OVERVIEW OF : 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  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 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

 Painful, swollen joints  Stiffness  Dactylitis (sausage-like swelling)  Enthesitis (tendon or ligament pain)  Nail and skin changes  Fatigue

SIGNS AND SYMPTOMS

Back Involvement (40%) DIP involvement (39%) Nail psoriasis (67%)

Dactylitis (48%)

Enthesopathy (38%) http://www.discoverpsa.com/ 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 Swelling, pain and stiffness stiffness Joint Involvement Ray pattern distribution Symmetrical distribution Extra-Articular Rheumatoid nodules Rheumatoid nodules Manifestations absent 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 Laboratory X-Rays: Rheumatoid Factor (RF): Pinpoint changes in the Usually absent in psoriatic affected joints arthritis Synovial Fluid: CT or MRI: Aspiration and examination of Identify changes in tendons or synovial fluid of an affected ligaments or otherwise more joint revealing uric acid crystals detailed examination of joints 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 

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 Current psoriasis: skin or plaque 2 (current) or disease confirmed by a Personal or family history of rheumatologist or dermatologist or psoriasis Family history: in 1st or 2nd degree relative 1 (history) Nail psoriasis Onycholysis, pitting, or 1 hyperkeratosis Negative rheumatoid factor 1 Dactylitis (current or history) Swelling of entire digit 1 Radiographic evidence of Found on x-rays of hand or foot 1 periarticular new bone (excludes osteophytes) formation 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 , 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 CASPAR

 Psoriasis  Inflammatory articular disease  (-) RF  Current psoriasis (2)  Inflammatory arthritis  Nail psoriasis (0)  Meets 1 of 5 subgroup types  Polyarticular, symmetric arthritis  Negative rheumatoid factor (1)  Oligoarticular and asymmetric  Dactylitis (0)  Distal interphalangeal joint predominant (DIP)  Radiographic evidence (0)  Spondylitis predominant  Arthritis mutilans

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 Assessment Methods  Body surface area (BSA) involvement  Psoriasis Area and Severity Index  Palm size = 1% BSA (PASI)  Rule of Tens  Physician Global Assessment (PGA)  Handprint = 1% BSA

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  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 COX-2

Cytoprotective prostaglandins Inflammatory prostaglandins (platelet aggregation, GI (pain, , mitosis, mucosal integrity, renal growth) function) NSAID SELECTIVITY

Nonselective COX-1 and Preferential COX-2 Selective COX-2 Inhibitors COX-2 Inhibitors 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//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:  Adverse effects:  GI (vomiting, diarrhea, stomatitis) Reduces production of nucleic acids Competitively inhibits Reduces synthesis of responsible for cell  Mucosal ulcers dihydrofolate reductase folate cofactors division and proliferation  Hepatotoxicity  Thrombocytopenia  Dosing:  Pulmonary toxicity  Initial: 2.5-5mg test dose  Contraindications:  Weekly: 7.5-25mg  Chronic liver disease  Folate supplementation  Immunocompromised  1-5mg/day except on days of MTX  Preexisting blood disorders  Pregnant/nursing METHOTREXATE: MONITORING

 CBC with differential and platelets  LFTs  Baseline  Baseline  7 to 14 days after initiating therapy or  Monthly for first 6 months dose increase  Every 1 to 2 months  Every 2 to 4 weeks for first few months  Every 1 to 3 months depending on leukocyte count and stability of patient  Pregnancy test  BUN and serum creatinine  Baseline and every 2 to 3 months  Calculate glomerular filtration rate if at  Chest x-ray and pulmonary function risk for renal dysfunction 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 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   Adalimumab  Golimumab  Certolizumab pegol TNF-ALPHA INHIBITORS

MOA:  TNF-α is a protein expressed on the surface of , T- lymphocytes, natural killer cells, smooth muscle cells, and fibroblasts  It is a proinflammatory implicated in the pathogenesis of many diseases, such as rheumatoid arthritis, inflammatory bowel disease, and  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.rxabbvi e.com/pdf/humirape n_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 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 Mind/Body Therapies  Reduce alcohol, gluten, and nightshades  Aromatherapy  Add fish oil, vegetables, and vitamin D  Chamomile, Tea Tree, Rose, Lavender  Special diets:  Meditation  Pagano  Mindfulness  Vegan  Spa therapy  Paleo Alternative Therapies Herbal Remedies  Acupuncture  Aloe Vera  Acupressure  Apple Cider Vinegar  Massage  Capsaicin Exercise  Tea Tree Oil  Yoga  Turmeric  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 THANK YOU!

Jamie L. McConaha, PharmD [email protected]