title: Drug-induced toxicity and patient reported outcomes in rheumatoid arthritis patients following intensive treated-to-target strategy: does ceasing therapy due to toxicity worsen outcomes in long term?
abstract: OBJECTIVE
  While the introduction of the treat-to-target (T2T) strategy has been an important advance in the management of rheumatoid arthritis (RA), the potential for increased toxicity due to use of concurrent drugs could adversely affect patient reported outcomes (PROs). The objective was to determine whether the cessation of therapy due to toxicity affects long-term improvement in PROs in patients treated according to T2T strategy.
  
  
  METHODS
  A total of 149 patients from an inception cohort of early RA were included. The occurrence and severity of toxicity were monitored at each visit over 3 years. PROs studied were function (measured using health assessment questionnaire); pain, fatigue and patient global assessment (PtGA) all assessed using a 100 mm visual analogue scale; helplessness and health-related quality of life (HRQoL). For each PRO, effect of drug withdrawal was measured by comparing mean change in PROs among patients with no/temporary vs. permanent withdrawal. In addition, effects of frequency of drug withdrawals, weeks to withdrawal and number of drugs withdrawn were analysed using linear regression.
  
  
  RESULTS
  After 3 years, 56 (37.4%) patients ceased at least one drug permanently due to toxicity. Patients with no/temporary withdrawal (n = 93) achieved significantly greater improvement in function (mean change = -0.54 vs. -0.31, p = 0.033), pain (mean change = -39.82 vs. -5.02, p = 0.018), fatigue (mean change = -29.14 vs. -14.76, p = 0.015) and PtGA (mean change = -29.64 vs. -17.00, p = 0.018) compared with their counterparts. Higher frequency of withdrawals was associated with lesser improvements in function, pain, fatigue and PtGA, while the number of drugs withdrawn and the weeks to withdrawal had lesser effects. However, the cessation of the drugs due to their toxicity did not have a significant association with HRQoL and helplessness.
  
  
  CONCLUSIONS
  Improvements in function, pain, fatigue and PtGA at 3 years were diminished for patients who ceased drugs due to toxicity while broader measures of HRQoL were not affected.
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Wabe
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.|School of Medicine, Flinders University, Adelaide, SA, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sorich
authors.affiliation: School of Medicine, Flinders University, Adelaide, SA, Australia.|Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.
authors.forename: M D
authors.initials: MD
authors.lastname: Wechalekar
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.|Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: L G
authors.initials: LG
authors.lastname: Cleland
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.
authors.forename: L
authors.initials: L
authors.lastname: McWilliams
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.|Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Spargo
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Metcalf
authors.affiliation: Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.|Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: S 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, Adelaide, SA, Australia.
authors.forename: M D
authors.initials: MD
authors.lastname: Wiese
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D018450:Disease Progression; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013021:South Australia / Q000453:epidemiology; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents