SAT0369 SPINAL RADIOGRAPHIC PROGRESSION IN EARLY SPONDYLOARTHRITIS: SIX-YEAR RESULTS FROM THE ESPERANZA COHORT

Background:There are few studies focused on the development of structural damage over time in patients with early SpAObjectives:The aim of this study is to analyze the mSASSS radiographic progression of spine in patients with early spondyloarthritis (SpA) in the Esperanza cohort.Methods:In this longitudinal study, 49 patients of the Spanish early spondyloarthritis (SpA) Esperanza cohort were included. Every patient had a baseline and a six years lateral X-Ray of the cervical and lumbar of spine. The assessment of spine structural damage was done by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Nine readers, blinded for the diagnosis, participated in the reliability exercise, all of them experienced rheumatologists and members of the Spanish spondyloarthritis working group (GRESSER). The mSASSS progression and development of new syndesmophytes was analyzed. The gold standard of every elemental lesion of the mSASSS and the total mSASSS score was the agreement achieved by the independent categorical opinion of at least five of the nine readers. For reliability, intraclass correlation coefficient (ICC) two-way mixed, absolute agreement was used.Results:Forty-nine patients were included, 69 % were males and 49%, HLA B27 positive. Mean ± SD baseline ESR, CRP, BASDAI, BASFI and mSASSS were 10.7±11.7, 5.4±7.1, 3.7±2.5, 2.1±2.0 and 0.326±0.85, respectively. Inter-reader ICC reliability of the 9 readers was 0.812 (CI 95%; 0.764-0.857). The mSASSS score at the six-year visit was 0.67 ± 1.6: thirty-nine patients did not present any changes in this score at the end of the follow-up, two patients had Δ mSASSS of – 1 and eight patients, an increase in this score (four patients, +1; three patients, +2 and one patient, +9 points).At baseline, five patients presented one syndesmophyte; at the six-year visit, seven had one syndesmophyte; one patient, two syndesmophytes and another one, one bone bridge. Only 2/5 patients (40%) with syndesmophytes at baseline showed an increase in Δ mSASSS; the two patients with a Δ mSASSS of -1 did not have syndesmophytes at baseline. Five out of eight patients (62.5%) with an increase of the Δ mSASSS presented this lesion at the six-year visit but only two of them showed syndesmophytes at baseline. On the other hand, two of the three patients who showed an increase of the ΔmSASSS without syndesmophytes at baseline presented an erosion in the anterior vertebral corner and the patient with the bone bridge had a previous syndesmophyte. Our results indicate that in early SpA much of the progression appears in patients without previous syndesmophytes.Conclusion:Spinal radiographic progression was very low in our early SpA cohort, with a mean progression of 0.3 mSASSS units. Only eight patients (16.3%) presented spinal structural progression, most of them not showing syndesmophytes at baseline. It is reasonable to consider that an early diagnosis and monitoring could result in a low radiographic progression.Disclosure of Interests:Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Jose Francisco Garcia LLorente: None declared, Claudia Urrego-Laurín: None declared, Maria Luz García-Vivar: None declared, Cristina Fernández-Carballido Consultant of: Yes, I have received fees for scientific advice (Abbvie, Celgene, Janssen, Lilly and Novartis), Speakers bureau: Yes, I have received fees as a speaker (Abbvie, Celgene, Janssen, Lilly, MSD, Novartis), María del Carmen Castro Villegas: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Xavier Juanola-Roura: None declared, Carolina Tornero: None declared, E. Galindez: None declared

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AB0700 RADIOGRAPHIC PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS UNDER TREATMENT WITH TNF INHIBITORS. DATA FROM REGISPONSERBIO (SPANISH REGISTER OF BIOLOGICAL THERAPY IN SPONDYLOARTHRITIDES)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6484 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1646-1646

Author(s):

M. Llop Vilaltella ◽

M. Moreno ◽

J. Gratacos-Masmitja ◽

V. Navarro-Compán ◽

E. De Miguel ◽

...

Keyword(s):

Clinical Practice ◽

Structural Damage ◽

Radiographic Progression ◽

Biological Therapy ◽

Axial Spondyloarthritis ◽

Change Score ◽

Tnf Inhibitors ◽

Research Support

Background:Clinical efficacy of TNF inhibitors (TNFi) in axial spondyloarthritis (axSpA) has been widely probed in randomized control trials. In clinical practice, some studies suggested that long-term (more than 4 years) treatment with TNFi could slow down radiographic progression in axSpA; however, whether this treatment inhibits structural damage remains unclear.Objectives:To evaluate radiographic progression in axSpA patients receiving long-term TNFi (over 4 years) in comparison with patients starting TNFi.Methods:A total of 204 patients with axSpA were included in the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO). Out of these, 80 patients (31 starting TNFi and 49 under long-term TNFi) were included in this study based on the availability of spinal radiographs (cervical and lumbar lateral views), at two time points. Radiographs in patients starting TNFi were available: i) at baseline (before TNFi) and ii) after 3 to 5 years of TNFi therapy (mean follow-up 3.7±0.8), while in long-term TNFi patients, these were available: i) at one follow-up visit at least 4 years later since TNFi was started and ii) after 3 to 5 years of this visit (mean follow-up 3.5±1.1). Two trained readers, not blinded for chronological order, independently scored lateral cervical and lumbar spine images according to the mSASSS system (0-72). Following definitions for progression were used: change of the absolute scores, change of ≥2 units, development of new syndesmophytes, and development of new syndesmophytes or growth of the existing syndesmophytes.Results:Reliability of both readers was excellent with intraclass correlation coefficients (ICCs) of 0.98 (0.98-0.99) at inclusion and 0.98 (0.97-0.99) at follow-up. Most patients (82.5%) were classified as radiographic axSpA. Mean BASDAI at first visit (i) was of 5.0±2.4 for starting TNFi patients and of 3.2±1.9 for long-term TNFi patients. The table depicted the results for radiographic scores and progression. Mean mSASSS score at first visit (i) was 15.8±21.5 and 15.1±18.4 units for starting TNFi and long-term TNFi patients, respectively. The change score between both visits was 2.3±4.2 and 2.3±4.1, respectively. Similarly, no differences were found for change of ≥2 points (32.3% in starting TNFi and 35% in long-term TNFi patients). However, development of new syndesmophytes or growth of the existing syndesmophytes were found to be more frequently (but not significant) in starting TNFi patients compare to long-term TNFi patients.Conclusion:In patients with axSpA treated with TNFi in clinical practice radiographic progression is observed, independently of the time under this therapy. Nevertheless, the development and growth of syndesmophytes seem to be lower in long-term treated patients.Table.Starting TNFi patientsLong-term TNFi patients*p-valuePresence of syndesmophytes at first visit, % (n)45.2% (14)53.1% (26)NSPresence of syndesmophytes at follow up, %51.6% (16)55.1% (27)NSMean change score, mean ± SD2.32 ± 4.192.26 ± 4.09NSChange of ≥ 2 units in the score % (n)32.3% (10)34.7% (17)NSDevelopment of new syndesmophytes, % (n)29% (9)18.4% (9)0.3Progression or development of new syndesmopyhtes % (n)29% (9)22.4% (11)0.5* Patients with more than 4 years under TNFi treatmentDisclosure of Interests:María LLop Vilaltella Speakers bureau: Janssen and Pfizer, Mireia Moreno: None declared, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Font Ugalde Pilar: None declared, Teresa Clavaguera Speakers bureau: novartis, BMS, Faes, Luis F. Linares Ferrando: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Xavier Juanola-Roura: None declared

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FRI0303 PERIPHERAL SYMPTOMS ARE ASSOCIATED WITH LESS SPINAL RADIOGRAPHIC PROGRESSION IN PATIENTS WITH EARLY AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3397 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 741-741

Author(s):

M. Torgutalp ◽

M. Protopopov ◽

F. Proft ◽

J. Sieper ◽

V. Rios Rodriguez ◽

...

Keyword(s):

Regression Analysis ◽

Ankylosing Spondylitis ◽

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Smoking Status ◽

Hla B27 ◽

Research Support ◽

Sum Score ◽

Multivariable Regression

Background:Peripheral symptoms (PS), such as arthritis, enthesitis, and dactylitis, are common in axial spondyloarthritis (axSpA); data showing the association of PS and spinal radiographic progression in axSpA are controversial.Objectives:To analyze the association of PS and spinal radiographic progression in patients with axSpA.Methods:A total of 210 patients with axSpA (115 with radiographic and 95 with non-radiographic axSpA) were selected for analysis. Spinal radiographs were scored by two readers in a random order according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Pelvic radiographs were scored according to the grading system of the modified New York criteria; a sacroiliitis sum score was calculated as a sum of the grades for both sacroiliac joints. Mann-Whitney and Fisher exact tests were performed for group comparisons. A multivariable regression analysis was performed to analyze the influence of PS on radiographic progression.Results:Of the 101 (48.1%) patients with PS, 78 had peripheral arthritis, 48 - enthesitis, 12 - dactylitis. 32 patients had ≤1 PS. Patients with PS were older, less frequently HLA-B27 positive, compared with patients with no PS (73 (73.0%) vs. 93 (85.3%), p=0.028), had higher disease activity (time-averaged ASDAS over 2 years 2.6 ± 0.9 vs. 2.3 ± 0.9; p=0.032), worse physical function (BASFI 3.5 ± 2.3 vs. 2.3 ± 2.2, p<0.001), higher exposure to disease modifying anti-rheumatic drugs (39 (38.6%) vs. 22 (20.2%), p=0.003) and lower baseline radiographic sacroiliitis sum score (3.8 ± 1.9 vs. 4.4 ± 2.1, p=0.026); other baseline characteristics were similar. Patients with PS had lower absolute progression in mSASSS after 2 years of follow-up than those without (0.28 ± 1.39 vs 1.15 ± 2.9, p=0.045); 7.9% of patients with PS had a progression of mSASSS by ≥2 points compared to 20.2% in patients without PS (p=0.011). Radiographic progression of sacroiliitis was similar in both groups. In a multivariable regression analysis, presence of PS was associated with a lower mSASSS progression and lower odds for the mSASSS progression by ≥2 points after 2 years of follow-up: β=-0.98 (95% -1.68 to -0.28) OR=0.33 (95% CI 0.12 to 0.91), respectively – Table 1.Table 1.Association of peripheral symptoms with radiographic progression in axial spondyloarthritis after 2 years of follow-up.Multivariable linear regression analysisOutcomeβ (95 %CI)mSASSS change score−0.98 (-1.68 to -0.28)*Change of the sacroiliitis sum score−0.06 (-0.32 to 0.20)**Multivariable logistic regression analysisOutcomeOdds ratio (95 %CI)Progression of mSASSS by ≥2 points0.33 (0.12 to 0.91)*Progression of sacroiliitis by at least 1 grade in opinion of both readers0.84 (0.33 to 2.09)**mSASSS - modified Stoke Ankylosing Spondylitis Spine Score.*Adjusted for the smoking status, HLA-B27 status, NSAIDs intake, baseline syndesmophytes, and time-averaged ASDAS.**Adjusted for the smoking status, HLA-B27 status, NSAIDs intake, sacroiliitis sum score at baseline, and time-averaged ASDAS.Conclusion:Presence of PS is associated with distinct characteristics of SpA including slower radiographic spinal progression which might be explained partly by the numerically lower mSASSS score at baseline.Acknowledgments:GESPIC has been financially supported by the German Federal Ministry of Education and Research (BMBF). As funding by BMBF was reduced in 2005 and stopped in 2007, financial support has been obtained from Abbott / Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Since 2010 GESPIC is supported by Abbvie.Dr. Murat Torgutalp was supported by the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Murat Torgutalp: None declared, Mikhail Protopopov Consultant of: Novartis, Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

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THU0211 RADIOGRAPHIC OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB AS MONOTHERAPY OR IN COMBINATION WITH METHOTREXATE: RESULTS AT 2 YEARS FROM THE SELECT-COMPARE AND SELECT-EARLY STUDIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1869 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 330-331

Author(s):

C. Peterfy ◽

V. Strand ◽

M. C. Genovese ◽

A. Friedman ◽

J. J. Enejosa ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Structural Damage ◽

Radiographic Progression ◽

Joint Damage ◽

Joint Space ◽

Inadequate Response ◽

X Rays ◽

Research Support ◽

Structural Progression ◽

Structural Joint

Background:For patients with rheumatoid arthritis (RA), long-term prevention of structural joint damage is a key treatment goal.1In the SELECT-EARLY and SELECT-COMPARE trials, upadacitinib (UPA), an oral JAK inhibitor, inhibited the progression of structural joint damage at 6 months and 1 year when used either as monotherapy or in combination with methotrexate (MTX) in patients (pts) with active RA.2Objectives:To describe the radiographic progression up to 2 years (96 wks) among pts with RA receiving UPA either as monotherapy or in combination with MTX.Methods:Both the SELECT-EARLY and SELECT-COMPARE phase 3, randomized controlled trials enrolled pts at high risk for progressive structural damage with baseline (BL) erosive joint damage and/or seropositivity.3,4In SELECT-EARLY, MTX-naïve pts (N=945) were randomized to UPA 15 mg or 30 mg once daily (QD) or MTX monotherapy. In SELECT-COMPARE, pts with an inadequate response to MTX (N=1629) were randomized to UPA 15 mg, placebo (PBO), or adalimumab (ADA) 40 mg every other wk, with all pts continuing background MTX; at wk 26, all pts receiving PBO were switched to UPA 15 mg, regardless of response. In both trials, mean changes from BL in modified Total Sharp Score (mTSS), joint space narrowing, and joint erosion as well as the proportion of pts with no radiographic progression (change in mTSS ≤0) were evaluated based on X-rays taken at wks 24/26, 48, and 96 for those patients in whom wk 96 X-rays were available. Data are reported as observed (AO).Results:BL demographics have been reported previously.3,4In the SELECT-EARLY study, at wk 96 UPA monotherapy (15 mg and 30 mg doses) significantly inhibited radiographic progression compared with MTX as measured by mean change in mTSS and by the proportion of patients with no radiographic progression (Figures 1 and 2). When patients who were rescued (MTX added to UPA or UPA added to MTX) were removed from the analysis, changes in mTSS from baseline remained similar. By the same measures, in SELECT-COMPARE, the degree of inhibition of structural progression observed was comparable between UPA and ADA. Following the switch of all PBO patients to UPA, the rate of progression slowed and was comparable to that observed in pts receiving UPA from BL. Among pts from both studies that had no radiographic progression at wk 24/26, >90% remained without radiographic progression at wk 48 and 96.Conclusion:UPA was effective in inhibiting the progression of structural joint damage through 2 years both in MTX-naïve patients receiving UPA monotherapy and MTX-inadequate responder patients receiving UPA in combination with MTX.References:[1]Smolen, et al.Ann Rheum Dis2017;76(6):960-77.[2]Peterfy, et al.Ann Rheum Dis2019;78(suppl 2):369-370.[3]Fleischmann, et al.Arthritis Rheumatol2019;71(11):1788-1800.[4]Van Vollenhoven, et al.Arthritis Rheumatol2018;70(suppl 10).Disclosure of Interests: :Charles Peterfy Consultant of: AbbVie, Acerta, Amgen, AstraZeneca, Bristol Myers Squibb, Centrexion, Daiichi Sankyo, Five Prime Therapeutics, Genentech, Gilead, Hoffman-La Roche, Janssen, Lilly USA, MedImmune, Merck, Myriad, Novartis, Plexxikon, Pfizer, Sanofi, Salix Santarus, Samsung, Samumed, Setpoint, Sorrento, UCB, Vorso, Employee of: founder and CEO of Spire Sciences, which provides imaging services to multiple pharmaceutical companies, Speakers bureau: Amgen, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Jose Jeffrey Enejosa Shareholder of: AbbVie, Employee of: AbbVie, Stephen Hall Grant/research support from: Abbvie, UCB, Janssen, Merck, Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Tim Shaw Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.

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POS1002 BASELINE CALPROTECTIN AND VISFATIN LEVELS PREDICT RADIOGRAPHIC SPINAL PROGRESSION AFTER 2 YEARS IN ANKYLOSING SPONDYLITIS PATIENTS ON TNF INHIBITOR THERAPY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3059 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 769.2-770

Author(s):

J. Rademacher ◽

M. Siderius ◽

L. Gellert ◽

F. Wink ◽

M. Verba ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Ankylosing Spondylitis ◽

Bone Formation ◽

Bone Turnover ◽

Radiographic Progression ◽

Serum Levels ◽

Tnf Inhibitor ◽

Research Support

Background:Radiographic spinal progression determinates functional status and mobility in ankylosing spondylitis (AS)1.Objectives:To analyse whether biomarker of inflammation, bone turnover and adipokines at baseline or their change after 3 months or 2 years can predict spinal radiographic progression after 2 years in AS patients treated with TNF-α inhibitors (TNFi).Methods:Consecutive AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort2 starting TNFi between 2004 and 2012 were included. The following serum biomarkers were measured at baseline, 3 months and 2 years of follow-up with ELISA: - Markers of inflammation: calprotectin, matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF) - Markers of bone turnover: bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide (sCTX), osteocalcin (OC), osteoprotegerin (OPG), procollagen typ I and II N-terminal propeptide (PINP; PIINP), sclerostin. - Adipokines: high molecular weight (HMW) adiponectin, leptin, visfatinTwo independent readers assessed spinal radiographs at baseline and 2 years of follow-up according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Radiographic spinal progression was defined as mSASSS change ≥2 units or the formation of ≥1 new syndesmophyte over 2 years. Logistic regression was performed to examine the association between biomarker values at baseline, their change after 3 months and 2 years and radiographic spinal progression. Multivariable models for each biomarker were adjusted for mSASSS or syndesmophytes at baseline, elevated CRP (≥5mg/l), smoking status, male gender, symptom duration, BMI, and baseline biomarker level (the latter only in models with biomarker change).Results:Of the 137 included AS patients, 72% were male, 79% HLAB27+; mean age at baseline was 42 years (SD 10.8), ASDAScrp 3.8 (0.8) and mSASSS 10.6 (16.1). After 2 years of follow-up, 33% showed mSASSS change ≥2 units and 24% had developed ≥1 new syndesmophyte. Serum levels of biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, whereas adipokine levels were not altered from baseline (Figure 1).Univariable logistic regression revealed a significant association of baseline visfatin (odds ratio OR [95% confidence interval] 1.106 [1.007-1.215]) and sclerostin serum levels (OR 1.006 [1.001-1.011]) with mSASSS progression after 2 years. Baseline sclerostin levels were also associated with syndesmophyte progression (OR 1.007 [1.001-1.013]). In multivariable logistic analysis, only baseline visfatin level remained significantly associated (OR 1.465 [1.137-1.889]) with mSASSS progression. Furthermore, baseline calprotectin showed a positive association with both, mSASSS (OR 1.195 [1.055-1.355]) and syndesmophyte progression (OR 1.107 [1.001-1.225]) when adjusting for known risk factors for radiographic progression.Univariable logistic regression showed that change of sclerostin after 3 months was associated with syndesmophytes progression (OR 1.007 [1.000-1.015), change of PINP level after 2 years was associated with mSASSS progression (OR 1.027 [1.003-1.052]) and change of visfatin after 2 years was associated with both measures of radiographic progression – mSASSS (OR 1.108 [1.004-1.224]) and syndesmophyte formation (OR 1.115; [1.002-1.24]). However, those associations were lost in multivariable analysis.Conclusion:Independent of known risk factors, baseline calprotectin and visfatin levels were associated with radiographic spinal progression after 2 years of TNFi. Although biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, these changes were not significantly related to radiographic spinal progression in our cohort of AS patients.References:[1]Poddubnyy et al 2018[2]Maas et al 2019Acknowledgements:Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of Interests:Judith Rademacher: None declared, Mark Siderius: None declared, Laura Gellert: None declared, Freke Wink Consultant of: AbbVie, Maryna Verba: None declared, Fiona Maas: None declared, Lorraine M Tietz: None declared, Denis Poddubnyy: None declared, Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, Lilly and Novartis, Grant/research support from: Abbvie, Pfizer, UCB, Novartis, Suzanne Arends Grant/research support from: Pfizer.

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Progression of sacroiliitis in men and women according to the cohort of early axial spondyloarthritis (CORSAR) over 3 years of follow-up

Rheumatology Science and Practice ◽

10.47360/1995-4484-2021-715-719 ◽

2021 ◽

Vol 59 (6) ◽

pp. 715-719

Author(s):

D. G. Timokhina ◽

T. V. Dubinina ◽

A. B. Demina ◽

O. A. Krichevskaya ◽

Sh. F. Erdes

Keyword(s):

Structural Damage ◽

Structural Changes ◽

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Chronic Inflammatory Disease ◽

Men And Women ◽

X Ray ◽

Delay In Diagnosis ◽

Reactive Protein ◽

The Right

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease with predominant involvement of the sacroiliac joints (SIJ) and/or the spine. Despite the fact that the prevalence of axSpA is almost the same in men and women, there is evidence of a delay in diagnosis and a more severe course of the disease in females. The available reports on the progression of structural changes in the SIJ in men and women with early axSpA are contradictory. Meanwhile, the analysis of radiographic progression in the SIJ has fundamental importance both for timely diagnosis and for assessing the effectiveness of therapy in axSpA. Such studies have not yet been carried out in the Russian Federation.Objective: to assess the radiographic progression of sacroiliitis (SI) over 3 years in men and women with early axSpA.Material and methods. The study included patients from the cohort of early axSpA CORSAR, formed at the V.A. Nasonova Research Institute of Rheumatology. Currently, it includes 175 patients with axSpA. We analyzed the data of 64 patients, followed for at least 3 years. To assess the radiographic progression of the disease at baseline and after 3 years, the sum of X-ray stages of SI in the left and right SIJ was determined (the total stage of SI). Progression was assessed by the change in the total stage of SI in the right and left SIJ (0-8) during the observation period. We also calculated the proportion of patients with deterioration (increase in the total stage of SI by at least 1 stage), with improvement (decrease in the total stage of SI by at least 1 stage) and without progression. In order to fully exclude the error in measuring the radiographic progression of SI, we counted patients with “net” progression, that is, the proportion of patients with improvement was subtracted from the proportion of patients with deterioration.Results. Among 64 patients with early axSpA, there were 37 (57.8%) men and 27 (42.2%) women. For 3 years, the median of the total stage SI in men was 0 [0; 1], in women - 0 [0; 2] (p>0.05). When assessing the progression of the total stage SI over 3 years, no significant differences were found between the number of men and women with improvement, with deterioration, “net” progression and without progression. Men with early axSpA showed a higher level of C-reactive protein (CRP) at baseline, women had higher BASDAI and ASDAS CRP values after 3 years. In 8% of patients, there was a regression of X-ray signs of SI.Conclusion. The radiographic progression of SI in patients with early axSpA does not depend on gender and disease activity. In some patients with early axSpA, reverse development of structural damage to the SIJ is possible.

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Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years

The Journal of Rheumatology ◽

10.3899/jrheum.210471 ◽

2021 ◽

pp. jrheum.210471

Author(s):

Désirée van der Heijde ◽

Mikkel Østergaard ◽

John D. Reveille ◽

Xenofon Baraliakos ◽

Andris Kronbergs ◽

...

Keyword(s):

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Hla B27 ◽

Link Type ◽

Long Term Effect ◽

Structural Progression ◽

Measuring Change ◽

Treatment Predictors ◽

Radiographic Changes

Objective To evaluate the long-term effect of ixekizumab on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and to identify potential predictors of progression. Methods This study evaluates patients from COAST-V (NCT02696785, bDMARD-naive) and COAST-W (NCT02696798, TNFi-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with ixekizumab (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Results Among patients with evaluable radiographs who were originally assigned to ixekizumab (N=230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of non-progressors over 2 years was 89.6% if defined as mSASSS change from baseline <2 and 75.7% if defined as mSASSS change from baseline ≤0. Predictors of structural progression at year 2 (mSASSS change >0) were age ≥40, baseline syndesmophytes, HLA-B27 positivity and male gender. Week 52 inflammation in SPARCC spine was also a predictor of radiographic progression at year 2 in patients with MRI-data in COAST-V (N=109). Conclusion The majority of patients with r-axSpA receiving ixekizumab had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.

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SAT0548 DEVELOPMENT AND VALIDATION OF THREE PRELIMINARY MRI SACROILIAC JOINT COMPOSITE STRUCTURAL DAMAGE SCORES IN A 5-YEAR LONGITUDINAL STUDY OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2683 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1231.1-1231

Author(s):

M. Wetterslev ◽

M. Ǿstergaard ◽

I. J. Sørensen ◽

U. Weber ◽

A. G. Loft ◽

...

Keyword(s):

Structural Damage ◽

Axial Spondyloarthritis ◽

Bone Destruction ◽

Symptom Duration ◽

Tnf Inhibitor ◽

Research Support ◽

Erosion Score ◽

Asas Criteria ◽

Structural Progression ◽

Score Range

Background:In axial spondyloarthritis (axSpA), MRI reliably detects structural lesions in the sacroiliac joints (SIJs). The SPARCC SIJ Structural Score (SSS)(1) is a reliable and validated method to assess the individual structural lesions of the SIJs, i.e. fat lesion, erosion, backfill (fat metaplasia in an erosion cavity) and ankylosis. Several MRI studies have indicated that bone destruction, i.e. erosion, is often followed by formation of new bone in the erosion cavity (backfill), ultimately leading to ankylosis(2).Objectives:The aim was to combine SPARCC SSS for erosion, backfill and ankylosis into a composite score for SIJ structural damage and to test this score in a 5-year follow up study.Methods:Thirty-three patients fulfilling ASAS criteria for axSpA were followed for 5 years after initiation of TNF inhibitor in the BIOSPA study(3). T1-weighted and STIR MRI sequences of the SIJs acquired at week 0, 46 and year 2, 3, 4, 5 were evaluated with SPARCC SSS. In each of 5 slices of each SIJ, erosion is scored 0-1 per joint quadrant (score range 0-40), backfill 0-1 per joint half (score range 0-20) and ankylosis 0-1 per joint half (score range 0-20). Based on the scores for erosion, backfill and ankylosis 3 versions of a preliminary Composite axSpA MRI SIJ Structural Damage Score (CSDS) were calculated:CSDS–A: (erosion score x0.5) + backfill score + ankylosis scoreCSDS–B: (erosion score x1) + (backfill score x4) + (ankylosis score x6)CSDS–C: (erosion score x1) < (backfill score x4) < (ankylosis score x6)The “<” indicates a hierarchical order, meaning that erosion was not scored if backfill was present in the same joint half and erosion and backfill were not scored if ankylosis was present in the joint half.Results:Patients were divided into two groups: patients with almost complete bilateral ankylosis (baseline SPARCC SSS Ankylosis ≥18, n=10) and patients with no/minor ankylosis (baseline SPARCC SSS Ankylosis ≤7, n=23). At baseline patients with no/minor ankylosis were younger, had shorter symptom duration, lower BASMI, higher SPARCC SIJ Inflammation, lower SSS Fat, Erosion, Backfill and Ankylosis, as compared with patients with almost complete ankylosis.At baseline, CSDS-A, -B and -C correlated positively with SPARCC SSS Fat and Ankylosis and modified New York criteria grading, and negatively with BASDAI and SPARCC inflammation. Change in CSDS-B and -C over 5 years correlated positively with change in SSS Fat and Ankylosis and negatively with change in SPARCC Inflammation. There was no change in the group with almost complete ankylosis.The annual progression for CSDS-B and -C was statistically significantly larger in year 1 compared with year 4 (p=0.01) and numerically larger compared with year 2 (p=0.075), 3 (p=0.382) and 5 (p=0.073). Figure 1 shows the annual change in patients with no/minor ankylosis.Conclusion:Three preliminary Composite Structural Damage Scores for MRI assessment of the SIJs in patients with axSpA, which allows scoring of MRI progression of erosion through backfill to ankylosis, were introduced. Progression was most pronounced the first year after TNF inhibitor initiation. This novel approach may be useful for monitoring structural progression in axSpA. We suggest that these methods are further tested for responsiveness and ability to differentiate between different therapies in randomized controlled trials.References:[1]Maksymowych WP et al. J Rheum 2015;42:79-86.[2]Maksymowych WP et al. Art Rheum 2014;66:2958-67.[3]Pedersen SJ et al. Scand J Rheum 2019;48:185-197.Disclosure of Interests:Marie Wetterslev: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Inge Juul Sørensen: None declared, Ulrich Weber: None declared, Anne Gitte Loft Grant/research support from: Novartis, Consultant of: AbbVie, MSD, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer and UCB, Gina Kollerup Speakers bureau: Eli Lilly, Lars Juul: None declared, Gorm Thamsborg: None declared, Ole Madsen: None declared, Jakob Møllenbach Møller: None declared, Susanne Juhl Pedersen Grant/research support from: Novartis

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Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-204055 ◽

2013 ◽

Vol 74 (1) ◽

pp. 52-59 ◽

Cited By ~ 95

Author(s):

Sofia Ramiro ◽

Carmen Stolwijk ◽

Astrid van Tubergen ◽

Désirée van der Heijde ◽

Maxime Dougados ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Time Course ◽

Radiographic Progression ◽

Linear Time ◽

Symptom Duration ◽

Hla B27 ◽

Group Level ◽

Constant Rate ◽

The Individual

ObjectivesTo describe the evolution of radiographic abnormalities of the spine in patients with ankylosing spondylitis (AS).MethodsPatients with AS were followed prospectively with 2 yearly radiographs for 12 years. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) was scored by two readers (R1 and R2). New syndesmophytes at uninvolved vertebral corners were computed. Radiographic progression was investigated using generalised estimating equations.Results809 radiographs (presenting 520 at 2 yearly intervals) from 186 patients (70% men, mean age 43 (SD 12) years, mean 20 (SD 12) years since symptom onset and 83% HLA-B27 positive) were included. Mean mSASSS at baseline was 11.6 (16.2). While the course of progression in individual patients was highly variable, and still occurred in patients with decades of symptom duration, mean 2 year progression was 2.0 (3.5) mSASSS units. Over the entire follow-up, at least one new syndesmophyte was found in 55% (R1) and 63% (R2) of patients (38% (R1) and 39% (R2) of all intervals). In 24% of patients (39% of intervals), there was no progression. A progression ≥5 mSASSS units occurred in 22% of patients (or in 12% of intervals). At the group level, a linear time course model fitted the data best, with a constant rate over the entire 12 year interval of 0.98 mSASSS units/year. Radiographic progression occurred significantly faster in men, in HLA-B27 positive patients and in patients with a baseline mSASSS≥10.ConclusionsLong term radiographic progression in AS is highly variable in the individual patient, more severe in HLA-B27 positive men and still occurs after decades of disease. At the group level, however, progression in AS follows an approximately linear course.

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POS1094 SYNOVITIS IS FACTOR OF OSTEOARTHRITIS KNEE PROGRESSION IN PATIENTS WITH LESS THAN 5 YEARS OF DISEASE DURATION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1577 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 827.1-827

Author(s):

L. Alekseeva ◽

N. Kashevarova ◽

E. Taskina ◽

D. Kusevich

Keyword(s):

Knee Pain ◽

Clinical Examination ◽

Disease Duration ◽

Radiographic Progression ◽

Musculoskeletal Ultrasound ◽

Knee Joints ◽

X Ray ◽

Knee Oa ◽

Radiological Stage

Background:There are many studies about investigation of risk factors (RF) of knee osteoarthritis (OA) radiologic progression. Especially, in patients with small disease duration. At the moment, there are ambivalent of results of previous studies, lead to uncertain role of synovitis.Objectives:The aim of study is to investigate relationship between knee OA synovitis and progression risk in patients with small disease duration during a follow-up period of 5 years.Methods:Eligible patients had knee OA based on ACR criteria with x-ray confirmation; baseline (BL) disease duration less than 5 years. Patients were evaluated at BL and at 5-year follow-up, using the questionnaires, clinical examination, knee joints pain by visual analog scale (VAS), musculoskeletal ultrasound and X-ray. Unadjusted p-values are presented.Results:Among 52 adults with knee OA (mean age ± standard deviation, 59.11 ± 8.95 years; 100% female) had the proportion of patients at BL 42.3% (n=22), 46.2 % (n=24), 11.5% (n=6) by disease stage 1,2 and 3, respectively. Patients were categorized into 2 groups by progression during 5 years from BL based on changes of radiological stage. After 5-years follow-up period the progression of knee OA was established in 14 patients (1 group) and in 38 patients (2 group) the progression by radiological stage was absent. BL patients’ characteristics were similar across 1st and 2nd groups: mean age 58.29±7.68 vs 56.05±8.74, р>0.05; disease duration 3.43±1.34 vs 3.47±1.33, р>0.05. Individuals with knee OA progression had worse knee joints pain during walking (60.36±18.33 vs 48.71±17.81, р=0.043), higher body mass index (BMI) (34.45±4.60 vs 28.92±4.92 kg/m2, р=0.001), higher frequency of knee synovitis by clinical examination (42.9% vs 10.5%, RR=4.07; 95%Cl (1,3-12,3), р=0.01) and by musculoskeletal ultrasound (57.1% vs 18.4%, RR=3.1; 95%CI (1.38-6.96), р=0.009). At 5-years follow-up knee pain was significantly greater for 1st group (69.64±18,49 vs 55.76±12.76, р = 0.003), higher BMI (35.74±5.83 vs 30.64±4.64, р = 0.002), also higher frequency of knee synovitis by clinical examination (57.1% vs 10.5%, RR = 5.4 (95%Cl 1.9-15.2), р=0.001) and by musculoskeletal ultrasound (50% vs 13.2%, RR=3.8 (95%Cl 1.4-10.0), р=0.009). Spearman correlation coefficients between radiologic stage and OA progression factors were indicated: between radiologic stage and knee pain during walking (r = 0.34, p<0.05), BMI (r = 0.46, p<0.01), knee synovitis by musculoskeletal ultrasound (r = 0.41, p<0.01). Multivariate (discriminant) analysis was determined that synovitis is a significant predictor of radiographic progression (p < 0.05).Conclusion:The proportion of patients with knee synovitis by clinical examination and musculoskeletal ultrasound data increased by 5-year follow-up from BL. Synovitis is a significant predictor of radiographic progression of knee OA in patients with small disease duration.Disclosure of Interests:None declared.Figure 1.

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Sacroiliac radiographic progression in recent onset axial spondyloarthritis: the 5-year data of the DESIR cohort

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211596 ◽

2017 ◽

Vol 76 (11) ◽

pp. 1823-1828 ◽

Cited By ~ 62

Author(s):

Maxime Dougados ◽

Alexandre Sepriano ◽

Anna Molto ◽

Miranda van Lunteren ◽

Sofia Ramiro ◽

...

Keyword(s):

New York ◽

Structural Damage ◽

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Human Leukocyte ◽

Hla B27 ◽

Recent Onset ◽

Leukocyte Antigen ◽

Radiographic Changes ◽

Generalised Estimating Equations

ObjectiveTo estimate sacroiliac joint radiographic (X-SIJ) progression in patients with axial spondyloarthritis (axSpA) and to evaluate the effects of inflammation on MRI (MRI-SIJ) on X-SIJ progression.MethodsX-SIJ and MRI-SIJ at baseline and after 2 and 5 years in patients with recent onset axSpA from the DESIR cohort were scored by three central readers. Progression was defined as (1) the shift from non-radiographic (nr) to radiographic (r) sacroiliitis (by modified New York (mNY) criteria) or alternative criteria, (2) a change of at least one grade or (3) a change of at least one grade but ignoring a change from grade 0 to 1. The effects of baseline inflammation on MRI-SIJ on 5-year X-SIJ damage (mNY) were tested by generalised estimating equations.ResultsIn 416 patients with pairs of baseline and 5-year X-SIJ present, net progression occurred in 5.1% (1), 13.0% (2) and 10.3% (3) respectively, regarding a shift from nr-axSpA to r-axSpA (1), a change of at least one grade (2) or a change of at least one grade but ignoring a change from grade 0 to 1 (3). Baseline MRI-SIJ predicted structural damage after 5 years in human leukocyte antigen-B27 (HLA-B27) positive (OR 5.39 (95% CI 3.25 to 8.94)) and in HLA-B27 negative (OR 2.16 (95% CI 1.04 to 4.51)) patients.ConclusionsFive-year progression of X-SIJ damage in patients with recent onset axSpA is limited but present beyond measurement error. Baseline MRI-SIJ inflammation drives 5-year radiographic changes.

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