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Outline
Ankylosing Spondylitis in 2014!
Lianne S. Gensler, M.D.!
Associate Professor of Medicine!
Director, Ankylosing Spondylitis Clinic!
UCSF Rheumatology!
•  Ankylosing Spondylitis defined
•  Epidemiology in the U.S.
•  Assessment & diagnosis in primary care
•  Initial treatment & treatment advances
•  Comorbidities to remember
ICD9 code – clinical diagnosis
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
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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Age = 26 years!
Bilateral THAs!
Spondyloarthritis: a family of diseases
30-40%!
Acute Anterior Uveitis
Ankylosing
Spondylitis:
sacroiliitis &
spondylitis
Inflammatory Bowel
Disease
PSORIASIS
10%!
American College of Rheumatology, Image Bank (#99-07-0014 )
8-10%!
Subclinical
Colitis !
25-60%!
Lin P et al., PLoS One. 2014; 9(8)
Outline
•  Ankylosing Spondylitis defined
•  Epidemiology in the U.S.
•  Assessment & diagnosis in primary care
•  Initial treatment & treatment advances
•  Comorbidities to remember
Reveille JD Nat. Rev. Rheumatol. (8)296–304 (2012)!
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HLA B27 in the U.S. population!
NHANES 2009-2010
•  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).
Weisman MH et al., Ann Rheum Dis. 2013 Mar;72(3):369-73.
•  Self-reported prevalence of AS = 0.55
Reveille JD et al., Arth Rheum Vol. 64, No. 5, May 2012, pp 1407–1411!
Reveille JD et al, Arthritis Care & Res. Vol. 64, No. 6, June 2012, pp 905–910
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
Case !
•  Ankylosing Spondylitis defined
•  Epidemiology in the U.S.
•  Assessment & diagnosis in primary care
•  Initial treatment & treatment advances
•  Comorbidities to remember
•  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.!
Your next step is to…!
Inflammatory Back Pain: hallmark feature
!
Feature!
Feature
Insidious
onset !
Insidious onset
Odds Ratios!
Odds Ratios
12.7
12.7!
Pain
(withimprovement
improvement
upon
getting
Painat
at night
night (with
upon
getting
up) up) !
20.4
20.4!
Ageat
at onset
onset <40
years
Age
<40
years !
9.9
9.9!
Improvement with exercise
23.1
Improvement
with exercise !
No improvement with rest
No improvement with rest !
7.7
23.1!
7.7!
Sensitivity 79.6% & Specificity 72.4%!
Positive LR = 79.6/(100-72.4) = 2.9 ~ Probability = 14%!
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!
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!
!
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Probability of Spondyloarthritis Using Multiple Clinical and Lab Features!
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!
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!
Elevated ac. phase reactants
HLA-B27
MRI
!
Pr =
98%!
LR 2.5!
!
LR 9.0!
!
LR 9.0!
LR 101 à !
Probability =!
84%!
!
!
!
!
!
LR 15.81 à!
Probability = 45%!
3.1 multiplied by 5.1 gives a likelihood product of 15.81.
fam hx à LR 15.81 x 6.4 = 101 !
Rudwaleit M, et al. Arthritis Rheum 2005; 52:1000-8!
Slide courtesy of Walter P. Maksymowych, with permission
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Axial SpA Epidemiology!
Prevalence ~ 1%
Axial SpA
Ankylosing Spondylitis!
Non-radiographic Axial SpA!
:
:!
(Milder disease !
Or !
early disease)!
Radiographic !
sacroiliitis!
1 : 2-3
HLA B27 85-95%!
Age of onset 16 – 40!
!
Bamboo spine!
DAMAGE!
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!
Inflammatory !
Back pain!
AP pelvis!
L spine MRI misses SI joints!
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AS Physical Exam!
Occiput to wall measure
(normal = 0cm)
Chest expansion score
(normal = ≥ 1.9 cm)
Anterior lumbar flexion
(modified Schober test)
Threshold = 2.0 cm
Assassi S et al., Arthritis Rheumatol Vol. 66, No. 9, September 2014, pp 2628–2637
AS Physical Exam!
Modified Schober test or Anterior Lumbar Flexion
(normal ≥ 2cm increase)
Thoracic (Chest) Expansion
Threshold = 1.9 cm
Assassi S et al., Arthritis Rheumatol Vol. 66, No. 9, September 2014, pp 2628–2637
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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!
NSAIDs!
Axial disease only!
NSAID
×
NSAIDs
TNF
inhibitors
sulfasalazine
If peripheral !
disease!
•  First line therapy!
•  NSAIDs better than
placebo!
•  No difference in efficacy
across NSAIDs (FDA
approved)!
!
Response to NSAIDs!
80
60
40
20
0
Ankylosing
Spondylitis!
Mechanical back
pain!
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!
Boulos P et al., Drugs 2005;65 (15):2111-27!
Amor B et al., Rev Rhum Engl Ed. 1995 Jan;62(1):10-5!
!
AS: Efficacy of TNFα inhibitors!
Do TNFi slow down damage?
ASAS 40 Responses in 5 separate trials!
TNF inhibitor!
47
45
Etanercept
13
adalimumab
48
44
39
14
Placebo!
15
12
Infliximab
Golimumab
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 ]!
!
16
Certolizumab
Van der Heijde et al., Arth Res & Ther 2009
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TNFi use: OR: 0.52; CI: 0.30-0.88; p=0.02
Benefit shown after
3.8 years
Haroon N et al., Arth Rheum 2013
Flare after withdrawal
Haroon N et al., Arth Rheum 2013
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!
50mg
20mg
placebo
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
Haibel H, et al. Ann Rheum Dis 2013;0:1–4!
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Smoking
Physical Therapy & Exercise!
•
•
•
•
•
1.
2.
3.
4.
5.
6.
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!
Dagfinrud H et.al., 2008; Cochrane Collaboration!
Brophy S et al., Semin Arth Rheum 2013 Jun;42(6):619-26!
Lee EN et al., 2008 Evid Based Complement Alternat Med 5, 457–62!
Fernandez-de-Las-Penas C, et al. (2006) Phys Rehabil Med 18, 39–61.!
Ince G et al., Phys Ther 86, 924–35!
Patterson S et al., ACR 2014!
•  Earlier onset of Inflammatory Back Pain
•  ñ inflammation
•  ñstructural damage (x-ray)
•  ñradiographic 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
Extra-articular manifestations
Depression 30%
•  Ankylosing Spondylitis defined
•  Epidemiology in the U.S.
•  Assessment & diagnosis in primary care
•  Initial treatment & treatment advances
•  Comorbidities to remember
Arachnoiditis
Cauda equina syndrome
Pulmonary Fibrosis (apical)
Restrictive lung disease
Sleep apnea
IgA nephropathy
Amyloidosis
Aortitis
First Degree AVB
Aortic Insufficiency
Ischemic heart disease
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
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Bone Health : AS!
•  Osteoporosis!
•  Osteoporosis!
– 21% age > 50!
•  Low Bone mass!
–  21% age > 50!
•  Low Bone Mass!
– 44%!
– 44%!
!
!
28 year old man with 3 years of disease
!
!
Klingberg et al., Arthritis Res Ther, 14: R108,2012
! et al., Int J Rheum Dis 14:68-73!
Vasdev
Ghoslani et al., Bone 2009 44:772-77 !!
!
!
!
!
!
!!
Bone Health : AS!
!
!
!!
!
!
!
TNF inhibitors effects on BMD
!
!
!
!
Klingberg et al., Arthritis Res Ther, 14: R108,2012
! et al., Int J Rheum Dis 14:68-73!
Vasdev
Ghoslani et al., Bone 2009 44:772-77 !!
!
!
!
!
43 year old man with long standing AS
!
!
!!
!
!
!
!
!!
Case
•  50 year old man with AS
presents with acute on
chronic neck pain
•  Minor fall 2 months
before
N.N. Haroon et al., Seminars in Arthritis and Rheumatism 44(2014)155–161
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Fracture in AS!
Fracture in AS!
!
2012 2011 2 3 2 4 3 4 5
6 1 year •  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 Sepsis Pneumonia Cardiovascular disease C-­‐Spine Fracture w/ SCI C-­‐Spine Fracture w/o SCI Thoracic spine fracture Lumbar spine fracture Lymphoma in TNFα inhibitor users
Odds Ra-o 95% CI p-­‐value 7.95 2.00 1.35 13.82 2.81 0.99 2.02 5.86-­‐10.79 1.47-­‐2.73 1.03-­‐1.77 8.23-­‐23.20 1.61-­‐4.88 0.56-­‐1.73 0.92-­‐4.45 <0.0001 <0.0001 0.031 <0.0001 <0.0001 0.960 0.078 Adjusted for all variables Wysham KD, ACR 2014
Hellgren K et al., Arthritis Rheumatol. 2014 May;66(5):1282-90
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Summary
Age = 26 years
•  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 )
Acknowledgements
2014
2024
2034
2034
2044
2032
Patients
American College of Rheumatology, Image Bank (#99-07-0014 - adapted)
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