Evaluating Psoriasis: Patient Reported Outcomes and Impact ... · Psoriasis Patient Expectations • Clearance of psoriasis: the more the better • After a patient is cleared; the

Bruce E. Strober, MD, PhDProfessor and Chair

Department of DermatologyUniversity of ConnecticutFarmington, Connecticut

Evaluating Psoriasis: Patient Reported Outcomes and Impact of Disease

DISCLOSURE OF RELEVANTRELATIONSHIPS WITH

INDUSTRY

Evaluating Psoriasis: Patient Reported Outcomes and Impact of Disease

F029Bruce Strober, MD, PhD

Consultant and Advisory Boards – AbbVie, Amgen, Astra Zeneca, Celgene, Dermira, Janssen, Leo, Eli Lilly, Cutanea-Maruho, Medac, Novartis, Pfizer, Sun Pharma,

Boehringer Ingelheim, UCBInvestigator – AbbVie, Amgen, Boehringer Ingelheim, Galderma, GlaxoSmithKline,

Novartis, Eli Lilly, Janssen, Merck, Sun Pharma, Celgene Scientific Director – CORRONA Psoriasis Registry

Grant Support to the University of Connecticut for Fellowship Program – AbbVie, Janssen

Responsegoal

Before2004

PASI ≤501 PASI 752 PASI 903 PASI 1004

Year 2004 2009 2014 and beyond

Is going from almost clear to clear MEANINGFUL?

Advances in Research have Resulted in a Decade of Rising Expectations

1. Carlin CS; et al. J Am Acad Dermatol. 2004;50:859-866.2. Leonardi CL; et al. N Engl J Med. 2003;349:2014-2022. 3. Papp KA; et al. Lancet. 2008;371:1675-1684.4. Leonardi CL; et al. N Engl J Med. 2012;366:1190-1199.

Question to Audience

Do you believe that patients consider higher levels of clearance in psoriasis clinically meaningful?

1. Yes; the efficacy of drugs does play the predominant role for patients. Higher levels of clearance are very important.

2. No; patients worry most about side effects related to drugs. Robust efficacy is a secondary concern.

Importance rank for dermatologists (%)1

Importance rank for patients (%)1

1. Side effects (87%) 1. Efficacy (78%)

2. Cost (80%) 2. Availability (55%)

3. Route of administration (68%) 3. Convenience (52%)

4. Availability (52%) 4. Side effects (52%)

5. Duration of response (38%) 5. Duration of response (50%)

6. Time required for treatment (35%) 6. How fast treatment works (46%)

Dermatologists and Patients View Psoriasis Differently1

• Patient preferences are often elicited but not subsequently used in decision-making2

• A well-informed; shared decision-making process is important for effective disease management1;2

1. Tan J; et al. J Cutan Med Surg. 2011;15:192-200.

2. Umar N; et al. Acta Derm Venereol. 2012;92:341-346.

Psoriasis Patient Expectations

• Clearance of psoriasis: the more the better• After a patient is cleared; the standards change

– Worsening disease after initial response is an extremely negative event• Patient-reported outcomes (PROs) complement and qualify

objective (“observer only”) tools– Not all PROs are equal– Certain symptoms of psoriasis are universal

• Not all body areas are equal• Gender and age biases are strong

• Dermatology Life Quality Index (DLQI)5

• Psoriasis-specific PROs– Psoriasis Symptom Assessment

(PSA) Scale6

– Psoriasis Symptom Diary® (PSD)7

– Psoriasis Symptom Inventory (PSI)8

• Psoriasis Area and Severity Index (PASI)1

• Physician’s or Investigator’s Global Assessment (PGA or IGA)2;3

• Body surface area (BSA)4

How do we Assess Patients with Psoriasis?

1. FredrickssonT; et al. Dermatologica. 1978;157:238-244.2. Langley RG; Ellis CN. J Am Acad Dermatol. 2004;51:563-9.3. Rich P; et al. Br J Dermatol. 2013;168:402-11. 4. Puzenat E; et al. J Eur Acad Dermatol Venereol. 2010;24S2:10-16.5. Finlay AY; Khan GK. Clin Exp Dermatol. 1994;19:210-216. 6. Shikiar R; et al. Health Qual Life Outcomes. 2003;1:53.7. Lebwohl M; et al. Int J Dermatol. 2014;53:714-722.8. Bushnell DM; et al. J Dermatolog Treat. 2013;24:356-360.

Clinical Assessments

Patient-reportedOutcomes

Clinical Assessments Provide Information on the Extent and Severity of Psoriasis Lesions

Features Assessed/Measured Limitations

PASI1Presence and severity of redness; thickness; and scaling; weighted by involvement of specific body areas

Complex calculation and wide range of score contribute to inter-rater scoring variation

PGA1

Overall disease severityLack of consistency/consensus in scale definition; may not agree well with PASI and BSAIGA2

BSA3 Percentage of body surface covered with psoriasis lesions Does not assess lesion severity

Clinical improvements in these measures do not necessarily translate into patient-perceived benefit

1. Langley RG; Ellis CN. J Am Acad Dermatol. 2004;51:563-569.2. Rich P; et al. Br J Dermatol. 2013;168:402-411.3. Puzenat E; et al. J Eur Acad Dermatol Venereol. 2010;24(Suppl 2):10-16.

Item* Score

1 Symptoms: itchy; sore; painful; or stinging

0 = Not at all1 = A little2 = A lot3 = Very much

2 Feelings: embarrassment or self-consciousness due to skin

3 Domestic activities: shopping or looking after home or garden

4 Clothing choice

5 Social or leisure activities

6 Participation in sports

7 Work or study

8 Relationships

9 Sexual interactions

10 Treatment (degree of mess or time necessary)

DLQI: Widely Used in Clinical Trials

*All items rated over the preceding weekFinlay AY; Khan GK. Clin Exp Dermatol. 1994;19:210-216.

Items are not psoriasis specific

DLQI Correlates with PASI Decrease

Mattei PL; et al. J Eur Acad Dermatol Venereol. 2014;28:333-337.

Correlation analysis of mean percent reduction in PASI vs mean reduction in DLQI

Mea

n re

duct

ion

in D

LQI s

core

Mean reduction in PASI (%)

R2 = 0.8055

12

10

8

6

4

2

025 35 45 55 65 75 85 95

Proportion of patients achieving DLQI 0 or 1

according to PASI response2

PASI < 75(n = 63)

PASI 75 to < 90(n = 15)

PASI 90 to < 100(n = 29)

PASI 100(n = 32)

% o

f p

atie

nts

wit

h

DL

QI 0

/1 a

t W

eek

16

100

80

60

40

20

0*

Mean improvement in DLQIaccording to PASI response1

0

–2

–4

–6

–8

–10

PASI 75 to 89

(n = 15)

PASI < 75

(n = 65)

PASI 100

(n = 32)

PASI 90 to < 100(n = 29)

Mea

n r

edu

ctio

n f

rom

b

asel

ine

DL

QI a

t W

eek

16

**

Increased Skin Clearance Leads to Greater Improvement in Quality of Life

*P = 0.0015 or lower vs PASI < 75. Other between-group differences P = NS

¶P < 0.05 for pairwise comparison vs PASI < 75 and P < 0.05 for pairwise comparison vs PASI 75 to < 90

NS = not significant

1. Edson-Heredia E; et al. IID. 2013.2. Edson-Heredia E; et al. J Eur Acad Dermatol Venereol. 2016;30:864-5.

¶¶


In terms of improvement in QoL; is there a difference between almost clear skin and completely clear skin?

1. No – almost clear is adequate and no different from clear.

2. Yes – but the difference is insignificant for most patients.3. Yes – the difference is substantial à clear is much better than almost clear.

Almost Double the Number of Patients with ‘Clear’ Skin Have DLQI 0 than Those with ‘Minimal’ Psoriasis

CHAMPION and REVEAL Secondary analysis from two phase III studies of adalimumab (combined n = 1469)Percentages of patients with DLQI total score = 0 by physician’s global assessment of disease activity at week 16

Patie

nts

(%) w

ith D

LQI 0

Physician’s global assessment of disease activity

70

60

50

40

30

20

0Clear

(n = 228)Minimal

(n = 408)Mild

(n = 220)Moderate(n = 333)

Severe(n = 167)

10

Revicki DA; et al. Dermatol. 2008;216:260-270.

Quality of Life Worsens Out of Proportion to Worsening in the Objective Signs of Disease

• REVEAL subanalysis: Patients who received adalimumab from baseline

and had a ≥ PASI 75 response at week 16 and week 33 were re-

randomized 1:1 at week 33 to receive blinded therapy with adalimumab 40

mg EOW or placebo EOW from week 33 to week 52.

• The DLQI and PASI relationship was compared for adalimumab-treated

patients while on therapy versus after protocol-mandated treatment

discontinuation.

Poulin Y; et al. Dermatol Ther. 2014;4:33-42.

Quality of Life Worsens out of Proportion to Worsening in the Objective Signs of Disease

*40 mg EOW from Week 1 after 80 mg at Week 0; ¶40 mg EOW from Week 17 after 80 mg at Week 16

Adalimumabn = 26¶

Adalimumabn = 22

Placebon = 240

≥ PASI 75 responders required to continue to

Period B

Adalimumabn = 580

Adalimumabn = 250

≥ PASI 75 responders required to continue to

Period C

Adalimumabn = 814*

Placebon = 398

N = 1212

REVEAL week0 16 33 52



Week 33n = 240

Week 52n = 237

PASI 75PASI 90PASI 100

100

80

60

40

20

0

Patie

nts

(%)


PASI DLQI

Baseline 19.5 11.6

Week 4 8.0 4.3

Week 33 1.2 1.0

Week 52 6.7 5.3


At Week 52; mean PASI scores were lower (improved); yet mean DLQI scores were higher (worse) than they had been early in treatment (Week 4).

Mean PASI and DLQI scores



The same PASI score predicted a higher DLQI score for patients at Week 52 than at Week 4.

Mea

n D

LQI s

core

Mean PASI scoreWeek 52Week 4



• Psoriasis patients who are effectively treated may display a “reset” of what disease level is tolerated.

• Treatment discontinuation after initial success may result in a rebound dissatisfaction with returning disease.

• Dose reduction after initial treatment success may result in a similar phenomenon.


Skin Symptom Location Can Significantly Affect Quality of Life in Patients with Psoriasis (REVEAL study)

*All departures from the reference(contribution to BSA) were statistically significant.Skin lesion severity on the head and upper extremitieshad disproportionately large impacts on DLQI compared

with BSA; particularly for younger women and men

Percentage contribution of body region*

40

30

Upper Trunk

Head

Lower

20

10

Aged <45 years

40

30

Upper Trunk

Head

Lower

20

10

Aged ≥45 years

Contribution (%) of body region to total DLQI score (male)Contribution (%) of body region to total DLQI score (female)Contribution (%) of body region to BSA (reference; combined male and female)Kimball AB; et al. AAD. 2012.


Do you feel we need additional assessment tools to help us better understand patient needs?

1. No – What we already have is adequate.

2. Yes – We cannot fully understand our patients and their needs with what is available.

Psoriasis-Specific PROs May Reflect Patient Status Better than DLQI

• Dermatology Life Quality Index (DLQI) does not adequately provide coverage for psoriasis-specific symptom measurement

• The use of a PRO that adequately captures symptoms associated with psoriasis is important in assessing treatment efficacy

• For example; the Psoriasis Symptom Inventory (PSI) was developed as a psoriasis-specific patient reported eight-item measure of symptom severity and has demonstrated good reliability and validity in patients with psoriasis

Bushnell DM; et al. J Dermatol Treat. 2013;24:356-360. Martin ML; et al. J Dermatolog Treat. 2013;24:255-260.

Psoriasis-Specific PROs Should Meet Four Criteria

• Assess patient experiences most relevant to psoriasis

• Ask questions about experiences in a manner patients can understand

• Avoid unreasonable burden on patients’ recollection of events

• Easy to complete in approximately five minutes

Lebwohl M; et al. Int J Dermatol. 2014;53:714-722.

PROs Provide Information on Patient Perception of Psoriasis

Disease factors assessed Recall period Comments

Dermatology Life Quality Index (DLQI)1

• Symptoms• Psychosocial impact• Physical impairment• Treatment

1 week Does not assess:•Some symptoms relevant to psoriasis•Symptom severity

Psoriasis Symptom Assessment (PSA) Scale2

• Symptom frequency and burden

2 weeks Does not assess:•Clinical severity of symptoms•Psychosocial impact

Psoriasis Symptom Inventory (PSI)3

• Symptom frequency and severity

1 dayor 1 week

Does not assess psychosocial impactInstrument has been used in clinical trials

Psoriasis Symptom Diary (PSD)®4;5

• Symptom frequency; burden; and severity

• Psychosocial impact• Physical impairment

1 day Instrument has been used in clinical trials

1. Finlay AY; Khan GK. Clin Exp Dermatol. 1994;19:210-216. 2. Shikiar R; et al. Health Qual Life Outcomes. 2003;1:53.

3. Bushnell DM; et al. J Dermatolog Treat. 2013;24:356-360.4. Lebwohl M; et al. Int J Dermatol. 2014;53:714-722.

5. Strober BE; et al. Value Health. 2013;16:1014-1022.

Longer recall periods and failure to assess symptoms relevant to psoriasis may limit utility of some PROs

Psoriasis Symptom Diary: Higher Levels of Skin Clearance Can Have a Meaningful Impact on Key Symptoms

Likelihood of a response at week 12Phase III ERASURE and FIXTURE studies of secukinumabGottlieb AB; et al. AAD. 2015.

PASI 75PASI 90

PSD itching PSD pain PSD scaling

100

80

60

40

20

0

Prob

abili

ty o

f res

pons

e (%

)

• Symptoms: itch; redness; scaling; burning; stinging; cracking; flaking; pain

• Each symptom is scored from 0 (not at all severe) to 4 (very severe)

• Total Score ranges from 0 (best) to 32 (worst)

For the following group of questions; the “last 24 hours” means from right now - back to yesterday at this time.

Not at all Mild Moderate Severe

Very Severe

1) Overall; during the last 24 hours; how severe was the itch from your psoriasis?

2) Overall; during the last 24 hours; how severe was the redness of your skin lesions?

3) Overall; during the last 24 hours; how severe was the scaling of your skin lesions?

4) Overall; during the last 24 hours; how severe was the burning of your skin lesions?

5) Overall; during the last 24 hours; how severe was the stinging of your skin lesions?

6) Overall; during the last 24 hours; how severe was the cracking of your skin lesions?

7) Overall; during the last 24 hours; how severe was the flaking of your skin lesions?

8) Overall; during the last 24 hours; how severe was the pain of your skin lesions?

1. Bushnell DM; et al. J Dermatol Treat. 2013;24:356-360. 2. Martin ML; et al. J Dermatolog Treat. 2013;24:255-260.

Psoriasis Symptom Inventory: 8-Item Measure of Psoriasis Symptom Severity1-2

Psoriasis Symptom Inventory: Higher Levels of Skin Clearance Can Have a Meaningful Impact on Key Symptoms

Feldman SR; et al. AAD. 2015.

Mean Total and Item PSI Scores in Patients with sPGA 0 vs 1

Tota

l

Mea

n to

tal P

SI S

core

s

6

5

4

3

2

1

0

Mea

n ite

m P

SI S

core

s

Redne

ss

Scalin

g

Burnin

g

Stingin

g

Crack

ing

Fakin

g

PainItch

1

0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

sPGA 0, n = 79

sPGA 1, n= 151

P < 0.001 for total and each item PSI scorePatients received ustekinumab; adalimumab; infliximab; or etanercept sPGA 0 = complete skin clearance; sPGA 1 = almost clear skin

Summary

• Patients may view psoriasis differently versus dermatologists– Priorities when considering treatment options – Expectations of treatment outcomes

• Higher levels of skin clearance can improve QoL; and may be associated with a meaningful impact on key patient reported symptoms

– Discontinuation of therapy can have negative effects in patients; including a loss of objective response and a disproportionately large negative impact on HRQoL

• Obtaining feedback from patients is an important part of clinical practice– PROs help patients better “weigh in” and validate PASI score reduction

HRQoL = health-related quality of life

Thank you

Bruce E. Strober; MD; [email protected]

Documents

Evaluating Psoriasis: Patient Reported Outcomes and Impact ... · Psoriasis Patient Expectations • Clearance of psoriasis: the more the better • After a patient is cleared; the