Thyroid Eye Disease Awareness

and Education Webinar

Tuesday, July 9, 2019

Welcome Panelists

Babak Larian, MD

Assistant Clinical Professor of Surgery, Division of Head and Neck Surgery, UCLA

David Geffen School of Medicine

Director, Head and Neck Cancer Center and Head and Neck Tumor Board, Cedar-

Sinai Medical Center

Raymond S. Douglas, MD, PhD

Director of Orbital and Thyroid Eye Disease Program

Cedars-Sinai Medical Center in Los Angeles

Christina Seeden

Advocate

Babak Larian, MD

Assistant Clinical Professor of Surgery, Division of

Head and Neck Surgery, UCLA David Geffen School of

Medicine

Director, Head and Neck Cancer Center and Head and

Neck Tumor Board, Cedar-Sinai Medical Center

Raymond S. Douglas, MD, PhD

Director of Orbital and Thyroid Eye Disease Program

Cedars-Sinai Medical Center in Los Angeles

THYROID EYE DISEASE: WHAT IS IT AND

HOW TO TREAT IT..

RAYMOND S. DOUGLAS MD PHD

PROFESSOR OF SURGERY

DIVISION OF OPHTHALMOLOGY

150 NORTH ROBERSTON SUTIE 314

BEVERLY HILLS CA

INFO@RAYMONDDOUGLASMD.COM

“The speaker declares no current financial

conflicts of interest”

WHAT IS THYROID EYE DISEASE ?

The Three Components of Graves’ Disease

Heterogeneous disease

Dis

ea

se

Time

Ideal

Immunomodulatory

Therapy

Active Phase

Stable Phase

18-36 months 5-7years

Surgery

Thyroid Eye Disease

Autoimmune inflammatory disease

often with extensive fibrosis

Permanent Facial disfigurement

No treatment to prevent disfigurement

“Standard of Care” watch and wait - then surgery

What about TED specific therapy ???

Heterogeneous disease

Delineate the common molecular mechanisms

Tsui et al J Immunology 181:4397 (2008)

IGF-1R Inhibition Can

Attenuate TSHR Signaling

Inhibition of IGF-1R with a mAb antagonist has potential to block pathological autoantigen signaling through both IGF-1R and TSHR

Teprotumumab Phase 2 IGF-1R Antagonist

RAYMOND S. DOUGLAS MD PHD

PRINCIPAL INVESTIGATOR

22 US AND INTERNATIONAL CENTERS

Graves’ Orbitopathy:

Disease Time CourseD

isease A

ctivity

Active Phase Stable Phase

1.5 2 3 6 years

Untreated

Smith & Douglas (2011)

Teprotumumab Efficacious

therapy

18

24-week randomized, double-masked, placebo-

controlled treatment trial of Teprotumumab

ǂ Excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent. There must be at least 6 weeks between last administration of steroids and study

randomization. *No additional treatment during at least the first 3 months unless medically indicated. i.e. decompression. Elective treatments should be avoided during the first 3 months of the follow up period.

Active

TED 18 to 75 years

< 9 mo. since active TED

onset with no prior

treatmentǂ

CAS ≥ 4

FT4 and FT3 <50% above or

below normal limits

Teprotumumab

Infusions q3w

(total of 8)

Placebo

Infusions q3w

(total of 8)

Sc

ree

nin

g

Ra

nd

om

iza

tio

n

Off Treatment

Follow Up Period

Week 24 assessment was

3 weeks after last dose

Week 72 assessment was

51 weeks after last dose

24 weeks 48 weeks

Study Design

•Less than 9 months since TED diagnosis

•Moderate – Severe disease

•CAS 4 or greater

Endpoints•Proptosis reduced by 2 mm

•Study designed to Medically REPLACE SURGERY

Smith TJ et al. N Engl J Med 2017;376:1748-1761

Clinical Activity Score

Smith TJ et al. N Engl J Med 2017;376:1748-1761

Proptosis Reduction

Individual Patient Plots (week 24)

22

Smith TJ et al. N Engl J Med 2017;376:1748-1761

Pre treatment

Week 24

control

Pre treatment

Teprotumumab

Week 24

• Teprotumumab, an antibody to the insulin-like growth factor I receptor, led to significant responses in 69% of patientswith decreased proptosis (intent to treat).

• 79% of patients (data available) had a decreased proptosis and response toTeprotumumab

• Proptosis reduction was >2.5 mm• Worse disease bigger effect• May replace surgery

Results

Single Stage Approach to Orbital

Decompression

Adequate decompression can dramatically

reduce need for eyelid surgery

Less than 5% need lower eyelid surgery

Aesthetic Functional Reconstruction

It IS about how we Look and Feel

It IS about how many surgeries and downtime

Single Stage Reconstruction

What is “aesthetic-functional”

reconstruction?

Form follows function

• Goal: Return to (Improve upon) pre disease appearance and function

Key Factors to Customized Surgical

Planning

• Patient Goals

• Type of disease fat vs muscle- Risk profile

• Disease severity

• Presence/risk of double vision

• Bony structure (bone available for decompression)

• Soft tissue structure

• Aesthetic contour of brow, eyelids, midface

Fat + Lateral/Superior Decompression

6mm proptosis

reduction, no

additional surgery

Natural lower eyelid appearance

Done by customizing decompression technique not

additional surgery

Normal Eyelid contour restored after decompression

Fat + Lateral Decompression

3-4 mm proptosis

reduction

Fat + Lateral / Superior Decompression

6mm proptosis

reduction

Improve Cheek junction

During decompression

Eyelid rectrator release

Orbitomalar ligament release

Midface lift / support

Cheek implants

40

Decompression and OML release-No eyelid surgery

42

43

44

Summary

• Orbital And Oculoplastic Surgery Service

• Available 24/7 consults

• Thyroid Eye Disease Program

• Research

• Integrated Multidisciplinary Clinical Care

• Financial Assistance Program from philanthropy

Christina’s Thyroid Eye Disease

Journey

Christina’s TED Journey

October 2006Diagnosed with Graves

August 2007 August 2011Before RAI

August 2012

Christina’s TED Journey

Before TED 2011 Active TED 2012 Active TED 2012 1 month after surgery

Christina’s TED JourneyFebruary 2013Before surgery

August 20133.5 months after surgery

Christina’s TED JourneyFebruary 2013 Now

Thank You Panelists

Babak Larian, MD

Assistant Clinical Professor of Surgery, Division of Head and Neck Surgery, UCLA

David Geffen School of Medicine

Director, Head and Neck Cancer Center and Head and Neck Tumor Board, Cedar-

Sinai Medical Center

Raymond S. Douglas, MD, PhD

Director of Orbital and Thyroid Eye Disease Program

Cedars-Sinai Medical Center in Los Angeles

Christina Seeden

Advocate