title: Efficacy and safety of down-titration versus continuation strategies of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis with low disease activity or in remission: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of down-titration (dose reduction/tapering) strategies compared with continuation of biological disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission.
  
  
  METHODS
  We searched the following electronic database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta-analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down-titration treatment with continuation treatment. Data on flare, defined as a 28-joint Disease Activity Score of ≥3.2, had to have been reported. Outcomes on efficacy or safety were collected.
  
  
  RESULTS
  Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down-titration and continuation groups was similar (risk ratio (RR)=1.14, 95% CI=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR=1.15, 95% CI=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningful difference in efficacy outcomes was observed by continuation treatment.
  
  
  CONCLUSIONS
  Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down-titration therapy, suggesting that a down-titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta-analysis was relatively low, future analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Feifeng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ruyu
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. hopetang@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents