Spondyloarthritis: Practice. New Concepts in. Epidemiology and Clinical

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1 New Concepts in Spondyloarthritis: Epidemiology and Clinical Practice Atul Deodhar MD Professor of Medicine Oregon Health & Science University Portland, OR Northwest Rheumatism Society, Seattle, April 28 th, 2017

2 New Concepts in SpA: Epidemiology & Clinical Practice: Outline Epidemiology: US Paradox: Population prevalence: axspa > RA (NHANES Study), but rheumatology practices: RA >> axspa Recent studies to understand the reasons behind this Paradox: Administrative Claims Database Study ProSpA Study Northern California Kaiser study The flip side: Over-diagnosis of axspa Clinical Practice: The ACR-SAA-SPARTAN Treatment Guidelines & the EULAR-ASAS Treatment guidelines T2T & Minimal Disease Activity in axspa

3 National Health & Nutrition Examination Survey NHANES NHANES: To monitor the health & nutritional status of the civilian, non-institutionalized population of the US Mobile Examination Centers Centers for Disease Control and Prevention National Center for Health Statistics

4 NHANES Study ( ) Groups N Frequency (%) Overall sample 5103 Age Group years years years Racial/Ethnic Groups Mexican-Americans Other Hispanic Caucasians, not Hispanic African-Americans Other Weisman MH et al. Ann Rheum Dis. 2013;72:

5 NHANES ( ): Prevalence of HLA-B27 in U.S. Adults Ages Years Selected Characteristic n N % SE 95% CI Overall US Prevalence ( ) Sex Males ( ) Females ( ) Race/ethnicity Non-Hispanic Whites ( ) Mexican-Americans ( ) Age Years ( ) Years ( ) Years ( ) Years ( )* Years ( )* Reveille JD et al. Arthritis Rheum May;64(5):

6 NHANES ( ): Prevalence of axspa by ESSG Criteria in U.S. Adults (20-69 yrs) Case Type n N % SE L 95% CI U 95% CI Overall AS (reporting as having a dx of AS) Overall axspa Age Years Years Sex Males Females Race/Ethnicity Mexican-Americans * Non-Hispanic Whites Non-Hispanic Blacks * Reveille JD et al. Arthritis Rheum May;64(5):

7 Estimated Prevalence, % Axial SpA may be More Common than RA in US France US Lithuania AS SpA RA France: Saraux A et al. Ann Rheum Dis 2005;64:431-5; Guillemin F et al. Ann Rheum Dis 2005;64: Lithuania: Adomaviciute D et al. Scand J Rheumatol. 2008;37: USA: Helmick CG et al. Arthritis Rheum. 2008;58:15-25.

8 If axspa is More Common Than RA in the US, Where are These Patients? axspa patients are seen by others before rheumatologists Family practice, Internal medicine Chiropractors, Osteopaths, Orthopedic surgeons, Spine surgeons, Neurosurgeons Dermatologists, Ophthalmologists, Gastroenterologists Commonest MRI scan ordered is L Spine: SI joints missed Are US rheumatologists missing axspa amongst patients with back pain they see? Transient nature of arthritis/enthesitis in true SpA patients Lack of reliable biomarkers outside of HLA-B27 95% of backache is mechanical : rheumatologists have little to offer

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10 Diagnostic prevalence of AS in KPNC Kaiser Permanante Northern California clinical databases analysis to estimate the prevalence of clinically recognized axspa Patients included with at least 12 months of enrollment in KPNC between Patients identified on basis of having at least 1 ICD-9 code of 720.X, and 3% of cases identified randomly selected for validation by detailed review of the medical records Overall, 5,568 KPNC members with at least 1 code of 720.X identified; (point prevalence for axspa of 0.23%) 53% (2,965) had a single code assigned by a PCP Upon examination of a random sample of these, only 1 of 44 patients actually had a confirmed diagnosis; therefore these patients were excluded For the 2,603 patients remaining the final point prevalence was 0.1% Curtis JR et al. Perm J. 2016;20:

11 Diagnostic prevalence of AS in KPNC: Summary Estimated point prevalence of axspa in KPNC registry using a validation of randomly selected cases was 1.07 per 1,000 (95% CI, ) These prevalence numbers are substantially lower than those observed in NHANES study Many of these patients were not referred to a rheumatologist Curtis JR et al. Perm J. 2016;20:

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13 AS diagnosis in patients with back pain in the US Retrospective, longitudinal cohort study using the Truven Health MarketScan US Commercial Claims Database Patients aged identified based on an initial diagnosis of back pain in a non-rheumatology setting Deodhar A et al. Clin Rheumatol. 2016;35: Total patients in MarketScan database during study period ( ) N = 127,137,195 Aged years n = 87,652,620 Back pain diagnosis between n = 14,774,758 (16.8%) Continuously eligible for 365 days before and after initial diagnosis of back pain n = 3,710,986 Diagnosis of AS after back pain diagnosis during the study period n = 4,245 Non-referred Cohort No rheumatologist visit n = 2,092 Referred Cohort First rheumatologist visit on or before AS diagnosis n = 1,244 Excluded Diagnosis of AS, RA, PsO, PsA, CD, or UC on or before back pain diagnosis (n = 71,093) HMO (n = 863,082) Not continuously eligible (n = 114) Missing data (n = 1) First rheum. visit on or before initial back pain diagnosis (n = 447) First rheumatologic visit after AS diagnosis (n = 347) Diagnosis confirmed by a rheumatologist (n = 145) Total patients with rheumatologistconfirmed AS diagnosis n = 1,389

14 Who is Making the AS Diagnosis in the US? These data suggest that 63% of patients were diagnosed with AS outside of a rheumatology practice; the breakdown of actual diagnosing provider is shown below Acute Care 3.4% Other 19.2% Diagnosis of AS after back pain diagnosis during the study period n = 4,245 Non-referred Cohort No rheumatologist visit n = 2,092 Referred Cohort First rheumatologist visit on or before AS diagnosis n = 1,244 Pain Mgmt 3.6% Rheumatologist 37.3% Orthoped.3.8% Chiro/PT 7.0% PCP 25.7% An additional 347 patients were initially diagnosed by a non-rheumatologist but had a rheumatologist visit after diagnosis. Of these, 145 (41.8%) had their AS diagnosis confirmed by the rheumatologist Deodhar A et al. Clin Rheumatol. 2016;35:

15 AS diagnosis in patients with back pain in the US: Summary Large proportion (63%) of patients with AS received their diagnosis from a non-rheumatologist Only 42% of patients with an initial diagnosis of AS by a nonrheumatologist had that diagnosis confirmed by a rheumatologist These results suggest non-recognition of AS features by nonrheumatologists Conclusion: Additional efforts to educate the non-rheumatologists re appropriate referrals for patients with suspected AS is warranted Deodhar A et al. Clin Rheumatol. 2016;35:

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17 Frequency of axspa in chronic back pain patients seen by US rheumatologists To determine the proportion axspa in a population of patients with: chronic back pain for 3 months starting before age of 45 years with one or more of the following: HLA-B27 +, current IBP or Imaging evidence of sacroiliitis 751 enrolled patients 46% were diagnosed as having axial SpA by the investigator, and 47% fulfilled the ASAS criteria Using investigator's clinical diagnosis as the gold standard, the specificity and sensitivity of the ASAS criteria were 79% and 81% Mean symptom duration in these patients was 14 years These findings indicate that among patients with CBP for 3 months beginning at ages younger than 45 years, the presence of 1 of 3 SpA features is an effective way to identify those with possible axial SpA. Deodhar A et al. Arthritis Rheum. 2016;68:

18 Problem of Over-diagnosis of axspa Based on SIJ MRI Scans Bottom line: In young adults with chronic LBP onset <45 years, MRI sacroiliitis was present in 21%, but expected prevalence of axspa in this population was 5%

19 Arthritis Rheumatol. 2016;68:282 98

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21 Recommendations for the treatment of active AS Slow-Acting Drugs (SSZ, pamidronate) Consider if peripheral arthritis or TNFi contraindications NSAIDs Use continuously No preferred drug Remains active TNFi contraindication Non-TNFi biologic Physical Therapy Active over passive Land-based over aquatic Systemic glucocorticoid Consider if peripheral flare, pregnancy, IBD flare LEGEND Strongly recommend Conditionally recommend Conditionally recommend against Strongly recommend against Qualifier Isolated sacroiliitis Peripheral arthritis Enthesitis TNFi Remains active Alternative TNFi No preferred drug Recurrent iritis IBD Local GC Local GC Local GC Use infliximab or adalimumab Use TNFi monoclonals Consider if joints; use infrequently Avoid achilles, patellar, quadriceps Monitor validated AS disease activity measure, and CRP or ESR regularly Unsupervised back exercises, formal group or individual self-management education, fall evaluation/counseling Ward M. et al. Arthritis Rheumatol. 2016;68:282 98

22 Recommendations for the treatment of stable AS NSAIDS Use on demand NSAIDs & TNFi Slow-acting drugs and TNFi Physical therapy TNFi alone (monotherapy) TNFi alone (monotherapy) Monitor validated AS disease activity measure, and CRP or ESR regularly Unsupervised back exercises, formal group or individual self-management education, fall evaluation/counselling LEGEND Strongly recommend Conditionally recommend Conditionally recommend against Strongly recommend against Qualifier Ward M, Deodhar A, Akl E. et al. Arthritis Rheumatol. 2016;68:282 98

23 2016 Treatment Recommendations for axspa (ASAS/EULAR) Most recommendations & overarching principals similar to 2010 recommendations, with following changes: 1 st line biologic treatment: In patients with persistently high disease activity despite conventional treatments: use biologic DMARDs TNFi & IL-17i. Start with TNFi (level of evidence 1a: meta-analysis of RCTs, and 1b for IL-17i one RCT) 2 nd line biologic treatment: TNFi failure patients: Switch to another TNFi (level of evidence 2) or IL-17i (level of evidence 1b from at least one RCT) Désirée van der Heijde et al. Ann Rheum Dis doi: /annrheumdis

24 ASAS-EULAR recommendations for use of biologic in axspa Désirée van der Heijde et al. Ann Rheum Dis doi: /annrheumdis

25 Treat to target in Spondyloarthritis Active SpA* Main target Adapt therapy to disease activity Remission Adapt therapy if state is lost Sustained remission Alternative target Use measures of clinical disease activity and acute phase reactants as needed Adapt therapy according to disease activity Low disease activity Use measure of clinical disease activity and acute phase reactants as needed Adapt therapy if state is lost Sustained low disease activity Smolen JS, et al. Ann Rheum Dis 2014;73:6 16

26 Is this patient s axspa in Remission? 63 year old man with known AS for 40+ years Advanced AS, fused spine, hip replacements On Etanercept for the last 6 years: very stable, BASDAI 1.8, CRP 0.2 mg/dl, ASDAS 1.2 Presents to the clinic with acute attack of AAU On enquiry: has had no back pain, enthesitis, peripheral arthritis for >3 years, but has had 3 attacks of AAU in the last year According to BASDAI & ASDAS, he is in remission..but does he have minimal disease activity? Mr. KM on Mount Hood, OR, at 11,000 feet, May 2003

27 Minimal Disease Activity (MDA) for axspa We need a MDA for axspa because the current disease activity measures concentrate only on spinal/peripheral arthritis, enthesitis, fatigue & stiffness axspa is a multifaceted disease: involving extra-articular tissues such as skin and nails, and can cause uveitis, IBD, dactylitis While separate disease activity measures are available for other aspects of disease (e.g. skin, nail, IBD, uveitis), no composite disease activity measure assesses all manifestations MDA could be such a composite measurement, and would be useful in daily clinical practice & clinical trials of T2T SPARTAN is undertaking the development of MDA in axspa

28 What have we learnt today? While according to NHANES, the prevalence of axspa is higher than that of RA, in practice most patients are being missed Only 37% of AS patients in the US are diagnosed by rheumatologists Patients with CBP starting before the age of 45 years, with either IBP, HLA B27 or sacroiliitis on imaging should be referred to rheumatologist nearly half of these patients have axspa The 2016 ASAS-EULAR treatment guidelines are similar to ACR-SAA-SPARTAN guidelines with some differences re mandatory disease activity measurements before changing therapy T2T in axspa patients needs careful measurement of disease activity in all aspects of the disease