ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1716

Evaluation of American College of Rheumatology Provisional Composite Response Index in Systemic Sclerosis in a Phase II Trial of Abatacept Vs. Placebo

Dinesh Khanna1 and Cathie Spino2, 1Division of Rheumatology, Department of Internal Medicine, University of Michigan Scleroderma Program, University of Michigan, Ann Arbor, MI, 2Biostatistics, University of Michigan, Ann Arbor, MI

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Abatacept, outcome measures and scleroderma

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Monday, October 22, 2018

Title: Systemic Sclerosis and Related Disorders – Clinical Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Treatment with CTLA4Ig, abatacept (ABA), in early diffuse cutaneous systemic sclerosis (dcSSc; the Phase 2 ASSETtrial) showed evidence of improvements in modified Rodnan skin score (mRSS) and secondary outcome measures at month 12 (2018 ACR abstract submitted); however, statistical significance was not always shown vs. placebo. The CRISS index, a composite outcome measure for trials in SSc1, is a 2-step process that assigns a probability of improvement for each subject ranging from 0 [no improvement] to 1 [marked improvement]. Step 1 assesses clinically meaningful decline in cardio-pulmonary-renal involvement with a probability of 0. For remaining subjects, probability of improvement is based on 5 variables: changes from baseline to month 12 in FVC%, mRSS, patient (PTGA) and physician global assessments (MDGA), and HAQ-DI. We assessed the performance of CRISS, a secondary outcome measure, in ASSET at month12.

Methods: ASSET was an investigator-initiated, multicenter double-blind, randomized placebo-controlled trial. Eligible subjects were randomized in a 1:1 ratio to either 12 months 125 mg SC ABA or matching placebo, stratified by duration of dcSSc (≤18 vs >18 to ≤36 months). Investigators reported SSc end organ involvement (Step 1 for CRISS) prospectively using a case report form. These and all AEs and SAEs were reviewed for cardio-pulmonary and renal involvement by the study PI. Step 2 calculated the CRISS index as previously defined. Treatment differences, adjusted for duration of dcSSc, in the CRISS score were assessed by the non-parametric Van Elteren test and by ANCOVA for individual CRISS components. We calculated Spearman’s correlation coefficients to assess the relationship between the CRISS score and its individual components. Multiple imputation was used for analysis, creating 25 complete datasets with estimates, standard errors and p-values pooled over each imputed dataset.

Results: 88 subjects (44 ABA, 44 PBO) were randomized; 63 (72%) had complete data for all relevant outcomes at month 12. 5 PBO and 5 ABA subjects met the pre-defined definition of worsening cardio-pulmonary-renal involvement(Step 1) and were given a score of 0. There is evidence of improved CRISS scores on ABA compared to the PBO at month 12 and the difference was statistically significant (p=0.03; Table). For individual variables, MDGA and HAQ-DI were statistically significant (p=0.004 and p=0.05) favoring ABA. Most variables, except HAQ-DI and PTGA, had statistically significant correlations with the CRISS (Table).

Conclusion: Although the degree of correlation is high between the mRSS and CRISS, there is evidence that CRISS may be more sensitive to clinically meaningful treatment changes than the standard skin score endpoint. This suggests further validation of CRISS as an independent primary endpoint for scleroderma clinical trials.

References:

  1. Khanna D. Arthritis Rheumatol. 2016

Table: Spearman Correlations between CRISS and individual components at 12 months and Comparison of ABA and PBO using CRISS index and individual components at 12 months;

Outcome

ABA

N=44

PBO

N=44

Treatment Difference

(ABA-PBO)

P-value^

CRISS (0.0-1.0)

median (IQR)

0.68 (1.00)

0.01 (0.86)

0.03

Spearman Correlation

LS mean (SE)

LS mean (SE)

LS mean

(SE)

P-value^^

ΔmRSS (0-51)

-0.75*

-6.7 (1.30)

-3.8 (1.23)

-2.9 (1.75)

0.10

ΔFVC% predicted

0.36*

-1.4 (1.30)

-3.1 (1.20)

1.7 (1.72)

0.32

ΔPTGA (0-10)

-0.17

-0.50 (0.392)

-0.30 (0.385)

-0.20 (0.557)

0.73

ΔMDGA (0-10)

-0.47*

-1.34 (0.282)

-0.18 (0.284)

-1.16 (0.403)

0.004

ΔHAQ-DI (0-3)

-0.21

-0.11 (0.079)

0.11 (0.076)

-0.22 (0.108)

0.05

^p-value for treatment comparisons based on Van Elteren test

^^p-value for treatment comparisons based on ANCOVA model with treatment, duration of SSc and baseline value as covariates

*p< 0.01 using Spearman correlation coefficient

Negative score denotes improvement, except for FVC% where negative score denotes worsening; LS mean = least squares mean; SE = standard error

Acknowledgment: This project was supported by NIH/NIAID Clinical ACE grant (5UM1AI110557-05) and an investigator-initiated grant by Bristol-Myers Squibb.


Disclosure: D. Khanna, Eicos Sciences, 1,Pfizer, Inc., 2,Horizon, 2,BMS, 2,Actelion, 5,Bayer, 5,Bayer, 2,Corbus, 5,Cytori, 5,EMD Serono, 5,Genentech, Inc., 5,Sanofi-Aventis, 5,GSK, 5,Boehringer Ingelheim, 5,Civi BioPharma, 3; C. Spino, None.

To cite this abstract in AMA style:

Khanna D, Spino C. Evaluation of American College of Rheumatology Provisional Composite Response Index in Systemic Sclerosis in a Phase II Trial of Abatacept Vs. Placebo [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/evaluation-of-american-college-of-rheumatology-provisional-composite-response-index-in-systemic-sclerosis-in-a-phase-ii-trial-of-abatacept-vs-placebo/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-american-college-of-rheumatology-provisional-composite-response-index-in-systemic-sclerosis-in-a-phase-ii-trial-of-abatacept-vs-placebo/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology