title: Tocilizumab as monotherapy or combination therapy for treating active rheumatoid arthritis: a meta-analysis of efficacy and safety reported in randomized controlled trials.
abstract: BACKGROUND
  Previous studies in patients with rheumatoid arthritis (RA) have shown that switching to tocilizumab (TCZ) monotherapy (TCZMONO) or combination therapy (TCZCOMBI) with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is efficacious in reducing disease activity in patients with inadequate response to csDMARDs. However, hitherto there is no consensus on whether TCZMONOis as effective as TCZCOMBI. The objective of this study was therefore to evaluate the efficacy and safety of TCZMONOversus add-on TCZCOMBIand both TCZ therapies versus continuing the current csDMARD therapy, by performing a systematic review and meta-analyses.
  
  
  METHODS
  The MEDLINE, EMBASE and CENTRAL databases were searched until February 2016 for relevant randomized controlled trials (RCTs). We performed meta-analyses of Disease Activity Score in 28 joints (DAS28 < 2.6), American College of Rheumatology (ACR) 20/50/70 responses, adverse events (AEs) and serious AEs (SAEs) to compare the three different strategies, whereas a random-effect model was used for pooling relative risks (RR) and 95 % confidence intervals (CI). In addition, sensitivity analyses were performed for evaluating differences in study duration.
  
  
  RESULTS
  In total, 13 RCTs were included in the meta-analysis, involving 6679 patients. When comparing both TCZ strategies, a marginally greater proportion of patients achieving DAS28 < 2.6 (RR 1.21; 95 % CI 1.09, 1.36) and ACR50 response (RR 1.14; 95 % CI 1.03, 1.26) was found in favor of the TCZCOMBIstrategy. However, the risk of SAEs was also significantly higher using this strategy (RR 1.40; 95 % CI 1.03, 1.92, p = 0.03). Pooled effect estimates showed statistical superiority of switching to either TCZ strategy compared to continuing csDMARD therapy.
  
  
  CONCLUSIONS
  In the management of active RA, almost similar efficacy can be expected in patients unable to tolerate csDMARDs, who switch to TCZMONOcompared to inadequate responders switching to add-on TCZCOMBI. Although TCZCOMBIis marginally superior to TCZMONOin achieving DAS28 < 2.6 and ACR50 response, this is at the cost of an increased risk of SAEs.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands. x.m.teitsma@umcutrecht.nl.
authors.forename: Xavier M
authors.initials: XM
authors.lastname: Teitsma
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
authors.forename: Anne Karien A
authors.initials: AK
authors.lastname: Marijnissen
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
authors.forename: Floris P J
authors.initials: FP
authors.lastname: Lafeber
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Jacobs
keywords: Biological; Disease-modifying anti-rheumatic drugs; Interleukin-6; Rheumatoid arthritis; Tocilizumab