What further tx in ps a
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This document discusses the pathogenesis and treatment of psoriatic arthritis (PsA) and psoriasis. It notes that PsA is thought to arise due to chronically elevated levels of cytokines such as TNF-alpha, IL-1 beta, and IL-17. Research has found that IL-23 plays a unifying role in spondyloarthritis including PsA, and that IL-23 alone can drive enthesitis. Studies show the efficacy of the monoclonal antibody ustekinumab, which targets the p40 subunit of IL-12 and IL-23, in treating both the skin and joint symptoms of psoriasis and PsA.
![Plaque Psoriasis with Nail Involvement
was Improved
Absolute NAPSI scores ± standard deviation for Initial
Responders improved from 4.2±1.84 at baseline and
1.1±1.47 at week 52 in the maintenance group
Rich P, et al. Br J Dermatol. 2013 Sep 30. doi:10.1111/bjd.12632. [Epub
ahead of print]](https://image.slidesharecdn.com/whatfurthertxinpsa-140917211325-phpapp01/85/What-further-tx-in-ps-a-35-320.jpg)
What further tx in ps a
- 1. What's MOA Got to Do With PsA/PsO? More and more new bioagent of Rheuamtoid arthritis, what about Psoriasis ?
- 3. NEJM Volume 361:496-509 Then ?
- 4. induces proliferation of keratinocytes NEJM 2009 Volume 361:496-509
- 7. paTHOGENESIS At least 10 psoriasis-susceptibility loci that involve functioning of the immune system are identified.1 Polymorphisms in the IL-12/IL-23 receptor, p40 subunit of IL-12 and IL-23, and p19 subunit of IL-23 strongly associate with psoriasis.1 Psoriasis and its comorbid conditions are thought to arise from chronically elevated levels of cytokines such as TNF-alpha, IL-1 beta, and IL-17.2 1 - Villaseñor-Park J et al. Cleve Clin J Med. 2012 Jun;79(6)413-23 2 - Kelley’s Textbook of Rheumatology. 9th ed
- 8. PsA : epidemiology • Prevalence – Exact prevalence unknown: estimated 0.04%-1.2% – Among patients with PsO varies from 6%-42% • Evidence suggests that 20-30% of PsO patients develop PsA • Male: female ratio 1:1 – Male predominance from axial form – Female predominance from peripheral form • Onset: usually between 35 and 55 years, but important variability and within 10 years of onset psoriasis
- 9. PSA: peripheral joints 63% polyarticular 13% oligoarticular Dactylitis 29-33.5% at first presentation 48% during follow-up Enthesitis 38% most common sites: Archilles and plantar fascia insertion Frequency (%) of peripheral limb joint involvement in 129 patients with early psoriatic arthritis as assessed by joint tenderness and swelling Kelley’s Textbook of Rheumatology, 9th ed
- 10. Peripheral Joint: Asymmetric Polyarticular Disease A. Distal interphalangeal joint involvement and forearm lymphedema. B, Toe dactylitis with skin and nail changes. C, Predominat distal interphalangeal joint involvement. D, Arthritis mutilans Image adapted from Kelley’s Textbook of Rheumatology. 9th ed
- 11. Psoriasis and enthesitis • 1/3 of patients of psoriasis have subclincal enthesitis Int J Tissue React 2005, 27:159-162 • I/3 of the total no. of entehses in psoriatic patients have sign of enthesitis Arthritis Rhum 2011, 40 :407-12
- 12. Nail and the enthesis: anatomic relationship McGonagle D, et al. Dermatology. 2009;218(2):97-102
- 14. IL23 is a unifying factor in SpA (spondyloarthritis) • IL23 sensitivity associated with PSO – IL 23R with SNPs (GA/Arg381Gln) • IL23 over production is associated with SpA – IL23 production in PSO – HLA B27 misfoldingIL23 production – Inflammatory bowel disease IL 23 production – Subclinical ileitis in 70% SpA without overt IBD • increase IL23 in terminal ileum in AS – Success of IL23 neutralization in PSO Nat Med 2011, 17(9)1055
- 15. IL-23 drives enthesitis in vivo Downr egulation of several inflammatory mediators, such as Il6 and Il1b, and genes involved in erosion of bone and tissue, such as Rankl, Ctsk and matrix metalloproteinases Nature Medicine 2012 : 1069-1077
- 16. Entheses contain an IL-23R+ resident cell Nature Medicine 2012 : 1069-1077 CD45+ entheseal :CD3+CD4- CD8-, located at the entheseal interface between the tendon and bone Entheses in culture respond to IL-23 by upregulating expression of Il17a, Il17f, Il22 and bone morphogenic protein 7 (Bmp7)
- 17. IL-23 alone is sufficient to drive enthesitis in vivo Nature Medicine 2012 : 1069-1077
- 18. IL-23R+CD4–CD8–T cells reside in the aortic root Nature Medicine 2012 : 1069-1077
- 19. Nature Reviews Rheumatology 6, 477-485
- 20. Nature Reviews Rheumatology 6, 399-405 (July 2010)
- 23. • Only for arthritis have benefit , no use in skin lesion
- 33. • Randomised placebo-controlled , phase 3 trial to assess the safety and efficacy of ustekinumab in a patients with active psoriatic arthritis • 104 sites, 14 countries (Nov 30, 2009-March 30, 2011) • Inclusion criteria: active PsA for 6 M or longer despite 3Ms or more of treatment with DMARS or 4 weeks or more of treatment with NSAIDs, or both, or with intolerance to these treatment • Active PsA: 5 or more swollen joints (of 66) , 5 or more tender joints ( of 68), CRP 3.0mg/L or more, active or documented Hx of plaque PsO Lancet. 2013 Aug 31;382(9894):780-9
- 34. Median change from baseline at week 24 and 52 dactylitis enthesitis % of pts, PSAI75 Lancet. 2013 Aug 31;382(9894):780-9
- 35. Plaque Psoriasis with Nail Involvement was Improved Absolute NAPSI scores ± standard deviation for Initial Responders improved from 4.2±1.84 at baseline and 1.1±1.47 at week 52 in the maintenance group Rich P, et al. Br J Dermatol. 2013 Sep 30. doi:10.1111/bjd.12632. [Epub ahead of print]
- 36. ustekinumab ustekinumab ustekinumab ustekinumab Ustekinumab ?
- 46. 謝謝聆聽