title: Association of Improvement in Pain With Therapeutic Response as Determined by Individual Improvement Criteria in Patients With Rheumatoid Arthritis.
abstract: To use statistical methods to establish a threshold for individual response in patient-reported outcomes (PROs) in patients with rheumatoid arthritis.
  
  
  
  We used an analysis of variance model in patients on stable therapy (discovery cohort) to establish critical differences (dcrit) for the minimum change associated with a significant individual patient response (beyond normal variation) in the PRO measures of pain (0-10), fatigue (0-10), and function (Funktionsfragebogen Hannover questionnaire; 0-100). We then evaluated PRO responses in patients initiating adalimumab in a noninterventional study (treatment cohort).
  
  
  
  In the discovery cohort (n = 700), PROs showed excellent long-term retest reliability. The minimum change that exceeded random fluctuation was conservatively determined to be 3 points for pain, 4 points for fatigue, and 16 points for function. In the treatment cohort (n = 2,788), 1,483 patients (53.2%) achieved a significant individual therapeutic response as assessed by Disease Activity Score in 28 joints (DAS28)-dcrit(≥1.8 points) after 12 months of adalimumab treatment; 68.5% of patients with a DAS28-dcritresponse achieved a significant improvement in pain, whereas approximately 40% achieved significant improvements in fatigue or function. Significant improvements in all 3 PROs occurred in 22.7% of patients; 22.8% did not have any significant PRO responses. In contrast, significant improvements in all 3 PROs occurred in only 4.4% of 1,305 patients who did not achieve a DAS28-dcritresponse at month 12, and 59.1% did not achieve any significant PRO responses.
  
  
  
  The establishment of critical differences in PROs distinguishes true responses from random variation and provides insights into appropriate patient management.
authors.affiliation: Schwerpunkt Rheumatologie/Klinische Immunologie Medizinische Klinik und Poliklinik II, Universität Würzburg, Würzburg, Germany.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Scharbatke
authors.affiliation: University Hospital Frankfurt, Goethe University, and Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt am Main, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Behrens
authors.affiliation: Schwerpunkt Rheumatologie/Klinische Immunologie Medizinische Klinik und Poliklinik II, Universität Würzburg, Würzburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmalzing
authors.affiliation: University Hospital Frankfurt, Goethe University, and Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt am Main, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Koehm
authors.affiliation: AbbVie Deutschland GmbH & Co. KG, Wiesbaden, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Greger
authors.affiliation: Abteilung Biostatistik, GKM Gesellschaft für Therapieforschung mbH, München, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Gnann
authors.affiliation: University Hospital Frankfurt, Goethe University, and Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt am Main, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Burkhardt
authors.affiliation: Schwerpunkt Rheumatologie/Klinische Immunologie Medizinische Klinik und Poliklinik II, Universität Würzburg, Würzburg, Germany. Tony_H@ukw.de.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Tony
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015331:Cohort Studies; D004185:Disability Evaluation; D005221:Fatigue / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D000071066:Patient Reported Outcome Measures; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000068879:Adalimumab