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Background:Remission/low disease activity is the primary treatment target in axial spondyloarthritis (axSpA), as per the treat-to-target (T2T) and international management recommendations [1]. Patients who do not respond to non-steroidal anti-inflammatory drugs (NSAIDs) can be treated with biological (b) (TNFi or IL-17i) disease modifying anti-rheumatic drugs (bDMARDs). There is a lack of trials comparing different strategies for achieving remission, making evidence-based recommendations for the choice of a particular drug or strategy for first or second line treatment difficult.Objectives:The aim of the AScalate study was to evaluate efficacy of a treatment strategy using the IL-17i secukinumab (SEC) as the first line bDMARD treatment, along with predefined criteria for treatment escalation (T2T arm) compared with a standard of care approach (SoC arm) over 36 weeks in patients with active axSpA.Methods:Study design and methodology have been previously described [2]. Briefly, this was a randomized, parallel-group, open-label, multicentric study involving patients with active axSpA (also fulfilling ASAS classification criteria) and objective signs of inflammation at screening [positive MRI of sacroiliac joints (SIJ) or spine or elevated quick C-reactive protein (CRP >5 mg/L)]. All patients were naive to b-/ts DMARDs and had an inadequate response to prior NSAID treatment. At baseline, patients were randomized 1:1 into one of two treatment groups: T2T or SoC arms. In the T2T group, patients received SEC 150 mg s.c. weekly until week 4, and then q4w. At week 12, those achieving clinically important improvement (CII) in ASDAS continued the initial treatment, while the remainder (inadequate responders (IR)) received SEC 300 mg s.c. q4w. At week 24, according to the second response assessment (ASDAS CII from baseline), responders continued SEC 150mg or SEC 300mg q4w treatment, and IR switched to adalimumab 40 mg s.c. q2w until Week 36. In the SoC arm, patients received treatment at the investigator’s discretion based on the prevailing standard of care. The primary endpoint of the study was the achievement of ASAS40 response at Week 24 with assumed superiority of the T2T over SoC. Secondary and exploratory endpoints included the achievement of ASAS responses as well as ASDAS low disease activity (ASDAS<2.1), ASDAS inactive disease (ASDAS<1.3) and BASDAI50 at Weeks 12, 24, and 36.Results:A total of 398 axSpA patients were screened, and 304 patients were randomized, 155 into the T2T arm and 149 into the SoC arm. The mean (±SD) age was 39.3±12.1 years, with 64% of patients being males. The symptom duration was 11±10.7 years, 73.4% were HLA-B27 positive, and 61.2% had definite radiographic sacroiliitis. Of the 155 patients randomized to the T2T arm, 64 (41.3%) escalated the SEC dose (150 to 300 mg) at week 12, while 44 (28,4%) switched to adalimumab at week 24. In the SoC arm, a total of 115 patients (77.7%) received TNF-i as starting treatment, 16 (10.8%) received IL-17i, while 11 received csDMARDs and 7 (4.7%) were treated without b/csDMARDs over 36 weeks. The primary endpoint was not met as no statistical difference on ASAS40 response achievement was reported between groups at week 24 (OR 0.69, 95% CI 0.43-1.10; p=0.119; Figure 1). Other endpoints exploring clinical response did not report significant difference between arms (see Figure 1). Post-hoc analysis on the time course of response rates in the treatment sequence SEC150-SEC300 of the T2T group showed that dose escalation for non-responders from week 12 (ΔASDAS CII<1.1) changed response pattern (Figure 2) improving response rate at week 24 for 28% of patients of this subgroup. Safety was comparable across the treatment modalities.Conclusion:With the methodology chosen, the AScalate study did not demonstrate superiority of T2T in axSpA over SoC. Observations are consistent with TICOSPA trial [3]. AxSpA patient care was found to be close to T2T strategy in the participating expert centers. SEC dose escalation was beneficial for approximately one third of patients.REFERENCES:[1] Ramiro S, et al. Ann Rheum Dis 2022;0:1–16.[2] Poddubnyy et al. BMJ Open 2020;10:e039059.[3] Molto et al. Ann Rheum Dis. 2021;80(11):1436-1444.Acknowledgements:NIL.Disclosure of Interests:Denis Poddubnyy AbbVie, Lilly, MSD, Novartis, and Pfizer; has received consultation and/or speaker fees from AbbVie, Biocad, BMS, Gilead, GSK, Lilly, MSD, Novartis, Pfizer, Samsung and UCB, Ludwig Hammel: None declared, Philippe Goupille Abbvie, Amgen, Biogen, BMS, Chugai, Fresenius, Galapagos, Janssen-Cilag, Lilly, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB, Fabian Proft: None declared, Julie BLANCHARD: None declared, Berenice Roesler: None declared, Xenofon Baraliakos AbbVie, BMS, Celgene, Chugai, Hexal, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi and UCB Pharma.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, increased impulsivity and emotion dysregulation. Linkage analysis followed by fine-mapping identified variation in the gene coding for Latrophilin 3 (LPHN3), a putative adhesion-G protein-coupled receptor, as a risk factor for ADHD. In order to validate the link between LPHN3 and ADHD, and to understand the function of LPHN3 in the etiology of the disease, we examined its ortholog lphn3.1 during zebrafish development. Loss of lphn3.1 function causes a reduction and misplacement of dopamine-positive neurons in the ventral diencephalon and a hyperactive/impulsive motor phenotype. The behavioral phenotype can be rescued by the ADHD treatment drugs methylphenidate and atomoxetine. Together, our results implicate decreased Lphn3 activity in eliciting ADHD-like behavior, and demonstrate its correlated contribution to the development of the brain dopaminergic circuitry.

Conventional radiography of the sacroiliac joints is the first imaging method if axial spondyloarthritis (axSpA) is suspected. The presence of definite radiographic sacroiliitis is needed to classify as radiographic (r-axSpA) based on the modified New York Criteria (mNYc). However, the reliability of radiographic sacroiliitis assessment is low, especially if performed locally. Expert central reading for classification purposes in clinical trials is time-consuming and still has high inter-reader variability. A possible solution to detect radiographic sacroiliitis with consistent reproducibility, could be the use of an artificial intelligence analysis of radiographs. Recently an artificial neural network showed an expert-level performance for classification and diagnostic settings[1,2]. The aim of this study was to evaluate the performance of this previously trained artificial network in a completely new cohort of patients previously evaluated as r-axSpA or nr-axSpA by central readers. Baseline radiographs of sacroiliac joints from RAPID-axSpA (NCT01087762, N=277) were evaluated by 3 central reader experts and the majority decision of fulfillment the mNYc was used as a reference. None of the patients nor any of the central readers participated in the studies used to pre-train the artificial network. For performance evaluation of the neural network, the area under the receiver operating characteristic curve (AUROC) was calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the prediction cut-offs were calculated along with their 95% Confidence Intervals (CI) using accelerated bootstrapping. Cohen's Kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers. Baseline characteristics are presented in Table 1. Sensitivity and specificity for the cut-off weighting both measurements were 0.82 (95% CI: 0.78, 0.86) and 0.81 (95% CI: 0.75, 0.87). The Cohen's kappa between the neural network and the reference judgements was 0.61 (95% CI: 0.51, 0.70), and the absolute agreement on the classification yielded 82% (95% CI: 0.78, 0.85). The neural network achieved an 0.89 (95% CI: 0.86, 0.93) PPV and a 0.70 (95% CI: 0.64, 0.77) NPV in recognition of definite radiographic sacroiliitis with AUROC of 0.88 (Figure 1). A pre-trained artificial neural network can enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA close to expert performance. In the present study, the previously trained network showed an excellent ability to generalize data that was completely new to the network. Our results show the potential for classification purposes in multi-center axSpA trials in the future, providing a reproducible and cost-effective tool without unnecessary time delays. [1]Bressem KK, Vahldiek JL, Adams L, et al. Arthritis Res Ther. 2021;23(1):106. [2]Poddubnyy D, Proft F, Hermann KA, et al. Rheumatology (Oxford). 2021;60(12):5868-5869. KKB is grateful for his participation in the BIH Charité Digital Clinician Scientist. Program funded by the Charité–Universitätsmedizin Berlin and the Berlin Institute of Health. Fabian Proft Speakers bureau: AMGEN, Abbie, BMS, Celgene, Jansen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB, Janis Lucas Vahldiek Paid instructor for: Merit Medical, Consultant of: Merit Medical, Joeri Nicolaes Shareholder of: UCB, Employee of: UCB, Rachel Tham Consultant of: UCB, Bengt Hoepken Shareholder of: UCB, Employee of: UCB, Baran Ufuktepe Shareholder of: UCB, Employee of: UCB, Keno Kyrill Bressem: None declared, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, MSD, Moonlake, Novartis, Pfizer, Samsung-Bioepis, UCB [Display omitted] [Display omitted]

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).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).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.

Cadherin-13 (CDH13), a unique glycosylphosphatidylinositol-anchored member of the cadherin family of cell adhesion molecules, has been identified as a risk gene for attention-deficit/hyperactivity disorder (ADHD) and various comorbid neurodevelopmental and psychiatric conditions, including depression, substance abuse, autism spectrum disorder and violent behavior, while the mechanism whereby CDH13 dysfunction influences pathogenesis of neuropsychiatric disorders remains elusive. Here we explored the potential role of CDH13 in the inhibitory modulation of brain activity by investigating synaptic function of GABAergic interneurons. Cellular and subcellular distribution of CDH13 was analyzed in the murine hippocampus and a mouse model with a targeted inactivation of Cdh13 was generated to evaluate how CDH13 modulates synaptic activity of hippocampal interneurons and behavioral domains related to psychopathologic (endo)phenotypes. We show that CDH13 expression in the cornu ammonis (CA) region of the hippocampus is confined to distinct classes of interneurons. Specifically, CDH13 is expressed by numerous parvalbumin and somatostatin-expressing interneurons located in the stratum oriens, where it localizes to both the soma and the presynaptic compartment. Cdh13 −/− mice show an increase in basal inhibitory, but not excitatory, synaptic transmission in CA1 pyramidal neurons. Associated with these alterations in hippocampal function, Cdh13 −/− mice display deficits in learning and memory. Taken together, our results indicate that CDH13 is a negative regulator of inhibitory synapses in the hippocampus, and provide insights into how CDH13 dysfunction may contribute to the excitatory/inhibitory imbalance observed in neurodevelopmental disorders, such as ADHD and autism.

Background:The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has embarked on an initiative to create a consensus definition for difficult-to-treat psoriatic arthritis (D2T-PsA). This condition presents significant challenges in clinical management and necessitates a comprehensive understanding of its intricacies. This survey results will play a crucial role in informing the D2T PsA project.Objectives:This study aims to collate and analyze the perspectives of healthcare professionals, members of GRAPPA, to harness their expertise in PsA. The objective is to integrate their insights into the broader D2T PsA project, contributing to a more robust and informed definition.Methods:Conducted from September to October 2023, an online survey was administered to GRAPPA members using Research Electronic Data Capture (REDCap). It targeted professionals actively managing PsA and consisted of demographic questions, structured queries, and open-ended sections. The structured responses were analyzed descriptively, while thematic analysis was applied to the open-ended responses.Results:The survey collected responses from 223 professionals across 47 countries (Figure 1), including 179 rheumatologists and 40 dermatologists. A notable 82.5% agreed on the necessity for separate definitions of D2T-PsA, characterized by persistent inflammatory activity, and Complex-to-Manage PsA (C2M-PsA), influenced by non-inflammatory factors leading to treatment failure. The factors contributing to D2T- and C2M-PsA varied, albeit with several overlaps. Most respondents (90.5%) agree on including objective signs of inflammation in the definition, with 69.5% supporting imaging methods like ultrasound (51.1%) and MRI (43.4%). However, there was no consensus about the inclusion of laboratory inflammatory markers, with a near-even divide for and against. Criteria for treatment failure varied, with 41.7% favoring the definition of failing at least one conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and two or more biological/targeted synthetic DMARDs (b/tsDMARDs) with different mechanisms of action (Figure 2). The inclusion of csDMARDs was advocated by 66.3% of respondents, while others preferred only b/tsDMARDs in the definition of D2T-PsA.Conclusion:The survey underscores a strong consensus among GRAPPA experts on differentiating D2T-PsA from C2M-PsA, emphasizing the importance of including objective signs of inflammation in the definition of D2T-PsA. The varied opinions on treatment failure criteria highlight the complexity of defining D2T PsA, indicating a need for more nuanced and individualized treatment approaches.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Andre Ribeiro: None declared, Shikha Singla: None declared, Vinod Chandran AbbVie, BMS, Eli Lilly, Janssen, Novartis, UCB, AbbVie, Nicholas Chronis: None declared, Wilson Liao Amgen, Janssen, Leo, and Regeneron, Christine Lindsay: None declared, Enrique R. Soriano Abbvie, Amgen, Bristol-Myers Squibb, Elea, Genzyme, Glaxo, Janssen, Lilly, Montpellier, Novartis, Pfizer, Raffo, Roche, Sandoz, UCB, Philip J. Mease AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, and UCB, Celgene, Corrona, Novartis, AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Gilead, Janssen, Eli Lilly, Merck, Pfizer, Sun, and UCB, Celgene, Novartis, AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, and UCB, Fabian Proft Novartis, Lilly, and UCB

Background:Patients with axial spondyloarthritis (axSpA) often exhibit microscopic intestinal inflammation and are reported to have elevated serum levels of biomarkers indicating a disturbed gut barrier, such as lipopolysaccharide-binding protein (LBP) and zonulin, compared to healthy controls [1].Objectives:To investigate the levels of zonulin, lipopolysaccharide-binding protein (LBP), and calprotectin as markers of disturbed gut barrier, bacterial translocation, and intestinal inflammation in patients with axSpA undergoing TNF inhibitor therapy and to analyze the association between disease activity, clinical response to therapy, and respective biomarker levels.Methods:Patients with radiographic axSpA (r-axSpA) from the German Spondyloarthritis Inception Cohort (GESPIC-AS) were included in this study. GESPIC-AS consists of patients with active disease at baseline, who were either biologic DMARD (bDMARD) naïve or had not been treated with bDMARDs for three months prior to enrollment. All patients began TNF inhibitor (TNFi) therapy post-enrollment. Control patients, selected from the OptiRef Study [2], presented with chronic back pain (CBP) and were confirmed not to have SpA. Serum levels of calprotectin, LBP, and zonulin were measured at baseline and after one year of TNFi treatment in patients with axSpA using commercially available ELISAs. Multivariable logistic and linear regression analyses were conducted to analyze the association between baseline biomarker levels and disease activity at baseline and after 1 year, as well as treatment response after 1 year. Treatment response was defined as a change in ASDAS ≥ 2.0 (major improvement - MI) or ≥ 1.1 (clinically important improvement - CII).Results:125 patients with r-axSpA were compared with 63 CBP controls. At baseline, r-axSpA patients had higher levels of LBP and calprotectin than controls. After one year of TNF inhibitor therapy, serum levels of calprotectin and LBP decreased significantly, with calprotectin normalizing to levels comparable to controls at baseline (Figure 1). Multivariable regression analyses showed an association between baseline LBP and calprotectin serum levels with CRP, ASDAS, and BASFI at baseline; and a negative association between baseline calprotectin levels and BASDAI and ASDAS at year 1 (Table 1). Patients responding clinically to therapy after one year exhibited higher baseline LBP serum levels. Those achieving ASDAS CII also had higher calprotectin levels at baseline. Patients achieving low disease activity (ASDAS LDA) after one year of TNF inhibitor therapy had higher baseline calprotectin levels. Baseline zonulin levels were not significantly associated with disease activity at baseline or year 1, or with treatment response.Conclusion:Patients with active r-axSpA showed higher serum levels of calprotectin and LBP compared to controls with chronic back pain. Serum levels of calprotectin and LBP decreased after one year of TNF inhibitor therapy, demonstrating an association with both clinical response and disease activity.REFERENCES:[1] Ciccia F, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017.[2] Proft F, et al. Comparison of an online self-referral tool with a physician-based referral strategy for early recognition of patients with a high probability of axial spa. Semin Arthritis Rheum. 2020.Figure 1.Serum levels of biomarkers under TNF inhibitor therapy. Serum levels of calprotectin, LBP and zonulin at baseline (BSL) and year 1 (Y1) of patients with radiographic axial spondyloarthritis (axSpA) and of controls with chronic back pain (HD) at baseline. Pairwise comparisons by Man Whitney U Test and Wilcoxon signed rank test. *** p<0.001.Table 1. Association of biomarker serum levels at baseline and disease activity at baseline and year 1 as well as treatment response after one year of TNF inhibitor treatment.Acknowledgements:This study was supported by the MASCARA consortium (FKZ 01EC1903E, Bundesministerium für Forschung und Bildung BMBF).Disclosure of Interests:None declared.

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) To investigate the impact of neuropathic pain and neuroplastic/ widespread pain on residual disease activity in patients with r-axSpA receiving (bDMARDs). 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. 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. [Display omitted] 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. [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. The GESPIC-AS cohort is partially financed by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung - BMBF) 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. Table 1Baseline characteristics.Characteristicn = 70Female sex49(70)Age, years37.27±10.77HLA-B27 positive64(91.4)BMI, kg/m²25.57±4.49Current smokers28(40)Symptom duration, years12.53±10.83Elevated CRP, >5 mg/l43(61.4)ASDAS-CRP3.41±0.82current NSAIDs intake56(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 drugsThe 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.

Background:Chronic back pain with inflammatory features characterizes the manifestations of Axial Psoriatic Arthritis (axPsA). Since no available classification criteria are specifically tailored for axPsA, the ASAS classification criteria for axial spondyloarthritis (axSpA) are commonly used but fail to classify such patients correctly.Objectives:Analysing the ATTRACT study cohort [1], we aimed to identify the proportion and clinical/instrumental features of patients with psoriasis and axial inflammation not fulfilling ASAS entry criteria.Methods:The patient cohort from the ATTRACT study [1] underwent reassessment based on the Dermatologic-Centered Screening tool (DCS) responses [2] and we identified those patients reporting: i) back pain onset after the age of 45 (late-onset back pain, LoBP), and ii) back pain lasting < 3 months (non-chronic back pain, NcBP). This group coined “Non-ASAS Back Pain” (non-ASAS/BP), underwent a complete rheumatologic and imaging assessment, and the results were compared with those of ATTRACT patient’s cohort fulfilling ASAS back pain entry criteria (ASAS/BP). This latter group has been assessed and recently fully described in the ATTRACT study [1].Results:From the ATTRACT cohort [1], 50/265 (18.8%) patients were categorised within the non-ASAS/BP group; specifically, 34/50 (68%) reported LoBP and 16/50 (32%) experienced NcBP.In this overall group, the mean age and the proportion of male gender patients were significantly higher compared to the ASAS/BP group (58.7±18.6 vs 49.2±15.5, and 58.0% vs 39.5%, respectively). Moreover, the non-ASAS/BP group reported a significantly lower prevalence of inflammatory back pain (IBP) than the ASAS/BP group, as defined by both ASAS and Berlin criteria for IBP (22.0% vs 76.6%, and 40.0% vs 79.0%, respectively). Particularly, the non-ASAS/BP patients reported lower occurrences of morning back stiffness, night-time back pain, improvement of back pain with exercises, and radiation to the buttocks. The rheumatologic examination showed similar overall score outcomes in both groups, with no significant differences observed in mean DAPSA, ASDAS-CRP, and BASDAI scores (12.8±9.2 vs 14.5±13.3, 1.64±0.76 vs 1.72±0.87, and 3.54±2.07 vs 4.18±2.37, respectively). However, the serum levels of C-reactive protein (CRP) were significantly higher in the non-ASAS/BP group than in the ASAS/BP group (0.59±0.87 vs 0.33±0.32, respectively), and in the NcBP group than in the LoBP group (1.19±1.44 vs 0.35±0.40, respectively). No relevant differences were observed in the back pain features between the LoBP and NcBP subgroups, except for the higher proportion of ASAS-defined IBP within the NcBP group. Within the non-ASAS/BP group, axPsA was confirmed in 6/50 (12%) patients (5/6 in the LoBP and 1/6 in the NcBP subgroup), while peripheral PsA diagnosis (without axial involvement) was made in 5/50 (10%). The proportion of axPsA patients was significantly lower in the non-ASAS/BP than in the ASAS/BP group (12.0% vs 29.0%, respectively). Among non-ASAS/BP patients diagnosed with axPsA, radiographic sacroiliitis (as per mNY criteria) was detected in 1/6 (16.7%) patients. Active inflammation and structural post-inflammatory changes on MRI were detected in 5/6 (83.3%) and 4/6 (66.7%) patients, respectively, for the sacroiliac joints, and in 1/6 (16.7%) and 2/6 (33.3%) patients, respectively, for the spine. Clinical and imaging data are detailed in Table 1 and Figure 1.Conclusion:This study demonstrates that among patients who experience late-onset or non-chronic back pain, thus not meeting ASAS entry criteria, a considerable proportion may be affected by active axPsA.These findings underscore the need for specific classification criteria tailored to axPsA, which should consider the later onset of back pain and the different clinical features compared with axSpA patients.REFERENCES:[1] Luchetti Gentiloni MM, et al. Rheumatology (Oxford) 2023;10.1093/rheumatology/kead566.[2] Proft F, et al. Ann Rheum Dis 2022;81:1534–40.Acknowledgements:NIL.Disclosure of Interests:Alice Agostinelli: None declared, Valentino Paci: None declared, Ilaria Cimaroli: None declared, Raffaella Sordillo: None declared, Federico Fiorini: None declared, Monia Ciferri: None declared, Marina Carotti: None declared, Francesco Sessa: None declared, Melania Giannoni: None declared, Anna Campanati Abbvie, Almiral, Amgen, Eli Lilly, Janssen, Leofarma, Novartis, Pfizer, Sanofi and UCB., Abbvie, Almiral, Amgen, Eli Lilly, Janssen, Leofarma, Novartis, Pfizer, Sanofi and UCB., Anna Maria Offidani Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB., Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB., Andrea Giovagnoni: None declared, Gabriele Polonara: None declared, Devis Benfaremo: None declared, Ennio Lubrano: None declared, Gianluca Moroncini AbbVie, Janssen, Novartis and Pfizer., AbbVie, Janssen and Pfizer, Fabian Proft Novartis, UCB, AbbVie, AMGEN, BMS, Celgene, Eli Lilly, Janssen, Hexal, Medscape, MSD, Pfizer and Roche, Denis Poddubnyy AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfize, and UCB., AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, Glaxo SmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB, AbbVie, Eli Lilly, MSD, Novartis and Pfizer, Michele Maria Luchetti AbbVie, Amgen, Eli Lilly, Janssen, Novartis and Pfizer., AbbVie, Janssen, Novartis and Pfizer, AbbVie.

BackgroundAxial spondyloarthritis (axSpA) is a chronic rheumatic disease which requires optimal management and disease control. Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40) is a stringent efficacy outcome in clinical trials, while in clinical practice the focus is on the achievement of sustained remission or low disease activity (LDA) according to Ankylosing Spondylitis Disease Activity Score (ASDAS). Patients (pts) can experience loss of response in the long term and maintenance of response is an internationally recommended treatment target.[1]Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL‑17A. BKZ has demonstrated consistent and sustained clinical efficacy to Week (Wk) 52 in pts across the full spectrum of axSpA in the phase 3 studies BE MOBILE 1 and 2.[2]ObjectivesTo report the maintenance of stringent clinical responses through one year of treatment with BKZ in pts with non‑radiographic axSpA (nr-axSpA) and radiographic-axSpA (r‑axSpA, i.e., ankylosing spondylitis)[3] in phase 3 studies.MethodsIn BE MOBILE 1 (NCT03928704; nr-axSpA; pts met ASAS criteria for axSpA) and BE MOBILE 2 (NCT03928743; r‑axSpA; pts fulfilled ASAS and modified New York criteria for r-axSpA), pts were randomised to receive subcutaneous BKZ 160 mg every 4 wks (Q4W) or placebo (PBO) to Wk 16. From Wks 16−52, all pts received BKZ 160 mg Q4W.[4,5]ASAS40 and ASDAS <2.1 (LDA) or <1.3 (inactive disease [ID]) responses to Wk 52 were assessed among BKZ‑randomised pts who responded at Wk 16. Missing ASAS40 data were imputed using non-responder imputation (NRI), and multiple imputation (MI) was used for missing ASDAS data. MI was based on Markov Chain Monte Carlo (for intermittent missing data) followed by monotone regression (for monotone missing data). Observed case (OC) data are also reported. Wk 16 and Wk 52 responder rates for all BKZ-randomised pts are included for context (NRI or MI).The number of treatment-emergent adverse events (TEAEs) to Wk 52 are reported for pts who received ≥1 dose of BKZ, including pts who switched from PBO to BKZ at Wk 16.ResultsA total of 128 and 221 pts were randomised to BKZ 160 mg Q4W in BE MOBILE 1 and 2, respectively. At Wk 16, 47.7% and 44.8% of these pts achieved the primary endpoint, ASAS40, and this increased to 60.9% and 58.4% at Wk 52 (NRI, Figure 1). Of pts that achieved ASAS40 at Wk 16, 82.0% and 83.8% maintained this response at Wk 52 (NRI, Figure 1).ASDAS LDA was achieved by 46.1% and 44.8% of BKZ-randomised pts at Wk 16 of BE MOBILE 1 and 2, respectively; this increased to 61.6% and 57.1% at Wk 52 (MI, Figure 1). Of pts that achieved ASDAS LDA at Wk 16, 88.9% and 88.4% maintained this response at Wk 52 (MI, Figure 1).At Wk 16 of BE MOBILE 1 and 2, ASDAS ID was achieved by 18.8% and 16.4% of BKZ‑randomised pts, respectively; and this increased to 25.2% and 23.4% at Wk 52 (MI). Among Wk 16 ASDAS ID responders, ASDAS ID was maintained by 79.2% and 75.1% at Wk 24, 85.3% and 71.7% at Wk 36, and 88.0% and 58.7% at Wk 52 (MI).To Wk 52 of BE MOBILE 1 and 2, 183/244 (75.0%) and 249/330 (75.5%) pts reported ≥1 TEAE whilst receiving BKZ, respectively; 9 (3.7%) and 20 (6.1%) reported serious TEAEs.ConclusionDual inhibition of IL-17F and IL-17A with BKZ provided robust maintenance of stringent clinical responses from Wk 16 to Wk 52 across the full axSpA disease spectrum. This is consistent with previously reported observations of BKZ treatment over three years in pts with r-axSpA in the phase 2b study BE AGILE and its open-label extension.[6]References[1] Smolen J. Ann Rheum Dis 2018;77:3–17;[2] Baraliakos X. Arthritis Rheumatol 2022;74 (suppl 9);[3] Boel A. Ann Rheum Dis 2019;78:1545–9;[4] Deodhar A. Ann Rheum Dis 2022;81:772–3;[5] van der Heijde D. Ann Rheum Dis 2022;81:12–3;[6] Navarro-Compán V. Presented at EULAR 2022, POS0938.AcknowledgementsThis study was funded by UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma.Disclosure of InterestsFabian Proft Speakers bureau: AbbVie, Amgen, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma, Grant/research support from: Eli Lilly, Novartis and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, Employee of: Director of Imaging Rheumatology BV, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Joerg Ermann Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB Pharma, Grant/research support from: Abbvie, Boehringer Ingelheim, Novartis and Pfizer, Carmen Fleurinck Employee of: UCB Pharma, Ute Massow Employee of: UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Vanessa Taieb Employee of: UCB Pharma, Astrid van Tubergen Speakers bureau: Pfizer, Consultant of: Novartis, Pfizer and UCB Pharma, Grant/research support from: MSD, Novartis, Pfizer and UCB Pharma, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Galapagos, Moonlake, MSD, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and Novartis.