title: Characterising deviation from treat-to-target strategies for early rheumatoid arthritis: the first three years.
abstract: BACKGROUND
  Treat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve outcomes for patients with rheumatoid arthritis (RA). However, successful implementation may be limited by deviations from the protocol. The aim of this study was to determine the prevalence of protocol deviation, explore the reasons and identify subsets of patients in whom treatment protocols are more difficult to follow.
  
  
  METHODS
  In this retrospective cohort study, treatment-naïve patients with RA of less than one year's duration, attending a dedicated early arthritis clinic between 2001 and 2013, were followed for three years from initiation of combination therapy with conventional DMARDs which was subsequently modified according to a T2T protocol. At each clinic visit, whether deviation from the protocol occurred, the type of deviation and the reasons for deviation were assessed. The relationship between protocol deviations and baseline variables was determined using linear regression analysis.
  
  
  RESULTS
  In total, 198 patients contributed 3,654 clinic visits. The prevalence of protocol deviations was 24.5% and deviation in at least at one clinic visit was experienced by 90.4% of patients. The median time to first deviation was 30 weeks. Continuing existing treatment rather than intensifying therapy was the most common type of deviation (59.9%). Patient and physician related factors were the most common reasons for deviation, each accounting for 24.7% of deviations, followed by toxicities (23.3%) and comorbidities (20.0%). The prevalence of protocol deviations was lower among patients who achieved remission after three years (13.1%; 162 deviations out of 1,228 visits) compared with those who were not in remission (30.9%; 523/1692) (P<0.0001). On multivariate analysis, only body mass index (P=0.003) and helplessness score (P=0.04) were independent predictors of protocol deviations although the predictive power of the model was not strong (R2=0.17).
  
  
  CONCLUSIONS
  Deviation from a T2T protocol occurred in one quarter of visits, indicating that applying the T2T approach is feasible in clinical practice. Failure to escalate dose when indicated was commonly encountered, and just under half of the observed deviations were related to either toxicities or comorbidities and were therefore justifiable on clinical grounds.
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, 5001, Australia. nasir.wabe@unisa.edu.au.
authors.forename: Nasir
authors.initials: N
authors.lastname: Wabe
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, 5001, Australia. michael.sorich@flinders.edu.au.|School of Medicine, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia. michael.sorich@flinders.edu.au.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sorich
authors.affiliation: School of Medicine, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia. Mihir.Wechalekar@health.sa.gov.au.|Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. Mihir.Wechalekar@health.sa.gov.au.
authors.forename: Mihir D
authors.initials: MD
authors.lastname: Wechalekar
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. Les.Cleland@health.sa.gov.au.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Cleland
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. Leah.McWilliams@Health.sa.gov.au.
authors.forename: Leah
authors.initials: L
authors.lastname: McWilliams
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. anitatylee@hotmail.com.|Discipline of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia. anitatylee@hotmail.com.
authors.forename: Anita
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. Llewellyn.Spargo@health.sa.gov.au.
authors.forename: Llewellyn
authors.initials: L
authors.lastname: Spargo
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. Robert.Metcalf@health.sa.gov.au.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Metcalf
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. cindy.hall@health.sa.gov.au.
authors.forename: Cindy
authors.initials: C
authors.lastname: Hall
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia. Susanna.Proudman@health.sa.gov.au.|Discipline of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia. Susanna.Proudman@health.sa.gov.au.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, 5001, Australia. Michael.Wiese@unisa.edu.au.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wiese
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D012074:Remission Induction; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents