Provisional American College of Rheumatology (ACR) Combined Response - - PowerPoint PPT Presentation

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Provisional American College of Rheumatology (ACR) Combined Response - - PowerPoint PPT Presentation

Jan 08, 2024 97 likes •232 views

Provisional American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) Score Correlates with Changes () in Patient-reported Outcomes (PROs) Robert Spiera, Laura Hummers, Lorinda Chung, Tracy

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SLIDE 1

Provisional American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) Score Correlates with Changes (Δ) in Patient-reported Outcomes (PROs)

Robert Spiera, Laura Hummers, Lorinda Chung, Tracy Frech, Robyn Domsic, Vivien Hsu, Daniel E. Furst, Jessica Gordon, Maureen Mayes, Robert Simms, Elizabeth Lee, Scott Constantine, Nancy Dgetluck, Quinn Dinh, Brad Bloom, and Barbara White

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SLIDE 2

Disclosures

  • Grants/Research Support
  • Roche-Genetech
  • GSK
  • BMS
  • Boehringer Ingelheim
  • Cytori
  • Chemocentryx
  • Corbus
  • Formation Biologics
  • Sanofi
  • Inflarx
  • Consulting
  • Roche-Genetech
  • GSK
  • CSL Behring
  • Sanofi
  • Janssen
  • Chemocentryx
  • Formation Biologics
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SLIDE 3

Background

  • ACR CRISS score is a composite outcome developed to assess the likelihood of

improvement from baseline in clinical trials in subjects with dcSSc

  • Several trials have reported positive outcomes using ACR CRISS score as a primary,

secondary, or post-hoc efficacy outcome

  • Primary efficacy outcomes should reflect clinical benefit, that is how the patient feels,

functions, or survives

3

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SLIDE 4

Objective

Determine whether ACR CRISS score reflects patient-reported outcomes, including two that are part of the ACR CRISS score itself (HAQ-DI and PtGA), Systemic Sclerosis Skin Symptoms Patient-reported Outcome1 (SSPRO) and PROMIS-29 domain scores

  • ver 12 months

4

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SLIDE 5

Methods

  • Determine Spearman correlation coefficients between ACR CRISS score and change in

PROs in a phase 2 study of lenabasum in dcSSc

  • Months 3 and 4 in double-blind placebo control Part A of study (n = 38 each) and

months 6, 12, 18, and 24 in open-label extension of study (N = 36, 31, 30, and 29, respectively)

  • Baseline was time of the first dose in Part A or the first dose in the OLE
  • For description purposes, correlations coefficients (r) are categorized as:
  • no (0 to 0.19)
  • low (0.20 to 0.34)
  • moderate (0.35 to 0.59)
  • strong (0.60 to 0.79)

5

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SLIDE 6

Results: ACR CRISS Score and Change in PtGA (Overall Health)

6 DBPC OLE Lenabasum DBPC OLE Lenabasum

Low to moderate correlations

  • 0.35
  • 0.38
  • 0.40
  • 0.21
  • 0.40
  • 0.32
  • 0.45
  • 0.40
  • 0.35
  • 0.30
  • 0.25
  • 0.20
  • 0.15
  • 0.10
  • 0.05

0.00 Correlation Between PtGA and ACR CRISS Score Week of Treatment * * * *

12 16 28 52 76 108 * P < 0.05

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SLIDE 7

Results: ACR CRISS Score and Change in HAQ-DI (Function)

7 DBPC OLE Lenabasum DBPC OLE Lenabasum

Moderate to strong correlations after week 16

  • 0.15
  • 0.45
  • 0.42
  • 0.46
  • 0.50
  • 0.64
  • 0.7
  • 0.6
  • 0.5
  • 0.4
  • 0.3
  • 0.2
  • 0.1

Correlation Between HAQ-DI and ACR CRISS Score Weeks of Treatment * *** ** ** ** 12 16 28 52 76 108

* P < 0.05 ** P < 0.01 *** P < 0.001

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SLIDE 8

Social Role Physical Function

Results: ACR CRISS Score and Change in PROMIS-29 Social Role and Physical Function Domains (Function)

0.39 0.50 0.39 0.46 0.56 0.1 0.2 0.3 0.4 0.5 0.6 Correlation Between Social Role and ACR CRISS Score

* ** ** * *

0.28 0.67 0.60 0.47 0.57 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Correlation Between Physical Function and ACR CRISS Score

Week of Treatment

*** ** *** **

12 28 52 72 108

1.7 1.6 1.8 3.8 3.6 3.2 3.9 4.1 4.5 4.8 5 4.9 4.3 4.5 5.9 5.2

2 4 6 8

0 4 8 12 0 4 20 36 60 76 92 108 Mean Change from Baseline

Week Placebo Lenabasum Double-blind Lenabasum OLE DBPC OLE Lenabasum

1.4

  • 0.7

2.2 3.2 2.8 3 2.32.5 3.73.94.2 3.83.9 4.7 4.3 3.9

  • 1

1 2 3 4 5 0 4 8 12 0 4 20 36 60 76 92 108 Mean Change from Baseline Week Placebo Lenabasum Double-blind Lenabasum OLE

Moderate to strong correlations

* P < 0.05 ** P < 0.01 *** P < 0.001

Improves Improves

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SLIDE 9

Results: ACR CRISS Score and Change in SSPRO and PROMIS-29 Pain Interference Domains (Symptoms)

9 DBPC OLE Lenabasum DBPC OLE Lenabasum

  • 0.40
  • 0.48
  • 0.23
  • 0.36-0.35
  • 0.6
  • 0.5
  • 0.4
  • 0.3
  • 0.2
  • 0.1

Correlation Between Pain Interference and ACR CRISS Score

* * **

  • 0.20
  • 0.36
  • 0.20
  • 0.31
  • 0.39
  • 0.45
  • 0.40
  • 0.35
  • 0.30
  • 0.25
  • 0.20
  • 0.15
  • 0.10
  • 0.05

0.00 Correlation Between SSPRO and ACR CRISS Score

Week of Treatment

* *

12 28 52 72 108

  • 2.5 -2.1
  • 2.8
  • 3.6
  • 3.6
  • 4
  • 2.8
  • 3.6
  • 4.9
  • 5.3
  • 4.3
  • 5.3
  • 5.4
  • 5.3
  • 5.8
  • 6.1
  • 8
  • 6
  • 4
  • 2

Mean Change from Baseline Week

Placebo Lenabasum Double-blind Lenabasum OLE 0 4 12 0 4 20 36 60 76 92 108

Low to moderate correlations

* P < 0.05 ** P < 0.01

Improves Improves

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SLIDE 10
  • 0.4
  • 0.2

0.2 0.4 0.6 Correlation Between Social Role

Week of Treatment

  • 0.6
  • 0.4
  • 0.2

0.2 0.4 0.6 0.8 Correlation Between Physical Function

  • 0.6
  • 0.5
  • 0.4
  • 0.3
  • 0.2
  • 0.1

0.1 0.2 Correlation Between Pain Interference

Week of Treatment

  • 0.8
  • 0.6
  • 0.4
  • 0.2

0.2 0.4 Correlation Between HAQ-DI

  • 0.50
  • 0.40
  • 0.30
  • 0.20
  • 0.10

0.00 0.10 0.20 Correlation Between PtGA

  • 0.50
  • 0.40
  • 0.30
  • 0.20
  • 0.10

0.00 0.10 0.20 0.30 Correlation Between SSPRO

Blue – ACR CRISS Orange - mRSS Function

ACR CRISS score has stronger correlations with PROs than change in mRSS

Overall Symptoms

Correlations of ACR CRISS Score vs. Change in mRSS with Change in PRO

12 28 52 72 108

12 16 28 52 76 108

Week of Treatment

12 28 52 72 108

* * * * * * * * * * * * * * * * * * * * * * * * P < 0.05

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SLIDE 11

Summary and Conclusions

  • The composite ACR CRISS score consistently correlated with patient-reported

function and symptoms outcomes, including patient-reported outcomes not captured in the ACR CRISS score calculation

  • ACR CRISS score correlated with these PRO more strongly than change in mRSS, a

physician measurement of skin thickness

  • ACR CRISS score may serve as an efficacy outcome that broadly reflects how the

patient feels and functions

11

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SLIDE 12

Investigators and study coordinators

12

Principal Investigator Study Coordinators Institution Robert Spiera Jessica Gordon Jesse Ojeda Sarah Jinich Anna Yusov Weill Cornell Medical College Lorinda Chung Joel Nicholus Stanford University School of Medicine Robyn Domsic Jennifer Peat-Fircak University of Pittsburgh School of Medicine Tracy Frech Jennifer Godina University of Utah School of Medicine Daniel E. Furst Omar Aly Pacific Arthritis Care Center Vivien Hsu Deborah McCloskey Robert Wood Johnson Medical School Laura Hummers Gwen Leatherman Margaret Sampedro Johns Hopkins School of Medicine Maureen Mayes Patricia Gonzales University of Texas, Houston Robert Simms Eric Stratton Connor Buchholz Boston University