The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis

Abstract

Introduction Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes of skin and internal organs. Our objective was to develop a composite response index in dcSSc (abbreviated CRISS) for use in randomized controlled trial (RCT. Methods We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not over a period of 1 year. Using profiles where raters reached a consensus on whether the patients were improved vs. not (79% of profiles examined), we fit logistic regression models where the binary outcome referred to whether the patient was improved or not, and the change in the core set items from baseline to follow-up were entered as covariates. We tested the final index in a previously completed RCT. Results Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. The logistic regression model that included the following core set items: changes in the Rodnan skin score, forced vital capacity (FVC)% predicted, patient and physician global assessments, and HAQ-DI over 1 year had sensitivity of 0.982 (95%CI: 0.981–0.983), specificity of 0.931 (95% CI: 0.930–0.932), and had the highest face validity. Subjects with a significant decline in renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. The index was able to differentiate the effect of methotrexate from placebo in a 1-year RCT (p< 0.05). Conclusion We have developed CRISS that is appropriate for use as an outcome assessment in RCT of early dcSSc.

Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator‐Initiated, Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Trial

“…These data should be interpreted with caution as no adjustments for multiplicity were made. In addition, there were statistically significant and clinically meaningful improvements in a new composite index, the ACR CRISS (15), that showed evidence in support of abatacept. The ACR CRISS was designed to capture the global or holistic evaluation of the likelihood of improvement in early SSc.…”

“…There was statistically significant and clinically meaningful improvement in a new composite index, the ACR CRISS, that showed evidence in support of abatacept. The median change at 12 months in the ACR CRISS score was 0.72 (IQR 0.99) versus 0.02 (IQR 0.75) (P = 0.03) with the proportion of patients whose score improved by ≥0.60 (the clinically meaningful cutoff point [15]) significantly higher in the abatacept group compared to the placebo group (62.8% versus 37.2%; P = 0.01 by Cochran-Mantel-Haenszel test with adjustment for dcSSc duration). Other secondary outcomes are presented in Table 2 and Supplementary Table 2.…”

Major lung complications of systemic sclerosis

“…These thresholds might be useful in the evaluation of treatment responses, making treatment decisions and identifying patients for inclusion (or exclusion) in clinical trials [109]. Change in lung function, assessed by fall in FVC, is an important component of the newly developed composite response index for SSc clinical trials [113], and a decrease in lung function is associated with worse outcomes [114]. Finally, as discussed above, particular ANAs are also associated with an increased or decreased risk of lung fibrosis [100,101].…”

The benefits and prospects of interleukin-6 inhibitor on systemic sclerosis

“…Recently, the Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis (CRISS) index was developed for a clinical trial of dcSSc [67]. This index was developed with the aim of assessing whether the symptoms of SSc were improved when performing the intervention trial.…”