Revised Composite Response Index in Systemic Sclerosis (ACR-CRISS) may be an improved method of assessing the likelihood of improvement in diffuse cutaneous systemic sclerosis (dcSSc), according to the results of study findings published in Annals of the Rheumatic Diseases.
ACR-CRISS, a weighted composite score that measures the likelihood of improvement in 5 physical or functional areas in patients with early systemic sclerosis (SSc), has had positive results as the primary outcome measure in recent studies. However, the researchers acknowledged that there has been concern that it is disproportionately influenced by the skin assessment component and is subject to ceiling effects.
To address these concerns, a modified ACR-CRISS was developed by analyzing data from 387 participants (80% women) with early dcSSc who participated in 3 randomized control trials. The mean age of participants was 48.7±12.4 years at baseline. The 5 core sets of measures that comprise the ACR-CRISS are the modified Rodnan skin score (mRSS), percent predicted forced vital capacity (%FVC), the health assessment questionnaire-disability index (HAQ-DI), and the patient (PGA) and clinical (CGA) global assessments. It was assumed that a greater percentage of the treatment groups would show statistically significant improvement in each of the 5 core components compared with the placebo groups and that a statistically significant percentage of participants in the treatment groups would improve by a certain threshold in more than 1 core component. A revised estimate was designed by varying the thresholds for relative improvement from baseline to year 1 for the 5 components and testing improvement predictions on the pooled trial data.
The percentage of participants who improved by 10% to 60% or more was greater in the treatment group compared with the control group for all 5 core measures. Improvement thresholds for %FVC at 5% and 10% were meaningful. ACR-CRISS showed both large floor and ceiling effects for both groups. When the threshold level was set to 10% or more and 20% or more, the median ACR-CRISS was 0.99 in individuals who had experienced improvement and 0.1 in individuals who had not (P <.001).
Revised CRISS may provide an anchor for clinical meaningfulness when assessing improvement in SSc, the investigators noted. The thresholds for improvement in future randomized control trials could either use a 20% or 25% cut-off point for each of the 4 core measures (and 5% or 10% for %FVC) or could be adjusted so that the percentage of patients who improve in the placebo group is less than 20% in the endpoint composite, they wrote. This may improve accuracy of endpoint measures in studies investigating the efficacy of potential treatments for SSc.
Limitations to this study include the use of data from trials with negative primary endpoint measures as well as heterogeneity in the risk differences observed in the development and validation data sets. In addition, all related studies did not use background immunosuppressive therapies, and thus the current results may not be generalizable to these studies.
Future research validating these findings as well as investigating if the findings can be applied to studies with background immunosuppressive therapies are warranted, the researchers concluded.
Disclosure: Several study authors have declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Khanna D, Huang S, Fin CJF, Spino C. New composite endpoint in early diffuse cutaneous systemic sclerosis: Revisiting the provisional American College of Rheumatology Composite Response Index in systemic sclerosis. [published online November 30, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020.219100