Therapeutic benefit of blocking interleukin‐6 activity with an anti–interleukin‐6 receptor monoclonal antibody in rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled, dose‐escalation trial

摘要: Objective To investigate the safety and efficacy of MRA, a recombinant human anti–interleukin-6 (anti–IL-6) receptor monoclonal antibody IgG1 subclass that inhibits function IL-6, in patients with established rheumatoid arthritis (RA). Methods A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted 45 active RA, as defined by American College Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive single intravenous dose either 0.1, 1, 5, or 10 mg/kg MRA placebo. The primary end point meeting ACR 20% response criteria at week 2 after treatment. Results Demographic features similar between treatment groups. At 2, significant difference observed 5 placebo, (55.6%) cohort none placebo achieving improvement. There no statistically other 3 cohorts 2. mean disease activity score those who received 4.8 4.7 (P < 0.001 P analysis variance), respectively. These scores significantly lower than 0.1- 1-mg/kg (6.4, 6.2, 7.0, respectively). erythrocyte sedimentation rate C-reactive protein values fell 5- 10-mg/kg normalized weeks treatment. Seventeen (5, 4, 6, 0 0.1-, 1-, 5-, cohorts, respectively) required corticosteroid disease-modifying antirheumatic drug because before study end. They regarded nonresponders from time they these treatments. Diarrhea most common adverse event, occurring 8% patients. Seven (15.6%) reported severe event (3, cohorts). serious events thought be related drug. Conclusion This is first randomized controlled showing inhibition IL-6 improved signs symptoms RA acute-phase reactants. Further research multiple dosing necessary define appropriate therapeutic regimen RA.