J. Sieper’s research while affiliated with Charité Universitätsmedizin Berlin and other places

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Publications (645)


POS0227 CLUSTER ANALYSIS IDENTIFIES PARTICULAR PAIN PROFILES IN PATIENTS WITH RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS RECEIVING BIOLOGICAL DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
  • Conference Paper

June 2024

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6 Reads

Annals of the Rheumatic Diseases

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Background Despite proper treatment with biologic disease modifying antirheumatic drugs (bDMARDs) patients with axial spondyloarthritis (axSpA) may suffer from residual symptoms. Both nociplastic and neuropathic pain components (NoP and NP) are thought to be contributors to the residual symptoms in axSpA. Objectives To identify specific pain profiles according to common features of NoP and NP in patients with radiographic axSpA (r-axSpA) on stable treatment with bDMARDs. Methods Patients were recruited between 2015 and 2019 in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). The Widespread Pain Index (WPI) was used to quantify NoP. The 19 regions of the WPI were used in a hierarchical cluster analysis with Ward’s method. Distances were calculated with the Jaccard method. NP was quantified using the PainDETECT questionnaire (PD). The seven main items of the PD assess the severity of different sensory symptoms that are common in NP. To eradicate interindividual differences, the mean of these items was calculated for every patient and subtracted from each item. The resulting normalized values were used in a hierarchical cluster analysis with Ward’s method using Euclidean distances. Results A total of 78 patients with r-axSpA receiving a bDMARD for at least 3 months were included in this analysis. At the time-point of the assessment, the mean duration of bDMARD therapy was 3.52±0.99 years. While 36 (46.2%) patients have a WPI score >2 indicating a probable NoP component only 7 (9%) patients have a PD score > 12 indicating a probable NP component. The cluster analysis of the WPI regions revealed three distinct pain distribution profiles as seen in Figure 1. Patients in cluster 1 show a diffuse distribution of pain over many pain regions especially the torso that indicates activation of the nociplastic pain mechanisms. Whereas in patients in cluster 2 pain is mainly localized in the lower back and neck that might be an indicator of the local pathology, either mechanical or residual inflammatory. Patients in cluster 3 did not indicate any painful regions and can be considered as good treatment responders. Patients in cluster 1 showed the highest values for WPI (4.1±2.1) and PD (7.6±5.4). • Download figure • Open in new tab • Download powerpoint Figure 2 shows the results of the cluster analysis of the PD items, which revealed 4 clusters with distinct sensory symptom profiles. Patients in cluster 1 mainly experience sudden pain attacks and pressure sensitivity that might be indicative of the presence of radiculopathy. For patients in cluster 2 pressure sensitivity with mild thermal sensitivity is prominent that might indicate nociplastic contribution. Whereas patients in cluster 3 suffer primarily from sudden pain attacks, which might be indicative of the neuropathic pain component. Most patients in cluster 4 did not suffer from any of the examined symptoms indicating good symptom control. The highest PD and WPI values were found in cluster 3 (PD: 8.8±5.6, WPI: 3.5±2.8) with cluster 1 having similarly high PD values (8.6±2.9). • Download figure • Open in new tab • Download powerpoint Conclusion Patients with r-axSpA can be divided into subgroups with specific pain distribution profiles and sensory symptom profiles that can provide clinically useful information on the leading mechanism of the residual symptoms. REFERENCES NIL Acknowledgements We would like to express our gratitude to Prof. Martin Rudwaleit for his contributions to the development of the initial cohort. Additionally, we extend our thanks to Dr. Susanne Lüders, Dr. Burkhard Muche, Dr. Laura Spiller, Dr. Uta Syrbe, and Dr. Anne-Katrin Weber for their valuable efforts in patient recruitment and follow-up during the cohort extension. Special appreciation goes to Sabrina Igel, Claudia Lorenz, Bianca Mandt, Caroline Höppner, and Sandra Päßler for the management of the cohort. Lastly, we appreciate the patients for their essential contributions to this research project. Disclosure of Interests Fares Al Mohamad: None declared, Valeria Rios Rodriguez: None declared, Hildrun Haibel AbbVie, Janssen, MSD, Novartis, Pfizer, Roche, UCB and Sobi, BI, Janssen, MSD, Novartis, SOBI and Roche., SOBI, Mikhail Protopopov: None declared, Judith Rademacher: None declared, Joachim Sieper Abbvie, Novartis, Merck, UCB, Murat Torgutalp: None declared, Henriette Käding: None declared, Fabian Proft grants and personal fees from Novartis, Eli Lilly and UCB and personal fees from AbbVie, AMGEN, BMS, Celgene, Galapagos, Hexal, Janssen, Medscape, MSD, Pfizer and Roche., Denis Poddubnyy AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB., AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB., AbbVie, Eli Lilly, MSD, Novartis, Pfizer.


POS0798 EFFICACY, SAFETY AND RADIOGRAPHIC OUTCOMES FROM THE PHASE 3 SELECT-AXIS 2 STUDY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND AN INADEQUATE RESPONSE TO BIOLOGIC DMARD THERAPY: 2-YEAR DATA

June 2024

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65 Reads

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1 Citation

Annals of the Rheumatic Diseases

Background Upadacitinib (UPA), an oral reversible JAK inhibitor, has shown efficacy and an acceptable safety profile in patients (pts) with AS (r-axSpA) in the SELECT-AXIS 1 and 2 studies, including pts with an inadequate response or intolerance to biologic DMARDs (bDMARD-IR) through 1 year in SELECT-AXIS 2. [1,2] Objectives To assess the 2-year efficacy, safety, and radiographic outcomes following treatment with UPA 15 mg once daily (QD) in bDMARD-IR pts with active AS in SELECT-AXIS 2. Methods The SELECT-AXIS 2 AS bDMARD-IR study design has been described previously. [1,2] Following a 14-week (wk) placebo (PBO)-controlled period, pts were eligible to enter a long-term extension and receive open-label UPA 15 mg QD. Efficacy was evaluated over 104wks in pts who received continuous UPA, and those who switched from PBO to UPA at wk14. Efficacy endpoints included ASAS40, ASAS partial remission (ASAS PR), ASDAS low disease activity (LDA; <2.1), and ASDAS inactive disease (ID; <1.3); and mean change from baseline (BL) in ASDAS, total back pain, BASFI, and ASAS health index (HI) scores. As observed (AO) and AO with non-responder imputation analyses (AO-NRI), where all observed data are used in the analysis and missing data are imputed as non-responders, are presented for binary endpoints. AO with mixed model repeated measures (AO-MMRM) analyses are used for continuous endpoints. Imaging outcomes included SpondyloArthritis Research Consortium of Canada (SPARCC) MRI inflammation scores (AO-MMRM) and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; AO-ANCOVA). Safety was assessed through wk104 in all pts who received ≥1 UPA dose. Treatment-emergent adverse events (TEAEs) are presented as exposure-adjusted event rates (events/100 patient-years [E/100 PY]). Results Of 420 randomized pts who received the study drug (continuous UPA: n=211; PBO to UPA: n=209), 331 (78.8%) completed 104wks of treatment (n=163 and n=168, respectively). Response rates for disease activity were maintained or improved from wk14 to wk104 in the continuous UPA group and at wk104 similar responses were achieved in the PBO to UPA group. Response rates at wk104 were comparable for the continuous UPA vs PBO to UPA groups, including ASAS40 (AO-NRI; 64.9% and 61.7%, respectively), ASAS PR (34.1% and 37.8%), ASDAS LDA (55.9% and 55.0%), and ASDAS ID (29.9% and 34.4%) (Figure 1). Mean change from BL was similar for continuous UPA vs PBO to UPA for ASDAS (-2.08 vs -2.04, respectively), total back pain (-4.86 vs -4.60), BASFI (-3.77 vs -3.73), and ASAS HI (-4.95 vs -4.55). Improvements from BL in MRI inflammation were maintained in both treatment groups. Mean change from BL in MRI SPARCC spine scores were -3.80 (BL mean: 9.97) and -4.55 (BL: 7.71) in the continuous UPA and PBO to UPA group, respectively; SI joints scores were -3.11 (BL: 5.98) and -3.96 (BL: 5.91). Most pts showed no radiographic progression (mean change from BL in mSASSS <2 continuous UPA: 94.9%; PBO to UPA: 93.8%). The least squares mean change from BL to wk104 in mSASSS scores was 0.12 for continuous UPA and 0.20 PBO to UPA. Safety was reported in 414 pts (687.2 PY) who received ≥1 UPA dose. TEAEs, serious TEAEs, and discontinuation of study drug rates were 165.2, 8.7, and 3.6 E/100 PY, respectively; one death (polytrauma, previously reported) occurred before wk52 (0.1 E/100 PY). [1] Rates of major adverse cardiovascular events, venous thromboembolic events, and malignancy (excluding non-melanoma skin cancer) occurred at 0.3 E/100 PY (Figure 2). Conclusion Efficacy was maintained or improved with UPA 15 mg to wk104 in bDMARD-IR pts with active AS and was similar in pts receiving continuous UPA compared with PBO to UPA. Inflammatory activity on MRI and rates of radiographic progression at wk104 were low in both groups. UPA 15 mg was generally well tolerated, with no new safety signals identified. REFERENCES [1] Baraliakos X et al. Arthritis Res Ther. 2023;25:172.[2] van der Heijde D et al. Ann Rheum Dis. 2022;81:1515–23. • Download figure • Open in new tab • Download powerpoint Figure 1. Efficacy over 104 weeks (AO and AO-NRI) • Download figure • Open in new tab • Download powerpoint Figure 2. TEAEs of special interest Acknowledgements AbbVie and the authors thank the participants, study sites, and study investigators who are participating in this study. AbbVie funded this study and contributed to its design, research, analysis, data collection, interpretation of data, and the review and approval of this abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK) and was funded by AbbVie. Disclosure of Interests Xenofon Baraliakos AbbVie, BMS, Chugai, MSD Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB Pharma, AbbVie and Novartis, Désirée van der Heijde AbbVie, ArgenX, Bayer, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Takeda, and UCB Pharma, Joachim Sieper AbbVie, Merck, and Novartis, AbbVie, Merck, Novartis, and UCB, AbbVie, Merck, and UCB, Robert Inman AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and Sandoz., AbbVie, Amgen, Janssen, and Novartis, Hideto Kameda AbbVie, Asahi-Kasei, Eisai, Janssen, Lilly, Mitsubishi-Tanabe, and UCB, AbbVie, Janssen, Lilly, Novartis, Sanofi, and UCB, AbbVie, Asahi-Kasei, Boehringer Ingelheim, Eisai, Mitsubishi-Tanabe, and Taisho, Walter P Maksymowych AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Medscape, Novartis, Peervoice, Pfizer, and UCB Pharma, AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Medscape, Novartis, Peervoice, Pfizer, and UCB Pharma, AbbVie, Novartis, Pfizer, and UCB Pharma, Anna Shmagel AbbVie, Ivan Lagunes AbbVie, Xianwei Bu AbbVie, Peter K Wung AbbVie, Atul Deodhar AbbVie, BMS, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Celgene, Lilly, MoonLake, Novartis, Pfizer, and UCB Pharma.


AB0093 COMPLEMENT IN THE DIAGNOSIS OF AXIAL SPONDYLOARTHRITIS (AXSPA). INVESTIGATIONS IN A CROSS-SECTIONAL COHORT (OPTIREF) OF PATIENTS SUSPECTED OF AXIAL SPONDYLOARTHRITIS

May 2023

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4 Reads

Annals of the Rheumatic Diseases

Background Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease without specific diagnostic biomarkers. However, recent evidence suggests an involvement of the innate immune system in the pathogenesis of axSpA [1]. The lectin pathway of complement activation serves essential functions in the innate immune system, regulates homeostasis and development. We have previously shown the lectin pathway proteins (LPPs) L-ficolin and M-ficolin to be elevated in axSpA-patients compared with clinically relevant controls with unspecific low back pain (uLBP). Objectives To investigate the diagnostic potential of LPP levels in patients recruited from a well-defined cross-sectional prospective cohort (OptiRef), including newly diagnosed axSpA-patients and uLBP-patients. Methods Serum samples were obtained from 515 individuals from the OptiRef cohort; 151 newly diagnosed axSpA-patients and 364 uLBP-patients [2]. All patients were assessed according to a standardized protocol, incl. clinical information as demographics, SpA features, symptom duration, and disease activity. Routine lab tests (HLA-B27 and CRP) were performed. Imaging (x-ray and MRI) was performed if deemed clinically relevant. Serum levels of all 10 LPPs (MBL, CL-L1, M-ficolin, H-ficolin, L-ficolin, MASP-1, MASP-2, MASP-3, MAp19, and MAp44) and the complement activation product C3dg were measured by immunoassays. Results Patient characteristics are shown in Table 1. L-ficolin, MASP-2, and C3dg serum levels were increased in axSpA-patients compared with uLBP-patients, whereas CL-L1 and MASP-3 serum levels were decreased (Figure 1). After adjustments for CRP, C3dg serum levels remained significantly increased in axSpA-patients, whereas M-ficolin and MASP-3 serum levels were decreased in axSpA-patients. The diagnostic potential of combining either L-ficolin, MASP-3, and C3dg with HLA-B27 increased specificity to 93-95% compared with HLA-B27 alone (77%) but decreased sensitivity to 29-33% compared with HLA-B27 alone (83%). In a univariate logistic regression analysis, CL-L1, MASP-2, MASP-3, and C3dg were associated with an axSpA-diagnosis, and C3dg and MASP-3 remained significant in a multivariate logistic regression analysis. Conclusion In this study, serum levels of C3dg, MASP-3, and CL-L1 differed significantly between axSpA-patients and uLBP-patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3, and C3dg increased diagnostic specificity for axSpA, it seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with the axSpA-diagnosis in multivariate logistic regression, indicating the complement system’s involvement in axSpA-pathogenesis. This should be further investigated. References [1]Ambarus, C., et al. Curr Opin Rheumatol. 2012[2]Poddubnyy, D., et al. Rheumatology (Oxford). 2021 View this table: • View inline • View popup Table 1. Patient characteristics of the included patients from the OptiRef cohort • Download figure • Open in new tab • Download powerpoint Figure 1. Serum levels of significantly altered complement LPPs in the two patient groups. Acknowledgements NIL. Disclosure of Interests Clara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft: None declared, Steffen Thiel: None declared, Laura Spiller: None declared, Valeria Rios Rodriguez: None declared, Burkhard Muche: None declared, Judith Rademacher: None declared, Anne-Katrin Weber: None declared, Susanne Lueders: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB.


POS0299 NEUROPATHIC AND NEUROPLASTIC PAIN COMPONENTS DETERMINE THE PRESENCE OF RESIDUAL SYMPTOMS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS RECEIVING BIOLOGICAL DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS

May 2023

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16 Reads

Annals of the Rheumatic Diseases

Background Several studies have investigated neuropathic pain (NP) as a component of chronic pain in patients with axial spondyloarthritis (axSpA)/ ankylosing spondylitis (AS) and showed a wide frequency range from 22 – 56.9% [1, 2]. Neuroplastic processes leading to central sensitization have been described as another component of pain chronification in rheumatic diseases [3]. Widespread pain is considered a characteristic of central sensitization [4]. It is, however, unclear, what is the relevance of neuropathic and neuroplastic components of pain for the treatment response and the presence of residual symptoms in patients with radiographic axSpA (r-axSpA) treated with biological disease-modifying anti-rheumatic drugs (bDMARDs) Objectives To investigate the impact of neuropathic pain and neuroplastic/ widespread pain on residual disease activity in patients with r-axSpA receiving (bDMARDs). Methods Patients with r-axSpA (AS fulfilling the modified New York criteria) and starting a bDMARD therapy were recruited between 2015 and 2019 and followed up in an extension of the prospective German Spondyloarthritis Inception Cohort (GESPIC). Neuropathic pain was quantified using the pain detect questionnaire (PD), whereas neuroplastic pain was quantified using the Widespread Pain Index (WPI). Disease activity was measured using the Ankylosing Spondylitis Disease Activity Score – C-reactive protein (ASDAS-CRP) score. Simple and multiple linear and logistic regression analyses were performed to determine the effects of NP and WPI on the ASDAS status score under bDMARD treatment. Results A total of 130 patients with r-axSpA were included in this cohort. PD and WPI scores were available at at least one follow-up time-point in 99 patients. Of these 70 were receiving bDMARD treatment (n=68 under TNFi and n=2 under IL17 inhibitors) with no missing data and could be included in this analysis. The first follow-up point with available PD and WPI scores while under bDMARD treatment was used for the analysis. Table 1. Baseline characteristics. Characteristic n = 70 Female sex 49(70) Age, years 37.27±10.77 HLA-B27 positive 64(91.4) BMI, kg/m² 25.57±4.49 Current smokers 28(40) Symptom duration, years 12.53±10.83 Elevated CRP, >5 mg/l 43(61.4) ASDAS-CRP 3.41±0.82 current NSAIDs intake 56(80) Data are expressed as n(%) or mean ± standard deviation, BMI: Body mass index, CRP: C-reactive protein, ASDAS-CRP: Ankylosing Spondylitis Disease Activity Score – C-reactive protein, NSAIDs: Nonsteroidal anti-inflammatory drugs The mean (±SD) bDMARD treatment duration was 2.79 ± 1.40 (range: 0.27 – 5.01) years at the time point of PD and WPI measurement. Higher PD and WPI scores at follow up showed a significant association with higher ASDAS-CRP scores in a multiple linear regression model. This was also true for age, HLA-B27 and the CRP level at follow-up. Logistic regression analysis showed that a high PD score and a high WPI score were also associated with higher odds of having high/ very high disease activity (ASDAS >2.1) independently of other factors including elevated CRP. Conclusion Both PD and WPI reflecting neuropathic and neuroplastic components of pain showed association with residual symptoms (as reflected by higher ASDAS) independently of systemic inflammation (as reflected by elevated CRP) in patients with r-axSpA receiving bDMARD treatment. References [1]Kim, T.W., S.M. Son, and J.S. Lee, Neuropathic pain in ankylosing spondylitis: a meta-analysis. Z Rheumatol, 2020. 79 (1): p. 95-102. [2]Borman, P., F. Kaygisiz, and A. Yaman, Neuropathic component of low back pain in patients with ankylosing spondylitis. Mod Rheumatol, 2021. 31 (2): p. 462-467. [3]Woolf, C.J., Central sensitization: implications for the diagnosis and treatment of pain. Pain, 2011. 152 (3 Suppl): p. S2-s15. [4]Nijs, J., et al., Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain. Pain Physician, 2014. 17 (5): p. 447-57. Acknowledgements The GESPIC-AS cohort is partially financed by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung - BMBF) Disclosure of Interests Fares Al Mohamad: None declared, Valeria Rios Rodriguez Speakers bureau: AbbVie, Falk e.V., Hildrun Haibel Paid instructor for: Boehringer, Janssen, MSD, Novartis, Sobi, Roche, Pfizer, AbbVie, and Sobi, Mikhail Protopopov Consultant of: Novartis, Judith Rademacher Consultant of: Novartis and UCB, Joachim Sieper Speakers bureau: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Consultant of: AbbVie, Lilly, Merck, Novartis, UCB, Murat Torgutalp: None declared, Henriette Käding: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc and UCB, Consultant of: AbbVie, BIOCAD, Gilead Sciences, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer Inc, Samsung Bioepis and UCB, Grant/research support from: AbbVie, MSD, Novartis and Pfizer.


OP0057 FACTORS ASSOCIATED WITH ACHIEVING REMISSION IN PATIENTS WITH EARLY PERIPHERAL SPONDYLOARTHRITIS: 10-YEAR RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT (GESPIC)

May 2023

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17 Reads

Annals of the Rheumatic Diseases

Background Depending on leading manifestation, Spondyloarthritis (SpA) is classified as axial (axSpA) or peripheral SpA (pSpA). Achieving of remission/inactive disease is key goal in treatment of SpA, including pSpA. Results from recent worldwide ASAS PerSpA study showed that nearly 10% of SpA patients were identified as having pSpA (as opposed to other forms of SpA) by rheumatologist, but there are still no long-term observational studies focusing on outcomes including disease activity/remission in pSpA. Objectives To investigate factors associated with disease activity and achievement of remission over a period of up to 10 years of clinical observation in early pSpA patients. Methods Data from patients diagnosed with pSpA in GESPIC (with predominant peripheral manifestations, symptom duration of up to 5 years and not classified as axSpA) according to rheumatologist were used for this study. Visits were scheduled every 6 months for 2 years, then annually up to year 10. Clinical characteristics, examination (arthritis, enthesitis), and activity (questionnaires and laboratory) were collected at visits. Association between parameters and disease activity/remission [defined by Disease Activity in Psoriatic Arthritis (DAPSA), Axial SpA Disease Activity Score (ASDAS), and clinical remission (complete absence of arthritis or enthesitis)], was analysed by generalized estimating equations (GEE). Results The mean age of 115 pSpA patients (51.3% male) was 37.3 ± 12.2 years, and 71 (61.7%) patients were HLA-B27 positive. Baseline DAPSA and ASDAS were 13.3 ± 8.1 and 2.4 ± 0.9. During follow up 48 (41.7%), 46 (41.7%), and 94 (81.9%) patients reached at least once DAPSA remission (DAPSA <4), ASDAS-Inactive disease (ASDAS<1.3), and clinical remission, respectively. In univariable analyses, female sex, older age, HLA-B27 negativity, current and history of psoriasis, steroid, csDMARDs and higher NSAID intake were associated with higher DAPSA and lower odds of remission. Similar results were observed regarding ASDAS and clinical remission (Table 1). Multivariable analyses showed that history of psoriasis, HLA-B27 negativity, steroid intake, and higher NSAID intake were associated with higher DAPSA and ASDAS scores (Figure 1A,B), while longer symptom duration, psoriasis history, steroid, TNFi and higher NSAID intake, and higher CRP were associated with lower odds of remission (Figure 1C). Conclusion Several parameters associated with higher disease activity and absence of remission were identified. Psoriasis and higher CRP were associated with lower odds of achieving clinical remission, while an association with drug usage is likely a consequence of high disease activity. Table 1. Univariable GEE analysis of association between clinical parameters and disease activity/remission. DAPSA ASDAS Clinical Remission Β (95% CI) β (95% CI) OR (95% CI) Male Sex -2.12(-4.69;0.46) -0.29(-0.63;0.05) 1.54(0.96;2.47) Age 0.12(0.03;0.21 ) 0.02(0.01;0.03 ) 1.00(0.98;1.02) HLA-B27 Positivity -3.95(-6.46;-1.45 ) - 0.56(-0.90;-0.23 ) 1.63(1.01;2.62 ) Symptom duration -0.27(-0.60;0.05) 0.01(-0.03;0.05) 1.14(1.03;1.26 ) Current psoriasis 4.29(1.34;7.23 ) 0.39(0.05;0.73 ) 0.27(0.13;0.53 ) Ever psoriasis 3.13(-0.01;6.26 ) 0.38(-0.03;0.79) 0.67(0.38;1.18) Current IBD -0.79(-2.66;1.08) -0.73(-1.01;-0.46 ) 0.26(0.03;2.01) Ever IBD -0.94(-5.31;3.43) -0.67(-1.00;-0.34 ) 0.65(0.11;3.93) Current Uveitis 3.68(-4.64;12.00) 0.54(-0.61;1.70) 0.28(0.05;1.59) Ever uveitis -2.81(-6.62;1.00) -0.31(-0.86;0.24) 1.74(0.99;3.07 ) CRP, mg/L 0.15(0.12;0.19 ) 0.03(0.02;0.03 ) 0.96(0.93;0.99 ) Steroid intake 3.96(1.62;6.30 ) 0.25(-0.02;0.52) 0.35(0.19;0.66 ) csDMARDs intake 1.52(-0.25;3.29) 0.05(-0.17;0.27) 0.48(0.31;0.75 ) TNF intake -0.50(-3.17;2.18) -0.13(-0.48;0.22) 0.37(0.16;0.82 ) NSAID intake score, (0-100) 0.08(0.06;0.11 ) 0.01(0.01;0.01 ) 0.97(0.97;0.98 ) Acknowledgements GESPIC has been financially supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung-BMBF). As funding by BMBF was reduced according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott/Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Disclosure of Interests Murat Torgutalp Speakers bureau: Abbvie, Xu Peng: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB, Valeria Rios Rodriguez Speakers bureau: AbbVie, Falk e.V., Judith Rademacher Consultant of: Novartis and UCB, Mikhail Protopopov Consultant of: Novartis, Hildrun Haibel Speakers bureau: Boehringer, Janssen, MSD, Novartis, Sobi, Roche, Pfizer, and AbbVie, Consultant of: Boehringer, Janssen, MSD, Novartis, Sobi, Roche, Pfizer, and AbbVie, Martin Rudwaleit Speakers bureau: Abbvie, Janssen, Celgene, BMS, Janssen, Novartis, Pfizer, UCB, Paid instructor for: Abbvie, Pfizer, Galapagos, UCB, Novartis, Consultant of: Abbvie, Janssen, Lilly, Novartis, Pfizer, UCB, Joachim Sieper Speakers bureau: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Consultant of: AbbVie, Lilly, Merck, Novartis, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis, and UC, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer.


POS0429 THE COMPLEMENT SYSTEM AND RESPONSE TO TNF INHIBITION IN PATIENTS WITH RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS. POST HOC ANALYSIS FROM CONSUL, A LONGITUDINAL MULTI-CENTER RCT COHORT OF R-AXSPA-PATIENTS WITH A HIGH RISK OF STRUCTURAL PROGRESSION INITIATING TREATMENT WITH TNF-INHIBITOR

May 2023

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17 Reads

Annals of the Rheumatic Diseases

Background The pathogenesis of axial spondyloarthritis (axSpA) remains largely unexplained, but recent evidence supports an involvement of the innate immune system. The lectin pathway (LP) of complement activation plays an essential role in innate immunity. Previous studies have shown that elevated levels of specific complement proteins are associated with disease activity in axSpA. However, little is known about alterations in LP proteins and complement activation in relation to treatment with TNF-inhibitors (TNF-I). Objectives To determine changes in LP protein levels and complement activation in a longitudinal multi-center cohort of axSpA-patients with high disease activity from the RCT CONSUL before and after 12 weeks of treatment with a TNF-I. Furthermore, to investigate the correlations between LP protein levels, and disease activity, and treatment response. Methods Serum samples at baseline and after 12 weeks of treatment with the TNF-I golimumab were obtained from 108 radiographic axSpA-patients with high disease activity (BASDAI ≥4) and high risk for radiographic progression (elevated CRP or ≥1 syndesmophyte present at inclusion) recruited from the CONSUL cohort. Serum levels of the LP proteins MBL, CL-L1, H-ficolin, L-ficolin, M-ficolin, MASP-1, MASP-2, MASP-3, and MAp44, and complement activation product C3dg were measured by immunoassays. Results Serum levels of L-ficolin, M-ficolin, MBL, MAp44, and C3dg decreased significantly after 12 weeks of treatment with TNF-I, whereas serum levels of MASP-3 and CL-L1 increased significantly (Figure 1). After adjustment for CRP, significant changes were observed for L-ficolin, M-ficolin, MASP-1, MASP-2, MASP-3, and MAp44. Baseline serum levels of L-ficolin, M-ficolin, and C3dg correlated positively with baseline ASDAS-CRP (Spearman’s rho 0.290, 0.190, and 0.328, respectively, all p <0.05), whereas baseline MASP-1 and MAp44 correlated negatively with baseline ASDAS-CRP (Spearman’s rho -0.204, and -0.218, respectively, both p <0.05). In a univariate logistic regression analysis, baseline serum levels of MASP-1 predicted achievement of clinical important improvement (ΔASDAS≥1.1) at week 12, and baseline serum levels of C3dg predicted inactive disease (ASDAS<1.3) at week 12. In corresponding multivariate logistic regression analyses, only C3dg remained significantly associated with inactive disease (ASDAS<1.3) ( p = 0.025). Conclusion Baseline serum levels of L-ficolin, M-ficolin and C3dg correlated positively with baseline ASDAS-CRP, and the protein serum levels decreased significantly after TNF-I therapy. Baseline levels of complement activation measured by C3dg predicted achievement of inactive disease (ASDAS<1.3) at week 12 in both a univariate and a multivariate logistic regression analysis. Our findings suggest an involvement of the complement system in the underlying inflammatory processes of axSpA and prompt further investigations. Table 1. Baseline demographics of the investigated patient population from the CONSUL RCT ( n = 108) Age, median (IQR) 38 (31-49) Male, n (%) 77 (71) HLA-B27 positive, n (%) 89 (82) Previous treatment with bDMARD, n (%) 26 (24) Time since diagnosis in years, median (IQR) 3.0 (0.0-9.0) Years since onset of symptoms, median (IQR) 12 (6.0-21.0) CRP, mg/L (IQR) 9.1 (4.1-20) Elevated CRP (> 5mg/L), n (%) 75 (69) mSASSS, median (IQR) 4.3 (0.3-18) # Syndemophytes present, median (IQR) 1.6 (0.0-6.3) # Presence of ≥1 syndesmophyte(s) § , n (%) 43 (48) # ASDAS-CRP, median (IQR) 3.6 (3.1-4.1) BASDAI, median (IQR) 6.2 (5.2-7.0) BASFI, median (IQR) 5.2 (4.0-6.4) § Determined by 3 calibrated readers blinded for clinical data. # data available on n = 89 Figure 1. Differences in lectin pathway protein serum levels were compared by paired t-tests. Bars indicate median and IQR (MASP-3, MAp44, and C3dg) or mean and sd (L-ficolin, M-ficolin, MBL, and CL-L1). REFERENCES NIL. Acknowledgements NIL. Disclosure of Interests Clara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, MSD, Novartis, Pfizer, and UCB, Grant/research support from: Novartis, Steffen Thiel: None declared, Burkhard Muche: None declared, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Mikhail Protopopov: None declared, Joachim Listing: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AbbVie, AMGEN, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche und UCB, Consultant of: AbbVie, AMGEN, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche und UCB, Grant/research support from: Novartis, Eli Lilly and UCB.


POS0043 COMPLEMENT IN RADIOGRAPHIC AXSPA – BIOMARKERS OF RADIOGRAPHIC PROGRESSION? POST HOC ANALYSIS FROM CONSUL, A LONGITUDINAL MULTI-CENTER RANDOMIZED CONTROLLED TRIAL COHORT OF AXSPA-PATIENTS WITH A HIGH RISK OF STRUCTURAL PROGRESSION INITIATING TREATMENT WITH TNF-I

May 2023

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8 Reads

Annals of the Rheumatic Diseases

Background The biological processes involved in the development of structural changes associated with radiographic axial spondyloarthritis (r-axSpA) remain largely unraveled. Still, high disease activity, elevated C-reactive protein (CRP), and existing syndesmophytes are associated with radiographic progression. The complement system is an inflammation-generating part of the innate immune system. Animal models have shown inhibition of complement activation to diminish structural changes associated with axSpA [1]. Objectives This project aimed to investigate complement activation and serum levels of complement proteins and their correlations with radiographic spinal progression over a two years follow-up period in a longitudinal cohort of axSpA patients with active r-axSpA, and high risk of radiographic progression, recruited from the randomized controlled trial CONSUL. Methods All patients had active r-axSpA and risk factors for radiographic spinal progression (BASDAI ≥4, and elevated CRP and/ or ≥1 syndesmophyte(s)). Serum samples were collected at baseline ( n = 96) and after 108 weeks ( n = 89) of TNF-I therapy and analyzed by immunoassays for complement lectin pathway proteins (L-ficolin, M-ficolin, H-ficolin, CL-L1, MBL, MASP-1, MASP-2, MASP-3, and MAp44) and the complement activation product C3dg. X-rays were performed at baseline and after 108 weeks and read blinded for clinical data and chronology by three independent expert readers. New bone formation was defined as the growth of syndesmophyte(s) and/or new syndesmophyte(s) determined by 3-reader-agreement. Results Patient characteristics are shown in Table 1. In total, 19 patients developed new bone formation at week 108. Baseline serum levels of MASP-1, MASP-2, and C3dg were elevated in patients with new bone formation, whereas baseline serum levels of MASP-3 were decreased (all p <0.05). Baseline MASP-1, MASP-3, and C3dg predicted the development of new bone formation in a univariate logistic regression analysis, whereas CRP did not. Baseline MASP-1, MASP-3, and C3dg remained significant in a multivariate logistic regression analysis. L-ficolin and C3dg levels at week 108 were elevated in patients with new bone formation, and the serum levels at week 108 predicted development of new bone formation in a univariate logistic regression analysis. In a multivariate regression analysis, C3dg remained significant ( p <0.05). Conclusion In this study, complement activation measured by C3dg and serum levels of MASP-1 and MASP-3, prior to TNF-I therapy, predicted development of new bone formation at week 108. Furthermore, elevated levels of C3dg and L-ficolin at week 108 were associated with new bone formation. These findings support the involvement of complement activation in new bone formation in r-axSpA. Reference [1]Yang C et al. Sci Rep. 2016. Table 1. Baseline demographics of the investigated patient population from the CONSUL RCT ( n = 96) Age, median (IQR) 37 (31-45) Male, n (%) 70 (73) HLA-B27 positive, n (%) 80 (83) Previous bDMARD treatment, n (%) 21 (22) Symptom duration in years, median (IQR) 12 (6.0-20) Smoking, n (%) 36 (38) mSASSS, median (IQR) 5.0 (0.3-18) Syndesmophytes, median (IQR) 1.8 (0-6.3) Presence of ≥1 syndesmophyte(s)δ, n (%) 47 (49) CRP, median (IQR) 9.2 (3.2-19) Elevated CRP (>5 mg/L), n (%) 64 (67) ASDAS-CRP, median (IQR) 3.6 (3.1-4.1) BASDAI, median (IQR) 6.2 (5.2-6.8) δDetermined by 3 expert readers blinded for clinical data. Figure 1. a ) Baseline MASP-1, MASP-2, MASP-3, and C3dg levels according to development of new bone formation at week 108. b ) L-ficolin and C3dg levels at week 108 according to development of new bone formation at week 108. New bone formation: growth of syndesmophytes and/or new syndesmophytes determined by 3-reader-agreement. p -values indicate comparisons between groups by t-test. Bars indicate median and IQR (MASP-1, MASP-2, MASP-3, C3dg), and mean and sd (L-ficolin). Acknowledgements NIL. Disclosure of Interests Clara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Steffen Thiel: None declared, Burkhard Muche: None declared, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Mikhail Protopopov: None declared, Joachim Listing: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB.


POS1122 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND AN INADEQUATE RESPONSE TO BIOLOGIC DMARD THERAPY: ONE-YEAR RESULTS FROM A PHASE 3 STUDY

May 2023

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3 Reads

Annals of the Rheumatic Diseases

Background Upadacitinib (UPA), a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients (pts) with ankylosing spondylitis (AS) in the phase 3 SELECT-AXIS 1 and 2 program, including pts with an inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR).[1,2] Objectives To assess the 1-year efficacy and safety of UPA 15 mg once daily (QD) in bDMARD-IR pts with active AS in SELECT-AXIS 2. Methods The design of the SELECT-AXIS 2 AS bDMARD-IR study has been described previously.[1] Pts who completed the 14-wk placebo (PBO)-controlled period were eligible to enter an ongoing long-term extension and receive open-label UPA 15 mg QD for up to 90 wks. This analysis evaluated efficacy over 52 wks in pts who received continuous UPA, and those who switched from PBO to UPA at wk 14. Efficacy endpoints included proportion of pts achieving Assessment of SpondyloArthritis international Society 40 response (ASAS40), ASAS partial remission (PR), ASDAS (AS Disease Activity Score with C-reactive protein [CRP]) low disease activity (LDA; <2.1), ASDAS inactive disease (ID; <1.3), and changes from baseline in ASDAS and high-sensitivity CRP (hsCRP). As-observed (AO) and non-responder imputation with multiple imputation (NRI-MI) analyses are presented for binary endpoints and mixed model for repeated measures (MMRM) analyses for continuous endpoints. Safety was assessed through the cut-off date of May 19, 2022 in all pts who received ≥1 dose of UPA. Treatment-emergent adverse events (TEAEs) and TEAEs of special interest are presented as exposure-adjusted event rates (events/100 pt-years [E/100 PY]). Results A total of 420 pts were randomized and received study drug (PBO to UPA: n=209; continuous UPA: n=211). Response rates were maintained from wk 14 to wk 52 in the continuous UPA group, and responses were similar in the PBO to UPA group at wk 52. NRI-MI response rates at wk 52 for the PBO to UPA and continuous UPA groups, respectively, were: ASAS40 (64.6% and 65.9%), ASAS PR (29.2% and 30.3%), ASDAS LDA (55.3% and 56.9%), and ASDAS ID (25.2% and 26.0%) ( Figure 1 ). Changes from baseline in ASDAS and hsCRP were also similar between groups (-1.9 and -2.0, and -10.6 and -10.0 for the PBO to UPA and continuous UPA groups, respectively). Safety was assessed in 414 pts (534.4 PY of exposure) who received ≥1 dose of UPA ( Table 1 ). Rates of serious TEAEs and TEAEs leading to study drug discontinuation were 9.9 and 3.0 E/100 PY, respectively. Rates of malignancy, major adverse cardiovascular events, and venous thromboembolic events were low (0.2, 0.2, and 0.4 E/100 PY, respectively). Conclusion UPA 15 mg demonstrated sustained efficacy up to wk 52 in bDMARD-IR pts with active AS. Similar efficacy was observed at wk 52 in pts with continuous UPA exposure and those who switched from PBO to UPA. UPA 15 mg was generally well tolerated in this bDMARD-IR population, with no new safety signals identified. References [1]van der Heijde D, et al. Lancet 2019;394:2108–2117.[2]van der Heijde D, et al. Ann Rheum Dis 2022;81:1515–1523. • Download figure • Open in new tab • Download powerpoint View this table: • View inline • View popup Table 1. Treatment-emergent adverse events Acknowledgements AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests Xenofon Baraliakos Speakers bureau: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Désirée van der Heijde Consultant of: AbbVie, Bayer, Bristol Myers Squibb, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology, Joachim Sieper Speakers bureau: AbbVie, Merck, and Novartis, Consultant of: AbbVie, Merck, Novartis, and UCB, Grant/research support from: AbbVie, Merck, and UCB, Robert Inman Consultant of: AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and Sandoz, Grant/research support from: AbbVie, Amgen, Janssen, and Novartis, Hideto Kameda Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol Myers Squibb, Chugai, Eisai, Gilead, Janssen, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, Asahi Kasei, Astellas, Bristol Myers Squibb, Chugai, Eisai, Gilead, Janssen, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Asahi Kasei, Chugai, Eisai, Mitsubishi Tanabe, and Taisho, Yihan Li Employee of: AbbVie, may own stock or options, Xianwei Bu Employee of: AbbVie, may own stock or options, Anna Shmagel Employee of: AbbVie, may own stock or options, Peter Wung Employee of: AbbVie, may own stock or options, In-Ho Song Employee of: AbbVie, may own stock or options, Atul Deodhar Speakers bureau: AbbVie, Amgen, Aurinia, BMS, Celgene, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Celgene, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB.



OP0021 TREATMENT WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IS ASSOCIATED WITH RETARDATION OF RADIOGRAPHIC SPINAL PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: 10-YEAR RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

June 2022

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14 Reads

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3 Citations

Annals of the Rheumatic Diseases

Background 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.


Citations (29)


... As expected from their treatment-refractory nature, efficacy outcomes at week 104 were slightly numerically lower in subgroups of patients who had prior exposure to treatment with a bDMARD (TNF inhibitor or IL-17 inhibitor) versus the total population, although low patient numbers limit interpretation of results observed in the IL-17 inhibitor subgroup. Among patients with prior exposure to bDMARD treatment in the current analysis, responses after 2 years of upadacitinib treatment showed similar trends, although were numerically lower, versus those observed in patients with active bDMARDinadequate response AS [30]. A lower treatment effect in patients with prior exposure to bDMARD treatment versus bDMARD-naïve patients is to be expected because patients with an inadequate response to bDMARD treatment have previously not responded to treatment with a TNF inhibitor or IL-17 inhibitor. ...

Reference:

Upadacitinib in active non-radiographic axial spondyloarthritis: 2-year data from the phase 3 SELECT-AXIS 2 study
POS0798 EFFICACY, SAFETY AND RADIOGRAPHIC OUTCOMES FROM THE PHASE 3 SELECT-AXIS 2 STUDY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND AN INADEQUATE RESPONSE TO BIOLOGIC DMARD THERAPY: 2-YEAR DATA
  • Citing Conference Paper
  • June 2024

Annals of the Rheumatic Diseases

... This underlines the importance of continuous training of young and inexperienced radiologists in the field of axSpA imaging using established and new methods. [25][26][27] Our results make a crucial contribution to overcoming existing shortcomings, as our findings reveal that, besides the experience of the reader itself, it is the choice of modality that has an important impact on overall diagnostic accuracy. However, the diagnosis cannot be established by imaging alone but clinical features need also consideration in the diagnostic process, as even highly experienced readers only achieve an accuracy of 85.9%. ...

POS1460 CONTRIBUTING TO THE TRAINING OF IMAGING IN RHEUMATOLOGY BY EXPERTS WORLDWIDE VIA INTERACTIVE MOBILE E-TEACHING: BERLINCASEVIEWER.
  • Citing Article
  • May 2022

Annals of the Rheumatic Diseases

... The authors concluded that tofacitinib, golimumab i.v. and infliximab had the highest SUCRA values for efficacy; however, the differences in efficacy were not significant, and the analyses were based on one small Phase II study for tofacitinib [70]. The current analysis includes Phase III trials for bimekizumab [60] and JAK inhibitors [79][80][81] which were not available at the time of the previous NMA, as well as data for nr-axSpA. The present analysis also includes new outcomes relative to the Deodhar study, including ASAS40, ASAS-PR and safety/tolerability outcomes. ...

POS0306 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS REFRACTORY TO BIOLOGIC THERAPY: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL
  • Citing Article
  • June 2022

Annals of the Rheumatic Diseases

... [28][29][30] PROOF [Patients With Axial Spondyloarthritis: Multicountry Registry of Clinical Characteristics (PROOF study), including radiographic progression and burden of disease over 5 years in real-life rheumatology clinical practice setting] was a large, multi-country, prospective, non-interventional study in recently diagnosed axSpA patients fulfilling the Assessment of SpondyloArthritis international Society classification that was conducted in 29 countries across 6 different geographical regions. [31][32][33] The aim of this registry was to collect data that could contribute to the understanding of radiographic progression, clinical characteristics, and impact of the disease on quality of life and work productivity over time of nr-ax-SpA and AS patients over a 5-year follow-up. The results of the patients who were recruited in the PROOF study from Greece are presented in the current manuscript to compare with the data from global PROOF analysis and complement national data on the characteristics and management of afflicted patients. ...

OP0149 RADIOGRAPHIC PROGRESSION FROM NON-RADIOGRAPHIC TO RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: RESULTS FROM A 5-YEAR MULTICOUNTRY PROSPECTIVE OBSERVATIONAL STUDY
  • Citing Article
  • June 2022

Annals of the Rheumatic Diseases

... Comorbidities add a significant burden to axSpA by contributing to disease activity, functional and work disability, and even mortality [86], but they can also have an impact on treatment decisions. For example, although NSAIDs have demonstrated efficacy in axSpA [41,98], NSAIDs should be prescribed with caution, especially for patients with documented CVD or in the presence of CVD risk factors. ...

OP0021 TREATMENT WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IS ASSOCIATED WITH RETARDATION OF RADIOGRAPHIC SPINAL PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: 10-YEAR RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT
  • Citing Article
  • June 2022

Annals of the Rheumatic Diseases

... In accordance with the recently updated international recommendations [17] of ASAS and European League Against Rheumatism (EULAR), the aim of the German S3 guideline update [19], was also to provide evidence-based, practicable recommendations for early detection and diagnosis, including appropriate referral strategies for primary care, aiming for a further reduction in diagnostic delays. Furthermore, recent international and national quality standards recognize referral as an important feature of care for patients with axSpA [15,16]. ...

Entwicklung von Qualitätsstandards für Patient*innen mit axialer Spondyloarthritis zum Einsatz in DeutschlandDevelopment of quality standards for patients with axial spondyloarthritis for use in Germany
  • Citing Article
  • Full-text available
  • August 2021

Zeitschrift für Rheumatologie

... 20,21 Similar methodology has recently been used to demonstrate that an MRI cut-off for BME of ≥ 4 vertebral corners achieved specificity of ≥ 95% for a positive MRI of the spine indicative of axSpA, according to global evaluation, and also had ≥ 95% positive predictive value for diagnosis of axSpA after 4.4 years of follow-up. 22 Several considerations suggest that optimal cut-offs for a positive MRI may differ in patients with PsA and axial inflammation. First, patients with PsA tend to be older and have a greater BMI than axSpA patients without psoriatic disease (PsD). ...

OP0251 DATA-DRIVEN DEFINITIONS BASED ON INFLAMMATORY LESIONS FOR A POSITIVE MRI OF THE SPINE CONSISTENT WITH AXIAL SPONDYLOARTHRITIS
  • Citing Article
  • June 2021

Annals of the Rheumatic Diseases

... For ankylosing spondylitis, all the study patients were noted to have inadequate response to NSAIDs and a comparison was made among patients receiving JAKi versus placebo by measuring clinical outcomes in the form of disease activity as ASAS20, ASAS40, and BASDAI50 as well as improvement in quality of life and resolution of inflammation on imaging. SELECT-AXIS1 trial studied the efficacy and safety of upadacitinib in patients with ankylosing spondylitis who are naïve to biologic DMARDs [15]. It was a multicenter, randomized, Content courtesy of Springer Nature, terms of use apply. ...

OP0144 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 1-YEAR RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY WITH OPEN-LABEL EXTENSION
  • Citing Article
  • June 2021

Annals of the Rheumatic Diseases

... Although a positive effect could not be demonstrated in studies conducted with RA patients until 2020, it was observed that more positive results were obtained in patients followed up with SpA. 31 38 In a more recent study, it was shown that TNFi treatment led to a significant increase in fat-free mass index (FFMI) and appendicular skeletal mass (ASM) in 6-month follow-up in SpA patients evaluated with BIA. 32 Hmamouchi et al. followed up on SpA patients treated with TNFi for 2 years and showed an increase in TLM with DXA in the first 6 months, but this increase did not continue in the follow-up. 39 In our study, a significant increase was also observed in GM muscle thickness, GM fascicle length, RF muscle thickness, RFCSA, RA muscle thickness, TA, and EO muscle thickness. ...

FRI0292 TREATMENT RESPONSE TO BIOLOGICAL DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS IS ASSOCIATED WITH FAVORABLE CHANGES OF THE BODY COMPOSITION IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Annals of the Rheumatic Diseases

... Even though MRI is not currently recommended for the monitoring and management of axSpA, several studies have shown that it could give valuable insights about disease activity status [45]. Another study reported that normal CRP at baseline, HLA-B27 negativity, higher spinal ankylosis scores, higher fatty degeneration scores at baseline MRI but lower ankylosis scores in the sacroiliac joint were associated with a higher risk for flares [46]. ...

SAT0389 FREQUENCY OF DISEASE FLARES UNDER LONG-TERM ANTI-TNF THERAPY IN PATIENTS WITH EARLY AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE ETANERCEPT VERSUS SULFASALAZINE IN EARLY AXIAL SPONDYLOARTHRITIS TRIAL
  • Citing Article
  • June 2020

Annals of the Rheumatic Diseases