Supporting Patient-Centered Care in Generalized Pustular Psoriasis: Communications Strategies to Improve Shared Decision-Making

Milan J. Anadkat, MD, and Dale V. Reisner discuss generalized pustular psoriasis in this CME activity titled "Supporting Patient-Centered Care in Generalized Pustular Psoriasis: Communications Strategies to Improve Shared Decision-Making." For the full presentation, please visit us at www.peervoice.com/HUM870.

1. PeerVoice

Supporting Patient-Centered Care in Generalized Pustular Psoriasis:
Communications Strategies to Improve Shared Deci:

Learning Objectives

Describe key information regarding the disease process and course following the
diagnosis of generalized pustular psoriasis (GPP)

Address common concerns raised by patients with GPP
Develop appropriate treatment plans with patients for the management of GPP

www.peervoice.com/HUM870

2. PeerVoice

Part 1 of 3: The Disease Process in GPP

Milan J. Anadkat, MD

Professor of Medicine (Dermatology) and
Director of Dermatology Clinical Trials
Washington University School of Medicine
St. Louis, Missouri

Dale V. Reisner
Patient Advocate
Yankton, South Dakota

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

3. PeerVoice

Milan J. Anadkat, MD, has a financial interest/relationship or affili

Consultant for Bioling Incorporated; Boehringer Ingelheim International GmbH; Eli
Company; Evommune, Inc; OnQuality Pharmaceuticals LLC. (relationship ended); and
SpringWorks Therapeutics, Inc.

Grant/Research Support from working as site principal investigator for AbbVie Inc.; AstraZeneca;
Eli Lilly and Company; Galderma Laboratories, L.P.; Hoth Therapeutics; Incyte; Lutris Pharm:
Moberg Pharma AB; Novartis AG; OnQuality Pharmaceuticals LLC.; Phoenicis; Regeneron
Pharmaceuticals, Inc.; and UCB Pharma Ltd.

Advisory Board or Panel for Boehringer Ingelheim International GmbH; Novocure GmbH; and UCB
Pharma Ltd.

n to this activity.

Dale V. Reisner has no financial interests/relationships or affiliations in relat

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

4. PeerVoice

Clinical Features and Different

| Diagnosis of GPP

Typical Features of GPP Differential Diagnosis of GPP

Drug eruptions
(eg, acute generalized
exanthematous pustulosis)

Multiple pustules,
some of which are confluent

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

5. PeerVoice

Pathogenesis of GPP: Uncontrolled Activation of IL-36 Pathway

Environmental Triggers Genetic Factors
Overexpression of IL-36 agonists LOF mutation in endogenous antagonist IL-36RA
can result in excessive signaling leads to pathway running unregulated
IL-36a / 8/Y@ e Mutated
@9 IL-36RA

IL-IRAcP
IL-36R

IL-364 / 8 / Y

ZA
TE He
domain °C ToWIL-1R

domain

Excess production of inflammatory cytokines,
leading to dysregulated inflammatory signaling

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

6. PeerVoice

Abbreviations and References

Clinical Features and Differential Diagnosis of GPP

Abbreviation(s): GPP: generalized pustular psoriasis.
Reference(s): Menter A et al. Dermatol Ther (Heidelb). 2021

Pathogenesis of GPP: Uncontrolled Activation of IL-36 Pathway

Abbreviation(s): IL-IRAcP: interleukin-1 receptor accessory protein; IL-36: interleukin-36; IL-36RA: IL-36 receptor
agonist; LOF: loss of function.
Reference(s): Marrakchi S, Puig L. Am J Clin Dermatol. 2022;23:13-19.

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

7. PeerVoice

Part 2 of 3: Addressing Concerns Regarding Disease Flares

Milan J. Anadkat, MD

Professor of Medicine (Dermatology) and
Director of Dermatology Clinical Trials
Washington University School of Medicine
St. Louis, Missouri

Dale V. Reisner
Patient Advocate
Yankton, South Dakota

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

8. PeerVoice

Milan J. Anadkat, MD, has a financial interest/relationship or affili

Consultant for Bioling Incorporated; Boehringer Ingelheim International GmbH; Eli
Company; Evommune, Inc; OnQuality Pharmaceuticals LLC. (relationship ended); and
SpringWorks Therapeutics, Inc.

Grant/Research Support from working as site principal investigator for AbbVie Inc.; AstraZeneca;
Eli Lilly and Company; Galderma Laboratories, L.P.; Hoth Therapeutics; Incyte; Lutris Pharm:
Moberg Pharma AB; Novartis AG; OnQuality Pharmaceuticals LLC.; Phoenicis; Regeneron
Pharmaceuticals, Inc.; and UCB Pharma Ltd.

Advisory Board or Panel for Boehringer Ingelheim International GmbH; Novocure GmbH; and UCB
Pharma Ltd.

n to this activity.

Dale V. Reisner has no financial interests/relationships or affiliations in relat

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

9. PeerVoice

Clinical Course of GPP

First episode of
widespread pustular flare

Chronic/

quiescent period

.com/HUM870 Copyright © 2010-2024, PeerVoice

10. PeerVoice

GPP Flares: What Are the Trigger Events?

m Longest Past Flare m Most Severe Past Flare m Typical Past Flare

Pregnancy

Treatment withdrawal

Infection

Stress

Unknown
472

o 10 20 30 40 50

Patients (N = 53), %
Infection comprises respiratory, urinary, and other.

www.peervoice.com/HUM870

Copyright © 2010-2024,

erveice

11. PeerVoice

Severity of GPP Flares

1 Longest Past Flare (n=14) m Most Sevore Past Flare (n=!) m Typical Past Flare (n= 37)

3-4 weeks

for Past Flares, %

1-2 weeks

«week

Pationts, %

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

12. PeerVoice

Clinical Assessment of G

+ Developed by 12 dermatologists in the a nel
US after 3 anonymous e-Delphi rounds
+ Two patients participated in 1 Signs
pre-Delphi round for item generation Body surface area
+ Initial evaluation included 14 physical aye
signs, 11 symptoms, and 13 laboratory
biomarkers PROMS

Skin pain
Itch

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

13. PeerVoice

Abbreviations and References

Clinical Course of GPP

Abbreviation(s): GPP: generalized pustular psoriasis.
Reference(s): Marrakchi S, Puig L. Am J Clin Dermatol. 2022;23:13-19.

GPP Flares: What Are the Trigger Events?
Reference(s): Choon SE et al. Dermatology. 2023;239:345-354.

Severity of GPP Flares
Reference(s): Choon SE et al. Dermatology. 2023;239:345-354.

Clinical Assessment of GPP

Abbreviation(s): PROMS: patient-reported outcomes.
Reference(s):

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

14. PeerVoice

Part 3 of 3: Selecting Appropriate Therapy for GPP

Milan J. Anadkat, MD

Professor of Medicine (Dermatology) and
Director of Dermatology Clinical Trials
Washington University School of Medicine
St. Louis, Missouri

Dale V. Reisner
Patient Advocate
Yankton, South Dakota

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

15. PeerVoice

Milan J. Anadkat, MD, has a financial interest/relationship or affili

Consultant for Bioling Incorporated; Boehringer Ingelheim International GmbH; Eli
Company; Evommune, Inc; OnQuality Pharmaceuticals LLC. (relationship ended); and
SpringWorks Therapeutics, Inc.

Grant/Research Support from working as site principal investigator for AbbVie Inc.; AstraZeneca;
Eli Lilly and Company; Galderma Laboratories, L.P.; Hoth Therapeutics; Incyte; Lutris Pharm:
Moberg Pharma AB; Novartis AG; OnQuality Pharmaceuticals LLC.; Phoenicis; Regeneron
Pharmaceuticals, Inc.; and UCB Pharma Ltd.

Advisory Board or Panel for Boehringer Ingelheim International GmbH; Novocure GmbH; and UCB
Pharma Ltd.

n to this activity.

Dale V. Reisner has no financial interests/relationships or affiliations in relat

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

16. PeerVoice

Treatment Goals in GPP
Goals for Most Common Symptoms f

Fever control

Control of systemic inflammation
Rapid control of pustules and
prevention of new eruptions

Control of pain, itching, edema
Prevention of recurrence of GPP
flares

www.peervoice.com/HUMB70 Copyright © 2010-2024, PeerVoice

17. PeerVoice

Treatment Options for GPP

Non-Systemic
Therapies

Non-Biologic
Systemic Therapies

Topical
Treatments

Phototherapy Cyclosporine
Mycophenola

mol
Hydroxyurea

Methotrexate

. peervoice.com/HUM870

Infliximab e AGUSAKIMAb' -
Adalimumab + Risankizumab Spesolimaby
Etanercept

Certolizumab

+ Ustekinumab

Brodalumab
Ixekizumab
Secukinumab

itor

Canakinumab
Gevokizumab
Anakinra

Copyright © 2010-2024, PeerVoice

18. PeerVoice

Mechanism of Action of Spesolimab

o o
e e Spesolimab

IL-36a / 8 / y

w-s6a/p/y Y O IL-36RA
09

IL-38

IL-IRAcP IL-36R IL-1RACP IR aso Lam

IL-36
proinflammatory signaling

No signaling No signaling

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

19. PeerVoice

Effisayil 1 Outcomes: Spesolimab for Flare Treatment

Primary endpoint: Secondary endpoint:
Difference vs PBO (95% CI) Difference vs PBO (95% CI)
49 (21-67) 32 (2-53)
% P<.001 P=.02
54 !
so
43
40
x
go
é
20
0
: | |
ó |
GPPGA Pustulation Subscore of O at Week 1 GPPGA Total Score of O or lat Week 1

= Spesolimab (n= 35) = PBO (n= 18)

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

20. PeerVoice

Effisayil 2 Outcomes: Spesolimab for Flare Prevention

Estimated Probability of
First GPP Flare

www.peervoice.com/HUM870

Up to Week 48
e

2

22

Time to First GPP Flare

Low 0057
Medium 027
High 0.16 (0.05-0.54) .0005

PBO (n = 31)

Spesolimab medium dose (n = 31)

Spesolimab low dose (n = 31)
>
‘Spesolimab high dose (n= 30)

24 28 32 36 40
Time, wk

4

as

52

Copyright © 2010-2024, PeerVoice

21. PeerVoice

Abbreviations and References

Treatment Goals in GPP

Abbreviation(s): GPP: generalized pustular psoriasis.
Reference(s): Krueger J et al. Am J Clin Dermatol. 2022;

Treatment Options for GPP

Abbreviation(s): IL: interleukin.
Reference(s): Krueger J et al. Am J Clin Dermatol. 2022;23:51-64.

Mechanism of Action of Spesolimab

Abbreviation(s): IL-IRAcP: IL-1 receptor accessory protein.
Reference(s): Bernardo D et al. Drugs. 2024;84:45-58.

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice

22. PeerVoice

Abbreviations and References (Cont'd)

Effisayil 1 Outcomes: Spesolimab for Flare Treatment

Abbreviation(s): GPPGA: Generalized Pustular Psoriasis Physician Global Assessment; PBO: placebo.
Reference(s): Bachelez H et al; Effisayil 1 Trial Investigators. N Engl J Med. 2021;385:2431-2440.

Effisayil 2 Outcomes: Spesolimab for Flare Prevention

Reference(s): Morita A et al. Lancet. 2023;402:1541-1551.
Spesolimab Prescribing Information. https://www.accessdata fda gov/drugsatfda_docs/label/2022/761244s000Iblpdf.
Accessed May 30, 2024.

www.peervoice.com/HUM870 Copyright © 2010-2024, PeerVoice