Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study

Abstract

ObjectivesTo evaluate effi cacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to diseasemodifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. Methods The rapid onset and systemic effi cacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. Results The primary effi cacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were signifi cantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Signifi cant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety fi ndings were consistent with the known tocilizumab safety profi le; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively.

Targeting Interleukin-6 in Rheumatoid Arthritis

“…States, who had an inadequate response to DMARDs (DMARDs-IR) [50]. Prior use The RADIATE (Research on Actemra Determining EffIcacy after Anti-TNF FailurEs) study is the only phase III multi-centre placebo-controlled trial which recruited only patients who had previously failed TNF inhibitors (TNF-IR) [6].…”

Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis

“…Cytokines play a crucial role in inflammatory processes, and monoclonal antibodies, blocking the interaction of certain proinflammatory cytokines (e.g., TNF and IL6) with their receptor, provide a substantial benefit to a fraction of RA patients (2)(3)(4). For example, a 50% reduction in American College of Rheumatology parameters (ACR50) has been documented in 35% and 40% of RA patients treated with adalimumab and tocilizumab, respectively (3,5,6).…”

“…For example, a 50% reduction in American College of Rheumatology parameters (ACR50) has been documented in 35% and 40% of RA patients treated with adalimumab and tocilizumab, respectively (3,5,6). Indeed, cytokine-blocking antibodies and antibody-based fusion proteins represent one of the largest sectors of modern pharmaceutical biotechnology.…”

Targeted Therapy and Infections in Rheumatic Diseases

“…При 24-месячном проспективном наблюдении нарастания риска СКИ не отмечено [43]. Тоцилизумаб В ходе РКИ и продолженных открытых исследований частота СКИ, развивавшихся у больных РА при лечении то-цилизумабом (ТЦЗ), колебалась в пределах 4,4-9,0 на 100 па-циенто-лет [44][45][46][47][48][49][50][51] и была аналогичной таковой у больных, получавших иФНОα. При увеличении суточной дозы с 4 до 8 мг/кг вероятность развития СКИ повышалась в 2,33 раза [52].…”