Adalimumab in Patients With RA and Over 5 Years of Therapy
Adalimumab in Patients With RA and Over 5 Years of Therapy
Introduction: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise.
Methods: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices. Adverse events (AEs) were tabulated by five time windows after the first ADA injection. Effectiveness measures included achievement of low disease activity (LDA), defined as Simplified Disease Activity Index (SDAI) ≤11, or remission, (REM), defined as SDAI ≤3.3.
Results: Of the 6,610 ReAct patients, 3,435 (52%) continued in ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272 patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious AEs occurred most frequently in the first 6 months and deceased thereafter. Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved by 50% and REM by 21% of patients at last observation.
Conclusions: Results of this large observational study of ADA in routine clinical practice were consistent with controlled trials, with no new safety concerns during a follow-up of more than 5 years. Effectiveness of ADA was maintained during long-term observation.
Patients with rheumatoid arthritis (RA) may not respond to treatment with disease-modifying anti-rheumatic drugs (DMARDs) alone. In patients who have failed DMARD therapy for RA, clinical studies have demonstrated the effectiveness of drugs directed against tumour necrosis factor (TNF) as monotherapy or when used in combination with DMARDs. Adalimumab (ADA) is a fully human anti-TNF monoclonal antibody for the treatment of moderate to severe RA. Initial clinical trials of ADA in patients with RA demonstrated a good safety profile, with improvements in disease signs and symptoms and functional ability, achievement of clinical remission and inhibition of radiographic disease progression.
The Research in Active Rheumatoid Arthritis (ReAct) phase 3b study was initiated in 2002 to assess the safety and effectiveness of ADA in RA patients who had failed treatment with at least one traditional DMARD. ADA was well tolerated and effective, alone or with DMARDs, in 6,610 patients with active RA over a mean treatment duration of 233 days. To evaluate the long-term safety and effectiveness of ADA in clinical practice settings over 5 years in patients who completed ReAct, the REgistry of HUMIRA™ in RA: a Long-Term Investigation of Safety and Efficacy (ReAlise) observational follow-up study was conducted (NCT00234884). The primary objectives of this analysis include examination of adverse events (AEs) and the temporal pattern of their occurrence and maintenance of response through 5 years of ADA treatment (i.e., from the first injection received in ReAct through the last observation in ReAlise).
Abstract and Introduction
Abstract
Introduction: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise.
Methods: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices. Adverse events (AEs) were tabulated by five time windows after the first ADA injection. Effectiveness measures included achievement of low disease activity (LDA), defined as Simplified Disease Activity Index (SDAI) ≤11, or remission, (REM), defined as SDAI ≤3.3.
Results: Of the 6,610 ReAct patients, 3,435 (52%) continued in ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272 patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious AEs occurred most frequently in the first 6 months and deceased thereafter. Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved by 50% and REM by 21% of patients at last observation.
Conclusions: Results of this large observational study of ADA in routine clinical practice were consistent with controlled trials, with no new safety concerns during a follow-up of more than 5 years. Effectiveness of ADA was maintained during long-term observation.
Introduction
Patients with rheumatoid arthritis (RA) may not respond to treatment with disease-modifying anti-rheumatic drugs (DMARDs) alone. In patients who have failed DMARD therapy for RA, clinical studies have demonstrated the effectiveness of drugs directed against tumour necrosis factor (TNF) as monotherapy or when used in combination with DMARDs. Adalimumab (ADA) is a fully human anti-TNF monoclonal antibody for the treatment of moderate to severe RA. Initial clinical trials of ADA in patients with RA demonstrated a good safety profile, with improvements in disease signs and symptoms and functional ability, achievement of clinical remission and inhibition of radiographic disease progression.
The Research in Active Rheumatoid Arthritis (ReAct) phase 3b study was initiated in 2002 to assess the safety and effectiveness of ADA in RA patients who had failed treatment with at least one traditional DMARD. ADA was well tolerated and effective, alone or with DMARDs, in 6,610 patients with active RA over a mean treatment duration of 233 days. To evaluate the long-term safety and effectiveness of ADA in clinical practice settings over 5 years in patients who completed ReAct, the REgistry of HUMIRA™ in RA: a Long-Term Investigation of Safety and Efficacy (ReAlise) observational follow-up study was conducted (NCT00234884). The primary objectives of this analysis include examination of adverse events (AEs) and the temporal pattern of their occurrence and maintenance of response through 5 years of ADA treatment (i.e., from the first injection received in ReAct through the last observation in ReAlise).