title: Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY).
abstract: OBJECTIVE
  In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy.
  
  
  METHODS
  Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage.
  
  
  RESULTS
  Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively.
  
  
  CONCLUSIONS
  No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.
authors.affiliation: Department of Rheumatology, Cochin Hospital, Paris, France. maxime.dougados@cch.aphp.fr
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Karsten
authors.initials: K
authors.lastname: Kissel
authors.forename: Tom
authors.initials: T
authors.lastname: Sheeran
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: Emilio Martín
authors.initials: EM
authors.lastname: Mola
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Howard
authors.initials: H
authors.lastname: Amital
authors.forename: Federico
authors.initials: F
authors.lastname: Navarro-Sarabia
authors.forename: Antony
authors.initials: A
authors.lastname: Hou
authors.forename: Corrado
authors.initials: C
authors.lastname: Bernasconi
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001799:Blood Sedimentation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011859:Radiography
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate