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

Abstract

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.

Keywords: DMARDs (biologic); Methotrexate; Rheumatoid Arthritis.

Figure 1

Patient disposition and study flow chart. ITT, intention-to-treat; MTX, methotrexate; PBO, placebo; TCZ, tocilizumab.

Figure 2

Efficacy results. (A) Percentage of patients receiving additional conventional disease-modifying antirheumatic drugs (DMARDs) between weeks 24 and 52. Results over time for (B) mean DAS28, (C) percentage of patients achieving ACR20, ACR50, ACR70 and ACR90, and (D) mean change from baseline in SJC and TJC. ACR, American College of Rheumatology; DAS28, Disease Activity Score based on 28 joints; DMARD, disease-modifying antirheumatic drug; TJC, tender joint count; SJC, swollen joint count. p values are for week 24 and week 52 intergroup data, respectively.

Figure 3

Radiographic results. (A) Mean change from baseline in total Genant-modified Sharp score (GSS), (B) patients without radiographic progression and (C) cumulative distribution plot of change from baseline to week 52 in total GSS. Area between grey lines is within SDC. GSS ≤1.5; patients without an assessment classified as progressors, p values from Cochran–Mantel–Haenszel χ² tests with strata defined by baseline score quartile and baseline DAS28 ≤ or >5.5; error bars=SE of the mean; baseline annualised progression rate was GSS divided by RA duration. DAS28, Disease Activity Score based on 28 joints; GSS, Genant-modified Sharp score; RA, rheumatoid arthritis. SDC, smallest detectable change.