EASING THE PATIENT BURDEN OF PSORIASIS AND … Psoriasis.pdf · EASING THE PATIENT BURDEN OF...

EASING THE PATIENT

BURDEN OF PSORIASIS

AND PSORIATIC ARTHRITIS:

THE ROLE OF THE

SPECIALTY PHARMACIST

Claire Lee, PharmD, CSP, CPHQClinical Quality Improvement Supervisor

DiplomatFlint, Michigan

Pharmacy Accreditation

Pharmacy Times Continuing

Education is accredited by the

Accreditation Council for Pharmacy

Education (ACPE) as a provider of

continuing pharmacy education. This

activity is approved for 1.0 contact

hour (0.10 CEU) under the ACPE

universal activity number 0290-

0000-16-022-L01-P. The activity is

available for CE credit through May

3, 2016.

Faculty Disclosure

Claire Lee, PharmD, CSP, CPHQ, has the following relevant financial relationships with commercial interests to disclose.

– Employee: Diplomat

This activity is sponsored

by Pharmacy Times

Continuing Education and

supported by an educational

grant from Lilly.

Learning Objectives

• Explain the pathophysiology, etiology, prognosis, clinical presentation, and comorbidities associated with psoriasis and psoriatic arthritis

• Identify current and emerging treatment options for psoriasis

• Examine current and emerging treatment options for psoriatic arthritis

• Determine the role of the specialty pharmacist in supporting patient education and adherence for psoriasis and psoriatic arthritis

Overview• Psoriasis

– Chronic inflammatory disorder of the skin

– Affects approximately 3.2% of adults over the age of 20 in the US

• 7.4 million adults over the age of 20 (2013)

• Psoriatic Arthritis

– Chronic systemic inflammatory disease

– Affects between 6 and 42% of patients with psoriasis

– Appears before skin manifestations of psoriasis in approximately 10-15% of

patients

• Both diseases affect male and female patients equally

Rachakonda TD, et al. J Am Acad Dermatol. 2014;70(3):512-516.; Mease PJ, et al. Drugs.

2014;74(4):423-441.; Griffiths CEM, et al. Lancet. 2007;370(9583):263-271.

Pathophysiology

From N Engl J Med, Nestle FO, Kaplan DH, Barker J. Psoriasis, 361(5):496-509.

Copyright © (2009) Massachusetts Medical Society. Reprinted with permission

from Massachusetts Medical Society.

Pathophysiology

Increased levels of pro-inflammatory

mediators

Secretion of inflammatory

cytokines

Long-term (ie, chronic)

disruption of immune cell

signaling

Lasting changes to

underlying cell mechanisms in

the skin and joints

Clinical presentation

Mease PJ, et al. Drugs. 2014;74(4):423-441.

Etiology

• Nine chromosomal loci have been associated with statistically significant linkage to psoriasis (PSORS1-PSORS9).

• Disease concordance studies among twins show that the risk of psoriasis is two-three times higher between monozygotic twins than it is among dizygotic twins.

Genetic Factors

• Infection (ie, streptococcal pharyngitis, HIV)

• Stress, trauma, smoking, cold weather, humidity, diet and obesity

• Drugs (ie, beta-blockers, lithium, anti-malarial, interferon)

Environmental Factors

Nestle FO, et al. NEJM. 2009;361(5):496-509.; Chandran V, et al. J Autoimmuni. 2010; 34(3):J314-321.

Clinical Presentation• Chronic Plaque Psoriasis

– Most common form of psoriasis (90%).

– Characterized by well-circumscribed, dry silvery-white scales of variable

thickness

– Lesions are typically located symmetrically and may be more apt to develop at

sites of trauma or injury (ie, Koebner’s phenomenon)

• Other types of psoriasis:

– Guttate

– Inverse (flexural)

– Pustular

– Erythrodermic

Griffiths CEM, et al. Lancet. 2007;370(9583):263-271.; Langley RGB, et al. Ann Rheum Dis. 2005;64(Suppl

II):ii18-ii23.

Clinical Presentation

• Psoriatic Arthritis- Five proposed subtypes

- Classic presentation: distal interphalangel joint involvement, dactylitis, and calcaneal enthesitis

- Nail involvement is more common in patients with psoriatic arthritis than psoriasis alone

- Development of diagnostic criteria has lagged behind that for other arthropathies (ie, rheumatoid arthritis)

Griffiths CEM, et al. Lancet. 2007;370(9583):263-271.; Langley RGB, et al. Ann Rheum Dis.

2005;64(Suppl II):ii18-ii23.; Helliwell PS, et al. Ann Rheum Dis. 2005;64(Suppl II):ii3-ii8.

Comorbidities

ComorbidityHospitalized with

Psoriasis (%)

Hospital-based

Control (%)OR (95% CI)

Metabolic

Syndrome4.3 1.1 5.92 (2.78-12.8)

Diabetes Mellitus

Type II11.7 5.8 2.48 (1.70-3.61)

Arterial

Hypertension21.9 10.2 3.27 (2.41-4.43)

Hyperlipidemia 5.2 2.8 2.09 (1.23-3.54)

Coronary Heart

Disease5.5 3.6 1.77 (1.07-2.93)

Sommer DM, et al. Arch Dermatol Res. 2006;298(7):321-328.

Comorbidities• Patients with psoriasis are at least 1.5 times more likely to experience

depression and use more anti-depressant medications than the general

population

• Psychological symptoms may not correlate with disease severity

• Psychosocial effects

– Shame and embarrassment (89%)

– Anxiety (58%)

– Lack of confidence (42%)

– Depression (24%)

– Family friction (26%)

– Reduction in participation in athletic activities (50%)

– Major difficulties at work (44%)

Dowlatshahi EA, et al. J Invest Dermat. 2014;134(6):1542-1551.; Perrott SB, et al. Physiol Behav.

2000;70(5):567-571.; Russo PAJ, et al. Australas J Dermatol. 2004;45(3):155-161.

Characterizing Disease Severity

• Body surface area affected:

• Patients generally categorized as mild-to-moderate or moderate-to-severe

• Moderate-to-severe typically defined as:– Involvement of more than 5% to 10% of body surface area (BSA)

– Involvement of face, palms, or soles of feet– Disease that is otherwise disabling

< 5%

5-10%

> 10%

Mild Psoriasis

Moderate Psoriasis

Severe Psoriasis

Menter A, et al. Lancet. 2007;370(9583):272-284.

Assessment and Prognosis

• Clinical Practice

– Patient interview

• Assessment Tools

– Psoriasis Area and Severity Index (PASI)

– Physician Global Assessment (PGA)

• Static form (standard)

• Dynamic form

– American College of Rheumatology (ACR) 20

• Quality of life assessment

Feldman SR, et al. Ann Rheum Dis. 2005;64(Suppl II):ii65-68.; Mease PJ, et al. Ann Rheum Dis.

2005;64(Suppl II):ii49-ii54.; Krueger GG, et al. J Am Acad Dermat. 2000;43(2 Pt 1):281-285.

Treatment

• Not a curable disease

• Goals of treatment:– Decrease lesion burden

– Improve quality of life

• Treatments categorized:– Topical

– Phototherapy

– Systemic


Treatment

TNF – tumor necrosis factor; MTX - methotrexate


Topical Therapy

• Used for the majority of patients with mild-to-moderate disease (80% of

patients with psoriasis)

• May be used as supportive therapy for resistant lesions in patients with

more extensive disease that are receiving other therapies

• Not recommended as monotherapy for patients with extensive disease

• High efficacy and safety

• Duration of therapy dependent on clinical goals and agent potency

• Adherence is generally poor

Menter A, et al. J Am Acad Dermatol. 2009;60(4):643-659.

Phototherapy

• Despite recent expansion in available

biologic options, it remains an essential

treatment option, Efficacious

– Cost effective

– No risk for systemic immunosuppressive

effects


Traditional Systemic Therapy

• Used when disease is extensive, debilitating, or

severely impacts quality of life

• Continue to play an important role in treatment

• Benefits include ease of administration and low cost (as

compared to biologics)

• Challenges include toxicity and efficacy (as compared to

biologics)


Traditional Systemic Therapy

Common

• Cyclosporine

• Methotrexate

• Acitretin

Less Common (off-label)

• Azathioprine

• Hydroxyurea

• Leflunamide

• Mycophenolate mofetil

• Sulfasalazine

• Tacrolimus

• 6-thioguanine

Menter A, et al. J Am Acad Dermatol. 2009;61(3):451-485.; Rosmarin DM, et al. J Am Acad Dermatol.

2010;62:838-53.; Jeffes EW III, et al. J Invest Dermatol. 1995;104:183-8.; Schiff MH, et al. Ann Rheum

Disease. 2014;73(8):1549-1551.; Soriatane [package insert]. Research Triangle Park, NC: Stiefel Laboratories,

Inc.; 2015.

Traditional Systemic Therapy• The role of methotrexate (MTX)

– Weekly dosages range from 7.5-25 mg

• Titration to optimal dose is recommended

• Consider intramuscular or subcutaneous injection for patients with adherence issues (equal efficacy)

• Patients not benefitting from oral MTX at doses ≥ 15 mg/week may benefit from subcutaneous administration

– Combination therapy

• For patients with psoriatic arthritis

• Evidence indicates combination therapy with etanercept or infliximab

results in better outcomes than biologic monotherapy for the treatment of psoriasis

Menter A, et al. J Am Acad Dermatol. 2009;61(3):451-485.; Jeffes EW III, et al. J Invest Dermatol

1995;104(2):183-188.; Menter A, et al. J Am Acad Dermatol. 2009;61(3):451- 485.; Schiff MH, et al. Ann

Rheum Disease. 2014;73(8):1549-1551.; Gottlieb AB, et al. British Journal of Dermatol. 2012;167(3): 649–

657.; Baranaskaite A, et al. Ann Rheum Disease. 2012;71(4):541-8.

Biologics

TNF-α inhibitors/ blockers

• Adalimumab

• Etanercept

• Golimumab

• Infliximab

IL-17A antagonist

• Ixekizumab

• Secukinumab

IL-12/23 antagonist

• Ustekinumab

Humira [package insert]. North Chicago, IL: AbbVie Inc; 2015.; Cimzia [package insert]. Smyrna, GA: UCB, Inc;

2013.; Enbrel [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.; Simponi [package insert]. Horsham, PA:

Janssen Biotech, Inc; 2013.; Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.; Cosenty

[package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2015.; Stelara [package insert].

Horsham, PA: Janssen Biotech, Inc; 2012.

Pathophysiology Revisited

From N Engl J Med, Nestle FO, Kaplan DH, Barker J. Psoriasis, 361(5):496-509.

Copyright © (2009) Massachusetts Medical Society. Reprinted with permission

from Massachusetts Medical Society.

Biologics

Drug Chronic Plaque Psoriasis Psoriatic Arthritis

Adalimumab X X

Certolizumab pegol X

Etanercept X X

Golimumab X

Infliximab X X

Ixekizumab X

Secukinumab X X

Ustekinumab X X

Humira [package insert]. North Chicago, IL: AbbVie Inc; 2015.; Cimzia [package insert]. Smyrna, GA: UCB, Inc;

2013.; Enbrel [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.; Simponi [package insert]. Horsham, PA:

Janssen Biotech, Inc; 2013.; Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.; Taltz [package

insert]. Indianapolis, IN: Eli Lilly and Company; 2016.; Cosenty [package insert]. East Hanover, NJ: Novartis

Pharmaceuticals Corporation; 2015.; Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2012.

Adalimumab

• TNF-α inhibitor

• Subcutaneous administration

• Moderate-to-severe chronic plaque psoriasis

– 80 mg at day 0, followed by 40 mg at day 7 and every other week

thereafter

• Psoriatic arthritis

– 40 mg every other week

• Loss of efficacy after restart; optimal treatment strategy is

continuous use

Humira [package insert]. North Chicago, IL: AbbVie Inc; 2015.; Menter A, et al. J Am Acad Dermatol.

2008;58(5):826-850.; Menter A, et al. J Am Acad Dermatol. 2008;58(1):106-115.

Certolizumab Pegol

• TNF-α blocker



– 400 mg at weeks 0, 2, and 4, followed by 200 mg

every other week thereafter

• 400 mg every 4 weeks can be considered for

maintenance therapy

Cimzia [package insert]. Smyrna, GA: UCB, Inc; 2013.

Etanercept

• TNF-α blocker


• Plaque psoriasis

– 50 mg twice weekly for 3 months, followed by 50 mg once weekly thereafter


– 50 mg once weekly +/- methotrexate

• Anti-etanercept antibodies possible

– Do not appear to reduce efficacy

• Potential for loss of efficacy over time

Enbrel [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.; Menter A, et al. J Am Acad Dermatol.

2008;58(5):826-850.

Golimumab

• TNF-α blocker



– 50 mg once monthly +/- methotrexate

Simponi [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.

Infliximab

• TNF-α blocker

• Intravenous infusion

• Plaque psoriasis and psoriatic arthritis

– 5 mg/kg at weeks 0, 2, and 6, followed by every 8 wees

thereafter

• Antibodies possible and likely reduce efficacy

– More likely to develop with intermittent therapy

– Continuous therapy is recommended

Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.; Menter A, et al. J Am Acad Dermatol.

2008;58(5):826-850.

Ixekizumab

• IL-17A antagonist


• Moderate-to-severe plaque psoriasis

– 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12,

and then 80 mg every 4 weeks thereafter

• Shown to be more efficacious than etanercept in clinical trials

• High levels of response through 60 weeks of treatment

• Most common adverse events: nasopharyngitis, upper respiratory tract infection

Campa M, et al. Dermatol Ther (Heidelb). 2015 Dec 29.; Griffiths CEM, et al. Lancet. 2005;386(9993):541-551.;

Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.

Secukinumab• IL-17A antagonist


• Moderate-to-severe plaque psoriasis– 300 mg at weeks 0, 1, 2, 3, and 4, followed by 300 mg

every 4 weeks thereafter• For some patients, 150 mg may be acceptable

• Psoriatic arthritis– When psoriasis also present, use plaque psoriasis

dosing

– Psoriatic arthritis only: 150 mg at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter

• Shown to be more efficacious than etanercept in the treatment of moderate-to-severe plaque psoriasis

Cosenty [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2015.; Langley RG, et al.

NEJM. 2014;371(4):326-338.

Ustekinumab• IL-12 and IL-23 antagonist


• Psoriasis

– Patients weighing ≤ 100 kg (220 lbs): 45 mg at weeks 0 and 4, followed by 45 mg every 12

weeks thereafter

– Patients weighing > 100 kg (220 lbs): 90 mg at weeks 0 and 4, followed by 90 mg every 12

weeks thereafter


– 45 mg at weeks 0 and 4, followed by 45 mg ever 12 weeks thereafter

– 90 mg dosing regimen should be given to patient with co-existent moderate-to-severe

plaque psoriasis weighing > 100 kg (220 lbs)

• Shown to be more effective than etanercept in treating moderate-to-severe

psoriasis

• Biologic least likely to be discontinued

Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2012.; Griffiths CEM, et al. NEJM.

2010;362(2):118-128.

Phosphodiesterase 4 (PDE4)

Inhibition

Schett G, Sloan VS, Stevens RM, Schafer P. Ther Adv Musculoskel Dis.

2010;2(5):271-78. copyright © 2010 by the authors. Reprinted by Permission of

SAGE Publications, Ltd.

Apremilast

• PDE4 inhibitor

• Oral administration

• Moderate-to-severe psoriasis and psoriatic arthritis

– 5 day titration, followed by 30

mg twice daily thereafter

(purpose is to reduce

gastrointestinal adverse effects)

Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.

Day AM Dose PM Dose

Day 1 10 mg --

Day 2 10 mg 10 mg

Day 3 10 mg 20 mg

Day 4 20 mg 20 mg

Day 5 20 mg 30 mg

Day 6 and

thereafter30 mg 30 mg

Clinical EndpointsDrug PASI 75 ACR 20

Adalimumab 71%-78% 58%

Certolizumab pegol N/A 52-58%

Etanercept 34%-49% 50%

Golimumab N/A 51%

Infliximab 75-88% 58%

Ixekizumab 87-90% N/A

Ustekinumab 65%-78% 42%-50%

Secukinumab 67%-87% 38-42%

Apremilast 29%-33% 32%-41%

Humira [package insert]. North Chicago, IL: AbbVie Inc; 2015.; Cimzia [package insert]. Smyrna,

GA: UCB, Inc; 2013.; Kircik LH, et al. J Drugs Dermatol. 2009;8(6):546-559.; Enbrel [package

insert]. Thousand Oaks, CA: Amgen Inc; 2013.; Simponi [package insert]. Horsham, PA: Janssen

Biotech, Inc; 2013.; Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.;

Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.; Stelara [package insert].

Horsham, PA: Janssen Biotech, Inc; 2012.; Cosentyx [package insert]. East Hanover, NJ: Novartis

Pharmaceuticals Corporation; 2015.; Otezla [package insert]. Summit, NJ: Celgene Corporation;

2014.

Emerging Therapies

• Agents targeting IL-23– BI-655066

– Guselumab

– Tildrakizumab

• Agents targeting IL-17– Brodalumab

Campa M, et al. Dermatol Ther (Heidelb). 2015 Dec 29.

BI-655066

• Targets IL-23

• Phase II trial (n=166)

– Patients with moderate-to-severely active psoriasis randomly assigned

to receive BI-655066 (18/0, 90/90, or 180/189 mg) or ustekinumab (45

or 90 mg, per weight), subcutaneously, at weeks 0 and 4

– 77.1% of patients receiving BI-655066 achieved PASI 90 after 12

weeks (compared to 40% with ustekinumab)

– Most common adverse effects: runny nose, sore throat, headache

• Trials ongoing

Campa M, et al. Dermatol Ther (Heidelb). 2015 Dec 29.; Papp K, et al. [abstract]. American Academy of

Dermatology; 2015 Mar 20-24; San Francisco, CA.

Guselkumab (CNTO-1959)• Targets IL-23

• Phase II trial (n = 293)

– Double-blind, randomized,

placebo-controlled, dose-

ranging, active-comparator

study

– Results

– Proportion of patients

achieving PGA score of 0 or 1

was significantly higher in the 50, 100, and 200 mg

guselkumab groups than in

the adalimumab group

• Phase III trials ongoing

Treatment

PGA Score of 0

(clear) or 1

(almost Clear at

16 Weeks

PASI 75 at 16

Weeks

Guselkumab 5 mg 34% 44%

Guselkumab 15

mg61% 76%

Guselkumab 50

mg79% 81%

Guselkumab 100

mg86% 79%

Guselkumab 200

mg83% 81%

Adalimumab† 58% 70%

Placebo 7% 5%

† 80 mg at week 0, 40 mg at week 1 and every other week thereafter.

Campa M, et al. Dermatol Ther (Heidelb). 2015 Dec 29.; Gordon KB, et al. NEJM. 2015;373(2):136-144.

Tildrakizumab (MK-3222)

• Targets IL-23

• Phase IIb trial (n = 355)

– Patients randomized to receive

tildrakizumab at a dose of 5, 25,

100, or 200 mg or placebo,

subcutaneously at weeks 0, 4, and

every 12 weeks thereafter

– After 16 weeks, the proportion of

patients achieving PASI 75 was significantly higher, when compared

to placebo, for all doses

– Low relapse rate after cessation of

therapy

• Phase III trials are ongoing

Treatments PASI 75

Tildrakizumab 5 mg 33.3%




Placebo 4.4%

Campa M, et al. Dermatol Ther (Heidelb). 2015 Dec 29.

Brodalumab

• Targets IL-17

• Initially showed very promising results for moderate-to-severe

plaque psoriasis in phase III trials

– PASI 75 in 83-86% of patients after 12 weeks (210 mg dose)

• Phase III trials were halted in May 2015 due to “events of suicidal

ideation and behavior in the brodalumab program, which…likely

would necessitate restrictive labeling”

– Importance of context

• Further development to be determined

Campa M, et al. Dermatol Ther (Heidelb). 2015 Dec 29.; Danesh MJ, et al. JAAD. 2016;74(1):190-192.

Role of the Specialty Pharmacist

• Promote adherence

– Extent to which patients take medications as

prescribed by their health care providers

– Types of adherence

• Intentional (ie, skipping doses, changing the dose,

self-discontinuation)

• Unintentional (ie, forgetfulness, running out,

carelessness)

Cramer J, et al. Value Health. 2008;11(1):44‐7.; Gadkari A , et al. BMC Health Serv Res. 2012;12:98‐110.


• Poor adherence rates– Up to half of patients do not adhere to

treatment

– Most commonly reported reasons:• Lack of efficacy/frustration

• Forgetting

• Too busy

• Regimen too time consuming or inconvenient

Richards HL, et al. J Eur Acad Dermatol Venereol. 2006;20(4):370-9.


• Memory aids

– Pill boxes/dose packaging

• Studies demonstrating impact also utilized educational

interventions

• Motivational interviewing

– Studies in psoriasis significantly demonstrate:

• Reductions in disease severity

• Improvements in psoriasis self-management levels

Lee JK, et al. JAMA. 2006;296(21):2563-71.; Larsen MH, et al. Br J Dermatol. 2014;171(6):1458-69.


• Technology

– Text message interventions in psoriasis

• Included reminders (3x/week) and educational tools (4x/week)

• Significant improvements seen in adherence and disease severity

• Patient access support

– Higher costs are correlated with lower adherence

– Copay assistance helps lower patient cost-share

• Copay cards

• Foundational assistance

Balato N, et al. Br J Dermatol 2013; 168(1):201-205.; Eaddy MT, et al. PT. 2012;37(1):45-55.


• Injection technique

– Patients may be new to injectable medications

– Coach on:

• Storage

• Proper injection sites and rotation

• Injection preparation

• Injection technique

• Proper disposal

Humira [package insert]. North Chicago, IL: AbbVie Inc; 2015.


• Adverse event counseling– Expectation setting

– Adverse event mitigation strategies

• Pharmacists often get questions related to injection site reactions and pain– Symptoms should go away within a few days

– Follow up with provider if persistent

– Review injection technique

• Infections– Follow up with provider; patient may need to interrupt

therapy

Humira [package insert]. North Chicago, IL: AbbVie Inc; 2015.

• Lifestyle modification

– Up-to-date vaccinations

– Healthy diet

– Avoid smoking, minimize alcohol

– Patient must know how to care for their skin

• Hygiene

• Clothing types

• Sun exposure

• Moisturizing

Balato N, et al. Br J Dermatol. 2013; 168(1):201-205.


Additional Resources

• The American Academy of

Dermatology (AAD)

• The National Psoriasis Foundation

EASING THE PATIENT BURDEN OF PSORIASIS AND … Psoriasis.pdf · EASING THE PATIENT BURDEN OF...

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