Upload
others
View
0
Download
0
Embed Size (px)
Citation preview
OVERVIEW OF PSORIATIC ARTHRITIS: CLINICAL CONSIDERATIONS FOR HEALTHCARE PROFESSIONALS
JAMIE L. MCCONAHA, PHARMD, NCTTP, BCACP, CDE
FACULTY DISCLOSURES
I have no conflicts of interest to disclose. I do not intend to discuss non-FDA approved drugs or investigational use of any product/device.
OBJECTIVES
Describe the epidemiology and pathophysiology of PsA
List the clinical features and manifestations of PsA that may aid in diagnosis and assessment of disease severity
Describe screening tools for patients suspected of having PsA
Discuss the importance of early detection of PsA and methods and tests used to diagnose the disease
Review treatment and management strategies for patients with PsA
PSORIATIC ARTHRITIS (PSA)
WHAT IS PSORIATIC ARTHRITIS?
Chronic, progressive, inflammatory arthritis
Considered a type of spondyloarthropathy
Swelling, stiffness, and pain in and around the joints, as well as overall fatigue
Early recognition, diagnosis and treatment is crucial to prevent permanent damage
INCIDENCE
Prevalence in patients with psoriasis ranges between 6-42%
Affects approximately 1% of the general population
Estimates vary due to delayed or missed diagnoses
Psoriatic arthritis. National Psoriasis Foundation. Available at:https://www.psoriasis.org/about-psoriatic-arthritis. Gelfand JM, et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol. 2005. Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014.
EPIDEMIOLOGY
Affects both men and women equally
Usually occurs between 30-50 years, but can affect any age
Relationship to psoriasis (skin):
85% of patients present with skin psoriasis first
10-37% have skin and joint disease simultaneously
6-18% have arthritis preceding psoriasis
Liu JT, Yeh, HM, Liu SY, Chen KT. Psoriatic arthritis: epidemiology, diagnosis, and treatment. World J Orthop. 2014. Sep 18; 5(4):537-543.
INCIDENCE AND PREVALENCE COMPARISON
Country Incidence (1/100000) Prevalence
China NA 0.02%
Japan 0.1 0.001%
Greece 3 0.17%
France NA 0.19%
Italy NA 0.42%
Germany NA 0.29%
Finland 23.1 NA
United States 7.2 0.16%
Mexico NA 0.02%
Liu JT, Yeh, HM, Liu SY, Chen KT. Psoriatic arthritis: epidemiology, diagnosis, and treatment. World J Orthop. 2014. Sep 18; 5(4):537-543.
PATHOPHYSIOLOGY
Exact cause is unknown
Complex interplay of genetic, environmental, and immunologic factors
Genetics: strong familial association
Environmental: may trigger immune response (viruses or physical trauma)
Immunologic: activated T cells in joint tissue; TNF-α guides inflammatory process
Husni ME. Psoriatic arthritis. Cleveland Clinic. Oct 2016. FitzGerald O, Winchester R. Psoriatic arthritis: from pathogenesis to therapy. Arthritis Res Ther. 2009; 11(1): 214.
COMORBID CONDITIONS
Psoriasis and psoriatic arthritis comorbidities:
Cancer
Cardiovascular disease
Crohn’s Disease
Depression
Diabetes
Metabolic syndrome
Obesity
Osteoporosis
Uveitis
Liver disease
Treatment of the underlying condition (psoriasis/arthritis) often alleviates comorbid condition symptoms or reduces risk
National Psoriasis Foundation. Comorbidities associated with psoriatic arthritis. https://www.psoriasis.org/about-psoriasis/related-conditions
SIGNS AND SYMPTOMS
Painful, swollen joints
Stiffness
Dactylitis (sausage-like swelling)
Enthesitis (tendon or ligament pain)
Nail and skin changes
Fatigue
SIGNS AND SYMPTOMS
http://www.discoverpsa.com/
Back Involvement (40%)
DIP involvement (39%)
Nail psoriasis (67%)
Enthesopathy (38%)
Dactylitis (48%)
SIGNS AND SYMPTOMS
Many patients experience nonspecific musculoskeletal symptoms before diagnosis
In a 2017 study by Eder et al, the following preclinical symptoms predicted the development of psoriatic arthritis:
Arthralgia in women (hazard ratio [HR] 2.59, P=0.02)
Heel pain (HR 4.18, P=0.02)
High fatigue score (HR 2.36, P=0.007)
High stiffness score (HR 2.03, P=0.045)
Eder L, et al. The development of psoriatic arthritis in patients with psoriasis is preceded by a period of nonspecific musculoskeletal symptoms: a prospective cohort study. Arthritis Rheumatol. 2017; Mar. 69(3):622-629.
PSORIATIC ARTHRITIS VS RHEUMATOID ARTHRITIS
PsA RA
Sex Distribution Males = Females Females > Males
Symptoms Swelling, pain and stiffness
Swelling, pain and stiffness
Joint Involvement Ray pattern distribution Symmetrical distribution
Extra-Articular Manifestations
Rheumatoid nodules absent
Rheumatoid nodules present
Nail involvement ~20 nail pits Absent
Blood Tests Seronegative Seropositive
Gladman DD, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64(Suppl II).
DIAGNOSIS
Imaging
X-Rays: Pinpoint changes in the affected joints
CT or MRI: Identify changes in tendons or ligaments or otherwise more detailed examination of joints
Laboratory
Rheumatoid Factor (RF): Usually absent in psoriatic arthritis
Synovial Fluid: Aspiration and examination of synovial fluid of an affected joint revealing uric acid crystals to rule out gout
There is no single test to confirm a psoriatic arthritis diagnosis.
CLASSIFICATION OF PSORIATIC ARTHRITIS
Moll and Wright Classification Criteria for PsA
Proposed in 1973
Oldest and best-known
Simple to use diagnostic criteria
Inflammatory arthritis (peripheral arthritis and/or sacroiliitis or spondylitis)
Presence of psoriasis
Absence of serological tests for rheumatoid factor
Classifies patients with PsA into 5 subgroups
Helliwell PS, Taylor WJ. Classification and diagnostic criteria for psoriatic arthritis. Ann Rheum Dis. 2005; 64(Suppl II).
MOLL AND WRIGHT CLASSIFICATION SYSTEM
5 subgroups:
Polyarticular, symmetric arthritis
Oligoarticular and asymmetric
Distal interphalangeal joint (DIP) predominant
Spondylitis predominant
Arthritis mutilans
https://psoriatic-arthritis.com/diagnostic-criteria/
CLASSIFICATION OF PSORIATIC ARTHRITIS (CASPAR)
Patient must have inflammatory articular disease (joint, spine, or entheseal) and >3 points
Category Description Points
Current psoriasis or Personal or family history of psoriasis
Current psoriasis: skin or plaque disease confirmed by a rheumatologist or dermatologist Family history: in 1st or 2nd degree relative
2 (current) or 1 (history)
Nail psoriasis Onycholysis, pitting, or hyperkeratosis
1
Negative rheumatoid factor 1
Dactylitis (current or history) Swelling of entire digit 1
Radiographic evidence of periarticular new bone formation
Found on x-rays of hand or foot (excludes osteophytes)
1
https://www.hopkinsarthritis.org/arthritis-info/psoriatic-arthritis/diagnosis/
CASE STUDY: CLASSIFICATION
CASE STUDY: CLASSIFICATION
Kim is a 38 year old white woman you have treated in your practice for five years. Kim has a 3-year history of mild scalp psoriasis but is an otherwise healthy mother of two who works as an attorney. At the end of her most recent annual physical, she mentions she has been experiencing intermittent low back and right sided hip pain with difficulty bending over when picking up her kids or cleaning around the house. Kim notes that the pain began about six months ago without injury and comes and goes without any obvious trigger, although the pain seems to be worse when she gets up in the morning. Kim states that she thinks it is normal “wear and tear” from years of running and standing long periods in court, but would like to know if there are any at-home or OTC remedies she can take when the pain begins. She denies fever, swelling and pain in other joints or worsening of her scalp psoriasis.
Clinical case: psoriatic arthritis. American College of Rheumatology.
CASE STUDY: CLASSIFICATION
Moll and Wright
Psoriasis
(-) RF
Inflammatory arthritis
Meets 1 of 5 subgroup types
Polyarticular, symmetric arthritis
Oligoarticular and asymmetric
Distal interphalangeal joint predominant (DIP)
Spondylitis predominant
Arthritis mutilans
CASPAR
Inflammatory articular disease
Current psoriasis (2)
Nail psoriasis (0)
Negative rheumatoid factor (1)
Dactylitis (0)
Radiographic evidence (0)
ASSESSMENT OF PSA
ASSESSMENT OF PSA
Requires consideration of all major disease domains
Peripheral arthritis
Axial disease
Enthesitis
Dactylitis
Psoriasis
Nail disease
Impact of disease on quality of life
Structural damage
Relevant comorbidities
PSORIASIS ASSESSMENT (SKIN)
General Principles
Body surface area (BSA) involvement
Palm size = 1% BSA
Rule of Tens
Handprint = 1% BSA
Assessment Methods
Psoriasis Area and Severity Index (PASI)
Physician Global Assessment (PGA)
ACR JOINT COUNT
American College of Rheumatology (ACR) uses joint counts in assessment of rheumatoid arthritis
Several types of joint count methods:
66/68 Joint Count
Ritchie Articular Index
Thompson-Kirwan Index
44-Swollen Joint Count
28-Joint Count
ACR JOINT COUNT
Stekhoven D, et al. Hypothesis-free analysis from a large psoriatic arthritis cohort support merger to consolidated peripheral arthritis definition without subtyping. Clinical Rheumatology. 2017; 36(9):2035-2043.
JOINT COUNTS IN PSA
ACR Joint Counts originally developed for RA
Limitations to use for patients with PsA
Modified ACR Count developed for PsA
Reproducibility verified by studies
Not tested specifically for sensitivity to change over time
Miedany Y. Recent developments in management of psoriatic arthritis. Current Rheumatology Reviews. 2005; 1:9-19.
DISEASE ACTIVITY INDEX FOR PSORIATIC ARTHRITIS (DAPSA)
Originally developed for reactive arthritis
Validated for use in PsA
Assesses 5 variables:
Tender and swollen joints
Patient pain assessment (PPA) and patient global assessment (PtGA)
Serum acute-phase response (c-reactive protein)
https://rheuma.charite.de/fileadmin/user_upload/microsites/ohne_AZ/m_cc13/rheuma/Templates/DAPSA_ENG.pdf
QUALITY OF LIFE ASSESSMENT
Important to assess the impact of disease on patient’s quality of life
Physical function
Participation
Measure of improvement in these areas with treatment
Many different scales to assess
Medical Outcomes Study Short Form 36 (SF-36)
Arthritis Impact Measurement Scales (AIMS and AIMS2)
Psoriatic Arthritis Quality of Life (PsAQoL)
Mease PJ. Psoriatic arthritis assessment tools in clinical trials. Ann Rheum Dis. 2005;64 (Suppl III):ii49-ii54.
ADDITIONAL ASSESSMENT TOOLS
Psoriatic Arthritis Screening and Evaluation (PASE)
Psoriasis Epidemiology Screening Tool (PEST)
Toronto Psoriatic Arthritis Screening Tool (ToPAS)
Early Arthritis for Psoriatic Patients Questionnaire (EARP)
PROGRESSION TO SEVERE DISEASE
The following factors indicate a higher likelihood of severe disease:
5+ swollen joints
Elevated acute-phase reactants
High medication use
Poor response to initial treatment
Radiologic evidence of bone erosion
PsA-related disability
MINIMAL DISEASE ACTIVITY (MDA)
5 out of 7 Criteria Met = MDA
Health Assessment Questionnaire <0.5
Swollen joint count <1
Tender joint count <1
Tender entheseal joints <1
PASI / BSA <1 or < 3
Patient assessment of pain on VAS <15
Patient global activity on VAS <20
Coates LC, Fransen J, Helliwell PS. Ann Rheum Dis. 2010 Jan; 69(1): 48-53.
PSORIATIC ARTHRITIS GUIDELINES
PSORIATIC ARTHRITIS GUIDELINES
American College of Rheumatology and National Psoriasis Foundation Clinical Practice Guidelines • Currently under peer review • Anticipated 2018 release European League Against Rheumatism (EULAR): Recommendations for Management of Psoriatic Arthritis with Pharmacologic Therapies • 2015 update
https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Psoriatic-Arthritis
GOALS OF TREATMENT
Reduction of pain
Improvements in the other signs and symptoms of disease (including skin and nail involvement)
Optimization of functional capacity and quality of life
Inhibition of the progression of joint damage
Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis & Rheumatology 2016; 68(5):1060-1071.
Figure reprinted with permission from Oxford University Press.
TREATMENT OPTIONS
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Corticosteroids
Traditional disease-modifying antirheumatic drugs (DMARDs) (oral agents)
Biologics
PDE-4 Inhibitor
JAK Inhibitor
Complementary and alternative medicine (CAM)
NSAIDS
Nonsteroidal Anti-Inflammatory Drugs
Available over-the-counter and by prescription
Alleviate joint symptoms
Examples:
Ibuprofen
Naproxen sodium
Sulindac
Indomethacin
Etodolac
Arachidonic Acid
COX-1
Cytoprotective prostaglandins (platelet aggregation, GI mucosal integrity, renal
function)
COX-2
Inflammatory prostaglandins (pain, inflammation, mitosis,
growth)
NSAID SELECTIVITY
Nonselective COX-1 and COX-2 Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Aspirin Meloxicam Celecoxib
Ibuprofen Etodolac
Diclofenac
Ketoprofen
Indomethacin
Naproxen
Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis & Rheumatology 2016; 68(5):1060-1071.
Figure reprinted with permission from Oxford University Press.
NSAID ADVERSE EFFECTS
Worsening of psoriatic skin lesions
Adverse effects by organ system:
Cardiovascular risk
Gastrointestinal
Renal
Central nervous system
CORTICOSTEROIDS
CORTICOSTEROIDS
MOA:
Provide relief from pain and stiffness by reducing inflammation
Glucocorticoids ------- >PLA2-------- >Eicosanoid + PAF synthesis
Prostaglandins Leukotrienes
The main mediators of pain and inflammation
CORTICOSTEROIDS
Corticosteroids are available in various formulations
Topical: 1st line treatment for skin psoriasis
Oral: not used for skin lesions; conditionally recommended for PsA
Injectable: used for mild PsA (minimal joints)
Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis & Rheumatology 2016; 68(5):1060-1071.
Figure reprinted with permission from Oxford University Press.
CORTICOSTEROID INJECTIONS
Periodic intra-articular injections can be used as 1st line as adjunct to NSAIDs
Mild peripheral disease, dactylitis, and enthesitis
Never used as monotherapy
Sometimes used as bridge therapy while DMARD is instituted or in case of acute flare-ups
Administered by a physician
Examples include:
Prednisone
Cortisone
Dexamethasone
Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis & Rheumatology 2016; 68(5):1060-1071. Gossec L, Smolen JS, Gaujoux-Viala C, et al. European League against Rheumatism European league against rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis. 2012;71(1):4–12.
CORTICOSTEROIDS
Provide relief from pain and stiffness by reducing inflammation
Long-term use should be avoided due to high risk of adverse effects
Psychosis
Retention of fluid/edema/hypertension
Weight gain
Peptic ulcer disease (PUD)
Infection
Osteoporosis
Gossec L, Smolen JS, Gaujoux-Viala C, et al. European League against Rheumatism European league against rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis. 2012;71(1):4–12.
TRADITIONAL DMARDS
Disease-Modifying Anti-Rheumatic Drugs
Available by prescription only
Induce remission of disease
Examples include:
Methotrexate
Leflunomide
Sulfasalazine
Cyclosporine
Antimalarial drugs
METHOTREXATE (MTX)
MOA:
Dosing:
Initial: 2.5-5mg test dose
Weekly: 7.5-25mg
Folate supplementation
1-5mg/day except on days of MTX
Adverse effects:
GI (vomiting, diarrhea, stomatitis)
Mucosal ulcers
Hepatotoxicity
Thrombocytopenia
Pulmonary toxicity
Contraindications:
Chronic liver disease
Immunocompromised
Preexisting blood disorders
Pregnant/nursing
Competitively inhibits dihydrofolate reductase
Reduces synthesis of folate cofactors
Reduces production of nucleic acids
responsible for cell division and proliferation
METHOTREXATE: MONITORING
CBC with differential and platelets
Baseline
7 to 14 days after initiating therapy or dose increase
Every 2 to 4 weeks for first few months
Every 1 to 3 months depending on leukocyte count and stability of patient
BUN and serum creatinine
Baseline and every 2 to 3 months
Calculate glomerular filtration rate if at risk for renal dysfunction
LFTs
Baseline
Monthly for first 6 months
Every 1 to 2 months
Pregnancy test
Chest x-ray and pulmonary function test
Lexi-Drugs (Methotrexate) Lexicomp Online. Hudson, OH: Lexicomp, Inc. Accessed August 9, 2018.
LEFLUNOMIDE
Prodrug that is metabolized into a pyrimidine synthesis inhibitor
T-cell anti-inflammatory effect in vivo
Dosing: 20mg QD
Patient response seen within 1 month
Jones P, White D. Reappraisal of the clinical use of leflunomide in rheumatoid arthritis and psoriatic arthritis. Open Access Rheumatol. 2010;2:53-71.
LEFLUNOMIDE + METHOTREXATE
In patients with RA who were resistant to methotrexate, leflunomide therapy may be added
Different, but complementary, mechanisms of action
Requires careful monitoring of liver function tests
LEFLUNOMIDE ADVERSE EFFECTS
Diarrhea
Hepatotoxicity
Anaphylaxis
Teratogen (possible carcinogen)
Pregnancy-absolute contraindication
SULFASALAZINE
Prodrug converted to sulfapyridine + 5-aminosalicyclic acid in the colon by enteric bacteria
Mechanism of action unknown, but thought to function as an anti-inflammatory agent
Dose:
Initial: 500 mg QD
Maintenance: 2-3 g daily in divided doses
Patient response seen within a month; may take up to 12 weeks in some patients
SULFASALAZINE ADVERSE EFFECTS
Nausea and vomiting
Hypersensitivity
Renal dysfunction
Anemia
Infertility (male)
Photosensitivity
May make urine/skin yellow
CYCLOSPORINE
MOA: suppresses IL-2 and TNF inflammatory actions of T-cells
A last resort DMARD
Effective for peripheral arthritis, axial involvement, and skin lesions
2 most serious side effects:
Nephrotoxicity
Hypertension
ANTIMALARIAL AGENTS
Not FDA-approved for use in PsA
May be beneficial to treat joint inflammation due to additional MOA aside from interfering with malarial parasites
Inhibition of transportation of neutrophils and chemotaxis of eosinophils
Reports of favorable responses have been offset by the worsening of skin disease
Efficacy and safety not yet established in PsA
Future possibilities:
Hydroxychloroquine
Chloroquine phosphate
Nash P, Clegg DO. Psoriatic arthritis therapy: NSAIDs and traditional DMARDs. Annals of the Rheumatic Diseases 2005;64(Suppl II):ii74-ii77.doi: 10.1136/ard.2004.030783
Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis & Rheumatology 2016; 68(5):1060-1071.
Figure reprinted with permission from Oxford University Press.
TRADITIONAL DMARDS-PLACE IN THERAPY
Traditional DMARDs are indicated for moderate-to-severe disease within multiple domains of psoriatic arthritis
Peripheral arthritis (first line)
Dactylitis (second line)
Typically indicated once a patient has insufficient response to NSAIDs and/or local glucocorticoid injections
BIOLOGIC DMARDS
TNF-Inhibitors
T-cell (T-lymphocyte) blockers
Interleukin blockers
JAK inhibitors
BIOLOGIC DMARDS: TNF-INHIBITORS
TNF-ΑLPHA INHIBITORS
Etanercept
Infliximab
Adalimumab
Golimumab
Certolizumab pegol
TNF-ALPHA INHIBITORS
MOA:
TNF-α is a protein expressed on the surface of macrophages, T-lymphocytes, natural killer cells, smooth muscle cells, and fibroblasts
It is a proinflammatory cytokine implicated in the pathogenesis of many diseases, such as rheumatoid arthritis, inflammatory bowel disease, and ankylosing spondylitis
Reduction of TNF-α leads to reduced chronic inflammatory responses in these diseases
Tauseef A, et al. Clinical use of anti-TNF therapy and increased risk of infections. Drug Health Patient Saf. 2013;5:79-99.
TNF-INHIBITORS: GENERAL PRINCIPLES
Contraindicated in patients with active, serious infections
PPD testing should be performed on all patients
Do not give live vaccines
Do not use in patients with multiple sclerosis (MS) or demyelinating diseases
Caution in patients with heart failure
Screening for hepatitis B infection when appropriate
ETANERCEPT
MOA: binds to TNF-α and blocks interaction with cell surface receptors
Dose: 50mg subQ once weekly
Off-label: 25mg twice weekly
Biosimilar: Etanercept-szzs
ETANERCEPT ADMINISTRATION
http://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/enbrel/enbrel_piu.ashx
INFLIXIMAB
MOA: binds to both the soluble and transmembrane TNF-α molecules, thereby neutralizing the effects of TNF-α
Dose:
IV 5mg/kg at 0, 2, and 6 weeks, followed by 3mg/kg every 8 weeks thereafter
Often given in combination with methotrexate
Biosimilars:
Infliximab-dyyb
Infliximab-qbtx
Infliximab-abda
ADALIMUMAB
MOA: binds to TNF-α
Interferes with binding to TNF-α receptor sites and subsequently cytokine-driven inflammatory processes
Dosing: 40mg subQ every other week
May continue methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIDs, and/or analgesics
Biosimilars:
Adalimumab-atto
Adalimumab-adbm
ADALIMUMAB: ADMINISTRATION
http://www.rxabbvie.com/pdf/humirapen_PIL.pdf
GOLIMUMAB
MOA: binds to TNF-α, thus interfering with endogenous TNF-α activity
Dose:
IV Golimumab: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter
SubQ Golimumab: 50mg once a month
Used alone or in combination with methotrexate or other nonbiologic DMARDs
CERTOLIZUMAB PEGOL
MOA: binds to and selectively inhibits TNF-α activity
Dose: SubQ
400mg (given as 2 injections of 200mg each)
Repeat dose 2 and 4 weeks after initial dose
Maintenance: 200mg every 2 weeks or 400mg every 4 weeks
BIOLOGIC DMARDS: T-CELL BLOCKERS
Abatacept
ABATACEPT
MOA: inhibits T-cell (T-lymphocyte) activation by binding to antigen presenting cells (APC), thus blocking the interaction between the two
Activated T-lymphocytes are found in the synovium
Without Abatacept With Abatacept
Illustrating drug binding to CD80/86 and blocking CD28 from binding
ABATACEPT
Dose:
IV: dosed based on body weight; initial infusion followed by repeat infusions at 2 and 4 weeks, then every 4 weeks thereafter
SubQ: 125mg once weekly
Given alone or in combination with nonbiologic DMARDs
BIOLOGIC DMARDS: INTERLEUKIN BLOCKERS
INTERLEUKIN BLOCKERS
Ustekinumab
Secukinumab
Ixekizumab
INTERLEUKIN BLOCKERS
USTEKINUMAB
MOA: inhibits IL-12 and IL-23
Dose:
45mg subQ at 0 and 4 weeks, then every 12 weeks thereafter
Similar to TNF-inhibitors, serious infections remain a concern
USTEKINUMAB: MONITORING/ADVERSE EFFECTS
Development of malignancies (1.3%)
Monitor at-risk patients for non-melanoma skin cancer
Other adverse effects include injection site reactions, headache and fatigue
Avoid live vaccines
SECUKINUMAB
MOA: selectively binds to IL-17
Dose:
With loading dose: 150mg subQ at weeks 0, 1, 2, 3, and 4 followed by 150mg every 4 weeks
Without loading dose: 150mg subQ every 4 weeks
IXEKIZUMAB
MOA: selectively binds to IL-17A
Dose: 160mg subQ given once, followed by 80mg every 4 weeks
*for patients with coexisting moderate-to-severe plaque psoriasis, the dosing schedule for plaque psoriasis is used
PDE-4 INHIBITOR
APREMILAST
Phosphodiesterase 4 (PDE-4) inhibitor
MOA:
PDE-4 regulates the conversion of cAMP AMP
Inhibition of PDE-4 allows for increased levels of cAMP
This results in decreased production of pro-inflammatory cytokines and increased production of anti-inflammatory mediators
Targeted synthetic DMARD
APREMILAST
Used in the treatment of peripheral disease as well as dactylitis and enthesitis
Limited to patients who have failed NSAIDs, corticosteroids, and both the traditional and biologic DMARDs
Dose: 30mg BID
APREMILAST ADVERSE EFFECTS
Depression
Weight loss
Diarrhea
Headache
Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis & Rheumatology 2016; 68(5):1060-1071.
Figure reprinted with permission from Oxford University Press.
JAK INHIBITOR
TOFACITINIB
MOA: inhibits JAK enzymes
Inhibition of these enzymes affects the signaling of multiple cytokines involved in inflammation
Dose:
Immediate release: 5mg BID
Extended release: 11mg QD
May use in combination with nonbiologic DMARDs
TOFACITINIB ADVERSE EFFECTS
Serious infections
Herpes zoster (shingles)
Infections in patients with diabetes
Cancer and immune system problems
Tears in stomach or intestines
COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)
COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)
The National Center for Complementary and Alternative Medicine (NCCAM) and The National Center for Health Statistics (part of the CDC) show that more than 1/3 of Americans use complementary and alternative medicine
Evidence support for CAM use in psoriatic arthritis is anecdotal
Options:
Diet and Nutrition
Herbal Remedies
Mind/Body Therapies
Alternative Therapies
Exercise (including Yoga & Tai Chi)
Complementary and Alternative Therapies. National Psoriasis Foundation. 2018. Accessed August 14, 2018.
COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)
Diet and Nutrition
Reduce alcohol, gluten, and nightshades
Add fish oil, vegetables, and vitamin D
Special diets:
Pagano
Vegan
Paleo
Herbal Remedies
Aloe Vera
Apple Cider Vinegar
Capsaicin
Tea Tree Oil
Turmeric
Mind/Body Therapies
Aromatherapy
Chamomile, Tea Tree, Rose, Lavender
Meditation
Mindfulness
Spa therapy
Alternative Therapies
Acupuncture
Acupressure
Massage
Exercise
Yoga
Tai Chi
SUMMARY
Psoriatic arthritis is a chronic, progressive type of inflammatory arthritis
Patients with psoriatic skin disease should be assessed for symptoms of psoriatic arthritis
Symptoms may include pain, stiffness and tenderness in the joints, as well as dactylitis, enthesitis, and nail changes
Treatment options include NSAIDs, corticosteroids, oral DMARDs, biologics, PDE-4 inhibitors, and JAK inhibitors