1. What’s Hot in Spondyloarthritis
Lianne Gensler, M.D.
Director, Ankylosing Spondylitis Clinic
UCSF Rheumatology

2. Spondyloarthritides

3. Outline How important is genetics?
What’s the difference between undifferentiated Spondyloarthritis and AS?
Can we improve the early diagnosis of AS?
What drugs and non-drug therapies work?
What drug side effects should you be aware of?
Are there any new drugs out there?
What should you eat?
What’s the best exercise?
Monitoring the disease – What should your doctor be following?

4. Genetics Genetics contributes towards 90% of the cause of AS
HLA B27 present in 90–95% of patients with AS
HLA B27 only accounts for 40% of the genetics?

5. HLA B27 ??
GENETICS = 90%

6. What are the other genes?
Welcome Trust Case control consortium: investigating 12 autoimmune diseases.
AS was one of them.
Validation cohort in US patients with AS. Many of you contributed!
ARTS-1 (ERAAP)
IL23R
IL-1
Together with HLA B27 may explain
70% of genetics of AS
WTCCC and TASC Nature Genetics 2007;

7. What does undifferentiated SpA mean?
Has clinical features of SpA but doesn’t have enough radiographic changes to be called Ankylosing Spondylitis.
Examples: Inflammatory back pain, enthesitis (achilles tendonitis) uveitis, psoriasis, sausage digits…or a combination excluding Psoriatic arthritis, IBD associated arthritis and reactive arthritis.

8. If you have Undifferentiated SpA – what’s the prognosis?
Not everyone goes on to develop AS or differentiated disease
Depends on the length of time you’ve had it.
Only predictor of developing AS is low grade sacroilitis on x-ray.

9. Ankylosing Spondylitis
Modified New York Criteria
fusion
Up to 7 to 10 years
Rudwaleit et al. Arthritis Rheum 2005; 52:

10. Can we improve the early diagnosis?
Better imaging techniques - MRI
Education for primary care doctors, eye doctors, spine doctors etc
Research
New classification criteria for Inflammatory back pain & Undifferentiated AS
Developing screening tools that will pick the disease up earlier (questionnaires)
Developing better criteria for diagnosis (including MRI)
Developing better blood tests that diagnose the disease and pick up disease activity.

11. Therapies (not including vitamins & supplements)
Non-pharmacologic
Physical therapy
Exercise/ Yoga/ Pilates
Pharmacologic
NSAIDs
Sulfasalazine
TNF inhibitors
Bisphosphonates

12. Eleven trials with a total of 763 participants were included.
Individual home-based or supervised exercise program is better than no intervention
Supervised group PT is better than home exercises; and that
Combined inpatient spa-exercise therapy followed by group PT is better than group physiotherapy alone
DagfinrudH, Hagen KB, Kvien TK. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database of
Systematic Reviews 2008, Issue 1. Art. No.: CD DOI: / CD pub3

13. NSAIDs
When AS patients are asked about the level of efficacy when treated with NSAIDs, 70–80% report at least good improvement of their symptoms.
In contrast, this level of response is reported by only 15% of patients with chronic low back pain of non-inflammatory causes
Up to 15% of patients with active AS treated with a full dose of an NSAID fulfill the ASAS International Working Group criteria for partial remission.

14. NSAIDs – Risk & Benefit Improves symptoms in most patients
One study suggesting improvement in radiographic progression when used regularly
Non-selective vs. COX II
Gastrointestinal effects (dyspepsia, ulcer, liver)
Cardiovascular (HTN, MI) 12 (0.6%) of 1780] than placebo [1 (0.24%) of 412
Renal

15. TNF- inhibitor (Golimumab)
Golimumab: fully humanized monoclonal antibody against membrane bound and soluble TNF- administered SQ qmonth
GO-RAISE (AS)
24% Asian
Adverse events: liver enzyme abnormalities
Primary endpoint ASAS 20
Undifferentiated Axial SpA
Advanced AS
Inman et al. A&R vol. 58, no. 11, november 2008, pp
Barkham et al. A&R, April 2009, Vol 60. No. 4:
Rudwaleit et al., Rheumatology 2009:1-7

16. What TNF alpha inhibitor is best for you?
All about effective as each other for the back
All of the SQ agents have co-pay assistance programs.
If no uveitis or IBD, Etanercept
If IBD, no Etanercept. Humira, Inflixamab ok. Golimumab not approved for IBD, but it will probably work.
Think of Golimumab as similar to Humira but dosed less frequently.

17. TNF Inhibitors – Risk & Benefit
60% have some improvement in symptoms
Decrease in inflammation – CRP, ESR, MRI
Possible decrease in progression of fusion at 4 years
Economic benefit
Infection
Cancer (not proven in AS)
Multiple sclerosis syndrome (rare)
Lupus like syndrome (rare)
Cost of drug

18. New drugs? An oral drug in studies now
Development of drugs to prevent fusion
Drugs used and proven in other autoimmune diseases will probably be tested in AS

19. Vitamins & Supplements
Strong evidence
Calcium & Vitamin D
Possible evidence
Omega 3 Fatty Acids(4.55 g omega-3/day)
Minimal to no evidence
Glucosamine and chondroitin sulfate
Sundström B, Stålnacke K, Hagfors L, Johansson G.Scand J Rheumatol Sep-Oct;35(5):

20. Management – New patient version
General principle for management
Disease monitoring
Management strategy
Non-drug treatment
Drug treatment – anti inflammatory (not steroids)
Drug treatment steroids (local injections)
Drug treatment – DMARDS
Drug treatment – anti-TNF
Drug treatment – pain killers
Surgery
Patient support groups
Kiltz et. Al. ARD October 28,2008 [Epub ahead of print]

21. Monitoring the Disease
Laboratory studies
Radiographs
Bone Density Imaging (especially with a history of steroids)
Vitamin D deficiency

22. Summary
A lot more is known about the family of diseases, the Spondyloarthritides including the genetics.
Significant research now focuses on the early disease
A lot more research still needs to be done to understand why certain patients progress.
Stay active. Stay active. Stay active

23. Questions?