title: The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug.
abstract: BACKGROUND
  Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1% of the UK adult population. Patients suffer considerable pain, stiffness and swelling and can sustain various degrees of joint destruction, deformity, and significant functional decline. In addition, the economic burden due to hospitalisation and loss of employment is considerable, with over 50% of patients being work-disabled within 10 years of diagnosis. Despite several biologic disease modifying anti-rheumatic drugs (bDMARD) now available, there is a lack of data to guide biologic sequencing. In the UK, second-line biologic treatment is restricted to a single option, rituximab. The aim of the SWITCH trial is to establish whether an alternative-mechanism-TNF-inhibitor (TNFi) or abatacept are as effective as rituximab in patients with RA who have failed an initial TNFi drug.
  
  
  METHODS
  SWITCH is a pragmatic, phase IV, multi-centre, parallel-group design, open-label, randomised, controlled trial (RCT) comparing alternative-mechanism-TNFi and abatacept with rituximab in patients with RA who have failed an initial TNFi drug. Participants are randomised in a 1:1:1 ratio to receive alternative mechanism TNFi, (monoclonal antibodies: infliximab, adalimumab, certolizumab or golimumab or the receptor fusion protein, etanercept), abatacept or rituximab during the interventional phase (from randomisation up to week 48). Participants are subsequently followed up to a maximum of 96 weeks, which constitutes the observational phase. The primary objective is to establish whether an alternative-mechanism-TNFi or abatacept are non-inferior to rituximab in terms of disease response at 24 weeks post randomisation. The secondary objectives include the comparison of alternative-mechanism-TNFi and abatacept to rituximab in terms of disease response, quality of life, toxicity, safety and structural and bone density outcomes over a 12-month period (48 weeks) and to evaluate the cost-effectiveness of switching patients to alternative active therapies compared to current practice.
  
  
  CONCLUSIONS
  SWITCH is a well-designed trial in this therapeutic area that aims to develop a rational treatment algorithm to potentially inform personalised treatment regimens (as opposed to switching all patients to only one available (and possibly unsuccessful) therapy), which may lead to long-term improved patient outcomes and gains in population health.
  
  
  BACKGROUND
  UKCRN Portfolio ID: 12343; ISRCTN89222125 ; NCT01295151.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Leeds, LS7 4SA, UK. n.navarrocoy@leeds.ac.uk.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals Trust, Leeds, LS7 4SA, UK. n.navarrocoy@leeds.ac.uk.
authors.forename: Nuria C
authors.initials: NC
authors.lastname: Navarro Coy
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. medsbro@leeds.ac.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brown
authors.affiliation: National Rheumatoid Arthritis Society (NRAS), Maidenhead, Berkshire, SL6 3RT, UK. ailsa@rheumatoid.org.uk.
authors.forename: Ailsa
authors.initials: A
authors.lastname: Bosworth
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. c.l.davies@leeds.ac.uk.
authors.forename: Claire T
authors.initials: CT
authors.lastname: Davies
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Leeds, LS7 4SA, UK. p.emery@leeds.ac.uk.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals Trust, Leeds, LS7 4SA, UK. p.emery@leeds.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. c.c.everett@leeds.ac.uk.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Everett
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. c.fernandez@leeds.ac.uk.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. j.c.gray@leeds.ac.uk.
authors.forename: Janine C
authors.initials: JC
authors.lastname: Gray
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. s.hartley@leeds.ac.uk.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hartley
authors.affiliation: Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, LS2 9LJ, UK. c.t.hulme@leeds.ac.uk.
authors.forename: Claire
authors.initials: C
authors.lastname: Hulme
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Leeds, LS7 4SA, UK. a.keenan@leeds.ac.uk.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals Trust, Leeds, LS7 4SA, UK. a.keenan@leeds.ac.uk.
authors.forename: Anne-Maree
authors.initials: AM
authors.lastname: Keenan
authors.affiliation: University of Alberta, 112 Street NW, Edmonton, Alberta, Canada. mccabe1@ualberta.ca.
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Leeds, LS7 4SA, UK. a.redmond@leeds.ac.uk.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals Trust, Leeds, LS7 4SA, UK. a.redmond@leeds.ac.uk.
authors.forename: Anthony
authors.initials: A
authors.lastname: Redmond
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. c.reynolds@leeds.ac.uk.
authors.forename: Catherine
authors.initials: C
authors.lastname: Reynolds
authors.affiliation: School of Medicine, University of East Anglia, Norfolk, NR4 7QN, UK. david.scott@leeds.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Scott
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK. l.sharples@leeds.ac.uk.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Sharples
authors.affiliation: Centre for Health Sciences Research, Leeds Institute of Health Sciences, University of Leeds, Leeds, LS2 9LJ, UK. s.pavitt@leeds.ac.uk.
authors.forename: Sue
authors.initials: S
authors.lastname: Pavitt
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Leeds, LS7 4SA, UK. m.buch@leeds.ac.uk.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals Trust, Leeds, LS7 4SA, UK. m.buch@leeds.ac.uk.
authors.forename: Maya H
authors.initials: MH
authors.lastname: Buch
mesh_terms: D000069594:Abatacept; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology / Q000627:therapeutic use*; D012107:Research Design; D000069283:Rituximab; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept