Ankylosing Spondylitis & Psoriatic Arthritis

Transcription

1 Ankylosing Spondylitis & Psoriatic Arthritis A Focus on Morbidity and Mortality John D. Carter, MD Associate Professor of Medicine Division of Rheumatology USF Health; Tampa FL 1

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4 Clinical Features of AS Skeletal Axial arthritis (eg, sacroiliitis and spondylitis) Arthritis of girdle joints (hips and shoulders) Peripheral arthritis uncommon Others: enthesitis, osteoporosis, vertebral, fractures, spondylodiscitis, pseudoarthrosis Extraskeletal Acute anterior uveitis Cardiovascular involvement Pulmonary involvement Cauda equina syndrome Enteric mucosal lesions Amyloidosis, miscellaneous 4

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7 Natural History of AS Highly variable Early stages: spontaneous remissions and exacerbations Spectrum of severity Mild with limited sacroiliac or lumbar joint involvement to severe, debilitating disease Pre-spondylitic phase unrecognized period of progressive structural damage over a 5-to-10-year period Average delay in diagnosis is 8.9 years 7

8 Genetic Predisposition for Development of Ankylosing Spondylitis (AS) AS and HLA-B27 strong association Ethnic and racial variability in presence and expression of HLA-B27 HLA-B27 positive AS and HLA- B27 positive Western European 8% 90% Whites African Americans 2% to 4% 48% 8

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10 Modified New York Criteria for the Diagnosis of AS (1984) 10 Clinical Criteria Low back pain, > 3 months, improved by exercise, not relieved by rest Limitation of lumbar spine motion, sagittal and frontal planes Limitation of chest expansion relative to normal values for age and sex Radiologic Criteria Sacroiliitis grade 2 bilaterally or grade 3 4 unilaterally Grading Definite AS if radiologic criterion present plus at least one clinical criteria Probable AS if: Three clinical criterion Radiologic criterion present, but no signs or symptoms satisfy clinical criteria

11 11 Sacroiliitis (plain radiographs)

12 12 Non-radiographic axial spondyloarthritis

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15 15 Spinal Ankylosis (plain radiograph)

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17 Pathogenesis of AS Incompletely understood, but knowledge increasing Interaction between HLA-B27 and T-cell response Increased concentration of T-cells, macrophages, and proinflammatory cytokines Role of TNF Inflammatory reactions produce hallmarks of disease 17

18 Burden of Illness Functional disability Potential complications Quality-of-life issues Pain, stiffness, fatigue, sleep problems Healthcare costs Co-morbidities Work disability 18

19 Obstacles to Desirable Outcomes in AS Until Recently Diagnostic and classification limitations Lack of universally accepted instruments to assess AS Until recently, limited treatment options NSAIDs, DMARDs Mostly symptomatic relief only However, recent data suggest a long-term radiographic protective effect with NSAIDs 19

20 Advances in Medicine: Hope for Patients With AS Increased understanding of pathophysiologic processes Advent of Anti-TNF agents International meetings by ASAS (ASsessment in AS working group) to address need for universal standards Development of ASAS guidelines US modifications to the ASAS International Guidelines to meet realities of clinical practice in the United States 20

21 Disease Activity Assessment Index BASFI BASDAI Disability level Metric Disease activity level ASAS - IC Composite sum of disease activity BASFI = Bath Ankylosing Spondylitis Functional Index BASDAI = Bath Ankylosing Spondylitis Disease Activity Index ASAS - IC = ASsessment in Ankylosing Spondylitis Improvement Criteria 21

22 Bath Ankylosing Spondylitis Functional Index (BASFI) Visual analog scale (VAS) 10 cm Mean score of 10 questions Questions level of functional disability, including: Ability to bend at the waist and perform tasks Looking over your shoulder without turning your body Standing unsupported for 10 minutes without discomfort Rising from a seated position without the use of an aid Exercising and performing strenuous activity Performing daily activities of living Climbing 12 to 15 steps without aid 22

23 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) A self-administered instrument (using 10-cm horizontal visual analog scales) that comprises 6 questions: Over the last one week, how would you describe the overall level of: Fatigue/tiredness AS spinal (back, neck) or hip pain Pain/swelling in joints other than above Level of discomfort from tender areas Morning stiffness from the time you awake How long does morning stiffness last? 23

24 ASsessment in Ankylosing Spondylitis (ASAS) ASAS 20: An improvement of > 20% and absolute improvement of > 10 units on a scale in > 3 of the following 4 domains: Patient global assessment (by VAS global assessment) Pain assessment (the average of VAS total and nocturnal pain scores) Function (represented by BASFI) Inflammation (the average of the BASDAI s last two VAS concerning morning stiffness intensity and duration) Absence of deterioration in the potential remaining domain (deterioration is defined as > 20% worsening) 24

25 Pathogenesis of Joint Destruction Macrophages Proinflammatory cytokines Chemokines Increased Inflammation Endothelium Adhesion molecules Increased Cell Infiltration TNF Synoviocytes Metalloproteinase synthesis Articular Cartilage Degradation Osteoclast progenitors RANKL expression Bone Erosions 25

26 Contraindications for Anti-TNF Therapy Current or recurrent infections Tuberculosis Multiple sclerosis Lupus Malignancy Pregnant or lactating 26

27 Anti-TNF Agents Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Golimumab (Simponi) Certolizumab (Cimzia) 27

28 Anti-TNF Agents: Summary Anti-TNF agents target underlying inflammatory process Alter disease progression Provide symptomatic relief Recommended treatment after trial of chronic daily NSAIDs, physical therapy, and regular exercise Good safety and tolerability profiles Still unclear if they truly delay radiographic progression Implement treatment guidelines to ensure proper treatment given to appropriate patients 28

29 Figure 1. Cumulative incidence of ischemic heart disease (IHD) in the ankylosing spondylitis group (dotted line) and non-as group (solid line). Huang Y-P, Wang Y-H, Pan S-L (2013) Increased Risk of Ischemic Heart Disease in Young Patients with Newly Diagnosed Ankylosing Spondylitis A Population-Based Longitudinal Follow-Up Study. PLoS ONE 8(5): e doi: /journal.pone

30 Cardiac Conduction Abnormalities in Ankylosing Spondylitis Cross-sectional study; 210 participants Mean age: 49 years (16-77 years) All received questionnaires, PE, ECG, lab tests Cardiac conduction disturbances 10-33% (depending conservative or less conservative predetermined criteria) Mostly 1 st Degree AV block and prolonged QRS; 7 with complete bundle branch blocks; one pacemaker Associated with age, male gender and weight; not with labs (including B27) or markers of inflammation 30 Forsblad-D Elia H, et al BMC Musculoskelet Disord

31 Bone Mineral Density in early AS Decreased BMD is common in AS Prevalence range 19-63%; these data mostly from patients with long disease duration Review of BMD in AS patients with disease duration of 10 years Decreased BMD T-score < -1.0 Overall prevalence of 54% L-spine and 51% in femoral neck 31 Van der Weijdan MA, et al Clin Rheumatol 2012

32 Vertebral Fractures (VF s) in AS Study the prevalence and risk factors of VF s in AS 204 patients; mean age 50 and disease duration 15 years VF s diagnosed in 24 (12%) Only previously noted clinically in 3 of the 24 VF s were significantly associated with older age, longer disease duration, higher disease activity, syndesmophytes, and smoking Strongly associated with BMD 32 Klingberg E, et al J Rheuamtol 2012

33 Increased Mortality in AS 677 patients followed for 24 years Crude mortality rate: 14.5% CVD, malignant, infectious: 40%, 26.8%,23.2% Factors associated with reduced survival: Diagnostic delay: OR 1.05 Increased CRP: OR 2.68 Work disability: OR 3.65 NOT using NSAIDs: OR Bakland G, et al Ann Rheum Dis 2011

34 Ankylosing Spondylitis: Healthcare Costs and Productivity Losses Study in UK; cross-sectional study of 612 patients Mean 3 month healthcare cost 2,802 BASDAI <4, 4-6, >6: 1331, 2790, 4840 Direct healthcare costs were just 15% of total costs Unemployment, absenteeism, reduced work productivity: 63.2%, 1.4%, 19% 34 Rafia R, et al. Clin Exp Rheumatol 2012

35 Trends of Long-Term Disability and Sick leave in AS 1993: 91 patients; mean age 35 years 31% on permanent disability 67% of workers had missed at least one day in the preceding 12 months 3%/yr went on permanent disability over the ensuing 5 years 2007: 185 patients; mean age 42 years 39% on permanent disability 40% missed at least one work day last 12 months 35 Ramos-Remus C, et al Clin Rheuamtol 2011

36 Psoriatic Arthritis (PsA): Basic Facts As many as 7.5 million Americans have psoriasis Common, chronic, inflammatory disease of skin and joints Auto-immune disease caused by both genetic and environmental influences Plaque psoriasis is the most common form

37 Other forms of psoriasis Guttate: Small, red, individual spots on skin. Usually appears on trunk and limbs. Pustular: White pustules surrounded by red skin. Inverse: Found in skin folds. Lesions are very red and usually lack scale. Erythrodermic: Fiery redness on large areas of skin. Often accompanied by severe itching and pain.

38 Nail psoriasis Pitting Peeling Discoloration Lifting up from the nail bed Ridging

39 Psoriatic arthritis Inflammatory joint disease found in 10-30% of patients with psoriasis Stiffness, pain, swelling and tenderness of the joints and surrounding ligaments and tendons Early recognition, diagnosis and treatment can help prevent progressive joint involvement and damage Skin symptoms usually appear before joint symptoms, but not always Axial vs peripheral vs both

40 Psoriatic arthritis Early diagnosis and treatment is the key to preventing long-term joint damage Sausage digit

41 Psoriatic arthritis Joint damage is irreversible

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43 Psoriatic arthritis Symptoms to be aware of Back pain/stiffness Pain in heel or bottom of foot Morning stiffness lasting longer than 30 minutes Generalized fatigue Reduced range of motion Swollen fingers and/or toes Can involve only the axial skeleton

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45 Diagnosing psoriatic arthritis There is no one test that can diagnose psoriatic arthritis Physical exam looking for signs of psoriasis and/or psoriatic arthritis Skin, joints, tendon insertion sites Other tests include X-rays or other imaging tests Blood test Other tests (e.g. sample of synovial fluid)

46 Treatments for psoriatic arthritis Disease-modifying antirheumatic drugs (DMARDs) may relieve more severe symptoms and attempt to slow or stop joint/tissue damage and the progression of psoriatic arthritis. Methotrexate (oral and injection) Leflunomide (oral) Sulfasalizine (oral)

47 Treatments for psoriatic arthritis Nonsteroidal anti-inflammatory drugs (NSAIDs) Over-the-counter (OTC) medications such as naproxen and ibuprofen Prescription strength products These will help with pain and inflammation but not with the progression of the disease.

48 Treatments for psoriatic arthritis Biologics approved by FDA for psoriatic arthritis: Etanercept (Enbrel ) Adalimumab (Humira ) Infliximab (Remicade ) Golimumab (Simponi ) Certolizumab (Cimzia) Ustekinumab (Stelara)

49 Most advanced drugs in pipeline for psoriatic arthritis Name Sponsor Mechanism Route Developmen t phase Apremilast Celgene Anti-inflammatory (PDE4 inihibitor) Tofacitinib Pfizer Anti-inflammatory (JAK3 inhibitor) Secukinumab (AIN457) Oral Oral Novartis IL-17 blocker Injectable III III III

50 Psoriasis and heart attacks Recent studies show that psoriasis, in and of itself, can cause cardiovascular risk The greater the psoriasis severity, the greater the risk Controlling psoriasis with certain medications shows promising results for reducing cardiovascular risk

51 Atherosclerosis and Other Vascular Diseases Psoriasis is associated with increased risk of: Ischemic heart disease - 78% Cerebrovascular disease - 70% Peripheral vascular disease - 98% * after controlling for age, sex, hypertension, diabetes mellitus, dyslipidemia, and tobacco

52 Mortality in PsA, RA, Ps Longitudinal cohort study from UK; PsA (n=8706); RA (n=41,752); Ps (n=138,424); controls (n=82,258) PsA: no increased risk of mortality [OR: ] regardless of DMARD use RA: increased risk of mortality [OR: ] regardless of DMARD use Ps: increased risk of mortality [OR: ; ] regardless of DMARD use, but even higher in those prescribed DMARDs 52 Ogdie A et al Ann Rheum Dis 2014

53 CV and All Cause Morbidity in PsA Large systematic review of 28 articles from 1966 to 2011 Studies on all cause mortality were mixed CV mortality more consistent Increased CV mortality and morbidity overall Surrogate markers increased, arterial stiffness, etc. CV risk factors more prominent (HTN, Dyslipidemia, Obesity) in PsA Suppression of inflammation linked to more favorable effect on CV surrogate markers 53 Jamnitski A, et al Ann Rheum Dis 2013

54 Work Disability in PsA Systematic review of 19 publications Unemployment ranged from 20-50% Work Disability 16-39% Predictors: longer disease duration, worse physical function, high joint count, low educational level, female gender, erosive disease, manual work Sparse low-quality evidence that disability is worse in those with PsA compared to Ps alone. 54 Tillett W, et al Rheumatology 2012

55 Work Disability in PsA treated with anti-tnf therapy Population based Swedish Cohort Study; patients with PsA (mean age 43) 67% were work disabled at treatment initiation (sick leave or disability pension) Avg # of work disabled days/month 12.5 to 10.6 (after 3 years of therapy) Control population 2.5 and 3.0 days Significant predictors of disability: prior work disability, anti-tnf failure, higher age, female gender, longer disease duration 55 Kristensen LE, et al Ann Rheum Dis 2013

56 Conclusions AS and PsA are both types of spondyloarthritis and share common features Both AS and PsA are associated with increased risk of CV disease AS, and possibly PsA, are associated with increased all-cause mortality Work disability is more common in both 56