difference in LSM of 4·2 (95% CI 2·0–6·4; nominal p=0·0002), as did time to treatment failure (hazard ratio 0·63 [95% CI 0·37–1·06]; nominal p=0·08). Change in LSM from baseline to week 48 in Health Assessment Ques
Details
- Database :
- OAIster
- Journal :
- Khanna , D , Lin , C J F , Furst , D E , Goldin , J , Kim , G , Kuwana , M , Allanore , Y , Matucci-Cerinic , M , Distler , O , Shima , Y , van Laar , J M , Spotswood , H , Wagner , B , Siegel , J , Jahreis , A , Denton , C P , Lucero , E , Pons-Estel , B , Rivero , M , Tate , G , Smith , V , De Langhe , E , Rashkov , R , Batalov , A , Goranov , I , Stoilov , R , Dunne , J , Johnson , S R , Pope , J E , Martinović Kaliterna , D , Mogensen , M , Olesen , A B , Henes , J C , Müller-Ladner , U , Riemekasten , G , Skapenko , A , Vlachoyiannopoulos , P , Kiss , E , Minier , T , Beretta , L , Gremese , E , Valentini , G , Asano , Y , Atsumi , T , Ihn , H , Ishii , T , Ishikawa , O , Takahashi , H , Takehara , K , Tanaka , Y , Yamasaki , Y , Bukauskiene , L , Butrimiene , I , Medrano Ramirez , G , Ramos-Remus , C , Sofia Rodriguez Reyna , T , de Vries-Bouwstra , J , van Laar , J M , Batko , B , Jeka , S , Kucharz , E , Majdan , M , Olesinska , M , Smolenska , Z , Alves , J , Santos , M , Mihai , C M , Rednic , S , Castellvi Barranco , I , Lopez Longo , F J , Simeon Aznar , C , Carreira , P , Walker , U A , Derrett-Smith , E , Griffiths , B , McKay , N , Denton , C P , Aelion , J , Borofsky , M , Fleischmann , R , Forstot , J Z , Furst , D E , Kafaja , S , Khan , M F , Kohen , M D , Martin , R W , Mendoza-Ballesteros , F , Nami , A , Pang , S , Rios , G , Simms , R , Sullivan , K M & Steen , V D 2020 , ' Tocilizumab in systemic sclerosis : a randomised, double-blind, placebo-controlled, phase 3 trial ' , The Lancet Respiratory Medicine , vol. 8 , no. 10 , pp. 963-974 .
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1250231675
- Document Type :
- Electronic Resource