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.

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).

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. CONCLUSION: 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.