Abstract: Previous studies showed that patients with non-radiographic and radiographic axial spondyloarthritis (nr- and r-axSpA) have similar disease burden and similar response to anti-inflammatory therapy given similar level of inflammatory activity. Only little is known, however, about long-term disease course in patients with early axSpA. Objectives: To investigate the long-term (up to 10 years) clinical course of patients with early axSpA. Methods: In total, 525 patients with early axSpA (r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included. The final patient classification was based on central reading results in 458 patients with available pelvic X-rays, and on local rheumatologist judgement in 67 patients. A total of 251 patients were finally classified as r-axSpA and 274 as nr-axSpA. Clinical evaluation, which included disease activity (BASDAI, C-reactive protein – CRP, ASDAS) as well as therapy recording, was performed at baseline and every 6 months thereafter until year 2 and annually thereafter till year 10. Treatment was conducted at the discretion of the local rheumatologist. Results: Since the cohort has started prior to introduction of TNF inhibitors (TNFi), only 2% patients received TNFi at baseline that increased to 23% at year 10 (15% in nr-axSpA and 31% in r-axSpA) – Figure 1. The use of NSAIDs and csDMARDs decreased in both groups (Figure 1), while use of systemic steroids did not change substantially (9% at baseline, 8% at year 10). The proportion of patients with low disease activity according to BASDAI ( 〈 4) was higher in r-axSpA as compared to nr-axSpA at almost all time points, while the proportion of patients with low disease activity according to ASDAS ( 〈 2.1), as well as with ASDAS inactive disease ( 〈 1.3) was similar between nr-axSpA and r-axSpA (Figure 2). In the group of patients who completed year 10 (n=134 in total, 68 with nr-axSpA, 67 with r-axSpA) the same trends in therapy and disease activity were observed. Conclusion: Patients with nr-axSpA and r-axSpA showed a similar disease course in terms of disease activity on the group level. The drop-out rate in this observational cohort was overall high, but comparable between groups. The lower proportion of patients with nr-axSpA being treated with TNFi might reflect a later introduction of TNFi for this indication. Acknowledgments: GESPIC has been financially supported by the German Federal Ministry of Education and Research as well as by Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. From 2010 till 2019 GESPIC has been supported by Abbvie. Disclosure of Interests: 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, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Murat Torgutalp: None declared, Maryna Verba: None declared, Johanna Callhoff: 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, Judith Rademacher: None declared, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, 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, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

Abstract: Observational cohort studies have shown that there is low, but still detectable progression level in radiographic sacroiliitis, which might also have an impact on the function in patients with axial spondyloarthritis (axSpA). Recent data showed that tumor necrosis factor inhibitors (TNFi) might retard spinal progression when initiated earlier and taken longer in patients with axSpA. However, the question of whether they also have such an effect on radiographic progression in sacroiliac joints (SIJs) is still unclear. Objectives: To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with TNFi in patients with early axial SpA in a long-term inception cohort. Methods: Based on the availability of at least two sets of SIJ radiographs, 301 patients (166 with nr-axSpA, symptom duration ≤5 years and 135 with r-axSpA, symptom duration ≤10 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included in this analysis. These patients contributed with a total of 737 2-year radiographic intervals. Two trained and calibrated central readers scored the radiographs according to the modified New York criteria. If both scored an image as definite radiographic sacroiliitis, the patient was classified as having r-axSpA. The sacroiliac sum score was calculated as a mean of both readers. The association between previous as well as current TNFi use and radiographic sacroiliitis progression, which was defined as the change in the sacroiliitis sum score over 2 years, was analysed using longitudinal generalized estimating equations (GEE) analysis. Results: At baseline, 9 (3.0%) patients were treated with a TNFi, and 87 (28.9%) patients received at least one TNFi during the entire follow-up period. A total of 141 of the radiographic intervals were covered with TNFi of any duration, while 109 of them were covered with a TNFi of at least 12 months. While receiving ≥12 months TNFi in the previous interval was associated with a lower progression of the sacroiliitis sum score compared to not receiving TNFi in the previous interval, this was not the case in patients who received TNFi ≥12 months in the current 2-year interval (Figure 1). The significant association between TNF ≥12 months in the previous interval and progression in the sacroiliitis sum score were confirmed in the adjusted multivariable longitudinal GEE analysis. In addition, a similar trend for the beneficial effects was observed in different models, which included other treatment definitions with TNFi in the previous 2-year interval (Table). Table 1. The longitudinal GEE analysis of the association between progression in the sacroiliitis sum score and TNFi use. TNFi treatment definition Reference β* (95% CI ) TNFi for ≥ 12 months in the previous 2-year interval No TNFi for ≥ 12 months in the previous 2-year interval -0.09 (-0.18, -0.003 ) Any TNFi use in the previous 2-year interval No TNFi use in the previous 2-year interval -0.09 (-0.17, 0.002) TNFi for ≥ 12 months in the current 2-year interval No TNFi for ≥ 12 months in the current 2-year interval -0.03 (-0.11, 0.06) Any TNFi use in the current 2-year interval No TNFi use in the current 2-year interval 0.05 (-0.05, 0.14) TNFi for ≥ 12 months in the previous and ≥ 12 months in the current 2-year interval No TNFi for ≥ 12 months in the previous and ≥ 12 months in the current 2-year interval -0.08 (-0.17, 0.004) * Parameter estimates from the multivariable models adjusted for sex , age at the beginning of the current 2-year interval, HLA-B27 positivity, symptom duration at the beginning of the current 2-year interval, time-averaged elevated CRP , time-averaged BASDAI , and time-averaged NSAID intake score in the current 2-year interval. Conclusion: Treatment with TNFi was associated with retardation of radiographic sacroiliitis progression in patients with axSpA. This effect becomes evident between 2 and 4 years after treatment initiation. References: Acknowledgements: GESPIC was initially supported by the BMBF. As a consequence of the funding reduction by BMBF according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. Starting from 2010, the core GESPIC cohort was supported by AbbVie. Disclosure of Interests: Murat Torgutalp: None declared, Valeria Rios Rodriguez: None declared, Maryna Verba: None declared, Mikhail Protopopov: None declared, Fabian Proft: None declared, Judith Rademacher: None declared, Hildrun Haibel: None declared, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Joachim Sieper: None declared, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer

Abstract: Crohn’s disease (CD) and ulcerative colitis (UC) are grouped as inflammatory bowel disease (IBD), and both are frequently found as extra-musculoskeletal manifestations in spondyloarthritis (SpA). Several studies have described the connection between SpA and IBD in both directions. Still until today, no studies have investigated possible differences in the musculoskeletal manifestations between the two main entities of inflammatory bowel disease: CD and UC. Objectives To evaluate the clinical characteristics associated with the presence of CD or UC in patients with spondyloarthritis from the international cross-sectional ASAS-perSpA study. Methods We analyzed 3152 patients from the ASAS per-SpA cohort who had a diagnosis of axial SpA or peripheral SpA according to the treating rheumatologist. Patients with IBD - confirmed by endoscopy - were identified and stratified by CD or UC. Patients in which their IBD disease was not specified, were excluded. Demographics, clinical characteristics, treatments and patient-reported outcomes were compared between both subgroups. Results Among the 146 patients diagnosed with IBD from the 3152 patients included in the analysis, 87 (59.6%) presented with CD (75 patients with axial SpA and 12 with peripheral SpA) and 39 (26.7%) with UC (34 patients with axial SpA and 5 with peripheral SpA) - Figure 1. A total of 20 (13.7%) patients with IBD were excluded, due to an inconclusive diagnosis of IBD. Patients with CD and UC had similar age (44.9 vs 44.0 years old) and sex distribution, although a slightly higher frequency of males was observed in CD than UC (63.2% vs 51.3%). The diagnostic delay for SpA was 7.0 years for CD and 8.1 years for UC. We did not find differences between both groups related to any musculoskeletal manifestations such as chronic back pain, uveitis, arthritis, enthesitis or dactylitis (Table 1). The only parameter showing a significant difference between CD and UC was the Bath Ankylosing Spondylitis Functional Index (BASFI) with a mean score of 3.3 vs 2.2 respectively (p=0.02) (Table 1). CD patients showed a higher tendency to be HLA-B27 positive (51.9% in CD vs. 39.4% in UC), but this did not reach statistical significance. No differences were observed regarding treatment patterns between both groups. Table 1. Demographics and clinical characteristics related to spondyloarthritis of patients with concomitant Crohn’s disease or ulcerative colitis (n=146). Crohn’s Disease N=87 Ulcerative Colitis N=39 P Age, mean (SD) 44.9 (13.5) 44.0 (13.0) 0.68 Sex, n/N (%) male 55/87 (63.2) 20/39 (51.3) 0.21 Smoker ever, n/N (%) 36/87 (41.4) 19/39 (48.7) 0.44 Diagnostic delay of SpA (years), mean (SD) 7.0 (6.9) 8.8 (8.1) 0.38 Psoriasis ever, n/N (%) 9/87 (10.3) 6/39 (15.4) 0.47 Uveitis ever, n/N (%) 17/87 (19.5) 11/39 (28.2) 0.28 Synovitis ever, n/N (%) 42/87 (48.3) 18/39 (46.2) 0.83 Enthesitis ever, n/N (%) 26/87 (29.9) 14/39 (35.9) 0.50 Dactylitis ever, n/N (%) 3/87 (3.4) 1/39 (2.6) 0.79 Axial involvement ever (according to the rheumatologist), n/N (%) 79/87 (90.8) 37/39 (94.9) 0.44 Sacroiliitis on X-ray, n/N (%) 64/87 (73.6) 26/39 (66.7) 0.19 HLA-B27 positive, n/N (%) 28/54 (51.9) 13/33 (39.4) 0.26 CRP mg/L, mean (SD) 11.1 (33.8) 15.3 (30.1) 0.13 ASDAS-CRP, mean (SD) 2.4 (1.0) 2.4 (1.1) 0.84 BASFI, mean (SD) 0-10 3.3 (2.6) 2.2 (2.1) 0.02 csDMARDs ever, n/N (%) 71/87 (81.6) 35/39 (89.7) 0.25 bDMARDs ever, n/N (%) 72/87 (82.8) 33/39 (84.6) 0.80 ASDAS, Ankylosing Spondylitis Disease Activity Score; BASFI, Bath Ankylosing Spondylitis Functional Index; bDMARD, biological disease-modifying antirheumatic drugs; CRP, c-reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drugs; SD, standard deviation; SpA, spondyloarthritis. Conclusion In our ancillary analysis of the ASAS-perSpA study in patients with SpA and concomitant CD or UC, no differences in the clinical presentation or demographic characteristics between the two subgroups were observed, except for the BASFI. Disclosure of Interests None declared

Abstract: There is some evidence that NSAIDs, in particular celecoxib (CEL), might possess not only symptomatic efficacy but also disease-modifying properties in radiographic axial spondyloarthritis (r-axSpA) formerly known as ankylosing spondylitis, retarding progression of structural damage in the spine if taken continuously. For biological disease-modifying antirheumatic drugs (bDMARDs), retardation of structural damage progression has also been demonstrated, but at least 4 years of treatment seem to be necessary (at least for tumour necrosis factor inhibitors – TNFi) to see such an effect. Therefore, a combination of an NSAID with a TNFi might bring additional benefits in terms of retardation of structural damage progression especially in high-risk patients. Objectives The aim of this RCT was to evaluate the impact of treatment with the COX-II-selective NSAID (CEL) when added to a TNFi (golimumab - GOL) compared with TNFi (GOL) alone on progression of structural damage in the spine over 2 years in patients with r-axSpA. Methods Eligible patients had r-axSpA and high disease activity (BASDAI ≥4), NSAID failure and risk factors for radiographic spinal progression: C-reactive protein 〉 5 mg/l and/or ≥1 syndesmophyte(s). The trial consisted of two phases: a 12-week run-in phase, in which all included patients received treatment with GOL 50 mg every 4 weeks sc, followed by a 96-week controlled treatment period, in which patients who achieved a BASDAI improvement of ≥2 points were randomly assigned to GOL + CEL 200 mg bid or GOL alone arms. The primary endpoint was radiographic spinal progression as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) after 108 weeks in the intent-to-treat population, read by 3 independent readers blinded for the treatment arm and the time-point. Results Of the 157 screened patients, 81.5% (n=128) were enrolled into the run-in phase. 109 patients fulfilled the BASDAI response criterion at w12 and were randomized 1:1 (54 vs. 55) to GOL+CEL or GOL alone; 97 (45 vs. 52) patients completed the study at w108. Clinical characteristics of the randomized patients are shown in Tab. 1. The mSASSS change after w108 was 1.1 (95%CI 0.2; 2.0) vs. 1.7 (95%CI 0.8; 2.6) in the GOL+CEL vs. GOL alone groups, respectively, p=0.79. Figure 1 shows the cumulative probability of the mSASSS change in both treatment arms. New syndesmophytes in the opinion of three readers occurred in 11% vs. 25% of the patients in the GOL+CEL vs. GOL alone groups, respectively, p=0.12. During the study, a total of 14 serious adverse events (SAE) were reported (7 in the GOL+CEL group, 5 in the GOL alone group and 2 during the run-in phase). Figure 1. Cumulative probability plot of mSASSS progression over 108 weeks of treatment. Conclusion In this study, a combined therapy with GOL+CEL did not show significant superiority over GOL monotherapy in retarding radiographic spinal progression over two years in r-axSpA patients. However, the observed numerical reduction in radiographic spinal progression associated with the combined treatment might be, however, clinically relevant for patients at high risk for progression. Table 1. Baseline characteristics of randomized patients Parameters GOL+CEL N=54 GOL alone N=55 All patients N=109 validn value validn value validn value Sex, male n (%) 54 40 (74.1) 55 41 (74.5) 109 81 (74.3) Age, years Mean (SD) 54 39.9 (9.9) 55 37.5 (10.8) 109 38.7 (10.4) Smoker n (%) 53 19 (35.8) 55 22 (40) 108 41 (38) HLA-B27 positivity n (%) 54 45 (83.3) 51 47 (92.2) 105 92 (87.6) BASDAI Mean (SD) 54 6.2 (1) 55 6.1 (1.1) 109 6.1 (1.1) BASMI Mean (SD) 54 2.6 (1.9) 54 2.9 (1.4) 108 2.8 (1.6) CRP 〉 5 mg/L n (%) 54 38 (70.4) 55 38 (69.1) 109 76 (69.7) ASDAS-CRP Mean (SD) 54 3.6 (0.6) 55 3.7 (0.9) 109 3.7 (0.8) Prior bDMARDs n (%) 54 17 (31.5) 55 9 (16.4) 109 26 (23.9) Presence of ≥ 1 syndesmophyte(s) n (%) 54 27 (50) 55 28 (50.9) 109 55 (50.5) mSASSS Mean (SD) 54 13.5 (16.9) 55 10.3 (13.2) 109 11.9 (15.2) Acknowledgements The CONSUL study has been supported by a grant from the German Ministry of Education and Research (BMBF), grant number FKZ 01KG1603 and study medication (golimumab) was provided free of charge by MSD Sharp & Dohme GmbH, Munich, Germany. Furthermore we would like to thank Anne Weber, Bianca Mandt, Claudia Lorenz, Hildrun Haibel, Judith Rademacher, Laura Spiller, Petra Tietz as well as all participating rheumatologist and included patients. Disclosure of Interests Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, UCB, Lilly, Burkhard Muche Speakers bureau: UCB Pharma, AMGEN, Consultant of: UCB Pharma, AMGEN, Valeria Rios Rodriguez Speakers bureau: AbbVie, Falk e.V., Murat Torgutalp: None declared, Mikhail Protopopov Consultant of: Novartis, Joachim Listing: None declared, Maryna Verba: None declared, Uta Kiltz: None declared, Jan Brandt-Juergens: None declared, Maren Sieburg: None declared, Swen Holger Jacki: None declared, Joachim Sieper Speakers bureau: AbbVie, Janssen, Merck, Novartis, Consultant of: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, and Pfizer.

Abstract: There are conflicting data regarding effect of nonsteroidal anti-inflammatory drugs (NSAID) on radiographic spinal progression in axial spondyloarthritis (axSpA). The analysis of the first 2-year of the GErman SPondyloarthritis Inception Cohort (GESPIC) showed that higher NSAID intake may retard new bone formation in r-axSpA. It remained, however, unclear, whether cyclooxygenase-2 selective inhibitors (COX2i) might have a stronger effect than non-selective (NS) ones and if the effect could be observed also in nr-axSpA. Objectives To investigate the effect of NSAIDs (COX2i and NS) intake on radiographic spinal progression in patients with r-axSpA and nr-axSpA. Methods Based on availability of at least two sets of spinal radiographs during 10-year follow-up, 243 patients with early axSpA (130 and 113 nr- and r-axSpA, respectively) from GESPIC were included in this analysis. The patients contributed a total of 540 2-year radiographic intervals. Radiographs were scored by 3 trained and calibrated readers according to modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Final mSASSS was calculated as a mean of 3 readers, and progression was defined as absolute mSASSS change score over 2 years. NSAID type, daily dose, and frequency of intake were recorded at visits. The ASAS index of NSAID intake (0-100) counting both dose and duration of intake was calculated for intervals. The association between NSAID intake (NSAID type and NSAID score) and radiographic spinal progression over 2 years was analysed using longitudinal generalized estimated equations (GEE). Results At baseline, 161 (66.3%) patients were treated with NSAIDs. While 289 (53.5%) and 128 (23.7%) 2-year radiographic intervals were covered by NS and COX-2i respectively, 123 (22.8%) intervals were not covered by NSAID. The significant association between higher NSAID intake and retardation of radiographic spinal progression was found in adjusted multivariable longitudinal GEE analysis. This effect was mostly attributable to patients with r-axSpA (Table 1). mSASSS progression was numerically lower in patients taking COX2i (irrespectively of dose) as compared to patients treated with NS-NSAIDs; in stratified analysis, however, there was no clear dose-dependency (as reflected by NSAID index) in both groups (Figure 1, Table 1). Table 1. The association between radiographic spinal progression (mSASSS change score) and NSAID intake in patients with axSpA in multivariable longitudinal GEE All axSpA β (95% CI )* (n=461 ) nr-axSpA β (95% CI )* (n=244 ) r-axSpA β (95% CI )* (n=217 ) NSAID intake score, per 10 points -0.04 (-0.09, 0.00 ) -0.02 (-0.06, 0.02) -0.07 (-0.13, 0.00 ) NSAID type §  NS inhibitors vs No NSAID 0.30(-0.07, 0.66) 0.25(-0.07, 0.57) 0.26(-0.40, 0.92)  COX2i vs No NSAID 0.17(-0.19, 0.54) 0.15(-0.15, 0.46) 0.18(-0.49, 0.85)  COX2i vs NS inhibitors -0.12(-0.37, 0.12) -0.10(-0.28, 0.09) -0.08(-0.57, 0.40) Analysis stratified according to NSAID type Non-selective NSAID intake score, per 10 points -0.06(-0.12, 0.00) -0.04(-0.09, 0.01) -0.07(-0.17, 0.03) COX2 selective NSAID intake score, per 10 points -0.06(-0.13, 0.02) -0.03(-0.07, 0.02) -0.09(-0.18, 0.01) axSpA: axial spondyloarthritis; COX2i, cyclooxygenase-2 selective inhibitors; n, number of current 2-year radiographic intervals in multivariable analyses; NS, non-selective COXi; NSAID, non-steroidal anti-inflammatory drugs. *All multivariable models were adjusted for sex, symptom duration at the beginning of the interval, time-averaged ASDAS the interval, classification as radiographic axSpA, smoking in the interval, mSASSS at the beginning of theinterval, and TNFi use in the interval. §NSAID intake score was added in this model. Conclusion Higher NSAID intake is associated with lower radiographic spinal progression, particularly in r-axSpA patients. COX2i might possess a stronger inhibitory effect on radiographic progression as compared to NS-NSAIDs. Disclosure of Interests Murat Torgutalp: None declared, Valeria Rios Rodriguez Consultant of: AbbVie, Grant/research support from: Falk e.V, Ani Dilbaryan: None declared, Fabian Proft Speakers bureau: Novartis, Lilly, UCB AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer, Roche and Janssen, Grant/research support from: Novartis, Lilly and UCB, Mikhail Protopopov Consultant of: Novartis and UCB, Maryna Verba: None declared, Judith Rademacher Consultant of: Novartis and UCB, Hildrun Haibel Consultant of: Boehringer, Janssen, MSD, Novartis, Sobi, Roche, Pfizer, AbbVie, and Sobi, Joachim Sieper Speakers bureau: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Consultant of: AbbVie, Lilly, Merck, Novartis, UCB, Martin Rudwaleit Speakers bureau: AbbVie, Boehringer Ingelheim, Celgen, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB., Consultant of: AbbVie, Boehringer Ingelheim, Celgen, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB., Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer.

Abstract: There are inconclusive data on the effect of tumor necrosis factor inhibitors (TNFi) on radiographic spinal progression in axial spondyloarthritis (axSpA). Although inflammation and new bone formation are linked in axSpA, TNFi failed to show inhibition of radiographic spinal progression over two years compared to historical cohorts in pivotal studies in radiographic axSpA. Subsequent observational studies suggested that a longer treatment duration, earlier treatment initiation and effective inflammation suppression might be required to achieve inhibition of radiographic progression. Objectives: The aim of the current study was to evaluate the effect of TNFi on radiographic spinal progression in patients with early axSpA in a long-term inception cohort. Methods: A total of 266 patients with early axSpA (with r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) with at least two sets of spinal radiographs obtained at least 2 years apart during a 10-year follow-up were included. These patients contributed with a total of 542 2-year radiographic intervals. Spinal radiographs were evaluated by three trained and calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The final mSASSS was calculated as a mean of three reader scores. The association between the current TNFi, previous TNFi and radiographic spinal progression defined as the absolute mSASSS change score over 2 years was analyzed using longitudinal generalized estimating equations (GEE) analysis. Results: Only 9 patients were treated with a tumor necrosis factor inhibitor (TNFi) at baseline, and a total of 77 patients received TNFi during the entire follow-up period that gave 103 2-year intervals covered by TNFi of any duration, and 78 intervals covered by TNFi with treatment duration of at least 12 months. Radiographic spinal progression in axSpA patients receiving TNFi in the current 2-year interval was not different from progression in patients not treated with TNFi, while TNFi in the previous 2-year interval was associated with lower progression compared to patients without TNFi in this interval (Figure 1). The latter was also evident for patients who received TNFi in both previous and current 2-year intervals, i.e. patients treated with TNFi over 4 years. The longitudinal GEE analysis confirmed no significant association between current TNFi treatment and radiographic spinal progression but a significant association between TNFi in the previous 2-year interval (especially if this was continued also in the current interval giving 4 years in total) and the progression in the current one (Table 1). Table 1. The association between the change of the mSASSS over two years and current and/or previous treatment with TNFi in the longitudinal generalized estimation equation analysis. TNFi treatment definition Reference β* (95% CI ) TNFi for ≥12 months in the previous 2-year interval TNFi for ≥12 months in the current 2-year interval Yes No TNFi for ≥12 months in the current 2-year interval -0.19 (-0.56 to 0.18) Yes No TNFi for ≥12 months in the previous 2-year interval -0.56 (-0.95 to -0.17 ) Yes Yes No TNFi for ≥12 months in the current and previous 2-year intervals -0.59 (-1.03 to -0.15 ) *Parameter estimates from the multivariable models adjusted for sex, symptom duration at the beginning of the current 2-year interval, time-averaged ASDAS in the current 2-year interval, smoking in the current 2-year interval, classification as non-radiographic or radiographic axSpA, and mSASSS at the beginning of the current 2-year interval. Conclusion: TNFi treatment exhibits a time-shifted inhibitory effect on radiographic spinal progression in axSpA that becomes evident only in the second 2-year interval after treatment initiation. Acknowledgements: GESPIC was initially supported by the BMBF. As consequence of the funding reduction by BMBF according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. Starting from 2010, the core GESPIC cohort was supported by AbbVie. Disclosure of Interests: Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Ani Dilbaryan: None declared, Maryna Verba: None declared, Fabian Proft: None declared, Mikhail Protopopov: None declared, Judith Rademacher: None declared, Hildrun Haibel: None declared, Joachim Sieper: None declared, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

Abstract: Therapeutic decisions in RA patients should be based on regular disease activity assessment using scores like the Simplified Disease Activity Index (SDAI) or the Clinical Disease Activity Index (CDAI) [1]. The CDAI has the benefit of being immediately available, while the SDAI encompasses with the C-reactive protein (CRP) an acute phase reactant and therefore is the recommended score for the use in clinical trials. However, CRP determination takes hours to days, thus hindering the treat-to-target concept using the SDAI. Quick quantitative CRP (qCRP) tests allow CRP measurement within a few minutes. Therefore, qCRP based SDAI (SDAI-Q) could combine the advantages of both scores. Objectives: To validate the SDAI-Q in a prospective, multicenter study of RA patients. Methods: The study was conducted in five centers in Berlin, Germany. Consecutive adult (≥ 18 years) RA patients were included. In addition to a rheumatological assessment, including patient reported outcomes, routine CRP was measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed locally (measurement range 0.5 - 200 mg/l). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for CRP, qCRP, SDAI, SDAI-Q and CDAI. Results: In this study 100 RA patients were included (mean age: 60.9 years, mean disease duration: 11.4 years, 73.0% were female, 63.0% RF positive, 57.0% ACPA positive, 49.0% positive and 29% negative for both parameters). 75.0% were treated with csDMARD, 15% with tsDMARDs, 39.0% with bDMARDs and 40% with glucocorticoids (mean prednisolone equivalent: 5.4 mg prednisolone/d). Mean CRP and qCRP-levels were 6.97 and 7.89 mg/l, respectively (ICC 0.992; 95%CI: 0.987; 0.995). Comparing SDAI-Q and SDAI, all patients (100%) achieved the same disease activity status (Table 1A); weighted Cohen´s kappa was 1.000 (95%CI: 1.000; 1.000). ICC for SDAI-Q- and SDAI-values was 1.000 (95%CI: 1.000; 1.000). The agreement of SDAI-Q and SDAI is shown in a Bland-Altman plot (Figure 1). When comparing the CDAI with the SDAI-Q 93 patients (93%) were assigned to the same disease activity category (Table 1B); weighted Cohen´s kappa was 0.929 (95%CI: 0.878; 0.981). ICC for numerical values of SDAI-Q and CDAI was 0.989 (95%CI: 0.978; 0.994). Conclusion: SDAI-Q showed an absolute agreement with SDAI on the assignment to disease activity categories with the important advantage of time. With SDAI-Q, rheumatologists could base their clinical decision-making immediately on an index-based disease activity measurement by using a composite score considering acute phase reactants. Consequently, SDAI-Q can be integrated in clinical routine and clinical trials and could be implemented into the treat-to-target concept in RA patients. References: [1]Smolen JS, et al. Ann Rheum Dis. 2016 Jan; 75(1):3-15. Table 1. A) Disease activity categories by SDAI-Q vs. SDAI; B) Disease activity categories by SDAI-Q vs. CDAI A SDAI-Q (n = 100 ) Remission (≤ 3.3) Low Disease Activity ( 〉 3.3 and ≤ 11) Moderate Disease Activity ( 〉 11 and ≤ 26) High Disease Activity ( 〉 26) SDAI Remission (≤ 3.3) 28 (28.0% ) Low Disease Activity ( 〉 3.3 and ≤ 11) 31 (31.0% ) Moderate Disease Activity ( 〉 11 and ≤ 26) 35 (35.0% ) High Disease Activity ( 〉 26) 6 (6.0% ) B SDAI-Q (n = 100 ) Remission (≤ 3.3) Low Disease Activity ( 〉 3.3 and ≤ 11) Moderate Disease Activity ( 〉 11 and ≤ 26) High Disease Activity ( 〉 26) CDAI Remission (≤ 2.8) 26 (26.0% ) Low Disease Activity ( 〉 2.8 and ≤ 10) 2 (2.0% ) 28 (28.0% ) 2 (2.0% ) Moderate Disease Activity ( 〉 10 and ≤ 22) 3 (3.0% ) 33 (33.0% ) High Disease Activity ( 〉 22) 6 (6.0% ) Fields highlighted in red indicate that disease activity categories do not match. SDAI = Simplified Disease Activity Index; SDAI-Q = SDAI calculated with a quick quantitative CRP assay; CDAI = Clinical Disease Activity Index. Figure 1. Bland-Altman plot for SDAI and SDAI-Q Acknowledgements The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study. Funding statement: The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland. Disclosure of Interests: None declared

Abstract: Psoriatic arthritis (PsA) is a heterogeneous disease with multiple musculoskeletal and dermatological manifestations. Due to this multifaceted clinical appearance, international guidelines do not provide a clear recommendation for one specific score to assess disease activity in PsA [1]. The Disease Activity Index for Psoriatic Arthritis (DAPSA), a validated, unidimensional score focusing on joint involvement, is one of the recommended options [1] . However, routine determination of C-reactive protein (CRP) to calculate DAPSA values takes hours to days. In contrast, quick quantitative CRP (qCRP) tests require only a few minutes and might facilitate regular assessment of the DAPSA (as Q-DAPSA) in clinical routine. Objectives: To validate the Q-DAPSA in a prospective, multicenter study of PsA patients. Since the Disease Activity Score 28 (DAS28) is not only used in rheumatoid arthritis, but also in PsA patients, the study also investigated the performance of a qCRP based DAS28 (DAS28-qCRP) in a PsA cohort. Methods: The study was conducted in five centers in Berlin, Germany. Consecutive adult (≥ 18 years) PsA patients were included. In addition to a rheumatological assessment, including patient reported outcomes (PROs), routine CRP and erythrocyte sedimentation rate (ESR) were measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed locally at the study center (measurement range 0.5 - 200 mg/l for hematocrit concentrations of 40 – 45%). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for DAPSA, Q-DAPSA, DAS28-CRP and DAS28-qCRP. Results: In this study 104 patients were included between January and October 2020 (mean age: 51.2 years, mean disease duration: 7.1 years, 49 patients (47.1%) were male). 53 patients (51.0%) were treated with a bDMARD and 37 patients (35.6%) with csDMARDs. CRP and qCRP showed mean values of 5.20 and 6.17 mg/l, respectively. With the Q-DAPSA, 103 patients (99.0%) were assigned to the same disease activity category when compared to DAPSA (Table 1). Weighted Cohen´s kappa was 0.990 (95%CI 0.970; 1.000). ICC for numerical values of DAPSA and Q-DAPSA was 1.000 (95%CI 0.999; 1.000). The agreement of Q-DAPSA and DAPSA is shown in a Bland-Altman plot (Figure 1). DAS28-CRP and -qCRP were available for 103 patients; 101 patients (98.1%) showed the same disease activity category in the DAS28-qCRP and weighted Cohen´s kappa was 0.951 (95%CI 0.886; 1.000). Conclusion: The Q-DAPSA and DAPSA showed an almost perfect agreement on the assignment to disease activity categories (99%) with the important advantage of time. With Q-DAPSA, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. Consequently, Q-DAPSA can be integrated in clinical routine and clinical trials and could be implemented into the treat-to-target concept in PsA patients. For rheumatologists who prefer DAS28-CRP for assessing disease activity in PsA patients, DAS28-qCRP may serve as a suitable alternative. References: [1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17. Table 1. Disease activity categories by Q-DAPSA vs. DAPAS Q-DAPSA (n = 104 ) Remission (≤ 4) Low Disease Activity ( 〉 4 and ≤ 14) High Disease Activity ( 〉 14 and ≤ 28) Very high Disease Activity ( 〉 28) DAPSA Remission (≤ 4) 36 (34.6% ) 1 (1.0% ) Low Disease Activity ( 〉 4 and ≤ 14) 39 (37.5% ) High Disease Activity ( 〉 14 and ≤ 28) 22 (21.2% ) Very high Disease Activity ( 〉 28) 6 (5.8% ) The fields highlighted in red indicate that disease activity categories do not match. DAPSA = Disease activity index for Psoriatic Arthritis, Q-DAPSA = DAPSA calculated based on a quick quantitative CRP Figure 1. Bland-Altman plot for Q-DAPSA and DAPSA Acknowledgements: The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study. Funding statement: The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland. Disclosure of Interests: None declared.

Abstract: It is presumed that the phenotype of the axial spondyloarthritis (axSpA) may differ in females and males; the published data are controversial. Objectives: To explore the sex differences in disease features and radiographic progression in 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 gender on radiographic progression. Results: Males (n=107; 51%) were significantly younger at disease onset (34.8 ± 10.3 vs. 31.5 ± 11.2 years, p=0.008) and at diagnosis (37.5 ± 10.2 vs. 34.1 ± 11.2 years, p=0.006); symptom duration at baseline was similar (4.1 ± 2.6 vs. 4.3 ± 2.8 years, p=0.66). Females were less often HLA-B27 positive (74 (72.5%) vs. 92 (86.0%), p=0.02), had higher baseline disease activity (BASDAI 4.3±2.2 vs 3.7±2.0; p=0.05), but lower baseline C-reactive protein level (7.1 ± 10.9 vs. 12.3 ±18.2 mg/l, p=0.08), and similar time-averaged ASDAS (2.5±0.8 vs 2.4±1.0; p=0.385). Males more frequently had definite radiographic sacroiliitis (70.1% vs. 38.8%; p 〈 0.001), higher sacroiliitis sum score (4.9 ±1.9 vs 3.2±1.8, p 〈 0.001), and higher mean mSASSS (6.1 ± 10.7 vs 2.4 ± 4.0; p=0.100) at baseline. Other variables were comparable between the groups. There was a trend for a higher radiographic progression in males in all explored outcomes, statistically significant only for the formation/progression of syndesmophytes (23 (21.5%) vs. 10 (9.7%), p=0.023), with no differences in the radiographic progression of sacroiliitis. In a multivariate logistic regression analysis, similar odds for spinal radiographic progression, new syndesmophyte formation and radiographic progression of sacroiliitis by ≥1 grade were seen – Table 1 . Conclusion: There was a trend for male patients to have more radiographic damage at the baseline and more progression after two years, as reflected by the percentage of patients with new syndesmophytes. : Table 1. Association of sex with radiographic progression in spine and sacroiliac joints after 2 years of follow-up. Parameter, n (%) or mean±SD Female (n=103) Male (n=107) P Spinal radiographic progression mSASSS change 0.46 ± 1.63 1.00 ± 2.85 0.25 Progression of mSASSS by ≥2 points 10 (9.7) 20 (18.7) 0.08 New syndesmophytes or progression of syndesmophytes 10 (9.7) 23 (21.5) 0.02 Progression of radiografic sacroiliitis Change of the sacroiliitis sum score 0.14 ± 0.94 0.13 ± 0.73 0.58 Progression of sacroiliitis by at least 1 grade in opinion of both readers 17 (16.5) 9 (8.4) 0.09 mSASSS – modified Stoke Ankylosing Spondylitis Spine Score; 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: Mikhail Protopopov Consultant of: Novartis, Murat Torgutalp: None declared, 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, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and 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, Valeria Rios Rodriguez Consultant of: Abbvie, 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

Abstract: Behçet’s Syndrome (BS) is a vasculitis of unknown origin. Vascular involvement, so-called vascular Behçet’s syndrome (VBS), may involve blood vessels of all sizes belonging to both venous and arterial system, with pulmonary artery involvement (PAI) being the most frequent form of arterial involvement. PAI in BS occurs in the form of aneurysms or thrombosis, and results in significant mortality. Objectives: To report the clinical characteristics of PAI in patients with BS and to define the predictors of relapses. Methods: We performed a retrospective analysis of BS patients with PAI who fulfilled international study group criteria. Among 460 patients with VBS, 66 were diagnosed with PAI. For final analyses, 61 patients with PAI, who had at least 2 follow-up visits (72.1% male, mean age at BS diagnosis 29.34 (SD 10.1) years), were included. The data of the patients were recorded. Relapse was defined as the reoccurrence of vascular event at any vascular structure. Factors associated with relapse were assessed by logistic regression analysis. Results: There were not any differences considering demographic and clinical features of the patients with and without PAI in VBS group except for that intracardiac thrombosis was more common in the patients with PAI than the patients without (19.7% vs 0.3%, respectively) (Figure 1). Among 61 patients with PAI, 50 (82.0%) had isolated pulmonary artery thrombosis (PAT), whereas 11 (18.0%) had pulmonary artery aneurysm (PAA) with or without PAT. The characteristics of 61 patients with PAI were shown in Table 1. A total of 37 relapses occurred in 24 (39.3%) patients during follow-up a median of 65.9 (IQR 20.1-109.0) months. To define the factors associated with relapses, the patients with isolated PAT were analysed. In multivariable logistic regression analysis, older age at BS diagnosis and anticoagulation usage seemed to be protective, even though they could not reach statistical significance (OR: 0.92 95% CI 0.86-1.02, OR: 0.34 95% CI 0.09-1.33, respectively). Table 1. Characteristics of the patients with pulmonary artery involvement All n= 61 Isolated PAT n= 50 PAA n= 11 Sex (male), n (% ) 44 (72.1) 35 (70.0) 9 (81.8) Age at diagnosis of BS, years (SD ) 29.3 (10.1) 28.8 (10.4) 31.9 (8.0) Age at diagnosis of PAI, years (SD ) 36.3 (12.83) 36.7 (13.8) 34.7 (6.7) Symptoms, n (% ) Dyspnea 28 (45.9) 23 (46.0) 5 (45.5) Hemoptysis 26 (42.6) 19 (38.0) 7 (63.6) Vascular event before PAI, n (% ) 21 (34.4) 20 (40.0) 1 (9.1) Other vascular events at PAI, n (% ) 33 (54.1) 28 (56.0) 5 (45.5) Thrombophlebitis, n (% ) 7 (21.2) 6 (21.4) 1 (20.0) Upper and/or lower extremity DVT, n (% ) 20 (60.6) 16 (57.1) 4 (80.0) SVCS, n (% ) 1 (3.0) 1 (3.6) 0 (0) IVCS, n (% ) 3 (9.1) 1 (3.6) 2 (40.0) Intracranial thrombosis, n (% ) 4 (12.1) 4 (14.3) 0 (0) Intracardiac thrombosis, n (% ) 8 (24.2) 7 (25.0) 1 (20.0) Arterial event other than PAI, n (% ) 4 (12.1) 3 (10.7) 1 (20.0) Relapse, n (% ) 24 (39.3) 20 (40.0) 4 (36.4) Time to the first relapse, median (IQR), month 49.8 (13.2-102.6) 54.1 (24.4-117.9) 3.9 (1.7-67.9) Death, n (% ) 2 (3.3) 0 (0) 2 (18.2) BS= Behçet Syndrome, PAI= pulmonary artery involvement, PAT= pulmonary artery thrombosis, PAA= pulmonary artery aneurysm, DVT= deep vein thrombosis, SVCS= superior vena cava syndrome, IVCS= inferior vena cava syndrome Figure 1. A ) Axial CT image shows thrombus formation in the left upper lobe pulmonary artery branch. B ) Giant thrombus is seen in the right ventricle (black arrow). Note the thrombus formation in the left lower lobe pulmonary artery branches (white arrows). Conclusion: Our results indicate that there is a higher frequency of intracardiac thrombosis in BS patients with PAI and an increasing current trend of PAT in patients with PAI. In addition, there might be a possible efficacy of anticoagulation usage in preventing relapses, which needs confirmation with further studies. Disclosure of Interests: None declared