Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study.
OBJECTIVE
To assess the 1-year efficacy and safety of a regimen of tocilizumab plus methotrexate or placebo, which was augmented by a treat-to-target strategy from week 24.


METHODS
ACT-RAY was a double-blind, 3-year trial. Adults with active rheumatoid arthritis despite methotrexate were randomised to add tocilizumab to ongoing methotrexate (add-on strategy) or to switch to tocilizumab plus placebo (switch strategy). Tocilizumab 8 mg/kg was administered every 4 weeks. Conventional open-label disease-modifying antirheumatic drugs (DMARDs) other than methotrexate were added at week 24 or later in patients with DAS28>3.2.


RESULTS
556 patients were randomised; 85% completed 52 weeks. The proportion of patients receiving open-label DMARDs was comparable in the add-on (29%) and switch (33%) arms. Overall, week 24 results were maintained or further improved at week 52 in both arms. Some endpoints favoured the add-on strategy. Mean changes in Genant-modified Sharp scores were small; more add-on (92.8%) than switch patients (86.1%) had no radiographic progression. At week 52, comparable numbers of patients had antidrug antibodies (ADAs; 1.5% and 2.2% of add-on and switch patients, respectively) and neutralising ADAs (0.7% and 1.8%). Rates of serious adverse events and serious infections per 100 patient-year (PY) were 11.3 and 4.5 in add-on and 16.8 and 5.5 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3× upper limit of normal were observed in 11% of add-on and 3% of switch patients.


CONCLUSIONS
Despite a trend favouring the add-on strategy, these data suggest that both tocilizumab add-on and switch strategies led to meaningful clinical and radiographic responses.
Rheumatology B Department, Paris-Descartes University, Cochin Hospital, , Paris, France.
Maxime
M
Dougados
Karsten
K
Kissel
Philip G
PG
Conaghan
Emilio Martin
EM
Mola
Georg
G
Schett
Roberto
R
Gerli
Michael Sejer
MS
Hansen
Howard
H
Amital
Ricardo M
RM
Xavier
Orrin
O
Troum
Corrado
C
Bernasconi
T W J
TW
Huizinga
D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects; D018501:Antirheumatic Agents / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011859:Radiography; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate
DMARDs (biologic); Methotrexate; Rheumatoid Arthritis