OVERVIEW OF PSORIATIC ARTHRITIS: CLINICAL CONSIDERATIONS FOR HEALTHCARE PROFESSIONALS JAMIE L. MCCONAHA, PHARMD, NCTTP, BCACP, CDE

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1 OVERVIEW OF PSORIATIC ARTHRITIS: CLINICAL CONSIDERATIONS FOR HEALTHCARE PROFESSIONALS JAMIE L. MCCONAHA, PHARMD, NCTTP, BCACP, CDE

2 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.

3 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

4 PSORIATIC ARTHRITIS (PSA)

5 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

6 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: Gelfand JM, et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs

7 EPIDEMIOLOGY Affects both men and women equally Usually occurs between 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 Sep 18; 5(4):

8 INCIDENCE AND PREVALENCE COMPARISON Country Incidence (1/100000) Prevalence China NA 0.02% Japan % Greece % France NA 0.19% Italy NA 0.42% Germany NA 0.29% Finland 23.1 NA United States % Mexico NA 0.02% Liu JT, Yeh, HM, Liu SY, Chen KT. Psoriatic arthritis: epidemiology, diagnosis, and treatment. World J Orthop Sep 18; 5(4):

9 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 FitzGerald O, Winchester R. Psoriatic arthritis: from pathogenesis to therapy. Arthritis Res Ther. 2009; 11(1): 214.

10 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.

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

12 SIGNS AND SYMPTOMS DIP involvement (39%) Back Involvement (40%) Nail psoriasis (67%) Dactylitis (48%) Enthesopathy (38%)

13 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):

14 PSORIATIC ARTHRITIS VS RHEUMATOID ARTHRITIS PsA Sex Distribution Males = Females Females > Males Symptoms Swelling, pain and stiffness RA Swelling, pain and stiffness Joint Involvement Ray pattern distribution Symmetrical distribution Extra-Articular Manifestations Rheumatoid nodules absent Nail involvement ~20 nail pits Absent Rheumatoid nodules present Blood Tests Seronegative Seropositive Gladman DD, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64(Suppl II).

15 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.

16 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).

17 MOLL AND WRIGHT CLASSIFICATION SYSTEM 5 subgroups: Polyarticular, symmetric arthritis Oligoarticular and asymmetric Distal interphalangeal joint (DIP) predominant Spondylitis predominant Arthritis mutilans

18 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 Nail psoriasis Current psoriasis: skin or plaque disease confirmed by a rheumatologist or dermatologist Family history: in 1 st or 2 nd degree relative Onycholysis, pitting, or hyperkeratosis 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) 2 (current) or 1 (history) 1 1

19 CASE STUDY: CLASSIFICATION

20 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 athome 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.

21 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)

22 ASSESSMENT OF PSA

23 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

24 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)

25 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

26 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):

27 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.

28 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)

29 /user_upload/microsites/ohne_az/ m_cc13/rheuma/templates/dapsa_ ENG.pdf

30 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.

31 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)

32 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

33 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 Jan; 69(1):

34 PSORIATIC ARTHRITIS GUIDELINES

35 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 Support/Clinical-Practice-Guidelines/Psoriatic-Arthritis

36 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

37 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): Figure reprinted with permission from Oxford University Press.

38 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)

39 NSAIDS Nonsteroidal Anti-Inflammatory Drugs Available over-the-counter and by prescription Alleviate joint symptoms Examples: Ibuprofen Naproxen sodium Sulindac Indomethacin Etodolac

40 Arachidonic Acid COX-1 COX-2 Cytoprotective prostaglandins (platelet aggregation, GI mucosal integrity, renal function) Inflammatory prostaglandins (pain, inflammation, mitosis, growth)

41 NSAID SELECTIVITY Nonselective COX-1 and COX-2 Inhibitors Preferential COX-2 Inhibitors Aspirin Meloxicam Celecoxib Ibuprofen Diclofenac Ketoprofen Indomethacin Naproxen Etodolac Selective COX-2 Inhibitors

42 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): Figure reprinted with permission from Oxford University Press.

43 NSAID ADVERSE EFFECTS Worsening of psoriatic skin lesions Adverse effects by organ system: Cardiovascular risk Gastrointestinal Renal Central nervous system

44 CORTICOSTEROIDS

45 CORTICOSTEROIDS MOA: Provide relief from pain and stiffness by reducing inflammation Glucocorticoids >PLA >Eicosanoid + PAF synthesis Prostaglandins Leukotrienes The main mediators of pain and inflammation

46 CORTICOSTEROIDS Corticosteroids are available in various formulations Topical: 1 st line treatment for skin psoriasis Oral: not used for skin lesions; conditionally recommended for PsA Injectable: used for mild PsA (minimal joints)

47 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): Figure reprinted with permission from Oxford University Press.

48 CORTICOSTEROID INJECTIONS Periodic intra-articular injections can be used as 1 st 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): 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.

49 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.

50 TRADITIONAL DMARDS Disease-Modifying Anti-Rheumatic Drugs Available by prescription only Induce remission of disease Examples include: Methotrexate Leflunomide Sulfasalazine Cyclosporine Antimalarial drugs

51 METHOTREXATE (MTX) MOA: Competitively inhibits dihydrofolate reductase Dosing: Initial: 2.5-5mg test dose Weekly: mg Folate supplementation Reduces synthesis of folate cofactors Reduces production of nucleic acids responsible for cell division and proliferation 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

52 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.

53 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.

54 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

55 LEFLUNOMIDE ADVERSE EFFECTS Diarrhea Hepatotoxicity Anaphylaxis Teratogen (possible carcinogen) Pregnancy-absolute contraindication

56 SULFASALAZINE Prodrug converted to sulfapyridine + 5-aminosalicyclic acid in the colon by enteric bacteria Mechanism of action unknown, but thought to function as an antiinflammatory 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

57 SULFASALAZINE ADVERSE EFFECTS Nausea and vomiting Hypersensitivity Renal dysfunction Anemia Infertility (male) Photosensitivity May make urine/skin yellow

58 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

59 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: /ard

60 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): Figure reprinted with permission from Oxford University Press.

61 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

62 BIOLOGIC DMARDS TNF-Inhibitors T-cell (T-lymphocyte) blockers Interleukin blockers JAK inhibitors

63 BIOLOGIC DMARDS: TNF-INHIBITORS

64 TNF-ΑLPHA INHIBITORS Etanercept Infliximab Adalimumab Golimumab Certolizumab pegol

65 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.

66 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

67 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

68 ETANERCEPT ADMINISTRATION

69 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

70 ADALIMUMAB MOA: binds to TNF-α Interferes with binding to TNF-α receptor sites and subsequently cytokinedriven inflammatory processes Dosing: 40mg subq every other week May continue methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIDs, and/or analgesics Biosimilars: Adalimumab-atto Adalimumab-adbm

71 ADALIMUMAB: ADMINISTRATION e.com/pdf/humirape n_pil.pdf

72 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

73 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

74 BIOLOGIC DMARDS: T-CELL BLOCKERS Abatacept

75 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

76 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

77 BIOLOGIC DMARDS: INTERLEUKIN BLOCKERS

78 INTERLEUKIN BLOCKERS Ustekinumab Secukinumab Ixekizumab

79 INTERLEUKIN BLOCKERS

80 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

81 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

82 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

83 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

84 PDE-4 INHIBITOR

85 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

86 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

87 APREMILAST ADVERSE EFFECTS Depression Weight loss Diarrhea Headache

88 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): Figure reprinted with permission from Oxford University Press.

89 JAK INHIBITOR

90 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

91 TOFACITINIB ADVERSE EFFECTS Serious infections Herpes zoster (shingles) Infections in patients with diabetes Cancer and immune system problems Tears in stomach or intestines

92 COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)

93 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 Accessed August 14, 2018.

94 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

95 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

96 THANK YOU! Jamie L. McConaha, PharmD