Employing Evidence‐Based Strategies for Diagnosing and...
Transcript of Employing Evidence‐Based Strategies for Diagnosing and...
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Employing Evidence‐Based Strategies for Diagnosing and Managing Patients With Psoriasis: The Role of the Primary Care Clinician
Steven R. Feldman, MD, PhDDepartment of DermatologyWake Forest University School of MedicineWinston‐Salem, North Carolina
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Employing Evidence‐Based Strategies for Diagnosing and Managing Patients With Psoriasis: The Role of the Primary Care Clinician
Steven R. Feldman, MD, PhD, has a financial interest/relationship or affiliation in the form of: Consultant for Advance Medical; Amgen Inc.; AbbVie Inc.; Baxter; Caremark; Celgene Corporation; Cosmederm Bioscience, Inc.; Eli Lilly and Company; Galderma Laboratories, L.P.; Gerson Lehrman Group, Inc.; Guidepoint Global, LLC; HanAll BioPharma Co., Ltd.; Informa PLC; Janssen Pharmaceuticals, Inc.; Kikaku America International; LEO Pharma Inc.; Merck & Co., Inc.; Merz, Inc.; Mylan Inc.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Qurient Co., Ltd.; Stiefel Laboratories, Inc./GlaxoSmithKline; Suncare Research Laboratories, LLC; and XenoPort, Inc.
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Anacor Pharmaceuticals, Inc.; Celgene Corporation; GaldermaLaboratories, L.P.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Stiefel Laboratories, Inc./GlaxoSmithKline.
Speakers Bureau participant with AbbVie Inc.; Galderma Laboratories, L.P.; Janssen Pharmaceuticals, Inc.; LEO Pharma Inc.; Stiefel Laboratories, Inc./GlaxoSmithKline; and Taro Pharmaceuticals U.S.A., Inc.
Advisory Board for Pfizer Inc.
Other Financial or Material Support from Informa Plc.; UpToDate, Inc.; and Xlibris; in the form of Royalties.
Dr. Steven Feldman is the Founder, Stock holder, and Chief Technology Officer of Causa Technologies, LLC.
He is also Stock/Majority Owner in the Medical Quality Enhancement Corporation and an Editor for Informa Plc.
Steven R. Feldman, MD, PhD, does intend to discuss either non−FDA‐approved or investigational use for the following products/devices: agents used o‐label or in clinical trials for psoriasis. 2
Please Remember…
•Complete Session Pre‐ and Post‐Test
•Complete Online Session Evaluation at End of Session
– https://www.surveymonkey.com/r/Nov18_315_Psoriasis
**Links found in Event App
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Epidemiology of Psoriasis1
1. https://www.psoriasis.org/about‐psoriasis. Accessed January 13, 2016.
About 1/3 OF PEOPLE with psoriasis also have a family member with the disease
Psoriasis appears EQUALLY in men and women
Psoriasis appears more frequently in patients between the ages of 15 and 35 years
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Economic Burden of Psoriasis1
Total Estimated US Cost$11.25 billion due to medical expenses and lost wages2
Annual Spending on Total Healthcare
More than $10,500 people with moderate to severe
psoriasis vs
about $3,5004
average healthy adults
Annual Work‐Related Costs
~60% missed an average of 26 days work due to their illness3
• 12% stopped work5
• 39% report work‐related
disability6
• 42% experienced limitations in job prospects7
1. Brezinski EA et al. JAMA Dermatol. 2015;151:651‐658. 2. https://www.psoriasis.org/sites/default/files/for‐media/MediaKit.pdf. Accessed January 13, 2016. 3. Horn E et al. J Am Acad Dermatol. 2007;57:963‐971. 4. Yu AP et al. Curr Med Res Opin. 2009;10:2429‐2438. 5. Armstrong AW et al. PLoS One. 2012;7:e52935. 6. Verstappen SM et al. Rheumatology. 2010;49:1570‐1577. 7. Ayala F. J Eur Acad Dermatol Venereol. 2014;28:1623‐1632. 5
Humanistic Burden of Psoriasis1,2
a Suicidal thoughts, suicide attempts, or completed suicides in patients compared with the general public.1. Armstrong AW et al. PLoS One. 2012;7:e52935. 2. Kurd SK et al. Arch Dermatol. 2010;146:891‐895.
44% increased suicidality riska
81% disfigured
87% embarrassed
87% helpless
89% angry
89% self‐conscious
Emotional Well‐Being
82% interferes with enjoyment of life
88% affects overall emotional well‐being
94% problem in daily life
Social Perceptions
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Impact of Psoriasis on HRQOL: Patient Perspective1
Psoriasis Symptom Triggers• Infection• Stress• Dry skin due to weather changes• Certain medications• Trauma
Psoriasis Symptoms• Plaques• Itching• Pain/discomfort• Erythema• Skin flaking
Symptom Modifiers• Effective treatment• Avoidance of triggers• Relaxation techniques
Family Relationship Impairment
• Lack of understanding and support
Activity Impairment• Avoidance of certain hobbies• Lengthy morning routines• Changing careers• Working from home• Continuous cleaning
Psychological Impacts• Poor self‐image• Embarrassment• Stress• Anxiety/nervousness• Frustration• Hopelessness• Uncertainty• Lack of control• Depression
Social Impacts• Stigma/discrimination• Secrecy to avoid disclosing diagnosis to others• Avoid leaving the home• Social isolation
1. Narayanan S et al. Psoriasis Targets and Therapy. 2014;2015:1‐7. 7
Possible Symptoms
Symptom Burden Associated With Psoriasis1
Physical SymptomsUp to 90% of patients suffer from symptoms which can be painful, disfiguring, and disabling
Patches of thick, red (inflamed) skin
Covered with silvery scales
Itching or soreness
Painful cracking of skin
1. http://www.niams.nih.gov/Health_Info/Psoriasis. Accessed January 13, 2016. 8
Major Clinical Categories of Psoriasis
Chronic plaque psoriasis1
• Most common form of psoriasis
• Red, thick, scaly plaque
Guttate psoriasis1
• Often the first outbreak of psoriasis
• Many small plaques distributed rather diffusely, usually all over the chest, stomach and back; may have scattered involvement on extremities
• Early treatment may delay progression to chronic plaque psoriasis
1. https://www.psoriasis.org/about‐psoriasis. Accessed January 13, 2016. 9
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Pustular psoriasis1
• Most common form involves the palms and soles, with potentially disabling pain
• Generalized form is associated with fevers and chills, systemic sickness, and high WBC count
• Pustules can be seen with the naked eye
Erythrodermic psoriasis1
• Whole skin is red from psoriasis
• Very severe, may lead to hospitalization or death
Major Clinical Categories of Psoriasis (Cont'd)
1. https://www.psoriasis.org/about‐psoriasis. Accessed January 13, 2016. 10
Major Clinical Categories of Psoriasis (Cont'd)
Inverse psoriasis1
• Primarily under the arms or in the groin
• Similar to a plaque‐type psoriasis; plaques are usually more red, less thick, and less scaly
Nail psoriasis2
• Causes the nails to be brittle and have fine pits
• Can cause debris under the nail bed and loosening of the nail
• May be a sign of PsA
PsA: psoriatic arthritis.1. https://www.psoriasis.org/about‐psoriasis. Accessed January 13, 2016. 2. Piraccini BM, Starace M. Psoriasis Targets and Therapy. 2015;2015:25‐33. 11
Diagnosis of Psoriasis
Psoriasis affects 2%‐3% of the population
Up to 3.6 million people live with undiagnosed psoriasis in the US1
Average delay in diagnosis = 2 years2
1. Kurd SK, Gelfand JM. J Am Acad Dermatol. 2009;60:218.2. https://www.psoriasis.org/sites/default/files/for‐media/MediaKit.pdf. Accessed January 13, 2016. 12
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Most Common Locations of Lesions in Patients With Psoriasis1
Although not as common,
involvement of hands and feet can be so painful that patients may not be able to
function
1. Van De Kerkhof PCM. In: van de Kerkhof PCM, ed. Textbook of Psoriasis. Oxford, UK: Blackwell Science Ltd; 2003:3‐29.
Location Psoriasis Patients, %
Scalp 80
Elbows 78
Legs 74
Knees 57
Arms 54
Trunk 53
Lower part of the body 47
Base of the back 38
Other 38
Palms and soles 12
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Psoriasis Coverage and Severity1
1. https://www.psoriasis.org/about‐psoriasis. Accessed January 13, 2016.
• Assess involvement using patient’s palm: 1% = surface area of the hand
Mild
Less than 3% of the body has psoriasis
Severe
More than 10% of the body has psoriasis
Moderate
3%‐10% of the body has psoriasis
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PsA in Patients With Psoriasis1
Early recognition, diagnosis, and treatment of PsA are critical to relieving pain and inflammation and helping to prevent progressive joint damage!
Up to 30% of people with psoriasis may develop PsA, making it the most common comorbidity
• Based on a recent study, up to 15% of people being treated for psoriasis could have undiagnosed PsA
Dermatologists and PCPs play an important role in assessment for PsA
• Most patients with PsA have coincidental skin involvement, although arthritis precedes the skin disease in ~15% of cases
1. https://www.psoriasis.org/sites/default/files/for‐media/MediaKit.pdf. Accessed January 13, 2016. 15
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Major Clinical Features of PsA
Clinical patterns described by Moll and Wright1:
Joint manifestations
Nail lesions
Pitting edema
Ocular involvement
Characterized by deforming and destructive arthritis
Asymmetric oligoarthritis
Similar to and, at times, indistinguishable from RA
Including both sacroiliitis and spondylitis
Distal arthritis
<5 small and/or large joints affected in asymmetric distribution
Screen for PsA at every visit, asking about joint pain, stiffness (particularly morning
stiffness), and back pain
DIP: distal interphalangeal; RA: rheumatoid arthritis.1. Wright V, Moll JM. Bull Rheum Dis. 1971;21:627.
Characterized by involvement of the DIP joints
Symmetric polyarthritis
Arthritis mutilans Spondyloarthritis
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Classification Criteria for Psoriatic Arthritis (CASPAR)1
1. Taylor W et al. Arthritis Rheum. 2006;54:2665‐2673.
To meet the CASPAR criteria, a patient must have inflammatory articular disease (joint, spine, or entheseal) with ≥3 points from the following 5 categories:
Points
1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of psoriasis• Evidence of current psoriasis on examination 2• Personal history 1• Family history 1
2. Typical psoriatic nail dystrophy (onycholysis, pitting, hyperkeratosis) on examination
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3. Negative test for rheumatoid factor 14. Dactylitis (inflammatory swelling of an entire finger or toe)
• Current dactylitis on examination 1• Personal history 1
5. Radiographic evidence of juxta‐articular new bone formation on plain radiographs of hands or feet
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Immunopathology of Psoriasis1
CCL: chemokine (C‐C motif) ligand; CXCL: chemokine (C‐X‐C motif) ligand; IFN: interferon; IL: interleukin; NKT: natural killer T cell; Th: T helper; TNF: tumor necrosis factor.1. Nestle FO et al. N Engl J Med. 2009;361:496‐509.
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Risk Factors for Psoriasis
Smoking
Genetics
Alcohol Obesity
Vitamin D deficiency?
Psoriasis
Drugs (eg, βblockers, lithium)
Infections
Address modifiable risk factors where appropriate
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Paradigm of the Natural History of Psoriasis and Comorbidities
• Genes
• Environment
Risk Factors
• Arthritis
• Cancer
• Cardiovascular disease
• Chronic kidney disease
• Infection
• Metabolic disease
• Mortality
• Psychiatric diseases
Outcomes
• Pathophysiology (inflammation, hyperproliferation, angiogenesis)
• Treatment
• Psychosocial impact
Mediating Factors
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Comorbid DiseaseOR for Psoriasis Overall
(95% CI)Adjusted P Value
Cancer 0.85 (0.71‐1.02) .11
Cerebrovascular disease 1.17 (0.94‐1.45) .21
Chronic obstructive pulmonary disease 1.08 (1.02‐1.15) .02
Congestive heart failure 1.08 (0.75‐1.56) .71
Dementia 1.32 (0.57‐3.04) .59
Diabetes mellitus 1.22 (1.11‐1.35) < .001
Diabetes with complications 1.34 (1.11‐1.62) .006
Hemiplegia 0.70 (0.32‐1.50) .44
Metastatic tumor 0.81 (0.32‐2.08) .67
Mild liver disease 1.41 (1.12‐1.76) .008
Moderate to severe liver disease 0.91 (0.33‐2.55) .81
Myocardial infarction 1.34 (1.07‐1.69) .03
Peptic ulcer disease 1.27 (1.03‐1.58) .04
Peripheral vascular disease 1.38 (1.07‐1.77) .02
Renal disease 1.28 (1.11‐1.48) .005
Rheumatologic disease 2.04 (1.71‐2.42) < .001
Atherosclerotic outcomes 1.28 (1.11‐1.47) .004
Association Between Psoriasis Severity and Prevalent Comorbid Diseases1
OR: odds ratio.1. Yeung H et al. JAMA Dermatol. 2013;149:1173‐1179.
Psoriasis is associated with
several comorbidities
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Complexity of the Association Between Psoriasis and Comorbidities1
• Trend in scientific literature and meeting presentations (as reported in 2009) has been to “upgrade” psoriasis from a cutaneous to a systemic disease Before accepting this hypothesis, limitations of observational study designs and
available evidence should be reviewed
• Presence of chronic inflammation (eg, elevated TNF‐α) provides a direct link between psoriasis and many possibly‐associated diseases
PsAHRQOL (impairment, depression)
PsoriasisObesity
Therapy
Comorbidity
Inflammatory state
Biases (eg, detection,
diagnostic bias)
Lifestyle changes (eg, smoking,
alcohol, exercise, diet)
Other Factors That May Play Important Roles and Confound Association
1. Nijsten T, Wakkee M. J Invest Dermatol. 2009;129:1601‐1603. 22
Complexity of the Association Between Psoriasis and Comorbidities1 (Cont'd)
• Existing databases were not designed to detect associations between psoriasis and comorbidities
Statistical associations ≠ causality
Psoriasis patients more likely to visit physicians because of their disease than “healthy” people from the general population
At risk for being screened for and diagnosed with other diseases
1. Nijsten T, Wakkee M. J Invest Dermatol. 2009;129:1601‐1603. 23
Absolute vs Relative Risk vs Clinical Relevance1
P values depend on observed differences between cases and controls and on sample sizes
• Use of very large study populations increases likelihood of detecting statistically significant differences and inaccurate absolute risk
IBD: inflammatory bowel disease.1. Nijsten T, Wakkee M. J Invest Dermatol. 2009;129:1601‐1603. 2. Dreiher J et al. J Invest Dermatol. 2009;129:1643‐1649.
• Absolute risk increment for developing comorbidities in psoriasis patients is almost always <5%
– Observed difference (patients vs controls) for developing osteoporosis was <2.5% (3.1% vs 1.7% for men; 22.3% vs 20.2% for women)
– Study included almost 8,000 patients, thus both differences were highly significant (P < .0001 and P = .008, respectively)2
» Absolute risk almost doubles in men, but in women it increases by only about 1/10
» Increased risk (adjusted for age, IBD, and several chronic conditions in multivariate logistic model) decreased to about 35% in men vs controls (adjusted OR = 1.35; 95% CI = 1.04‐1.75), and disappeared in women, despite considerable residual confounding2
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Unmet Needs in Psoriasis
Based on recent survey results, underdiagnosis, nontreatment, and undertreatment remain significant problems for patients with psoriasis1,2
1. Armstrong AW et al. JAMA Dermatology. 2013;149:1180‐1185. 2. Lebwohl M et al. J Am Acad Dermatol. 2014;70:871‐881.
88% of psoriasis patients with a body surface area of ≥4 palm lesions were receiving no
treatment or topical therapy alone2
52% of psoriasis patients were dissatisfied with their treatment1Unmet
Medical Need
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Treatment Pathways for Psoriasis1
PUVA: ultraviolet A used with psoralen drugs; UVB: ultraviolet B. 1. https://www.aad.org/practice‐tools/quality‐care/clinical‐guidelines/psoriasis. Accessed January 13, 2016. 26
Topical Treatment for Localized Psoriasis1
1. Adapted from Uva L et al. Int J Endocrinol. 2012;2012:561018. 27
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Phototherapy for Extensive Psoriasis
1. Fleischer AB Jr et al. J Invest Dermatol. 1997;109:170‐174. 2. Carlin CS et al. Arch Dermatol. 2003;139:436‐442.
Sun exposure
Referral for office‐based phototherapy
Home phototherapy
Tanning beds (though effective,1,2 AAD discourages use)
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Non‐Biologic Systemic Treatment Considerations1
Treatment Considerations
Methotrexate
• Antimetabolite and antifolate with several side effects; effective and overall safe treatment for psoriasis when used short‐term at low doses and properly monitored
• Effective as monotherapy, but also commonly used in combination with biologics
Cyclosporine
• Antimetabolite; useful as a “rescue drug” for patients who need rapid response with symptomatic relief
• Associated with many side effects (specifically renal toxicity); limit use to short‐term therapy
Acitretin
• Most commonly prescribed oral retinoid; typically used to treat severe psoriasis nonresponsive to other treatments
• Appropriate for long‐term maintenance of psoriasis, as there are no time‐limit restrictions
• Has been used in combination with UVB therapy resulting in more effective, convenient, and safer treatment (particularly for plaque‐type psoriasis)
• Contraindicated in women of childbearing age (very potent teratogen)
Apremilast• Recently approved phosphodiesterase‐4 inhibitor• Less efficacy vs biologics, but offers an alternative to patients who prefer an
oral agent or who do not respond adequately to biologics
1. https://www.psoriasis.org/sites/default/files/systemics_booklet.pdf. Accessed January 13, 2016. 29
Monitoring of Oral Treatment1
Methotrexate
• Complete blood counts, liver function tests regularly
Acitretin
• Liver function tests, triglycerides
Cyclosporine
• Blood pressure, creatinine, triglycerides, magnesium
Apremilast
• No blood monitoring required
1. https://www.psoriasis.org/sites/default/files/npf_treatment_comparisonchart_2015.pdf. Accessed January 13, 2016. 30
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AgentApproved for PsA
Mech. of Action
Route of Admin.
Safety Considerations
Adalimumab1 TNF‐α
inhibitorSubQ
Black Box Warning: Serious infections, malignancyAdverse Reactions: Infections, injection‐site reactions, headache, rash
Etanercept2 TNF‐α
inhibitorSubQ
Black Box Warning: Serious infections, malignancyAdverse Reactions: Infections, injection‐site reactions
Infliximab3 TNF‐α
inhibitorIV
Black Box Warning: Serious infections, malignancyAdverse Reactions: Infections, infusion‐related reactions, headache, abdominal pain
Ustekinumab4 IL‐12/23 inhibitor
SubQAdverse Reactions: Nasopharyngitis, upper respiratory tract infection, headache, fatigue
Secukinumab5 IL‐17A
antagonistSubQ
Adverse Reactions: Nasopharyngitis, diarrhea, upper respiratory tract infection
IL: interleukin; PsA: psoriatic arthritis; TNF: tumor necrosis factor.1. Humira (adalimumab) Prescribing Information. http://www.rxabbvie.com/pdf/humira.pdf. Accessed January 13, 2016. 2. Enbrel (etanercept) Prescribing Information. http://pi.amgen.com/united_states/enbrel/derm/enbrel_pi.pdf. Accessed January 13, 2016. 3. Remicade (infliximab) Prescribing Information. http://www.remicade.com/shared/product/ remicade/prescribing‐information.pdf. Accessed January 13, 2016. 4. Stelara (ustekinumab) Prescribing Information. http://www.stelarainfo.com/pdf/PrescribingInformation.pdf. Accessed January 13, 2016. 5. Cosentyx (secukinumab) Prescribing Information. http://www.pharma.us.novartis.com/product/pi/pdf/cosentyx.pdf. Accessed February 17, 2016.
Biologic Options for Moderate to Severe Psoriasis
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A Closer Look at Secukinumab: Efficacy1
• IL‐17A is considered to be central to the pathogenesis of psoriasis• Sensoready pen; prefilled syringe; lyophilized powder in vial for reconstitution
a P < .0001 vs placebo. b P < .0001 vs etanercept.
IGA mod 2011: investigator global assessment 2011 modified version; PASI: Psoriasis Area Severity Index.1. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DermatologicandOphthalmicDrugsAdvisoryCommittee/UCM419023.pdf. Accessed January 13, 2016.
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A Closer Look at Secukinumab: Safety1
Adverse Reactions Reported by >1% of Patients With Plaque Psoriasis Through Week 12 in ERASURE, JUNCTURE, FEATURE, and FIXTURE
• Caution should be exercised when considering use of secukinumab in patients with chronic infection or history of recurrent infection
• Exacerbations of Crohn’s disease observed in clinical trials with secukinumab
Adverse Reactions, n, %
Secukinumab Placebo (n = 694)300 mg (n = 691) 150 mg (n = 692)
Nasopharyngitis 79 (11.4) 85 (12.3) 60 (8.6)
Diarrhea 28 (4.1) 18 (2.6) 10 (1.4)
Upper RTI 17 (2.5) 22 (3.2) 5 (0.7)
Rhinitis 10 (1.4) 10 (1.4) 5 (0.7)
Oral herpes 9 (1.3) 1 (0.1) 2 (0.3)
Pharyngitis 8 (1.2) 7 (1.0) 0 (0)
Urticaria 4 (0.6) 8 (1.2) 1 (0.1)
Rhinorrhea 8 (1.2) 2 (0.3) 1 (0.1)
RTI: respiratory tract infection.1. Cosentyx (secukinumab) Prescribing Information. http://www.pharma.us.novartis.com/product/pi/pdf/cosentyx.pdf.Accessed February 17, 2016.
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Therapeutic Agents in Development for Moderate to Severe Psoriasis
Class/Target Pathway AgentRoute of
Administration
Small molecules
JAK inhibitor Tofacitinib Oral; topical
Biologic agents
TNF blocker Certolizumab SubQ
Direct inhibition of IL‐17Ixekizumab SubQ
Brodalumab SubQ
IL‐23 blockerTildrakizumab SubQ
Guselkumab SubQ
Ongoing trials evaluating anti‐TNF biosimilars
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When to Initiate Systemic or Biologic Therapy1
Poor or no response to topicals, UVB, PUVA therapy• PUVA involves treatment with either oral or bath psoralen followed
by ultraviolet A (UVA) radiation (320‐400 nm) under strict medical supervision; UVA penetrates deeper into the dermis than UVB and does not have the latter's potential for burning the skin
Received maximum “safe” cumulative PUVA dose
Psoriasis covers >10% BSA
More inflammatory forms of psoriasis
Localized/recalcitrant disease
Physical restrictions
Negative impact on QOL
Status of disease (PASI >10, BSA >10, DLQI >10)
BSA: body surface area; DLQI: Dermatology Life Quality Index; PUVA: UVA used with psoralen drugs; UVB: ultraviolet B.1. Menter A et al. J Am Acad Dermatol. 2009;61:451‐485. 35
Trends in Biologic Use in the United States1,2
Phototherapy or oral systemics
or biologics
Both American Academy of Dermatology and National Psoriasis Foundation support use of biologic as first‐line agent
for patients with moderate to severe psoriasis
“Step therapy”
Phototherapythen oral systemics
then biologics
1. Menter A et al. J Am Acad Dermatol. 2008;58:826‐850. 2. Hsu S et al. Arch Dermatol. 2012;148:95‐102.36
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Biologic Medication Workup1
1. http://www.the‐dermatologist.com/content/choosing‐best‐biologic‐therapy‐patients‐psoriasis.Accessed January 13, 2016.
Skin and joint examinations with medical history• Age appropriate cancer screening• Cancer and infection history• Vaccination history• Total‐body skin exams
Social history• Weight• Alcohol• Tobacco
Family planning
Labs• Complete blood count and comprehensive metabolic panel• Hepatitis (B and C) HIV screen• Tuberculosis test/QuantiFERON Gold (yearly)
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When a Patient Is on a Biologic Agent1 …
• Avoid administering live vaccines– Intranasal flu vaccine, herpes zoster, varicella,
measles/mumps/rubella, oral polio, rotavirus, yellow fever, rabies, BCG, typhoid
– Inactivated or subunit vaccines are generally considered safe but efficacy may be compromised
• Monitor for signs or symptoms of infection– Opportunistic fungal infections– Reactivation of latent TB, underlying hepatitis B/C, shingles
• What if a patient becomes pregnant?
• Surgery
BCG: Bacillus Calmette‐Guerin.1. Hsu S et al. Arch Dermatol. 2012;148:95‐102.
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Which Biologic/Small Molecule Should You Choose First?
Long‐term skin efficacy = durability
Short‐term skin efficacy =
PASI 75
Safety
ConvenienceEfficacy in
psoriatic arthritis
Cost
Considerations for choosing an agent
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Short‐Term Efficacy of Biologics/Small Molecules
• Gives everyone confidence in treatment approach
• Patients and doctors prefer drugs that work quickly
• Patients prefer complete skin clearance or PASI 100
• Many dermatologists treat to minimal disease (clear or almost clear skin)
Paradigm shift needed?
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Comparative Efficacy of Biologics: Data From RCTs1
1. Signorovitch JE et al. Br J Dermatol. 2015;172:504‐512. 41
CLEAR: An RCT of Secukinumab vs Ustekinumab1
a P < .0001. b P = .0001.1. Thaci D et al. J Am Acad Dermatol. 2015;73:400‐409.
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Comparative Efficacy of Biologics: Real‐World vs RCT PGA Clearance1‐3
nb‐UVB: narrow‐band UVB; PGA: Physician Global Assessment.
1. Gelfand JM et al. Arch Dermatol. 2012;148:487‐494. 2. Takeshita J et al. J Am Acad Dermatol. 2014;71:633‐641. 3. Almutawa F et al. Am J Clin Dermatol. 2013;14:87‐109.
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Long‐Term Skin Efficacy With Biologics/Small Molecules
Immunogenicity accounts for most cases of loss of response to biologics
• Stopping and starting: NOT GOOD
• Decreasing dose: NOT GOOD
• Slow and well‐defined decreasing of dose interval: May be OK
Reasons for discontinuation:• Side effects• Cost/insurance coverage
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A Closer Look at the Safety of Biologics1
Agent Most Common Adverse Effects
AdalimumabUpper RTI, urinary infections, abdominal pain, headache, rash, and injection‐site reactions
EtanerceptUpper RTI, dizziness, sore throat, cough, stomach pain, injection‐site reactions, headache, rhinitis
InfliximabInfusion reactions, upper RTI, headache, rash cough, stomach pain
Secukinumaba
Nasopharyngitis, upper RTI, headache
UstekinumabUpper RTI, headache, tiredness, redness at injection site, back pain, fatigue
Golimumabb
Upper RTI, nasopharyngitis
1. Vaidya T et al. Journal of Nature and Science. 2015;1:e53.
a Secukinumab approved January 21, 2015, for the treatment of moderate to severe plaque psoriasis in adults and lacks long‐term safety data; available data are acquired from phase 3 studies of short duration. b Golimumab currently not approved for treatment of plaque psoriasis, but is approved for treatment of PsA. 45
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Risk of Serious Infection With Biologic and SystemicTreatment of Psoriasis: Results From PSOLAR1
PSOLAR: Psoriasis Longitudinal Assessment and Registry• Large intercontinental, prospective, psoriasis‐based registry
MTX: methotrexate. 1. Kalb RE et al. JAMA Dermatol. 2015;151:961‐969.
a Infections defined as serious if associated with 1 or more of the following: (1) death, (2) a life‐threatening condition, (3) persistent or significant disability or incapacitation, (4) a cause or prolongation of hospitalization, or (5) another medically important condition. b Received biologic agent before (prevalent population) or after (incident population) enrolling in registry. c May have been exposed to a different biologic previously. 46
Comorbid Disease in Psoriasis1
Extracutaneous Disorders Linked to Psoriasis
• Psoriatic arthritis
• Obesity
• Metabolic syndrome
• Cardiovascular, cerebrovascular, and peripheral vascular disease
• Malignancy
• Autoimmune diseases
• Chronic kidney disease
• Nonalcoholic fatty liver disease
• Cardiac arrhythmia
• COPD
• Obstructive sleep apnea
• Parkinsonism
• Psychosocial effects
• Psychiatric disorders
• Alcohol abuse
• Smoking
1. http://www.uptodate.com/contents/comorbid‐disease‐in‐psoriasis. Accessed January 13, 2016.47
CV Risk Factor Standard Screening Recommendations
OGTT: oral glucose tolerance test.1. Wolff T, Miller T. Evidence of the Reaffirmation of the US Preventative Services Task Force Recommendations on Screening for High Blood Pressure. Rockville, MD: Agency for Healthcare Research and Quality; 2007. 2. American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S5‐S13. 3. Goff DC et al. Circulation. 2014;129(suppl 2):S49‐S73.
Hypertension1
• Every 2 years, if BP <120/80 mmHg• Yearly, if BP 120‐139/80‐89 mmHg
Diabetes (fasting blood glucose, HbA1C, or OGTT)2
• Adults ≥45 years• Adults with BMI ≥25 kg/m2 + at least one additional risk factor• Repeat every 3 years
CV risk assessment3
• Traditional risk factors every 4‐6 years in patients 20‐79 years• Estimate 10‐year risk in those 40‐79 years of age
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Does Treating Psoriasis Lower CV Disease Risk?
CsA: cyclosporine; MACE: major adverse cardiovascular events; VA: Veterans’ Affairs.1. Prodanovich S et al. J Am Acad Dermatol. 2005;52:262‐267. 2. Wu JJ et al. Arch Dermatol. 2012;148:1244‐1250.3. Ahlehoff O et al. J Int Med. 2013;273:197‐204. 4. Chen YJ et al. Arthritis Rheum. 2012;64:1879‐1887.5. Abuabara K et al. Br J Dermatol. 2011;165:1066‐1073. 6. Ryan C et al. JAMA. 2011;306:864‐871.
YES
VA cohort• Low‐dose MTX associated with lower
risk of vascular disease compared with no MTX (RR 0.50, 95% CI 0.31‐0.79)1
Kaiser Permanente cohort• Lower rate of MI associated with TNF
inhibitors vs topical (HR 0.50, 95% CI 0.32‐0.81) and MTX vs topical (HR 0.52, 95% CI 0.31‐0.85)2
Danish cohort• Lower rate of death, MI, and stroke
associated with biologic (HR 0.28, 95% CI 0.12‐0.64) and MTX (0.50, 95% CI 0.26‐0.97) treatment vs other therapies (CsA, phototherapy, acitretin)3
NO
Taiwan claims data• No effect of MTX vs other treatments (CsA, retinoids, azathioprine, mycophenolate) (HR 0.97, 95% CI 0.79‐1.19)4
US claims data• No effect of MTX, CsA, biologics vs phototherapy (HR 1.33, 95% CI 0.90‐1.96)5
Meta‐analysis of RCTs of TNF inhibitors and IL‐12/23 inhibitors• No benefit on MACE; possible harm6
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Impact of Weight on Biologic Efficacy1,2
1. Clark L, Lebwohl M. J Am Acad Dermatol. 2008;58:443‐446. 2. Rich P et al. Br J Dermatol. 2013;170:398‐407. 3. Cosentyx (secukinumab) Prescribing Information. http://www.pharma.us.novartis.com/product/pi/pdf/cosentyx.pdf.Accessed February 17, 2016.
• Secukinumab clearance and volume of distribution ↑ as body weight ↑3
– Based on post hoc subgroup analyses in patients with moderate to severe psoriasis, patients with lower body weight and lower disease severity may achieve an acceptable response with secukinumab 150 mg (vs 300 mg)
Biologic Weight/BMI PASI 75, %
InfliximabBMI <25BMI >30
7874
AdalimumabBMI <25BMI >30
7965
Etanercept≤89 kg>89 kg
41, 5325, 43
Ustekinumab (45 mg)≤100 kg>100 kg
7454
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Patients With Higher BMI Are Less Likely to Achieve Clear/Almost Clear Skin With Fixed‐Dose Biologics1
1. Hong Y et al. J Invest Dermatol. 2014;134(suppl 1):s50 (abstract 289). 51
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Psoriasis and Infection1
• Screen for streptococcal infection with guttate flares
• Screen for HIV in severe psoriasis
• Vaccination recommendations for patients with psoriatic disease
– Influenza: annual TIV or LAIV before therapy; inactivated vaccine if on systemic therapy
– Pneumonia: PCV13 followed by PPSV23 (6 months later)
– Zoster: 1 dose for adults ages ≥50 years; contraindicated if on therapy
– Hepatitis B
– HPV (ages 9‐26 years)
HPV: human papillomavirus; LAIV: live attenuated influenza vaccine; PCV13: pneumococcal conjugate vaccine; PPSV23: pneumococcal vaccine polyvalent; TIV: trivalent influenza vaccine.
1. Wine‐Lee L et al. J Am Acad Dermatol. 2013;69:1003‐1013.52
Elevated Cancer Risk in Psoriasis
• Biopsy patients with atypical features of psoriasis and/or those not responding to treatment
• Encourage patients to stay up‐to‐date on age‐appropriate cancer screeninga
– Cervical cancer: pap test (ages 21‐65, every 3 years)1
– Breast cancer: mammography (ages 50‐74, every 2 years)2
– Colon cancer: (ages 50‐75) fecal occult blood every year, sigmoidoscopy every 5 years + fecal occult blood testing every 3 years, or colonoscopy every 10 years3
– Lung cancer: annual low‐dose computed tomography for patients ages 55‐80 with ≥30 pack‐year history and current smoker or quit within 15 years4
Large, long‐term follow‐up studies necessary to determine risk of cancer with psoriasis treatments
a Earlier or modified screening recommended in those at high risk.1. http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cervical‐cancer‐screening. Accessed January 13, 2016. 2. http://www.uspreventiveservicestaskforce.org/Page/Document/Recommendation StatementFinal/colorectal‐cancer‐screening. Accessed January 13, 2016. 3. http://www.uspreventiveservicestask force.org/Page/Document/UpdateSummaryFinal/breast‐cancer‐screening1. Accessed January 13, 2016. 4. Moyer VA et al. Ann Intern Med. 2014:160:330‐338.
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The Institute of Medicine’s Perspective on Shared Decision Making1
Patients should be given the necessary information and the opportunity to exercise the degree of control they choose over healthcare
decisions that affect them.
The health system should be able to accommodate differences in patient
preferences and encourage shared decision making.
1. Committee on Quality of Health Care in America, Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academies Press; 2001.
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Medication Adherence in Psoriasis1
Common reasons for medication discontinuation:• Loss of efficacy• Lack of initial response• Adverse events• Inconvenient administration
• Optimizing treatment adherence• Accommodating patient preferences• Emphasizing strong patient‐physician
communication• Conceptualizing treatment risk
Can improve patient satisfaction and clinical outcomes
Nonadherence to biologic treatment regimens
Can lead to anti‐drug antibody formation that
can prevent full medication response
1. Vaidya T et al. Journal of Nature and Science. 2015;1:e53.55
Practical Strategies to Improve Adherence1
Schedule a follow‐up visit shortly after treatment initiation
Ask patients about preferred vehicle for topical therapy (gels and creams vs ointments)
Build patient trust by:• Being empathetic, listening to the patient, physically
examining their skin, practicing good communication skills
Clarify treatment goals in the context of patient expectations
Provide cues to medication administration (eg, setting a phone reminder, environmental cues, behavioral cues)
1. Bewley A, Page B. J Eur Acad Dermatol Venereol. 2011;25(suppl 4):9‐14. 56
Practical Strategies to Improve Adherence1 (Cont’d)
Educate patients about psoriasis as a disease state
Provide information about diagnosis, drug dosing, and treatment duration
Provide an in‐office demonstration showing how to properly apply/administer the prescribed medication• Assure understanding by asking patient to repeat back
treatment instructions
Provide information about alternative treatment options
1. Bewley A, Page B. J Eur Acad Dermatol Venereol. 2011;25(suppl 4):9‐14.57
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Approach to Self‐Management of Psoriasis1
Psoriasis Self‐Management
Address treatment expectations and goals by establishing a personalized doctor‐patient partnership
Topical therapies
• Written recommendations
• Simplify regimens
• Choice of vehicle
Psychosocial
• Awareness of psychiatric comorbidities and acknowledgement of social restrictions
• Utilization of educational resources: ie, National Psoriasis Foundation
• Establish a support system1. Pathak SN et al. Psoriasis: Targets and Therapy. 2014;2014;4:19‐26. doi:10.2147/PTT.S23885.
Systemic therapies
• Provide information on efficacy and safety
• Monitoring for side effects
Medical
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Psoriasis Educational Resources1
National Psoriasis Foundation http://www.psoriasis.org • Provides psoriasis education, online
community support for patients, and information on research and events
TalkPsoriasishttp://www.talkpsoriasis.com • Provides online support for psoriasis patients
and caregivers
Psoriasis Cure Now http://www.psoriasis‐cure‐now.org • Provides current psoriasis news, information
on public policy, and the opportunity to write to Congress for increased research funding
National Library of Medicine Psoriasis Tutorial http://www.nlm.nih.gov/medlineplus/tutorials/psoriasis/htm/index.htm • Provides an online tutorial of psoriasis and its
treatments
Psoriatic Arthritis Information
Arthritis Foundation http://www.arthritis.org
National Psoriasis Foundation http://www.psoriasis.org
Arthritis, Musculoskeletal and Skin Diseases http://www.niams.nih.gov • Provides general information
about psoriatic arthritis
1. Pathak SN et al. Psoriasis: Targets and Therapy. 2014;2014;4:19‐26. doi:10.2147/PTT.S23885.59
When to Refer and Coordination of Care
When to Refer to a Dermatologist
Defined treatment goals are not met
Patient dissatisfaction with treatment outcomes
Discomfort with treating moderate to severe disease
Patients with psoriasis and multiple comorbidities
Involve other healthcare providers in the education, follow‐up, and long‐term care of patients
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• Primary care is essential to psoriasis management– Identify patients who have the condition– Manage mild to moderate cases– Refer where appropriate
» Coordinated care to manage comorbidities
• Screening and treatment for psoriatic arthritis can prevent permanent joint damage
• Psoriasis has a great impact on patients’ lives, but we now have great treatments for this disease
• Our biggest need is not new treatment, but better use of the resources we currently have
Conclusions
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• Complete Session Pre‐ and Post‐Test• Complete Online Session Evaluation at End of Session
• https://www.surveymonkey.com/r/Nov18_315_Psoriasis
**Links found in Event App
Please Remember…
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