Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): results from the CanACT study

Abstract

Background: This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA).

Methods: Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events.

Results: A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated.

Conclusions: This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA.

Trial registration: NCT00649545.

Figures

Figure 1

Changes Over Time in the Mean 28-joint Disease Activity Score (DAS28). Mean change (95% confidence intervals [CI]) in DAS28 in patients receiving adalimumab 40 mg administered subcutaneously every other week with concomitant standard antirheumatic therapy. A.) All randomized patients. The mean DAS28 at Weeks 4, 8, and 12 were significantly lower than the mean DAS28 at baseline (P < 0.001). B.) Subgroup analysis of randomized patients on the basis of experience with biological DMARD (BDMARD) therapy. The mean DAS28 at Weeks 8 and 12 was significantly lower in BDMARD-naïve patients than in patients who experienced prior BDMARD therapy (P < 0.05).

Figure 2

Response in American College of Rheumatology (ACR) Criteria Following Adalimumab Treatment. Percentages of patients who met the AC R criteria for 20%, 50%, and 70% improvement (ACR20, ACR50, and ACR70, respectively) with adalimumab 40 mg administered subcutaneously every other week with concomitant standard antirheumatic therapy. A.) All randomized patients. B) Subgroup analysis of randomized patients on the basis of experience with biological DMARD (BDMARD) therapy.