title: ROUTINE-a prospective, multicentre, non-interventional, observational study to evaluate the safety and effectiveness of intravenous tocilizumab for the treatment of active rheumatoid arthritis in daily practice in Germany.
abstract: OBJECTIVE
  To evaluate the tolerability, effectiveness and utilization of tocilizumab for the treatment of RA in a usual care setting.
  
  
  METHODS
  ROUTINE was a prospective, non-interventional, observational 52-week study performed at 174 sites throughout Germany. RA patients were selected and treated according to label. Study objectives included the targeted documentation of infections, other adverse events, and various effectiveness outcomes (e.g. DAS28, clinical disease activity). Statistical analyses were performed primarily based on the data as observed.
  
  
  RESULTS
  A total of 850 patients (75% women, mean age: 56 ± 13 years, mean RA duration: 10.3 ± 8.6 years) were enrolled. Most patients (79%) were pretreated with TNF-inhibitors, whereas 21% were pretreated with conventional DMARDs only. Most common DMARD pretreatments were MTX (79%), LEF (68%), adalimumab (53%) and etanercept (50%). At baseline, 60.5% of patients received tocilizumab in combination with any other RA drugs, while 39.5% were treated in monotherapy. Mean baseline DAS28 was 5.5 ± 1.3, and this decreased to 2.6 ± 1.6 at week 52. At week 52, good EULAR response was achieved in 62.3%, low disease activity state in 66.4%, and DAS28 remission in 55.1% of patients (adjusted relative frequencies). 35.3% of patients discontinued the study prematurely; common reasons were lack of effectiveness (10.5%) and intolerability (7.3%). Any infections and severe infections occurred in 37.6% and 7.2% of patients, respectively (N = 836); serious infections were seen in 5.3% (N = 850). Event rates of any, severe and serious infections were 70.3, 9.8 and 4.4 events/100 patient-years, respectively.
  
  
  CONCLUSIONS
  Tocilizumab administered in a real-life setting showed clinically meaningful improvements and a safety profile that was consistent with data reported from pre-approval Phase III studies.
authors.affiliation: Department of Nephrology and Rheumatology, Medicine III, University Clinic Hamburg-Eppendorf, Hamburg, Germany, gerd.burmester@charite.de.
authors.forename: Christof
authors.initials: C
authors.lastname: Iking-Konert
authors.affiliation: Private Practice, Hildesheim, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Hinüber
authors.affiliation: Private Practice, Stuttgart, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Richter
authors.affiliation: Private Practice, Dresden, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schwenke
authors.affiliation: Private Practice, Neuss, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Gürtler
authors.affiliation: Private Practice, Erfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kästner
authors.affiliation: Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
authors.forename: Birgit
authors.initials: B
authors.lastname: Klapperich
authors.affiliation: Roche Pharma AG, Grenzach-Wyhlen, Germany and.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Peters
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D005858:Germany; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: Germany; Interleukin-6; antibodies; biological products; humanized; monoclonal; observational study; rheumatoid arthritis; treatment outcome