UCI grand rounds 2014 4 Outline • Ankylosing Spondylitis defined • Epidemiology in the U.S. •...
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12/2/14 1 Ankylosing Spondylitis in 2014 Lianne S. Gensler, M.D. Associate Professor of Medicine Director, Ankylosing Spondylitis Clinic UCSF Rheumatology Outline • Ankylosing Spondylitis defined • Epidemiology in the U.S. • Assessment & diagnosis in primary care • Initial treatment & treatment advances • Comorbidities to remember Diagnosis vs. Classification • Diagnostic criteria are developed to be highly sensitive to identify as many patients with the disease as possible • The value of diagnostic tests/ parameters depends on the prevalence of the disease (pretest probability) • Should allow for flexibility in diagnostic confidence (definite, probable, possible) • Applied to the individual patient • Classification criteria are developed to define a homogeneous group for the purpose of research • High specificity to avoid misclassification • No dependence of disease prevalence as patients are already diagnosed • Applied to a group Evidence based medicine ICD9 code – clinical diagnosis Outline • Ankylosing Spondylitis defined • Epidemiology in the U.S. • Assessment & diagnosis in primary care • Initial treatment & treatment advances • Comorbidities to remember
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Transcript of UCI grand rounds 2014 4 Outline • Ankylosing Spondylitis defined • Epidemiology in the U.S. •...
12/2/14
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Ankylosing Spondylitis in 2014!
Lianne S. Gensler, M.D.!Associate Professor of Medicine!
Director, Ankylosing Spondylitis Clinic!UCSF Rheumatology!
Outline
• Ankylosing Spondylitis defined
• Epidemiology in the U.S.
• Assessment & diagnosis in primary care
• Initial treatment & treatment advances
• Comorbidities to remember
Diagnosis vs. Classification • Diagnostic criteria are
developed to be highly sensitive to identify as many patients with the disease as possible
• The value of diagnostic tests/parameters depends on the prevalence of the disease (pretest probability)
• Should allow for flexibility in diagnostic confidence (definite, probable, possible)
• Applied to the individual patient
• Classification criteria are developed to define a homogeneous group for the purpose of research
• High specificity to avoid misclassification
• No dependence of disease prevalence as patients are already diagnosed
• Applied to a group
Evidence based medicine
ICD9 code – clinical diagnosis
Outline
• Ankylosing Spondylitis defined
• Epidemiology in the U.S.
• Assessment & diagnosis in primary care
• Initial treatment & treatment advances
• Comorbidities to remember
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American College of Rheumatology, Image Bank (#99-07-0014 )
Age = 26 years! Bilateral THAs!
PSORIASIS
Spondyloarthritis: a family of diseases
Ankylosing Spondylitis: sacroiliitis & spondylitis
30-40%!
8-10%!Subclinical Colitis !25-60%!
10%!Inflammatory Bowel
Disease
Acute Anterior Uveitis
Lin P et al., PLoS One. 2014; 9(8)
Reveille JD Nat. Rev. Rheumatol. (8)296–304 (2012)!
Outline
• Ankylosing Spondylitis defined
• Epidemiology in the U.S.
• Assessment & diagnosis in primary care
• Initial treatment & treatment advances
• Comorbidities to remember
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HLA B27 in the U.S. population!
Reveille JD et al., Arth Rheum Vol. 64, No. 5, May 2012, pp 1407–1411!
NHANES 2009-2010
Reveille JD et al, Arthritis Care & Res. Vol. 64, No. 6, June 2012, pp 905–910
Weisman MH et al., Ann Rheum Dis. 2013 Mar;72(3):369-73.
• 19.2% chronic axial pain • In patients with chronic axial pain, 28-35.5% had IBP • Prevalence of IBP 5-6%
• Between non-Hispanic white persons and non-Hispanic • black persons: (5.9 vs 3.3%; t=3.99, p<0.01).
• Self-reported prevalence of AS = 0.55
Axial SpA in Chronic back pain populations
• Primary Care clinics (n = 364) • In chronic low back pain patients 20 to 45 yrs of age
Van Hoeven L., Arthritis Care Res (Hoboken). 2014 Mar;66(3):446-53. !
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Outline
• Ankylosing Spondylitis defined
• Epidemiology in the U.S.
• Assessment & diagnosis in primary care
• Initial treatment & treatment advances
• Comorbidities to remember
Case !• 24 year old man with low back pain that started
7 years ago. He has seen several chiropractors and an orthopedic surgeon with ongoing symptoms.!
• Initially alternating buttock pain, worse in the morning with associated am stiffness lasting 60 minutes. Pain would awaken him from sleep around 3am. The pain is made better with ibuprofen and exercise and he feels almost normal by midday.!
Inflammatory Back Pain: hallmark feature !
Feature Odds Ratios Insidious onset 12.7 Pain at night (with improvement upon getting up) 20.4 Age at onset <40 years 9.9 Improvement with exercise 23.1 No improvement with rest 7.7
Sieper J, et al. Ann Rheum Dis. 2009; Rudwaleit M, et al. Ann Rheum Dis. 2009; Ozgocmen S, Akgul O, Khan MA. J Rheumatol. 2010!
Feature! Odds Ratios!Insidious onset ! 12.7!Pain at night (with improvement upon getting up) ! 20.4!Age at onset <40 years ! 9.9!Improvement with exercise ! 23.1!No improvement with rest ! 7.7!
Sensitivity 79.6% & Specificity 72.4%!Positive LR = 79.6/(100-72.4) = 2.9 ~ Probability = 14%!
1. Check HLA B27!2. Check ESR/CRP!3. Order imaging study!4. Obtain additional history!Evaluate for other symptoms:!peripheral joint pain, heel pain, bloody stools/ diarrhea, rashes!Evaluate for other diagnoses:!Acute anterior uveitis, IBD, Psoriasis!Assess Family history:!20% AS pts will have a FDR with AS!!
Your next step is to…!
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Case cont.!• The patient tells you his father has
Ankylosing Spondylitis!
• How does this additional data change your assessment?!
AS in Chronic Low Back Pain Population 5%!
Inflammatory back pain ! LR 3.1!
3.1 multiplied by 5.1 gives a likelihood product of 15.81. fam hx à LR 15.81 x 6.4 = 101 !
Elevated ac. phase reactants LR 2.5!
Heel pain (enthesitis) ! LR 3.4!Peripheral arthritis ! LR 4.0!Dactylitis ! LR 4.5!Acute anterior uveitis LR 7.3 !Positive Family history LR 6.4 !Good response to NSAIDs LR 5.1 !
HLA-B27 ! LR 9.0 !MRI ! ! LR 9.0 !
!!!!
LR 15.81 à! Probability = 45%!
Rudwaleit M, et al. Arthritis Rheum 2005; 52:1000-8!
Probability of Spondyloarthritis Using Multiple Clinical and Lab Features!
LR 101 à !Probability =! 84%!!
Pr = 98%!
Slide courtesy of Walter P. Maksymowych, with permission
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Axial SpA Epidemiology!Ankylosing Spondylitis!Non-radiographic Axial SpA!
Radiographic !sacroiliitis!
Bamboo spine!
:! : 1 : 2-3
DAMAGE!
HLA B27 85-95%!Age of onset 16 – 40!!(Milder disease !
Or !early disease)!
Helmick CG et al, Arthritis Rheum 2008; 58: 15-25!Reveille JD et al., Arth & Rheum Vol. 64, No. 5, May 2012, pp 1407–11!Reveille JD et al., Arthritis Care Res. 2012; 64:905!
Axial SpA Prevalence ~ 1%
Inflammatory !Back pain!
L spine MRI misses SI joints!
AP pelvis!
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AS Physical Exam!
Occiput to wall measure (normal = 0cm)
Chest expansion score (normal = ≥ 1.9 cm)
AS Physical Exam!
Modified Schober test or Anterior Lumbar Flexion (normal ≥ 2cm increase)
Anterior lumbar flexion (modified Schober test)
Assassi S et al., Arthritis Rheumatol Vol. 66, No. 9, September 2014, pp 2628–2637
Threshold = 2.0 cm
Thoracic (Chest) Expansion
Assassi S et al., Arthritis Rheumatol Vol. 66, No. 9, September 2014, pp 2628–2637
Threshold = 1.9 cm
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Outline
• Ankylosing Spondylitis defined
• Epidemiology in the U.S.
• Assessment & diagnosis in primary care
• Initial treatment & treatment advances
• Comorbidities to remember
Case
The patient returns to see you with a new diagnosis of AS. He is most bothered by the night pain and has 90 minutes of morning stiffness. A rheumatology appointment is scheduled for 6 weeks. He asks if you can prescribe something while he waits to be seen.
When I was an intern…!• Only drugs approved for AS were NSAIDs!• No biologics shown to be effective in AS!!
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AS: Treatment!
NSAID NSAIDs sulfasalazine TNF inhibitors
Axial disease only!
If peripheral !disease!
Physical Therapy Braun J, et al.,, Ann Rheum Dis 2011; 70: 896-904!van der Heijde D, et alAnn Rheum Dis 2011; 70:905-08!
×
NSAIDs!
• First line therapy!• NSAIDs better than
placebo!• No difference in efficacy
across NSAIDs (FDA approved)!
!
Boulos P et al., Drugs 2005;65 (15):2111-27!Amor B et al., Rev Rhum Engl Ed. 1995 Jan;62(1):10-5!!
0 20 40 60 80
Ankylosing Spondylitis!
Mechanical back pain!
Response to NSAIDs!
AS: Efficacy of TNFα inhibitors!
45 39
47 44 48
14 13 12 15 16
Etanercept adalimumab Infliximab Golimumab Certolizumab
ASAS 40 Responses in 5 separate trials!TNF inhibitor! Placebo!
Davis et al, Arthritis & Rheum, 48 (11), Nov 2003: 3230-3236!Van der Heijde et al., Arthritis & Rheum, 54, 7. July 2006: 2136-2146 [ATLAS]!Van der Heijde et al., Arthritis & Rheum, 52, 2. Feb 2005: 582-591 [ASSERT]!Inman et al., Arthritis & Rheum, 58 (11) Nov 2008: 3402-12 [GO-RAISE]!Landewe et al., Annals Rheum Dis. 2014 Jan;73(1):39-47 [RAPID-axSpA ]!!
Do TNFi slow down damage?
Van der Heijde et al., Arth Res & Ther 2009
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Haroon N et al., Arth Rheum 2013
Benefit shown after 3.8 years
TNFi use: OR: 0.52; CI: 0.30-0.88; p=0.02
Haroon N et al., Arth Rheum 2013
Flare after withdrawal
Haibel et al. Barkam et al. Song et al. Sieper et al. Arthritis Rheum Ann Rheum Dis Ann Rheum Dis Ann Rheum Dis 2013; 65: 2211-3 2009; 68 (Suppl. 3):72 2012; 71(7): 1215-15 2013 Jun 5
Glucocorticoids not recommended in AS!
• Double blind RCT 2 week trial!• Prednisolone 20mg vs. 50mg vs placebo!• Only 50mg/day à short-term response sig higher
than placebo!
Haibel H, et al. Ann Rheum Dis 2013;0:1–4!
50mg 20mg placebo
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Physical Therapy & Exercise!• PT meta-analysis showing benefit!• Exercise improves function!• Tai chi improves disease activity & flexibility!• Aerobic & pulmonary exercise!• Interaction between exercise & TNFα
inhibitors to improve long term function!
1. Dagfinrud H et.al., 2008; Cochrane Collaboration!2. Brophy S et al., Semin Arth Rheum 2013 Jun;42(6):619-26!3. Lee EN et al., 2008 Evid Based Complement Alternat Med 5, 457–62!4. Fernandez-de-Las-Penas C, et al. (2006) Phys Rehabil Med 18, 39–61.!5. Ince G et al., Phys Ther 86, 924–35!6. Patterson S et al., ACR 2014!
!!
Smoking
• Earlier onset of Inflammatory Back Pain • ñ inflammation • ñstructural damage (x-ray)
• ñradiographic progression (dose-related)
1. Chung HY et al., Annal Rheum Dis 2012; 71:809-816 2. Ward MM et al., Arth Care & Res 2009; 61 (7): 859-866 3. Poddubnyy D et al., Arth Rheum 2012; 64(5): 1388-1398 4. Haroon N et al., Arth Rheum 2013; 65(10):2645-54
Outline
• Ankylosing Spondylitis defined
• Epidemiology in the U.S.
• Assessment & diagnosis in primary care
• Initial treatment & treatment advances
• Comorbidities to remember
Extra-articular manifestations
IgA nephropathy Amyloidosis
Pulmonary Fibrosis (apical) Restrictive lung disease Sleep apnea
Aortitis First Degree AVB Aortic Insufficiency Ischemic heart disease
Arachnoiditis Cauda equina syndrome
Osteoporosis Vertebral fractures & pseudo-fractures
Bremander et.al., Arthritis Care Res, 63:550, 2011 Klingberg et.al., Arthritis Res Ther, 14:R108, 2012 Berdal et.al., Arthritis Res Ther, 14:R19, 2012. Rudwaleit et al. Best Practice & Research Clinical Rheumatology 20:451, 2006
Depression 30%
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Bone Health : AS!• Osteoporosis!
– 21% age > 50!• Low Bone Mass!
– 44%!!!!!!!
28 year old man with 3 years of disease
Klingberg et al., Arthritis Res Ther, 14: R108,2012 ! ! ! !Vasdev et al., Int J Rheum Dis 14:68-73!Ghoslani et al., Bone 2009 44:772-77 !!
! ! ! ! ! ! ! !!
Bone Health : AS!• Osteoporosis!
– 21% age > 50!• Low Bone mass!
– 44%!!!!!!!
Klingberg et al., Arthritis Res Ther, 14: R108,2012 ! ! ! !Vasdev et al., Int J Rheum Dis 14:68-73!Ghoslani et al., Bone 2009 44:772-77 !!
! ! ! ! ! ! ! !!
43 year old man with long standing AS
TNF inhibitors effects on BMD
N.N. Haroon et al., Seminars in Arthritis and Rheumatism 44(2014)155–161
Case • 50 year old man with AS
presents with acute on chronic neck pain
• Minor fall 2 months before
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Fracture in AS!
1 year
2
4 3
6 5
2 3
4
2011 2012
Fracture in AS!!
• Vertebral fractures in 30% Normal BMD (11.1%)!
!• Population studies :OR 3.26 -7.7!
– Men > women!– ↑after the 5 yrs of diagnosis!!
• Fracture risk: Low BMI, Rigidity, balance & fall risk!
!• C spine fracture & fall, MVA & ETOH!
Cooper et al., J Bone Miner Res 7: 221-227!Cooper et al., J Rheumatol 21:1877-1882!Vosse et al., Annals Rheum Dis 68:1839,2009!Wysham KD et al. ACR 2014!!
Clinical variables associated with mortality in discharged AS patients:
multivariable analysis
Variable Odds Ra-o 95% CI p-‐value Sepsis 7.95 5.86-‐10.79 <0.0001 Pneumonia 2.00 1.47-‐2.73 <0.0001 Cardiovascular disease 1.35 1.03-‐1.77 0.031 C-‐Spine Fracture w/ SCI 13.82 8.23-‐23.20 <0.0001 C-‐Spine Fracture w/o SCI 2.81 1.61-‐4.88 <0.0001 Thoracic spine fracture 0.99 0.56-‐1.73 0.960 Lumbar spine fracture 2.02 0.92-‐4.45 0.078 Adjusted for all variables
Wysham KD, ACR 2014
Lymphoma in TNFα inhibitor users
Hellgren K et al., Arthritis Rheumatol. 2014 May;66(5):1282-90
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Summary
• Genetics & Microbiome
• U.S. prevalence ~ 0.55 -1.4
• Consider a diagnosis with inflammatory axial pain
• Start NSAIDs (+/- PT) if no contraindications while referral pending
• Smoking cessation
• Osteoporosis & Fracture – Screen for osteoporosis & Fall assessment
American College of Rheumatology, Image Bank (#99-07-0014 )
Age = 26 years
American College of Rheumatology, Image Bank (#99-07-0014 - adapted)
2014 2024 2034 2034 2032 2044
Acknowledgements
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