Juan Zhao1, Wei Zhou1, Yangfeng Wu2, Ping Ji2, Li Yang3, Xiaoyan Yan2, Zhuoli Zhang4. 1. Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, 100034, China. 2. Peking University Clinical Research Institute (PUCRI), Beijing, 100083, China. 3. Peking University School of Public Health, Beijing, 100083, China. 4. Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, 100034, China. zhuoli.zhang@126.com.
Abstract
BACKGROUND:Tumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX. METHODS: It will be a two-stage trial. In the first stage, all RA patients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)]. DISCUSSION: The aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA. Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2 .
RCT Entities:
BACKGROUND:Tumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX. METHODS: It will be a two-stage trial. In the first stage, all RApatients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)]. DISCUSSION: The aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA. Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2 .
Authors: A Migliore; E Bizzi; U Massafra; F Vacca; L S Martin Martin; C Ferlito; E Podesta; M Granata; B Lagana Journal: Int J Immunopathol Pharmacol Date: 2011 Jan-Mar Impact factor: 3.219
Authors: M van den Broek; N B Klarenbeek; L Dirven; D van Schaardenburg; H M J Hulsmans; P J S M Kerstens; T W J Huizinga; B A C Dijkmans; C F Allaart Journal: Ann Rheum Dis Date: 2011-04-24 Impact factor: 19.103
Authors: Amir Hashemi-Meshkini; Shekoufeh Nikfar; Elizabeth Glaser; Ahmadreza Jamshidi; Seyed Alireza Hosseini Journal: Value Health Reg Issues Date: 2015-12-04
Authors: Jonas K Eriksson; Martin Neovius; Johan Bratt; Ingemar F Petersson; Ronald F van Vollenhoven; Pierre Geborek; Sofia Ernestam Journal: JAMA Intern Med Date: 2013-08-12 Impact factor: 21.873
Authors: J R O'Dell; C E Haire; N Erikson; W Drymalski; W Palmer; P J Eckhoff; V Garwood; P Maloley; L W Klassen; S Wees; H Klein; G F Moore Journal: N Engl J Med Date: 1996-05-16 Impact factor: 91.245
Authors: Jonas K Eriksson; Johan A Karlsson; Johan Bratt; Ingemar F Petersson; Ronald F van Vollenhoven; Sofia Ernestam; Pierre Geborek; Martin Neovius Journal: Ann Rheum Dis Date: 2014-04-15 Impact factor: 19.103