Steroid Sparing Therapy in Sarcoidosis

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Steroid Sparing Therapy in Sarcoidosis

Clinical Endpoints in

Sarcoidosis

Robert P. Baughman


Endpoints for clinical trials of

• R.P. Baughman

• M, Drent

• D.A. Culver

• J.C. Grutters

• T. Handa

• M. Humbert

• M.A. Judson

Sarcoidosis in press

sarcoidosis

• E.E. Lower

• J.Mana

• C.A. Pereira

• A. Prasse

• R. Sulica

• D. Valyere

• V. Vucinic

• A.U.Wells


Reason for Clinical Endpoints

Task Force

• Better define what instruments can be used to

assess response to treatment in sarcoidosis

• Establish which instruments should be used to

assess response to treatment in sarcoidosis

– Based on current evidence

• Determine what studies are needed to validate

current instruments or develop new instruments


Task Force Progress

• Initial meeting to establish what instruments are

available

– Maastricht 2011

– Results to be published

• Voting on the instruments that were proposed

– Done summer 2012

• Refine the proposed instruments for different end

point trials

– Cleveland 2012

• Future meetings

– OMERACT


Primary Endpoint for Organ Specific Trial

• The central hypothesis to be tested in the

trial

• Should most if not all of following

• Known reproducibility

• Ideally been shown to respond to treatment in prior

trials (sarcoidosis or others)

• Have clinical relevance

• An established minimal clinically important

difference

• Safe

• Cost effective

• Widely available


Secondary Endpoint for Organ Specific Trial

• Can be used to support the primary endpoint

• May also be used to understand basic

mechanism of disease

• Should most if not all of following

• Known reproducibility

• Ideally been shown to respond to treatment in prior

trials (sarcoidosis or others)

• Have clinical relevance

• Safe

• Cost effective

• Widely available


Endpoint in All Sarcoidosis Trials

• An endpoint that should be collected for all

sarcoidosis trials

• Useful to compare/characterize the disease

• Should most if not all of following

• Known reproducibility

• Ideally been shown to respond to treatment in prior

trials (sarcoidosis or others)

• Have clinical relevance

• Safe

• Cost effective

• Widely available


OMERACT

• An organization working with American College

or Rheumatology

• Used to establish endpoints for specific conditions

– Rheumatoid arthritis

– Psoriasis

• Formal process of evaluation instruments

• Often used by FDA in establishing endpoints in

Phase 3 clinical trials

• Provides a specific “filter” to assess individual

instruments


Instrument

Concepts

Face Validity

Truth

Content Validity

Construct Validity

Criterion Validity


Instrument

Concepts

Discrimination

Discriminatory

Reliable

Reproducible

Sensitive to Change


Instrument

Concepts

Feasibility

Cost Effective

Easy to Interpret Results

Readily Available

Safe for Patients


Questions to be answered in the

future

• For instruments accepted, do we feel

comfortable assigning preliminary threshold

of change?

• For instruments accepted, what are the

questions that need to be answered to secure

their validation as an outcome measure?


Cleveland Meeting

• Round two of evaluation of instruments for

individual clinical endpoints

– Those introduced in Maastricht

– New instruments

• Voting will be possible using WASOG

website

• Move forward proposal for OMERACT


Categories

• Primary endpoint for specified type of

clinical trial

• Major secondary endpoint for specified

type of clinical trial

• Secondary endpoint for all sarcoidosis

clinical trials


Pulmonary:

Dominique Valeyre and Marc Judson

FVC

FEV-1

FEV-1/FVC

DLCO

6 minute walk

SGRQ

Chest X-ray

Scadding

Chest X-ray Muers

HRCT Score


Pulmonary: Survey Results


Pulmonary Hypertension

Tomohiro Handa, Roxanne Sulica, Joseph Parambil

Initial Pulmonary hemodynamics

Change in hemodynamics

Initial Echo estimate of PA systolic

pressure

Change in Echo estimate of PA

systolic pressure

6 minute walk test

Time to clinical worsening

NYHA/WHO class

SF-36

SGRQ

SHQ

Vital prognosis

BNP/NT-ProBNP

MRI


Pulmonary Hypertension Survey Results


Pulmonary Hypertension Survey Results


FAS

FACIT-F

FS

SF-36

SGRQ

SHQ

WHO-QOL BREF

Fatigue/Quality of Life

Marjolein Drent, Elyse Lower

• FAS: fatigue assessment scale

• FACIT-F: Functional

Assessment of Chronic Illness

Therapy-Fatigue

• FS: Fatigue Scale

• SF-36: short form-36

• SGRQ: Saint George

Respiratory Questionnaire

• SHQ: Sarcoidosis Health

Questionnaire

• WHO-QOL BREF: World

Health Organization-Quality of

Life Brief.


Fatigue/Quality of Life Survey Results


Cutaneous

Dan Culver, Robert Baughman, Juan

Mana, Misha Rosenbach

Physician Global Assessment

SASI

LuPASI

Photographs

Lesion counts

Skin biopsies


Cutaneous Survey Results


STAI

COS

Phenotypes

Antje Prasse, Carlos Pereira

Scadding stage

Wasfi

Prasse

• STAI: sarcoidosis

three-dimensional

assessment instrument

• COS: clinical outcome

score


Clinical Phenotype

Survey Results


Conclusion

• Several clinical endpoints have been

evaluated for various clinical manifestations

of sarcoidosis

• New instruments are also being introduced


Next Steps

• Survey WASOG community about specific

instruments

– Will be performed on WASOG website

– Will provide detailed information about

individual instruments

• Submit to OMERACT proposal to study

clinical endpoints in sarcoidosis

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