title: Effect of Adherence to Protocolized Targeted Intensifications of Disease-modifying Antirheumatic Drugs on Treatment Outcomes in Rheumatoid Arthritis: Results from an Australian Early Arthritis Cohort.
abstract: To investigate the association between adherence to treat-to-target (T2T) protocol and disease activity, functional outcomes, and radiographic outcomes in early rheumatoid arthritis (RA).
  
  
  
  Data from a longitudinal cohort of patients with early RA were used. Adherence was determined at each followup visit over 3 years according to predefined criteria. The primary endpoint was remission according to Disease Activity Score in 28 joints (DAS28) and Simplified Disease Activity Index (SDAI) criteria. Functional and radiographic outcomes measured by modified Health Assessment Questionnaire and modified total Sharp score, respectively, were secondary endpoints.
  
  
  
  A total of 198 patients with 3078 clinic visits over 3 years were included in this analysis. After adjusting for relevant variables, although there was no significant association between adherence to T2T and remission rate after 1 year, the associations reached significance after 3 years for both DAS28 (OR 1.71, 95% CI 1.16-2.50; p = 0.006) and SDAI criteria (OR 1.94, 95% CI 1.06-3.56; p = 0.033). After 3 years, adherence was also associated with improvement in physical function (β=0.12, 95% CI 0.06-0.18; p < 0.0001). None of the radiographic outcomes were associated with adherence after either 1 or 3 years, although there was a trend for higher adherence to be associated with less radiographic progression at the end of the study (p = 0.061).
  
  
  
  Increased adherence to T2T was associated with better longterm disease activity and functional outcomes, which suggests that the benefit of a T2T protocol may be enhanced by ensuring adequate adherence.
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia. wabnt001@mymail.unisa.edu.au.
authors.forename: Nasir T
authors.initials: NT
authors.lastname: Wabe
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sorich
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Mihir D
authors.initials: MD
authors.lastname: Wechalekar
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Cleland
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Leah
authors.initials: L
authors.lastname: McWilliams
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Anita T Y
authors.initials: AT
authors.lastname: Lee
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Llewellyn D
authors.initials: LD
authors.lastname: Spargo
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Metcalf
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Cindy
authors.initials: C
authors.lastname: Hall
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.affiliation: From the School of Pharmacy and Medical Sciences, University of South Australia; Sansom Institute for Health Research, University of South Australia; School of Medicine, Flinders University; Department of Rheumatology, Royal Adelaide Hospital; Discipline of Medicine, University of Adelaide, Adelaide, Australia.N.T. Wabe, MPharm, MSc, PhD candidate, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research; M.J. Sorich, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, and School of Medicine, Flinders University; M.D. Wechalekar, MBBS, MD, FRACP, School of Medicine, Flinders University; L.G. Cleland, PhD, Professor, Department of Rheumatology, Royal Adelaide Hospital; L. McWilliams, BN, Associate Clinical Services Coordinator, Department of Rheumatology, Royal Adelaide Hospital; A.T. Lee, MBBS (Hons), FRACP, PhD, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; L.D. Spargo, BSc (Hons), Department of Rheumatology, Royal Adelaide Hospital; R.G. Metcalf, PhD, Department of Rheumatology, Royal Adelaide Hospital; C. Hall, Department of Rheumatology, Royal Adelaide Hospital; S.M. Proudman, MBBS (Hons), FRACP, Associate Professor, Department of Rheumatology, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide; M.D. Wiese, PhD, Associate Professor, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wiese
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001315:Australia; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D008297:Male; D055118:Medication Adherence; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D008727:Methotrexate
keywords: CLINICAL GUIDELINES; PHYSICIAN ADHERENCE; TREAT TO TARGET; TREATMENT PROTOCO