Axial Spondyloarthritis- Rheumatology Presentation Powe

Axial Spondyloarthritis- Rheumatology Presentation Powe

1. Axial Spondyloarthritis Presenter: Bethlehem A. (IMR3) Moderator- Dr. Berhanu Demelash (Consultant Internist and Rheumatologist)

2. Outline Spondyloarthirtis Axial spondyloarthritis Introduction Epidemiology Pathogenesis Clinical manifestations Work up Diagnosis Management

3. Spondyloarthirtis a family of disorders classified in 2009 by the Assessment of Spondyloarthritis International Society (ASAS) into axial and peripheral spondyloarthritis may be associated with psoriasis, inflammatory bowel disease, uveitis regarded as a family of arthritides that includes: Ankylosing Spondylitis (AS )/ radiographic axSpA Psoriatic arthritis Arthritis and spondylitis associated with IBD Reactive arthritis Juvenile-onset SpA Undifferentiated SpA

4.  different forms of SpA share a group of clinical features i nflammation of axial joints Asymmetric oligoarthritis d actylitis enthesitis Additionally: skin and genital lesions eye and bowel inflammation association with preceding or ongoing infectious disorders positive family history elevated acute phase reactants

5. Axial Spondyloarthritis ( axSpA ) an inflammatory arthritis of the spine, usually presenting as chronic back pain , almost always before the age of 45 has predominantly axial involvement. Includes: AS (radiographic axial spondyloarthritis ) - has typical features of sacroiliitis on plain radiography Non-radiographic axial spondyloarthritis (nr- axSpA ) – has no definite radiographic changes of sacroilitis Traditionally, AS has been regarded as the prototype of SpA

6. Epidemiology considerable variation in the prevalence of SpA reported worldwide SpA Axial SpA is the most frequent type of SpA Reactive arthritis is the least common form of SpA Prevalence of AS in various regions : North America - 31.9/10,000 Europe - 23.8/10,000 Asia - 16.7/10,000 Latin America - 10.2/10,000 Africa - 7.4/10,000

7. male to female ratio is 2:1 in radiographic axial SpA (r- axSpA ) 1:1 in nonradiographic axial SpA (nr- axSpA ) Compared to males, females with AS: a re slightly younger at disease onset by 1 to 2 years. a re diagnosed later than male patients on average by 1 to 2 years. h ave milder form the disease with less ankylosis and damage of the spine Prevalence of r- axSpA is 5-6% among people who are HLA-B27 positive the sex distribution in peripheral SpA is equal between males and females

8. Age Generally occurs in people less than 45 years. Peak age of onset between 20 and 30 years. Up to 4 to 6% of patients may develop ax- SpA after 45 years

9. Risk Factors Genetic HLA-B27 MHC genes other than HLA-B27 ERAP1/2 Gut microbiota and associated factors Altered gut microbiota Lack of gut-induced protection by absence of breast feeding Respiratory tract infections and tonsillitis during childhood hospitalization Mechanical stress Male gender Vitamin D deficiency Smoking (including e-cigarettes) Hwang MC, Ridley L, Reveille JD. Ankylosing spondylitis risk factors: a systematic literature review. Clin Rheumatol . 2021 Aug;40(8):3079-3093. doi : 10.1007/s10067-021-05679-7. Epub 2021 Mar 22. PMID: 33754220; PMCID: PMC9044547.

10. Pathogenesis a complex network of interactions involving the following: t he axial skeleton and its entheses t he peripheral entheses and joints g enetic influences t he innate and perhaps also the adaptive immune systems t he bowel

11. Overview Needs a certain genetic background There is interaction of the gut microbiome , innate like lymphoid cells and mechanical stress at the anatomic structures that are disease targets. The disease targets are for axial SpA , the entheses along the axial skeleton, and for peripheral SpA , the peripheral joints . The major mediators are TNF-alpha and IL-17A . At the enthesis both osteoclastic (destructive inflammation) and osteoblastic ( syndesmophytes ) activities occur.

12. Genetic factors International Genetics of Ankylosing Spondylitis Consortium (IGAS), Cortes A, Hadler J, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 2013; 45:730

13. Genetic factors: HLA-B27 HLA-B27 is present in approximately 80-95% of patients with AS In the US 6% of the general population is HLA-B27 positive 1-5% HLA-B27 positive people go on to develop AS At least 160 subtypes of HLA-B27 have been characterized. HLA-B27 05 and HLA-B27 04 - the most frequent subtypes. HLA-B27 06 and HLA-B27 09 - not associated with SpA

14. It is not entirely clear what role HLA-B27 plays in the pathogenesis of SpA . However, there are some prevailing theories as to the mechanism. Antigen-dependent theories. The arthritogenic peptide hypothesis The molecular mimicry hypothesis Antigen-independent theories The misfolding hypothesis The HLA-B27 heavy chain homodimer formation hypothesis

15. Gut mucosal lesions and dysbiosis Normally, the gut microbiome is separated from the host by a gut epithelial barrier and a gut vascular barrier . However, when the integrity of the barriers is compromised, the microbes become capable of initiating a systemic immune response . The composition of the gut microbiome , differs in patients with SpA from patients with RA and from healthy individuals. There is an increase in the Ruminococcus gnavus species in patients with AS who had active disease.

16. Entheses and Mechanical Stress In SpA , inflammation is observed mostly in anatomic regions subjected to mechanical stress. Such as the axial skeleton or the heels, especially at entheses . Because of the mechanical load, entheses are highly susceptible to micro-injury. Such micro-injuries can activate resident immune cells and release of proinflammatory cytokines and chemoattractants

17. Bone erosion and new bone formation Through 3 stages Initial phase – inflammation, cytokines such as TNF and IL-17 directly or indirectly activate osteoclast precursor cells . 2 nd phase – reparative process at the vertebral corners and other sites of the axial skeleton. Final phase – New bone formation driven by IL-22 and perhaps by IL-17. findings are in contrast to those in RA, where only bone erosion is observed.

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19. Entheses describes the insertion of tendons and ligaments into the bone surface. essential structures for the transduction of mechanical forces from muscles to bones. more than 100 entheses can be found in the human body

20. Schett G, Lories RJ, D'Agostino MA, Elewaut D, Kirkham B, Soriano ER, McGonagle D. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol . 2017 Nov 21;13(12):731-741. doi : 10.1038/nrrheum.2017.188. PMID: 29158573.

21. Clinical Manifestations The major musculoskeletal features include: SI joints and spinal involvement Hip and shoulder involvement Costovertebral , manubriosternal , sternoclavicular , and costochondral inflammation Peripheral arthritis (in joints other than the hip and shoulder) Extraspinal enthesitis Dactylitis

22. low back pain and neck pain present in almost all pts with axial spa Inflammatory back pain according to ASAS criteria age of onset <40 yrs i nsidious onset i mprovement with exercise n o improvement with rest p ain at night ( with improvement upon arising) back pain that does not fulfill the criteria  mechanical low back pain Neck pain Can be a presenting sx in early disease become one of the principal problems caused by disease in nearly ½ of axial SpA pts with established disease and radiographic features

23. in the diagnosis of axSpA : 20% of individuals with other causes of low back pain complain of IBP 40 % of IBP patients resolve spontaneously without developing axSpA . considerable number of patients with axSpA will not have IBP. Thus, presence or absence of IBP alone is insufficient to determine the diagnosis. should be used together with other features of SpA in the diagnostic assessment.

24. Buttock pain e sp. alternating between the two sides but sometimes only one sided may be indicative of SI involvement Hip pain 20-25% of pts with r- axSpa associated with higher degree of disability and a worse prognosis g roin pain, typical sx , but pain may be referred to the medial thigh or even the knee Hip involvement may be more severe in pts with early onset AS, axial and entheseal disease

25. Peripheral arthritis s een in 30% of pts with axSpA a nkle, hip, knee, shoulder and sternoclavicular joint Enthesitis classic feature of axial SPA p ain, stiffness and tenderness of insertions usually without much swelling 35% of nr- axSpa and 29% of r- axSpA Other areas of enthesitis include calcaneal attachment of plantar fascia, heel, patella, shoulder, costochondral joint

26. Dactyltiis Diffuse swelling of toes and fingers i n 6% of axial SPA

27. Impaired spinal mobility in advanced disease m ore severe in advanced r- axSpA p rogressive spinal fusion may lead to extreme impairment of spinal mobility and also chest expansion Postural abnormalities in advanced disease Hyperkyphosis (hunchback) Typical stooped posture of r- axSpA patients with advanced disease is due to a combination of flexion deformity of neck, thoracic hyperkyphosis , loss of lumbar lordosis and flexion deformities of the hips

28. Extraarticular Manifestations (EAMs) SpA-related EAMs c ommon (10 to 50% of patients). c linically evident inflammation c an occur at any point during disease evolution a ctivity may fluctuate with the axial or peripheral joint symptoms include acute anterior uveitis , psoriasis and IBD Non-SpA-related EAMs r are (1% of patients). a re typically subclinical o ccur in patients with longstanding disease. a re unrelated to the activity of joint or spine symptoms i nclude conditions affecting the heart , kidneys , and lungs .

29. Acute anterior uveitis in 25 to 35% of patients. t ypically presents as acute unilateral pain, photophobia, and blurring of vision. m ay be the first problem to require medical evaluation. t he activity and severity are not correlated with articular disease. r ecurrence is common but seldom leads to permanent impairment of vision.

30. Inflammatory bowel disease 50% of axial SpA patients will have mucosal inflammation on histologic examination . However, overt IBD is found in approximately 6.4% of patients with nr-axSpA and 4.1% of those with AS. a t least one-third of patients with IBD show some features of axSpA and peripheral SpA with changes in the SI joints visible on imaging. However , only 10% of the IBD patients with chronic back pain or peripheral joint complaints eventually received a diagnosis of SpA from a rheumatologist.

31. Psoriasis i s present in up to approximately 10% of patients with nr-axSpA and AS. m ore frequent peripheral joint involvement and possibly a more severe axSpA disease course compared with axSpA patients without psoriasis. association between HLA-B27 and AS is weaker in the presence of established psoriasis compared with AS alone (also for IBD).

32. Sex differences in disease pattern Females More cervical involvement. More peripheral joint involvement. More IBD More psoriasis Males More structural damage to SI joint and spine. More progression of radiographic abnormalities. More limitations in chest expansion and thoracic kyphosis. More reports of inflammatory back pain as a first symptom.

33. Cardiovascular disease Increased risk of hypertension , CHF , ACS , strokes , VTE , conduction abnormalities , and, rarely, disease of the aortic root and valve . attributed to the systemic inflammation and increased prevalence of traditional cardiovascular risk factors . Aortic root disease due to sclerosing inflammatory process involving the aortic root (aortitis), the aortic valve cusps, and the interventricular septum. Results in cusp retraction , aortic regurgitation , and conduction abnormalities.

34. Pulmonary disease Restrictive pulmonary disease 1.3-15 % have evidence of other pulmonary changes such as apical pulmonary fibrosis by plain radiography . Usually asymptomatic and associated with a long duration of disease. HRCT abnormalities such as mosaic pattern , subpleural nodules , and parenchymal bands may be present even early in the disease. Spontaneous pneumothorax.

35. Neurologic manifestations Spinal cord injury cervical spine more often than the thoracic and lumbar spine. May cause paraparesis or tetraparesis in some patients. Atlantoaxial subluxation Can lead to spinal cord compression if it is not recognized and stabilized. Cauda equina syndrome Rare complication typically reported in patients with longstanding disease who have marked ankylosis of the spine. Subclinical neuropathy, myelopathy, and myopathy are common but rarely symptomatic.

36. Other complications/comorbidities Fibromyalgia Osteopenia and osteoporosis Vertebral fragility fractures Poor psychosocial status Renal disease.

37. Pregnancy d isease flares were seen in: 25 to 80% of patients during pregnancy, and 30 to 100% after delivery. There is also an increased risk of: p rematurity s mall-for-gestational-age births e lective cesarean delivery

38. Work up: Laboratory NCNC anemia - typically in patients with very active disease . Elevated ESR and CRP – in 50-70% of patients with active AS . Elevated bone-specific ALP . Elevated IgA are also common. Synovial fluid findings are typical of inflammatory arthritis . HLA-B27 is present, but not invariably so.

39. Imaging: SI joint Radiography All patients suspected of axSpA should have x-ray. i n the first few years, the radiographic changes can be quite subtle. f indings include: Joint-space narrowing Sclerosis Erosive change and Bony ankylosis Erosions begin on the iliac side of the SI joint where cartilage is thinner than on the sacral side.

40. SI joint cont’d The SI joint abnormalities are typically graded from 0 to 4 as follows: Grade 0 : Normal . Grade 1 : Suspicious (but not definite) changes. Grade 2 : Minimal abnormality Small localized areas with erosions or sclerosis , without alteration in the joint width . Grade 3 : Unequivocal abnormality Moderate or advanced sacroiliitis with one or more of the following: erosions , sclerosis , joint-space widening, narrowing , or partial ankylosis . Grade 4 : Total ankylosis of joints. The modified New York criteria requires bilateral grade 2 or unilateral grade 3/4 changes to diagnose AS.

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42. SI joint cont’d MRI w hen radiographs do not reveal sacroiliitis or findings are uncertain, and when there is a high index of clinical suspicion of SpA to diagnose nr-axSpA. s emicoronal (coronal oblique) view should be obtained, because of the tilt of the SI joints. Only two sequences are necessary: T1-weighted, plus Either short tau inversion recovery (STIR) sequences or T2-weighted sequences with fat suppression. Contrast enhancement is not necessary, unless the findings without contrast are uncertain and a high suspicion of axSpA remains.

43. Bone Marrow Edema(BME) - Hyperintense signal on STIR images and Osteitis - Hyperintense signal on contrast-enhanced T1 -weighted fat-saturated images The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis J Sieper , M Rudwaleit , X Baraliakos , J Brandt, J Braun, R Burgos-Vargas, M Dougados , K-G Hermann, R Landewé , W Maksymowych and D van der Heijde Ann Rheum Dis 2009;68;ii1-ii44

44. SI joint cont’d… © 2022 UpToDate, Inc. and/or its affiliates.

45. SI joint cont’d… CT scan It is more sensitive than radiography for detecting erosion. It is not generally recommended to establish the diagnosis of sacroiliitis. However, it may be useful in clinical practice if Radiographs are ambiguous and structural changes are suspected or If MRI cannot be performed . Limitations of CT include the inability to assess the activity of inflammation .

46. Spine Radiography: characteristic radiographic findings include: Squaring of the vertebral bodies Syndesmophytes Ankylosis of the facet joints Bamboo spine Anterior atlantoaxial (C1-C2) subluxation

47. Radiographic progression endpoint of radiographic progression of r- axSpA is total fusion in the form of a bamboo spine In a followup over 12 yr of r- axSpA Initial changes were erosions and sclerosis at the vertebral corners followed by appearance of syndesmophytes then bridging of syndesmophytes across vertebrae led to fusion 25% of pts do not show progression 25% of pts clinically important progression 50 % fall in between

48. Spine cont’d… nnals of the Rheumatic Diseases 1989; 48: 628-631 Pathogenesis of square bodies in ankylosingspondylitis © 2022 UpToDate, Inc. and/or its affiliates.

49. Diagnosis based upon the recognition of a pattern of clinical, laboratory, and imaging findings characteristic of axSpA . no single disease feature, with sufficient specificity by itself to establish the diagnosis. excluding other diseases that may explain findings is necessary. Several classification criteria exist to classify patients as having axSpA Modified New York criteria for ankylosing spondylitis (1984) Amor criteria for SpA (1990/1991) European Spondyloarthropathy Study Group (ESSG) criteria for SpA (1991) ASAS classification criteria for axSpA (2009)

50. axSpA should be considered in pts with chronic continuous lower back pain before the age of 45 yrs unlikely if patient lacks typical findings (inflammatory back pain, HLA B-27 and imaging changes of sacroilitis )

51. Skeletal Mobility Cervical spine- Flesche test Thoracic spine- chest expansion, measures the RoM of the costo -vertebral joints Measured at 4 th ICS Pt asked to raise his arm above the head and to exert maximal forced expiration followed by a maximal inspiration Lower spine Schober test Test more useful for serial comparisons of a given individual Lateral spine flexion

52. Snow, J.C., Simpson, K., Rahman, P. et al. Spinal mobility in radiographic axial spondyloarthritis: criterion concurrent validity of classic and novel measurements. BMC Musculoskelet Disord 22, 464 (2021). https://doi.org/10.1186/s12891-021-04352-z

53. If diagnosis cannot be made with confidence, wait and see policy regarding diagnosis and symptomatic treatment with follow-up is important

54. Management Goals of management Relief of symptoms (pain, stiffness, and fatigue) Maintenance of function Prevention of complications of spinal disease Minimization of extraspinal and extraarticular manifestations and comorbidities. Maintenance of effective psychosocial functioning

55. General principles of management care by an expert in rheumatologic disease, such as a rheumatologist is recommended. Appropriate clinical specialists should be involved, such as a dermatologist (psoriasis), a gastroenterologist (IBD), and an ophthalmologist (uveitis). Disease activity should be regularly measured and therapy adjusted accordingly All patients should receive nonpharmacologic measures. Pharmacotherapy includes NSAIDs, non-NSAID analgesics, csDMARDs , and bDMARDs . Oral glucocorticoids have no role, but IA injections may be helpful. Anxiety, depression, fatigue, sleep disturbance, and helplessness should also be treated

56. Initial therapy: Nonpharmacologic interventions Patient education about: The nature of their disease and the lifestyle adjustments needed The importance of regular follow-up and management of comorbidities The need for adhering to regular drug administration and for potential side effects of therapies. The need for monitoring of disease activity Counseling regarding smoking cessation Depression screening and psychosocial support Exercises and physical therapy Exercise improves the disease activity of SpA patients. Include postural training, range of motion exercises, stretching, recreational activities, and sometimes hydrotherapy.

57. Initial drug therapy with NSAIDs NSAIDs are recommended as initial therapy. no evidence that one NSAID is more effective than another in axial SpA. Regardless of the NSAID used, the maximum dose is often required. Efficacy of one NSAID should be assessed on a regular continuing basis for at least 2-4 weeks before switching to a second NSAID. Approximately 70-80% of AS patients report substantial relief of their symptoms with NSAIDs. 15% in patients with chronic mechanical low back pain.

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59. Initial drug therapy with NSAIDs Duration of NSAID therapy On-demand use vs continuous use. Evidence for continuous use In a 2005 trial involving 215 patients treated with celecoxib (100 to 200 mg twice daily) either continuously or as needed , those receiving continuous therapy exhibited less radiographic progression in the spine at two years . Evidence for on-demand use In a randomized trial, in which 167 patients with AS were treated with diclofenac either continuously or as needed, found no evidence at two years for reduced radiographic change in the group assigned to continuous therapy .

60. Initial drug therapy with NSAIDs cont’d 2019 Update of the American College of Rheumatology/Spondylitis Association of America /Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

61. Inadequate response to NSAIDs Inadequate response to initial therapy with two different NSAIDs used consecutively in an adequate dose for at least 2-4 weeks each. Tumor necrosis factor (TNF)-alpha inhibitor are recommended rather than continuing treatment with NSAIDs alone. In patients who have contraindications to TNF inhibitors, treatment with an anti-IL-17 antibody ( secukinumab or ixekizumab ) is recommended. In patients with symptoms and findings predominantly of peripheral arthritis , use of a csDMARD before switching to a biologic is recommended.

62. Inadequate Response to NSAIDs cont’d… Interleukin 17 inhibitors (secukinumab or ixekizumab) Have similar level of efficacy with TNFi . Less experience with their use in clinical practice. Preferred biologic in patients in whom there is high risk for TB. Screening for latent TB is recommended. However, there are no reports of latent TB reactivation under secukinumab treatment. Have been reported to induce or exacerbate IBD. Systemic glucocorticoids for axial disease v ery limited data suggest that only very high doses of prednisolone may have some benefit for very short-term therapy. a re not indicated for patients with axial SpA.

63. TNF Inhibitors Etanercept-50 mg once weekly SC Infliximab---5mg/kg IV infusion at zero, 2,6wks followed by every 6-8wks Adalimumab …40mg sc every 2wks Golimumab Certolizumab Predictors of response to TNF inhibitors elevated CRP presence of SIJ inflammation on MRI presence of sacroilitis ( NY grading : grade 2 bilaterally or grade 3 unilaterally

64. Contraindications Active infection Latent TB Demyelinating disease ( e.g …optic neuritis, MS) Moderate to severe heart failure ( NHYA class III/IV) TNF inhibitors can be used during pregnancy but should be discontinued in 2 nd or early 3 rd trimester Certolizumab is compatible for use throughout pregnancy

65. IL-17 Inhibitors as effective as TNF-I in controlling arthritis more effective than TNF-I in controlling psoriasis ineffective in suppressing bowel inflammation in pts with crohns disease and may induce or exacerbate IBD less effective in suppressing anterior uveitis Secukinumab 150mg SC weekly for 4 wks and Q 4wk Ixekuzumab Bimekizumab

66. Contraindications Latent TB (should be treated first) Secukinumab no latent TB reactivation, so preferred in pts in whom there is high risk for TB no information on use of these agents on pregnancy Adverse effects candidiasis new onset IBD or exacerbating preexisting IBD with IL-17 inhibitors has been reported

67. Janus Kinase Inhibitors tsDMARDs oral synthetic drugs targeting the JAK enzymes tofacitinib and upadacitinib can be taken orally and can be stored in room temperature also useful for psoriatic pts and ulcerative colitis patients should be used after inadequate response to TNF inhibitors or IL-17 inhibitors

68. Should not be used in pts with active infection Should be used cautiously in pts above 50 years or in pts with increased CVS risk due to increased CVS, malignancy and thrombotic risk of tofacitinib compared with TNF inhibitors contraindicated during pregnancy Adverse effect Higher risk of venous arterial thromboembolic events pts aged above 65 should be treated with tofacitinib only if no alternative agent is not available Increased herpes zoster infection

69. Inadequate Response or Intolerance to Initial Biologic 2 types of failure to respond to biologic : Primary failure – If a patient never experiences an improvement after receiving at least 12 weeks of therapy with biologic. Secondary failure – If a patient, in whom there is initial improvement with drug therapy, experiences a subsequent relapse or if a patient doesn’t tolerate the particular biologic.

70. Inadequate Response or Intolerance to Initial Biologic cont’d… Approach to inadequate response: Primary failure to TNFi – switch to an anti-IL-17 antibody (different mechanism) Secondary failure to TNFi – switch to a second TNFi (initial benefit) Intolerance to TNFi - switch to an anti-IL-17 antibody . Secondary failures of 2 consecutive TNFi – Both TNFi and anti-IL-17 antibody are reasonable options, although the likelihood of responding to a 3 rd TNFi is lower after two failures.

71. Inadequate Response or Intolerance to Initial Biologic cont’d… Primary drug failures with both a TNFi and anti-IL-17 antibodies Repeat the diagnostic evaluation to assure that the diagnosis is correct. Using any of the other TNFi or the alternate anti-IL-17 antibody Infliximab – trough levels can be monitored Inadequate response or intolerance of anti-IL-17 antibodies as initial agent lack of evidence that compares options for these specific patient populations. u se TNFi as the next agent. i n those unable to use a TNFi , an alternative agent would be required

72. Resistance to Standard Therapies Agents of possible benefit Janus kinase (JAK) inhibitors Thalidomide Brodalumab (anti-IL-17 receptor-A monoclonal antibody) Bimekizumab (anti-IL-17) – under investigational isolated active sacroiliitis - injection of glucocorticoids into the SI joints can be used

73. Resistance to Standard Therapies cont’d Agents not effective for axSpA Abatacept , a T-cell costimulation blocker Tocilizumab and sarilumab , IL-6 inhibitors Ustekinumab , an anti-IL-12/23 p40 monoclonal antibody Risankizumab , an anti-IL-23 p19 monoclonal antibody Apremilast , an oral phosphodiesterase 4 (PDE4) inhibitor Rituximab , a monoclonal anti-CD20 antibody that depletes B cells

74. Role of non-NSAID analgesics in patients who need additional temporary pain relief, in addition to NSAIDs, we add acetaminophen opiods should be avoided and if needed, only for very short period of time might be considered for residual pain after previously recommended treatments have failed, are contraindicated, and/or poorly tolerated

75. Monitoring of patients While on NSAIDs: Every 2-4 weeks to assess the response Then every 1-3 months once stable or when starting a biologic. While on biologic: After at least 12 weeks of TNFi or anti-17 therapy. Subsequent monitoring can take place every 3-6 months when the disease is under control. Imaging should be repeated only when the results might alter the treatment strategy.

76. Disease activity assessment BASDAI a ctive disease A BASDAI score of ≥4 c linically significant improvement A 50% improvement of the BASDAI score or an absolute change of ≥2 and ASDAS c ategorizes the disease activity as inactive, low, high, or very high. change of ≥1.1 in the ASDAS score is considered a significant improvement, while a change of ≥2.0 is a major improvement.

77. Originally published in: Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994; 21:2286. Reproduced with permission from: the Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Bath. https://www.ruh.nhs.uk/ . Copyright © 1994

78. https://www.asas-group.org/instruments/asdas-calculator/

79. Surgerical Management Hip and spine surgery (total hip arthroplasty and spinal corrective osteotomy) may be beneficial in selected patients with axSpA. Indications for surgery include: s evere hip involvement, with persistent pain or severe limitation in mobility and quality of life a tlantoaxial subluxation with neurologic impairment s evere flexion deformities with impaired ability to look in a forward direction

80. Management of comorbidities 2019 Update of the American College of Rheumatology/Spondylitis Association of America /Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

81. Prognosis Poor prognostic indicators: Cigarette smoking, Increasing severity of radiographic changes Active disease (assessed by a disease activity index) Functional impairment (assessed by a self-report) Lower educational attainment Presence of other diseases related to SpA ( eg , psoriasis, IBD, enthesitis, uveitis) Male sex Presence of HLA-B27 Older age Elevated CRP

82. References Harrison’s principles of Internal Medicine, 21 st edition UpToDate online Firestein and Kelly text book of Rheumatology, 2021 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis 2019 Update of the American College of Rheumatology/Spondylitis Association of America /Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

83. Thank You