Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study

Abstract

ObjectiveTo 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.MethodsACT-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.Results556 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.ConclusionsDespite 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.

Targeting Interleukin-6 in Rheumatoid Arthritis

“…The radiographic progression was defined as any change in GSS > the smallest detectable change (SDC) computed based on the difference between the x-ray readers. The results showed that the overall radiographic progression was small in both groups although it was statistically significant (add-on therapy versus switch to monotherapy); 8% and 14% respectively [46].…”

“…This was done over a 2 year period in patients who had an inadequate response to methotrexate (MTX-IR). The results are now available at 52 weeks [46]. 556 patients were randomly assigned either to continue methotrexate with the addition of tocilizumab 8 mg/kg 4-weekly or switch to tocilizumab monotherapy.…”

Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial

“…ACT‐RAY was a 3‐year, double‐blind, placebo‐controlled, parallel‐group clinical trial (NCT00810199) 3, 4. Briefly, eligible patients had active RA with DAS28 using the erythrocyte sedimentation rate (ESR) of >4.4 at baseline, and received methotrexate (MTX) for ≥12 weeks, with a stable dosage of ≥15 mg/week.…”

“…Two specific phases of the ACT‐RAY study offer a unique opportunity to investigate relevant aspects of flares: 1) assessment of the flare rate (according to published criteria [2]) between weeks 24 and 52, during which a large patient subgroup received constant treatment 3, 4, and 2) comparison (using sensitivity and specificity) of the flare criteria implicitly used by the investigators with published criteria 2 in the second year, during which patients reaching sustained DAS28 remission discontinued tocilizumab (TCZ) and subsequently other treatments, which were re‐started after investigators diagnosed a disease flare based on their clinical judgment.…”

Is Methotrexate (MTX) Necessary in Combination Therapy with Tocilizumab and MTX for Rheumatoid Arthritis in Remission? Cohort Study Carried by the Michinoku Tocilizumab Study Group

“…The first one was the ACT-RAY study, which reported a comparison between TCZ and TCZ+MTX. The data suggest that both TCZ add-on and switch strategies led to meaningful clinical and radiographic responses, despite a trend favoring the add-on strategy [8]. The second was the SURPRISE study.…”