Hybrid score may provide clearer picture of treatment effect on disease activity in trials of rheumatoid arthritis drugs.
New hybrid score may provide clearer picture of treatment effect on disease activity in trials of rheumatoid arthritis drugs.
Noting that the American College of Rheumatology (ACR) 20%, 50%, and 70% response criteria (ACR20/50/70), European League Against Rheumatism (EULAR) criteria, and Disease Activity Score 28-joint count (DAS28) are effective-yet-limited measures for assessing response to treatment for rheumatoid arthritis (for example, DAS28 “does not give an indication of the proportion of patients who improve with treatment,” whereas ACR20/50/70 and EULAR “may not be as sensitive to change as continuous measures of improvement”), the authors of this study evaluated the usefulness of the recently approved ACR hybrid score (which combines “ACR20/50/70 scores with the mean percent change from baseline in all 7 ACR core set components, allowing for detection of smaller differences between active treatments while preserving ACR20/50/70 responses as benchmarks to facilitate standardized reporting”) compared to other RA treatment response measures in assessing the effects of combination treatment with certolizumab pegol plus methotrexate in patients with active RA.
The article based on the study, “American College of Rheumatology Hybrid Analysis of Certolizumab Pegol plus Methotrexate in Patients with Active Rheumatoid Arthritis,” was published in the January 2011 issue of Arthritis Care & Research.
For the study, the authors looked at data from the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID-1) trial, in which patients diagnosed with adult-onset RA received 400 mg certolizumab pegol at baseline and at weeks 2 and 4 (followed by either 200 mg or 400 mg certolizumab pegol every other week for 52 weeks, depending on treatment arm) plus methotrexate, or placebo plus methotrexate for 52 weeks.
End points included ACR20/50/70 response rates and change in DAS28 from baseline.
ACR hybrid score was calculated based on “the mean percent change from baseline across the 7 ACR core set measures for each patient” and “determining whether the patient achieved ACR20, ACR50, or ACR70 responses.” Baseline patient demographics and disease activity were “comparable across treatment groups, with all core set values indicating that patients had high baseline disease activity.”
Data show that certolizumab pegol 200 mg plus methotrexate “conferred significantly greater benefit” than placebo plus methotrexate, based on ACR20 responder rates, ACR hybrid scores, and DAS28 change from baseline. Improvement was observed during week one, increasing through week 12 and maintaining until the conclusion of the study. The certolizumab pegol 400 mg plus methotrexate group experienced similar response rates. ACR20 response rate for the certolizumab pegol 200 mg plus methotrexate group was significantly higher than the placebo plus methotrexate group. Median ACR hybrid scores were also significantly higher.
ACR hybrid scores for the certolizumab pegol 200 mg plus methotrexate group indicated that at least half of the patients had “at least a 20% mean improvement in core set measures at week 1 of treatment.” However, less than half of patients with a mean improvement in core set measures of 20% or more “had a concurrent ACR20 response,” indicating that “the ACR hybrid may be more sensitive than the ACR20 in detecting small improvements, such as those that occurred early on during treatment.”
In their discussion of these results, the authors wrote that “comparison between the ACR hybrid scores and the ACR response rates suggests that the latter measure may underestimate differences between active treatment and placebo.” The ACR hybrid score “also incorporates worsening of disease activity, so it may provide a better assessment of the overall average change in disease activity during the course of a clinical trial.”
Lead author R.F. van Vollenhoven, from the Karolinska Institute in Stockholm, Sweden, said in statement that “The ACR hybrid score suggested similar results to other standard outcome measures, in that certolizumab pegol treated patients had significantly higher improvement in signs and symptoms of RA over placebo,” but what makes these results potentially interesting is that “the ACR hybrid score may represent a more sensitive and accurate measure of RA treatment response than the current accepted standard and could be considered as a valuable primary end point in future clinical trials.”