AS – the facts! Andrew Keat

AS, axSpA, nr-axSpA or what?

This slide is to refresh the memory of the audience concerning the diseases belonging to the concept of spondyloarthritis. Almost 40 years ago, the concept of seronegative spondyloarthritis was established. SpA was considered a group of disorders that were related to each other, by sharing several clinical features, showing familial clustering, and a linkage to HLA B27. AS is considered the key disorder of SpA. After some modifications over time, the other subgroups of SpA are now reactive arthritis, acute anterior uveitis, PsA, undifferentiated SpA, juvenile SpA and arthritis associated with IBD. In each subgroup features of AS may develop.

Spectrum of Axial Spondyloarthritis Non-radiographic stage Patients with chronic back pain ≥3 months and aged <45 years Axial SpA (ASAS criteria) Non-radiographic stage X-ray-negative Ankylosing Spondylitis (modified New York criteria) MRI positive sacroiliitis Radiographic stage X-ray-positive sacroiliitis Radiographic stage X-ray-positive sacroiliitis and/or spinal changes*** Estimated proportion of affected individuals* Epidemiology Time * Heights reflect an estimate of the proportion of patients in each group ** Clinical arm if non-radiographic axial SpA *** Radiographic evidence if inflammatory spinal changes including i.e., syndesmophytes, fusion or posterior element involvement

What exactly is inflamed?

The Spine….. …and Sacroiliac joints

Spondylitis Enthesitis

What about treatment?

Does exercise really do any good?

Does exercise really do any good? Back to Action Does exercise really do any good? The Book Exercising safely in a gym with AS Copy distributed free to all UK rheumatology departments during 2012 Available to purchase from NASS online shop (www.nass.co.uk) Available to download free of charge as a PDF from exercise pages on NASS website Back to Action is an exercise programme specifically designed for people with AS Created by physiotherapists working with NASS and exercise therapists and doctors who treat military personnel It uses the most up to date knowledge from the fields of physiotherapy and sports medicine

Exercise leads to Improved strength and fitness (=feel better) Reduced IL-6 Reduced CRP Increased IL-10

Exercise leads to =Less inflammation ……….if it is regular! Improved strength and fitness (=feel better) Reduced IL-6 Reduced CRP Increased IL-10 =Less inflammation ……….if it is regular!

After anti-TNF?

DANBIO: Survival curves of TNF inhibitor use in AS 0.0 1.0 0.8 0.6 0.4 0.2 (A) Sex Men Women 1 2 3 4 5 6 7 (B) Baseline BASDAI 1.0 0.8 0.6 0.4 0.2 1. quartile (low) 2. quartile 3. quartile 0.0 4. quartile (high) 1 2 3 4 5 6 7 Glintborg B et al. Ann Rheum Dis 2010;69:2002–2008.

DANBIO registry: drug adherences by treatment course 1 2 3 Course N Maintaining treatment after 2 years, % Drug survival, years Median (95% CI) 1 1436 58 3.1 (2.6-3.7) 2 432 47 1.6 (1.0-2.2) 3 137 49 1.8 (0.9-2.7) Drug survival decreased after switching ( p<0.0001) Glintborg B et al. Ann Rheum Dis. 2013;72(7):1149-55.

What next? Anti-TNFs: Certolizumab Other Biologics: Secukinumab Small molecules: Apremilast Biosimilars

Terms Definitions Implications Biosimilar Copy version of already authorized medicinal product: Demonstrated similarity in chemical structure, efficacy and safety Only very small differences from original. Extrapolation of indications justifiable

Terms Definitions Implications Biosimilar Copy version of already authorized medicinal product: Demonstrated similarity in chemical structure, efficacy and safety Only very small differences from original. Extrapolation of indications justifiable Me-too biologic Biological medicinal product developed on its own and not directly compared with a licensed biological Not known whether chemical, clinical differences exist between it and other biologicals in the same class. Therefore extrapolation of indications is problematic

Terms Definitions Implications Biosimilar Copy version of already authorized medicinal product: Demonstrated similarity in chemical structure, efficacy and safety Only very small differences from original. Extrapolation of indications justifiable Me-too biologic Biological medicinal product developed on its own and not directly compared with a licensed biological Not known whether chemical, clinical differences exist between it and other biologicals in the same class. Therefore extrapolation of indications is problematic Biobetter/second generation biologic Structurally or functionally altered biologic to achieve improved or different performance Usually considered as a new agent. Claim to be “better” would have to be stringently demonstrated

Terms Definitions Implications Biosimilar Copy version of already authorized medicinal product: Demonstrated similarity in chemical structure, efficacy and safety Only very small differences from original. Extrapolation of indications justifiable Me-too biologic Biological medicinal product developed on its own and not directly compared with a licensed biological Not known whether chemical, clinical differences exist between it and other biologicals in the same class. Therefore extrapolation of indications is problematic Biobetter/second generation biologic Structurally or functionally altered biologic to achieve improved or different performance Usually considered as a new agent. Claim to be “better” would have to be stringently demonstrated

Don’t forget surgery! Images courtesy of Dr Keat.