Strengthening our knowledge in Spondylarthritides: Focusing on Ankylosing Spondylitis and Psoriatic Arthritis

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1 Department of Pathophysiology Metical School National and Kapodestrian University of Athens Strengthening our knowledge in Spondylarthritides: Focusing on Ankylosing Spondylitis and Psoriatic Arthritis Panayiotis G. Vlachoyiannopoulos MD Professor of Medicine-Immunology

2 Disclaimer This presentation is provided to you in response to your query for your personal use This may contain information on products or indications currently under investigation and/or that have not been approved by the regulatory authorities. This presentation is intended for non-promotional scientific purposes only and is accurate at the time of presentation. Any data about non-novartis products are based on publicly available information at the time of presentation. Novartis will not be responsible for any subsequent use outside the intended purpose or changes to the presentation by you or any third party. 2

3 Conflict of interest The speaker was paid by Novartis for this presentation through the Special Research Account of National and Kapodistrian University of Athens 3

4 Outline Spondyloarthritis: definition and prevalence Ankylosing spondylitis and psoriatic arthritis Clinical features Pathophysiology of SpA Diagnosis and treatment Comorbidities and disease load

5 Identifying and referring Spondyloarthritis Spondyloarthritis (SpA) can have diverse symptoms and be difficult to identify McAllister K, et al., BMJ 2017;356:j839 5

Spondyloarthritis Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases comprising ankylosing spondylitis (AS), psoriatic arthritis

run in families and are associated with HLA-B27 SpA can also be characterized as axial or peripheral according to predominant articular features at

and dactylitis Πλάγια ακτινογραφία οσφυϊκής μοίρας σπονδυλικής στήλης σε ασθενή με σοβαρή AS δείχνει γέφυρες συνδεσμόφυτων (ακίδες) σε πολλαπλά επίπεδα.

8 Spondyloarthritis Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases comprising ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, undifferentiated SpA and SpA associated with inflammatory bowel disease These interrelated disorders share clinical features, run in families and are associated with HLA-B27 SpA can also be characterized as axial or peripheral according to predominant articular features at clinical presentation Axial SpA involves spondylitis and sacroiliitis, whereas the main features of peripheral SpA are peripheral arthritis, enthesitis and dactylitis Πλάγια ακτινογραφία οσφυϊκής μοίρας σπονδυλικής στήλης σε ασθενή με σοβαρή AS δείχνει γέφυρες συνδεσμόφυτων (ακίδες) σε πολλαπλά επίπεδα. 5 van Tubergen, A. Nat. Rev. Rheumatol. 11, (2015). Khan, M. A. Ann. Intern. Med. 136, (2002). Rudwaleit, M. Curr. Opin. Rheumatol. 22, (2010).

9 Οι οροαρνητικές αρθρίτιδες χαρακτηρίζονται από διαβρώσεις και οστεοπαραγωγή Ρευματοειδής αρθρίτιδα Διαβρώσεις μεταταρσοφαλαγγικών Ψωριασική αρθρίτιδα Διαβρώσεις αλλά και εξωαρθρική περιοστίτιδα

10 Features of the Spondyloarthritis van Tubergen, A. Nat. Rev. Rheumatol. 11, (2015); 10

11 ASAS classification criteria for axial and peripheral SpA van Tubergen, A. Nat. Rev. Rheumatol. 11, (2015); 11

12 Diseases That Make Up the SpA Syndrome Share Common Features Disorders share distinctive clinical, radiographic, and genetic features: Rheumatic diseases characterized by sacroiliitis, spondylitis, enthesitis, dactylitis and synovitis Extra-articular manifestations (uvea, gut, skin) Strong association with HLA B27 Positive family history of SpA Sacroiliitis (Grade II) Synovitis of SI joint Enthesitis Uveitis Gut lesions in Crohn s disease Psoriasis Images taken from: ASAS Assessment of SpondyloArthritis International Society. Accessed 5 August Spondylitis anterior and posterior

13 Diffuse idiopathic skeletal hyperostosis vs spa

14 Diffuse idiopathic skeletal hyperostosis vs spa

15 AS Has a Multitude of Effects on the Body Shoulder swelling Flaky scalp Emotional health Spine and neck pain Neck pain Impaired vision Stooped shoulders Stiff spine Elbow pain Weak muscles CV/circulatory effects Weak hip PsA in hands Scaly skin Respiratory effects Scaly skin Weakness in knees Foot problems AS in knees Foot function PsA Impacts Both Physical and Emotional Well-being AS, ankylosing spondylitis; CV, cardiovascular. (accessed 14 July 2015) PsA, psoriatic arthritis (accessed 6 July 2015)

Prevalence of SpA The prevalence of SpA ranged from 0.20% (95% CI 0.00 0.66) in South-East Asia to 1.61% (95% CI 1.27 2.

16 Prevalence of SpA The prevalence of SpA ranged from 0.20% (95% CI ) in South-East Asia to 1.61% (95% CI ) in Northern Arctic communities The following characteristics were significantly associated with variation in prevalence of SpA: - proportion of females - mean age of the sample - geographic area and setting - year of data collection - case finding and case ascertainment (methodologic characteristics) The prevalence of SpA has been reported higher in more recent studies (year of data collection from 2000 onwards) Stolwijk et al., Arthritis Care & Research Vol. 68, No. 9, September 2016, pp

Prevalence of AS The prevalence of AS ranges ~ 0,5-1,9% globally Additionally there is some gender disparity within AS, with reported gender ratios of around 2:1 male to female There were also

17 Prevalence of AS The prevalence of AS ranges ~ 0,5-1,9% globally Additionally there is some gender disparity within AS, with reported gender ratios of around 2:1 male to female There were also differences between the sexes regarding some AS-related clinical manifestations. I.e. anterior uveitis was more common in men, and peripheral arthritis and psoriasis were more common in women AS usually initially presents during the second and third decade of life, and rarely after the age of 45 years There is a considerable delay (8 to 15 years) in obtaining a definitive diagnosis from a specialist AS prevalence correlates with the prevalence of HLA- B27 Shapira et al., Nature Reviews Rheumatology volume 6, pages (2010) doi: /nrrheum Exarchou et al. Arthritis Research & Therapy (2015) 17:118

18 Prevalence of AS in Greece

Patients with psoriasis who develop PsA (%) PsA prevalence in psoriasis pa ents Prevalence of PsA The development of PsA appears to occur at a constant rate during each year following psoriasis

with psoriasis 25 % of patients with psoriasis who develop PsA per annum Cumulative% of patients with psoriasis who develop PsA 80 70 60 20 50 15 40 30 10 20 5 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26

19 Patients with psoriasis who develop PsA (%) PsA prevalence in psoriasis pa ents Prevalence of PsA The development of PsA appears to occur at a constant rate during each year following psoriasis diagnosis, resulting in a steady increase in PsA prevalence The prevalence of psoriatic arthritis among patients with psoriasis increased significantly on the basis of the body surface area involved with psoriasis 25 % of patients with psoriasis who develop PsA per annum Cumulative% of patients with psoriasis who develop PsA <1% 1% 2% 3% 10% >10% Body surface area (BSA) involvement Duration of psoriasis (years) Christophers E et al. J Eur Acad Dermatol Venereol May;24(5): Gelfand JM et al. J Am Acad Dermatol. 2005;53:

20 Outline Spondyloarthritis: definition and prevalence Ankylosing spondylitis and psoriatic arthritis Clinical features Pathophysiology of SpA Diagnosis and treatment Comorbidities and disease load

21 Ankylosing spondylitis (AS) Taureg et al., N Engl J Med 374;26

22 Σκελετός με αλλοιώσεις ΑΣ που περιγράφηκε από τον Bernard Connor το 1695

AS classification AS is axial SpA with significant X-ray changes manifested through sacroiliitis, meeting the modified New York criteria (1984) for AS 1,2 ASAS,

23 AS classification AS is axial SpA with significant X-ray changes manifested through sacroiliitis, meeting the modified New York criteria (1984) for AS 1,2 ASAS, Assessment of SpondyloArthritis international Society 1. Sieper J et al. Ann Rheum Dis. 2009;68(Suppl II):ii1-ii44; 2. Rudwaleit M et al. Arthritis Rheum. 2005;52:

24 Clinical features of AS Clinical features Long-term disease that causes inflammation of joints between spinal bones and the joints between the spine and pelvis 1 Eventually causes affected spinal bones to fuse together 1 Clinical features include inflammation, structural damage, and repair 2 Negative impact on QoL and psychological well-being 3 Likely related to genetic and environmental factors 4 It is majorly diagnosed in young men Laboratory features No laboratory test is diagnostic of AS 1 HLA-B27 - Presence of the gene HLA-B27 is a strong predictor of axial SpA 1,2 - Approximately 80-95% of patients with AS are HLA-B27 positive 1,3,4 C-reactive protein (CRP) 3 - Levels of CRP increase in response to inflammation and may be associated with structural changes in the spine associated with axial SpA Erythrocyte sedimentation rate (ESR) 1 - A measure of inflammation - Commonly used in the assessment of RA and other inflammatory disorders 1. Spondylitis Association of America. Ankylosing Spondylitis. Available at: Accessed on 8 November 2011; 2. Maksymowych W. Nat Rev Rheumatol. 2010;6:75-81; 3. Sieper J et al. Ann Rheum Dis. 2002;61:iii8-iii18; 4. El-Gabalawy H et al. J Rheumatol. 2010;37(Suppl 85):2-10; 5. Jang JH et al. Radiology. 2011;258: HLA, human leukocyte antigen; RA, rheumatoid arthritis 1. Sieper J et al. Ann Rheum Dis. 2002;61(Suppl III):iii8 iii18; 2. Rudwaleit M et al. Ann Rheum Dis 2009;68:777 83; 3. Rudwaleit M et al. Arthritis Rheum. 2009;60: ; 4. Chung HY et al. Ann Rheum Dis. 2011;70:

Inflammatory vs mechanical back pain Mechanical

that arises from an injury to a specific structure

the first few weeks has morning stiffness <30 min

25 Inflammatory vs mechanical back pain Mechanical back pain: is much more frequent refers to pain that arises from an injury to a specific structure within the spine has usually a full recovery within the first few weeks has morning stiffness <30 min is improved with rest Taurog et al., N Engl J Med 374;26

26 Little H et al. Am J Med. 1976;60: New bone formation progressively leads to ankylosis

27 Clinical features of PsA Ritchlin et al., N Engl J Med 376;10

28 Clinical manifestations of PsA Psoriasis Nail psoriasis Arthritis Enthesitis 35% Dactylitis 35% Axial involvement (40%) Peripheral involvement (60-90%) Polyarthritis (RA-like) 25% 65% Oligoarthritis 65% 25% Erosions of Distal phalanx (OA-like) 10-20% Erosive arthritis <1%

29 Clinical features Peripheral arthritis Dactylitis Anterior Uveitis Achilles enethesitis Crohn s disease Psoriasis

30 Outline Spondyloarthritis: definition and prevalence Ankylosing spondylitis and psoriatic arthritis Clinical features Pathophysiology of SpA Diagnosis and treatment Comorbidities and disease load

31 Mechanical stress is a key trigger for enthesitis in AS and PsA Genetics (e.g., HLA-B27) Plus and or Mechanical stress Enthesitis Impaired barrier function (e.g., microbial stress) Mechanical stress can induce an inflammatory response at the enthesis in genetically susceptible individuals and/or those under microbial stress Haroon M, et al. Ann Rheum Dis. 2016;75:155 62; 2. Kehl AS, et al. Arthritis Rheumatol. 2016;68:312 22; 3. Sieper J, Poddubnyy D. Lancet. 2017;90:73 84; 4. McGonagle D, Benjamin M. Topical Reviews. 2009;4:1 6.

Enthesitis differentiates AS and PsA from

33 Enthesitis differentiates AS and PsA from rheumatoid arthritis Primary synovial membrane disease vs. entheseal disease with secondary synovial membrane involvement Aids differential diagnosis of AS / PsA vs. rheumatoid arthritis Schett, G. et al. (2017) Enthesitis: from pathophysiology to treatment Nat. Rev. Rheumatol. doi: /nrrheum

34 Pathophysiology of enthesitis

35 IL-17A is an amplifier of enthesitis, leading to irreversible structural damage Mechanosensation & immune activation Innate inflammatory response Mesenchymal proliferation New bone formation Triggers Mechanical stress Disturbed barrier function Infections PGE2 IL-23 Vasodilation gdt cells ILC3 Activation gdt cells ILC3 IL-17 TNF Neutrophils MSCs gdt cells IL-17 IL-22 ILC3 MSCs Hedgehog PTHrP Wnts BMPs Osteoblast Bone Hypertrophic chondrocyte Muscle Bone Tendon Enthesis ILC= innate lymphoid cells ILC1 IFN-γ ILC2 IL-5,IL-6, IL-13 ILC3 IL-17, IL-22 BMP, bone morphogenic proteins; IL-22, interleukin 22; PTHrP, parathyroid hormone related-peptide; MSC, mesenchymal stem cell Adapted from Schett G, et al. Nat Rev Rheumatol. 2017;13:

36 IL-17 stimulates osteoblast to express RANKL which stimulates Osteoclast to destroy the bone

37 Taureg et al., N Engl J Med 374;26 Pathogenic Mechanisms in Axial Spondyloarthritis

38 Pathogenic Pathways in Ankylosing Spondylitis Προσαρμογή από Paine A et al. Curr Opin Rheumatol 2016;28:66-75 Uluckan O, et al. Transl Med 2016;8:330ra37; Shaw AT, et al. Arthritis Res Ther 2016;18:104

39 Outline Spondyloarthritis: definition and prevalence Ankylosing spondylitis and psoriatic arthritis Clinical features Pathophysiology of SpA Diagnosis and treatment Comorbidities and disease load

40 Percentage of Patients (%) Delay in diagnosis in AS Currently, there is a long delay, from 5 to 10 years, between the first occurrence of AS symptoms and a diagnosis of AS. Two major reasons can be named for such a delay: (a) There is certainly a low awareness of AS among non-rheumatologists and it can be seen as a major challenge for any physician in primary care to think of and to identify patients with inflammatory spine disease among the large group of patients with chronic back pain, most often of another origin. (b) Radiographic sacroiliitis grade 2 bilaterally or grade 3 or 4 unilaterally is usually a requirement for making the diagnosis of AS according to the modified New York criteria First diagnosis Mean delay in diagnosis: 8.8 years B27(+) 8.5 vs B27(-) Men (n=920) Women (n=476) Age in years The delay in diagnosis and the worsening of AS symptoms leads to physical, emotional and disease-related work disability Feldtkeller E et al. Rheumatol Int 2003;23:61 66 Sengupta R & Stone MA. Nat Clin Pract Rheumatol 2007;3:

41 Delay in diagnosis of AS Alamanos Y. Rheumatology 2004;43:

42 Diagnosis of AS: Indexes that are commonly used in clinical trials Axial skeleton Peripheral skeleton Enthesitis Radiographic findings Functionality/ Quality of life Mobility BASDAI BASMI BASFI MEI/MASES/ SPARCC/LEI ASAS 20/40 ASAS 5/6 ASDAS HAQ SF-36 msasss Pain Dactylitis Inflammation indexes

43 Disease severity Progression of psoriatic arthritis Severe pain and disability Erosion of at least 5 joints 55% At least 1 erosion 47% Increased mortality due to CVD Psoriasis onset Έτη (30% of pts will be diagnosed with PsA) 20%: Severe/Erosive disease Gladman DD et al. Ann Rheum Dis Mar;64 Suppl 2:ii14-7

Odds Ratio (OR) Rheumatologist s diagnosis Delay in diagnosis > 6 months 80 71 5 4.25 60 53 4 % 40 30 3 2 2.2 1.47 20 1 0.

44 Odds Ratio (OR) Rheumatologist s diagnosis Delay in diagnosis > 6 months % < 6 months < 1 year < 2 years 0 Erosions Functional disability (HAQ) No. of DMARDs/ TNFi failures DMARD/ TNFi free Haroon M et al. Ann Rheum Dis Jun;74(6):

45 Odds ratio (95% CI) Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis after a mean of 10 years of follow-up ( ) ( ) ( ) 2.3 ( ) 2.2 ( ) 0.4 ( ) 0 Erosions Number of deformed joints (score) Sacroiliitis Arthritis mutilans Functional disability (HAQ score) DMARD/ anti-tnf free Clinical features recorded as percent, unless otherwise stated CI, confidence interval; DMARD, disease-modifying anti-rheumatic drug; OR, odds ratio Haroon M, et al. Ann Rheum Dis. 2015;74:

46 Smolen JS et al. Ann Rheum Dis Jul 6.

47 Ann Rheum Dis 2011;70: Treatment

48 Spondyloarthritis Current treatments NSAIDs DMARDs : Methotrexate Sulfasalazine Cyclosporine (?) Leflunomide TNF-a inhibitors Ustekinumab (anti-p14, IL-12/IL-23) Apremilast (ts DMARD) Secukinumab (anti-il-17a) Olivieri, I. et al. Nat. Rev. Rheumatol. 10, (2014)

49 New compounds in spondyloarthritis van Mens et al. Curr Opin Rheumatol 2018, 30:79 86

50 Efficacy of biologics and other novel drugs in SpA and other chronic inflammatory diseases Sieper and Poddubnyy, Nat Rev Rheumatol May;12(5): doi: /nrrheum

51 Efficacy of biologics and other novel drugs in SpA and other chronic inflammatory diseases Sieper and Poddubnyy, Nat Rev Rheumatol May;12(5): doi: /nrrheum

52 Outline Spondyloarthritis: definition and prevalence Ankylosing spondylitis and psoriatic arthritis Clinical features Pathophysiology of SpA Diagnosis and treatment Comorbidities and disease load

53 Anna Moltó et al. Ann Rheum Dis 2016;75: Prevalence of evaluated comorbidities in the 3984 patients with spondyloarthritis

54 Withdrawal from work due to disease-related disability in patients with AS in the period before biologic treatments Ann Rheum Dis 2001;60:

55 Efficacy and Safety of secukinumab (anti-il-17a) up to 4 years of treatment

56 The MEASURE Clinical Trial Program: Assessment of Secukinumab in AS Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q1 Q2 Q3 Q4 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 MEASURE 1 N = 371 i.v. loading (10 mg/kg) s.c. maintenance dosing (75 or 150 mg) Extension Study MEASURE 2 N = 219 s.c. loading (75 or 150 mg) s.c. maintenance dosing (75 or 150 mg) Pre-filled syringe MEASURE 3 N = 226 i.v. loading (10 mg/kg) s.c. maintenance dosing (150 or 300 mg) MEASURE 4 N = 350 s.c. 150 mg with or without s.c. loading (Pre-filled syringe) MEASURE 1 is a 2-year study with 3-year extension study; MEASURE 2 is a 5-year study; MEASURE 3 is a 3-year study; MEASURE 4 is a 2-year study. The primary endpoint for all studies is at Week 16. i.v., intravenous; s.c., subcutaneous. Clinicaltrials.gov: NCT (MEASURE 1); NCT (MEASURE 2); NCT (MEASURE 3); NCT (MEASURE 4).

57 % Responders % Responders Secukinumab 150 mg Provided Sustained ASAS20/ASAS40 Responses Through 4 Years Secukinumab 10 mg/kg i.v. 150 mg s.c. Observed data Imputed data (N = 87) ASAS % 76.4% ASAS40 weeks % 58.0% Obs n = Core study Extension study weeks ASAS, Assessment of Spondyloarthritis International Society; n, number of pts evaluated in the treatment group; N, total number of pts in the extension trial; Obs, observed data. Solid lines represent observed data through Week 208. Dashed lines represent multiple imputation data through Week

58 Secukinumab 150 mg Provided Sustained Improvement in BASDAI, BASFI and BASMI Through 4 Years Mean Change from Baseline BASDAI BASFI BASMI Core study Extension Core study Extension Core study Extension Week Obs n = Secukinumab 10 mg/kg i.v. 150 mg s.c. BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; n, number of pts evaluated in the treatment group; Obs, observed data. Observed data through Week 208

59 The FUTURE Clinical Trial Program: Assessment of Secukinumab in PsA Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 FUTURE 1 N = 606 i.v. loading (10 mg/kg) s.c. maintenance dosing (75 and 150 mg) Extension study FUTURE 2 N = 397 s.c. loading (75, 150, and 300 mg) s.c. maintenance dosing (75, 150, and 300 mg) Pre-filled syringe FUTURE 3 N = 414 s.c. loading (150 and 300 mg) s.c. maintenance dosing (150 and 300 mg) Autoinjector FUTURE 4 N = 341 s.c 150 mg with or without s.c. loading Pre-filled syringe FUTURE 5 N = 996 s.c 150 mg and 300 mg with or without s.c. loading (Pre-filled syringe) FUTURE 1 is a 2-year study (primary endpoint at Week 24) with 3 year extension study; FUTURE 2 is a 5 year study (primary endpoint at Week 24); FUTURE 3 is a 3 year study (primary endpoint at Week 24); FUTURE 4 is a 2 year study (primary endpoint at Week 16); FUTURE 5 is a 2 year study (primary endpoint at Week 24). i.v., intravenous; s.c., subcutaneous Clinicaltrials.gov: NCT (FUTURE 1); NCT (FUTURE 2); NCT (FUTURE 3); NCT (FUTURE 4); NCT (FUTURE 5).

60 Percentage of subjects Sustained Improvement in ACR20/50/70 Responses Through 3 years (Overall Population) 100 Overall (Multiple Imputation) 100 Anti TNF-naive (Observed Data) 100 Anti TNF-IR (Observed Data) n=161 n=161 n=161 ACR20 ACR50 ACR70 0 n=116 n=116 n=116 ACR20 ACR50 ACR70 0 n=39 n=39 n=39 ACR20 ACR50 ACR70 Secukinumab IV 150 mg Mease PJ, et al. Arthritis Rheumatol. 2016;68 (suppl 10): abstract 961.

61 Percentage of patients Percentage of patients Secukinumab Provided Sustained Resolution of Dactylitis and Enthesitis Through 3 years (Overall Population) Resolution of Dactylitis Resolution of Enthesitis Week 52 Week Week 156 Week 52 Week 104 Week 156 Secukinumab 10 mg/kg i.v. 150 mg s.c. (Daktylitis: N = 83) (enthesitis: N = 99 ) Secukinumab 10 mg/kg i.v. 75 mg s.c. (Daktylitis: N = 77) (enthesitis: N = 91 ) Αποδρομή Δακτυλίτιδας και Ενθεσίτιδας σε ασθενείς με αυτά τα συμπτώματα κατά την έναρξη Mease PJ, et al. Arthritis Rheumatol. 2017;76 (suppl 2): abstract SAT0470.

62 Percentage of Responders Percentage of Responders Sustained Improvement in ACR20 Responses with or without co-treatment with methotrexate * * n = 44 n = 44 n = 47 n = 50 n = 56 n = 56 n = 52 n = 48 Co-treatment With MTX 0 No MTX Treatment Secukinumab 300 mg s.c. Secukinumab 150 mg s.c. Secukinumab 75 mg s.c. Placebo *P < ; P < 0.001; P < 0.01; P < 0.05 vs. placebo Missing values were imputed as nonresponse (nonresponder imputation) up to Week 52 McInnes IB, et al. Lancet Jun 26. pii: S (15)

63 Percentage of Responders Percentage of Responders Secukinumab 300 and 150 mg provided Significant and Sustained Improvements in PASI 75 and PASI 90 Through Week 104 (Overall Population) 100 PASI 75 (NRI data at Week 24; MI data at Week 52 and Week 104) 100 PASI 90 (NRI data at Week 24; MI data at Week 52 and Week 104) * n=41 n=58 n=43 n=41 n=58 n=56 n=53 Week 24 Week 52 Week n=41 n=58 n=43 n=41 n=58 n=56 n=53 Week 24 Week 52 Week 104 Secukinumab 300 mg Secukinumab 150 mg Placebo *P < ; P < 0.001; P < 0.01 vs. placebo P-values at Week 24 adjusted for multiplicity of testing Data from subjects with psoriasis 3% body surface area at baseline. McInnes IB, et al. Lancet. 2015;386: ; McInnes IB, et al. Poster presentation at the American College of Rheumatology (ACR) 2016 Annual Scientific Meeting, Washington DC, USA. Abstract no

64 a Skin involvement while on etanercept. b Marked improvement on week 4 of secukinumab administration. c Significant improvement on week 36 of secukinumab administration Pelechas et al., Rheumatol Ther (2017) 4:

65 Conclusions spas are diseases which increase morbidity and mortality spas decrease drastically the quality of life Early detection and referral the patients to the specialist is important in decreasing disease progression Criteria for early identification of spa cases are available Criteria for measuring disease activity are available and helpful in evaluating the efficacy of drugs used for treatment of spas Anti-TNF agents, moabs to P40 subunit of IL-12 and IL-23 and moabs to IL-17 are important therapeutic agents in our era.

Concept of Spondyloarthritis (SpA)

Concept of Spondyloarthritis (SpA) Spondyloarthritis: Characteristic Parameters Used for Diagnosis I Symptoms Inflammatory back pain Imaging Lab ESR/CRP Patient s history Good response to NSAIDs Spondyloarthritis-Characteristic