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Background:Systemic diseases most frequently associated with uveitis are spondyloarthritis (SpA). Differences in the presentation of uveitis have been described in each type of SpA, however, this information is contradictory and scarce in the literature. The differentiation of these associated inflammatory processes has important therapeutic and prognostic implications and may condition the treatment of the underlying disease in Ophthalmology/Rheumatology Ocular Inflammation Interdisciplinary Units.Objectives:The aim of the study is to analyze the characteristics of non-infectious ocular inflammation in the different types of spondyloarthritis in a multidisciplinary ocular inflammation practice.Methods:Descriptive observational study including data from patients with a non-infectious inflammatory ocular process secondary to SpA evaluated in a multidisciplinary ocular inflammation consultation from January 2012 to January 2024. Demographic, ocular involvement, sequelae, and therapy data are comparatively analyzed. Quantitative variables were described as median and interquartile range (IQR) or mean and standard deviation (SD), and frequencies were used for the qualitative variables. Comparative analysis was performed using the IBM SPSS 21.0 program and the comparison of proportions using the chi-square test. P-values <0.05 were considered statistically significant.Results:From our “Inflammatory ocular process Registry” at La Paz University Hospital with a total of 564 patients included, we collected data from 147 patients with SpA (26%). Table 1 shows clinical characteristics in the global sample and in the different types of spondyloarthritis. In the comparative analysis, according to the type of spondyloarthritis, significant differences were found in the percentage of positive HLAB27 (p<0.01); being more frequent in ankylosing spondylitis (AS) and axial spondyloarthritis (AxSpA) than in the rest of the groups. The age of onset was significantly higher in AS and psoriatic arthritis (PsA) than in others (p<0.01). Regarding the ocular involvement, significant differences were found (p<0.01) in the pattern and course. Recurrent acute anterior uveitis (RAAU) pattern and the recurrent acute course were predominant in AS, axSpA and PsA. Bilateral acute anterior uveitis (BAAU) pattern and chronic forms were more frequent in peripheral spondyloarthritis (pSpA) and inflammatory bowel disease associated with spondyloarthritis (IbdSpA). Concerning the ophthalmological examination, significant differences (p<0.05) were found in the presence of keratic precipitates (more frequent in AS, axSpA and PsA), vitritis (higher proportion in PsA) and cataract (more frequent in AS, IbdSpA and PsA). No differences were found in sex, location/laterality of the uveitis (anterior and unilateral involvement are predominant in all cases), neither in complications such as visual impairment, synechiae, cystic macular edema, glaucoma, retinal vasculitis, epiretinian membrane or papilitis. Regarding therapy, there were significant differences (p<0.05) in the use of systemic corticosteroids; most commonly used in pSpA and PsA. The use of disease-modifying anti-rheumatic drugs (DMARDs) was also more frequent in pSpA and PsA without reaching statistical significance (p=0.056). There were no significant differences in the use of biological therapy.Conclusion:This study reveals differences in the inflammatory ocular involvement regarding the type of spondyloarthritis. Bilateral and chronic forms of uveitis were more frequently observed in IbdSpA o pSpA. Additionally, the use of systemic steroids and DMARDs was most common in pSpA and PsA.Table 1.REFERENCES:NIL.Acknowledgements:To the Ophthalmology/Rheumatology Ocular Inflammation Interdisciplinary Unit of La Paz University Hospital.Disclosure of Interests:None declared.

ObjectivesColor Doppler ultrasound (CDUS) of the temporal arteries (TA) is becoming the first test to be performed for suspected giant cell arteritis (GCA). Our aim was to assess the added value of including CDUS of large vessels (LV) in the diagnosis of GCA.MethodsWe performed an observational and retrospective study of consecutive patients with suspected GCA. Baseline CDUS of the TA and LV (axillary, subclavian, and carotid) were conducted. We defined the CDUS finding as positive if the halo sign was present.ResultsOf 198 patients with suspected GCA, 87 were eventually diagnosed with GCA: 45 (51.7%) had a cranial pattern exclusively, 31 (35.6%) had both a cranial and an LV pattern, and 11 (12.6%) had an isolated LV pattern. CDUS of the TA had a sensitivity of 83.9%, specificity of 97.3%, and positive and negative predictive values (PPV, NPV) of 96.1% and 88.5%, respectively. When LV was added, sensitivity increased to 96.6% and NPV to 98.2%. Specificity was 97.3% and PPV was 96.6%. As for LVs, the axillary, subclavian, and carotid arteries were involved in 87.8%, 77.4%, and 34.4%, respectively. Isolated axillary examination resulted in a loss of 12.2% of patients with LV involvement; however, inclusion of the axillary and subclavian arteries retained 100% of patients with LV involvement.ConclusionsDetection of GCA by ultrasound should routinely include examinations of the TA and LV (at least the axillary and subclavian arteries) to improve diagnostic accuracy. More than 12% of patients in our cohort had isolated LV involvement. Key Points• Extracranial involvement in GCA is very common: half of patients have extracranial vasculitis and more than 12% isolated LV involvement that can be demonstrated with CDUS.• Adding a CDUS examination of LV to TA increased sensitivity (from 83.9 to 96.6%) and the negative predictive value (from 88.5 to 98.2%) for diagnosis of GCA.• In our cohort, if we only examined the axillary arteries, 12.2% of the CGA with LV involvement would not have been diagnosed.• We propose a CDUS protocol that includes examination of the TA and LV (at least the axillary and subclavian arteries) routinely in cases of suspected GCA.

Background:Difficult-to-manage (D2M) axial spondyloarthritis (axSpA) is an emerging concept, whose definition is yet to be established. The characterisation of these subgroup of patients is relevant, as it may contribute to a broader understanding of the reasons behind treatment failure and to the development of new therapeutic strategies [1].Objectives:To develop a predictive model to forecast patients from the early stages of treatment with b/tsDMARDs.Methods:We analysed data from an observational prospective cohort from La Paz Hospital between 2004-2019 which included patients diagnosed of axSpA initiating a b/tsDMARD, and who fulfilled one of these two definitions: a) D2M: failure to at least 2 b/tsDMARDs, b) good responders (GR): patients remaining their first bDMARD for at least 3 years or withdrawing it because of sustained disease control. Clinical, laboratory, therapy-related information and disease activity measures prior to starting the first b/tsDMARD (baseline), as well as disease activity measures 6-months after initiating it, were collected. Delta-ASDAS was estimated as the difference between baseline and 6-month ASDAS. After excluding the variables with the greater number of missing values, all the variables associated with D2M-axSpA in the univariable regression analyses were selected in order to create Classification And Regression Tree (CART) models. The cohort was randomly split into two independent groups: a training set (80%) and a validation set (20%). Later on, the CART model inputted the most associated factors with D2M-axSpA selecting an optimal cut-off point for classification. Subsequent splits were made, using the Gini index, to divide the population into two branches, until the terminal node. Finally, the model’s performance was assessed using the validation set.Results:Among the 101 patients included in the cohort, 41 (41.6%) were classified as D2M, 59 (58.4%) were male with a mean age of 43 years old. D2M patients were less frequently HLA-B27 positive, had more peripheral manifestations (enthesitis), extra-musculoskeletal manifestations (IBD), comorbidities, and scored higher in composite disease activity indices 6 months after starting a first bDMARD (but did not in baseline indices). Two different CART models were obtained, with a lesser number of patients included in the second model because of the missing values. These 2 models with their cut-off points and the probability of D2M axSpA after each step are shown in Figure 1. The first model (Figure 1, model a) had a pre-test probability of D2M of 44%, and identified BASDAI (cut-off point < 4) after 6 months of therapy with the first bDMARD and age at the beginning of the first bDMARD (cut-off point ≥ 44 years old) as the most relevant factors. The second model (Figure 1, model b) had a pre-test probability of D2M of 47%. It used delta-ASDAS (cut-off point ≥ 1.1) as the variable for the first step, and tender joint count (cut-off point < 1) after 6 months of therapy with the first bDMARD and baseline age (cut-off point ≥ 53) for the second step. After validation, the CART models achieved an AUC of 0.94 (95% CI 0.87-1) and 0.83 (95% CI 0.67-1), respectively, and both of them classified properly 83% of the patients.Conclusion:This study identified two predictive models, which may be applied using everyday information, and could identify D2M-axSpA patients only after the first 6 months of bDMARD therapy. Next step will involve further validation in an external cohort.REFERENCES:[1] Wendling D, Verhoeven F, Prati C. Is the Difficult-to-Treat (D2T) concept applicable to axial spondyloarthritis? Joint Bone Spine. 2023;90(3):105512.Figure 1.CART models predicting D2M-axSpA. The value at each node represents the most frequently expected outcome (D2M in red or GR in green).GR: good responders, D2M: difficult-to-manage, BASDAI: Bath Ankylosing Spondylitis Disease Activity, ASDAS: Ankylosing Spondylitis Disease Activity Score, TJC: tender joint count.Acknowledgements:NIL.Disclosure of Interests:Manuel Juárez: None declared, Diego Benavent Eli Lilly, Janssen and UCB Pharma, Victoria Navarro-Compán Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma, AbbVie, Eli Lilly, Galapagos, Moonlake, MSD, Novartis, Pfizer and UCB Pharma, AbbVie and Novartis, Mariana Díaz-Almirón: None declared, Marta Novella-Navarro UCB, Lilly, Galapagos and Janssen, Diana Peiteado: None declared, Alejandro Villalba Janssen, Irene Monjo-Henry Roche, Novartis, UCB and Gedeon Richter, Laura Nuño: None declared, Alejandro Balsa AbbVie, Amgen, Pfizer, Galapagos, Novartis, Gilead, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB and Roche, Chamaida Plasencia-Rodríguez AbbVie, Pfizer, Novartis, Lilly and Roche.

Background:Since the publication of difficult-to-treat rheumatoid arthritis (D2TRA) criteria1, several studies have attempted to establish the most appropriate pharmacological and non-pharmacological strategies for the management of these patients. However, data on the treatment of choice for patients who become D2TRA are still scarce.Objectives:To evaluate the survival of different biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling the D2TRA criteria. To assess clinical factors related to the survival of these treatments.Methods:This retrospective cohort study included D2TRA patients according to EULAR definition. Sociodemographic characteristics, clinical and serological features and disease activity data were collected at the start of the 1st b/tsDMARD. The DAS28 was also collected at the start of the following treatment after meet D2T classification and at 6 months and patients were followed-up at least for one year. Drug retention of the subsequent line of b/tsDMARD was assessed by Kaplan–Meier plots using the log-rank test. Predictive factors affecting the discontinuation were evaluated using the univariate and multivariate analysis by the Cox proportional hazard model.Results:Of the 122 patients included, 75 maintained active treatment (61.5%) with the subsequent line after D2T compared to 37 patients (38.5%) who discontinued this treatment and required more sucessive lines of b/tsDMARDs. The treatments used after D2T were TNFi (17 patients), anti-IL6R (31 patients), abatacept (27 patients), rituximab (27 patients) and JAKi (20 patients). The mean survival of the treatments was 78.3 ± 7.6 months and the percentage of patients who maintained the treatment after D2T was 29.4% for TNFi, 29.6% for abatacept, 74.2 % for anti-IL6R, 88.9 % for rituximab and 75.0% for JAKi.Significant differences were assessed between different b/tsDMARDs (log-rank p<0.01) (Figure 1). To evaluate these differences, a Cox regression was performed taking each b/tsDMARD as a reference and comparing with the others. The main differences were found between TNFi and abatacept with rituximab, meanwhile, anti-IL6R and JAKi did not show significant differences (Table 1).Table 1.line of DMARDTNFianti-IL6RAbataceptRituximabJAKiTNFi-0.030.65<0.010.03Anti-IL60.03-<0.010.110.98Abatacept0.98<0.01-<0.01<0.01Rituximab<0.010.11<0.01-0.13JAKi0.030.98<0.010.13-DAS28 values 6 months after initiation of the subsequent b/tsDMARD were higher in those patients who discontinued versus those who remained on treatment [4.4 (1.2) vs 3.5 (1.3), p= 0.01]. No significant differences were found in age at diagnosis or at initiation of the 1st b/tsDMARD, neither for previous or concomitant treatments, extra-articular manifestations, erosions or serological status. A multivariate Cox regression model was performed in which the subsequent treatment after D2T [HR=1.26 (95%CI 1.06-1.05)] and higher DAS28 values at 6 months [HR=1.41 (95%CI 1.15-1.72)] were independent risk factors associated with discontinuation of this treatment.Conclusion:Once patients meet D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival is rituximab, followed by JAKi and anti-IL6R being TNFi and abatacept the choices with leass retention rate. Moreover, the DAS28 in the first 6 months of starting the treatment after D2T was an independent risk factor for drug survival.REFERENCES:[1] Nagy G et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31-5.Figure 1.Survival plot for each line of treatment after fulfilling D2TRA classificationAcknowledgements:NIL.Disclosure of Interests:Marta Novella-Navarro Lilly, UCB, Galapagos and Amgen, Virginia Ruiz: None declared, Natalia López-Juanes: None declared, Chafik Alejandro Chacur: None declared, Irene Monjo-Henry Lilly, UCB, Abbvie, Laura Nuño: None declared, Monica Giselle Kafati Sarmiento: None declared, Diana Peiteado: None declared, Alejandro Villalba: None declared, Elisa Fernández-Fernández: None declared, María Sanz-Jardón: None declared, Raimon Sanmarti: None declared, Chamaida Plasencia-Rodríguez Lilly, UCB, Amgen, Galapagos, Pfizer, Alejandro Balsa Roche, Lilly, Abbvie, Galapagos, UCB, Pfizer.

BackgroundDespite pharmacological options for axial spondyloarthritis (axSpA) have increased recently, still one out of three patients do not achieve the recommended target [1].ObjectivesTo determine patient and disease characteristics in patients with “difficult to treat” (D2T) axSpA in comparison with “good responders” (GR) and to identify predictive factors of D2T-axSpA.MethodsData from an observational prospective cohort recruiting consecutively patients diagnosed of axSpA initiating the first bDMARD from La Paz Hospital between 2004-2019 were analysed. Patients who fulfilled one of the following definitions were included: i) D2T: failure to at least two b/tsDMARDs, ii) GR: patients remaining treated with the first bDMARD for at least 3 years or stopping it due to disease control. Clinical characteristics, laboratory tests, concomitant treatment and disease activity measures prior to starting the first bDMARD and after 6 months were collected. Also, b/tsDMARD courses were registered. Chi-square or Fisher test were used for qualitative variables and unpaired t-student was used for quantitative variables. Univariable and multivariable logistic binary regression analyses were used.ResultsOut of 101 patients included, 41.6% were classified as D2T and 58.4% as GR. When initiating the first bDMARD, compared with GR, D2T patients had statistically significant shorter symptom duration and more frequently enthesitis, inflammatory bowel disease (IBD), concomitant NSAIDs, smoking habit and comorbidities (hypertension, dyslipidemia, depression or anxiety and fibromyalgia), all p<0.05 (Table 1). However, no significant differences were found in age, sex, BMI, subtype of axSpA, dactylitis, peripheral arthritis, uveitis, psoriasis, concomitant csDMARDs, diabetes mellitus or cardiopathy. While no differences were found for disease activity composite measures (ASDAS, BASDAI) and CRP or ESR, D2T patients had greater scores in BASDAI questions for pain and morning stiffness, TJC, PtGA and PhyGA. After 6 months of starting the first bDMARD, the scores for all disease activity measures, including ASDAS, BASDAI, CRP and ESR were significantly higher in D2T patients. Reasons for b/tsDMARDs discontinuation in D2T patients are shown in Figure 1. In multivariable analysis, smoking habit (OR=6.5, p<0.05), HLAB27 negative (OR=5.8, p<0.05), enthesitis (OR=48.1, p<0.01), baseline TJC (OR=1.2, OR<0.05) and baseline PhyGA (OR=1.05, p<0.05) were independently associated with D2T.ConclusionCompared with GR, patients with D2T-axSpA have more frequently poor prognostic factors for therapy response (smoking and HLAB27 negative) and worse response to first bDMARD after 6 months. Further strategies to implement recommendations for not smoking and control of comorbidities should be implemented.Reference[1]Smolen JS, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2018.Table 1.Stratified characteristics. Results are shown as absolute numbers (%) or mean ± standard deviation.GR (n=59)D2T (n=42)p valueSymptom duration until first bDMARD (year)10.5±10.75.5±7.7<0.01Current smoking habit7 (11.9)13 (31)<0.05HLAB27 +48 (82.8)27 (64.3)<0.05Enthesitis35 (59.3)40 (95.2)<0.001IBD2 (3.4)6 (14.3)<0.05ComorbiditiesHypertension15 (25.4)20 (47.6)<0.05Dyslipidemia23 (39)28 (66.7)<0.01Depression or anxiety14 (23.7)23 (54.8)<0.01Fibromyalgia1 (1.7)6 (14.3)<0.05Concomitant NSAIDs43 (81.1)35 (97.2)<0.05BaselineASDAS3.3±13.6±0.90.2BASDAI5.6±2.16.4±1.70.06BASDAI-spinal pain6.4±2.77.5±2.1<0.05BASDAI-stiffness severity5.9±2.87.1±2.5<0.05BASDAI-stiffness duration4.7±2.76.1±2.8<0.05TJC1.1±2.74.4±6.7<0.01PtGA59.9±22.470.4±18.7<0.05PhyGA39.9±19.750±20.2<0.056-monthASDAS1.6±0.92.8±1.1<0.001BASDAI3.3±2.15.4±2<0.001CRP (mg/L)1.7±2.75.9±7.9<0.01Figure 1.Reasons for b/tsDMARD discontinuation in D2T-axSpA.Disclosure of InterestsManuel Juárez: None declared, Diego Benavent Speakers bureau: Janssen, Roche, Galapagos, Grant/research support from: Novartis, Abbvie, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie and Novartis, Marta Novella-Navarro Speakers bureau: Galapagos, UCB, Lilly and Janssen, Grant/research support from: UCB, Lilly and Janssen, Diana Peiteado: None declared, Alejandro Villalba: None declared, Irene Monjo Speakers bureau: Roche, Novartis, UCB, Gedeon Richter, Consultant of: Roche, Laura Nuño: None declared, Alejandro Balsa Speakers bureau: Pfizer, Abbvie, Lilly, Galapagos, BMS, Sandoz, Nordic Pharma, Gebro, Roche, Sanofi, UCB, Consultant of: Pfizer, Abbvie, Lilly, Galapagos, BMS, Nordic Pharma, Sanofi, UCB, Grant/research support from: Pfizer, Abbvie, BMS, Nordic Pharma, Gebro, Roche, UCB, Chamaida Plasencia Speakers bureau: Pfizer, Abbvie, Lilly, Sandoz, Sanofi, Biogen, Roche, Novartis, Grant/research support from: Pfizer and Abbvie.

BackgroundCD4+CXCR5+PD-1hi follicular helper (Tfh) T cells typically dwell in the germinal centers (GCs) of lymphoid organs, provide help to autoantibody secreting B cells and play an important role in the pathogenesis of Rheumatoid Arthritis (RA). Circulating counterparts of Tfh (cTfh) cells have been described in human peripheral blood, their frequencies seem to correlate with the pool of prototypical GC Tfh cells, and are expanded in patients with autoimmune conditions including RA. Abatacept (ABT), by interfering with costimulation, can restrain the generation of Tfh cells. The pathogenic implication of Tfh cells may be more prominent in RA patients with higher cTfh cell frequencies and these subjects could be more likely to respond to therapeutic costimulation blockade with ABT.ObjectivesTo examine a). The effect of treatment escalation using TNF blockers (TNFb) or ABT, on the frequency of cTfh cells in RA, and b). The relation of the baseline cTfh cell frequency with the clinical response.MethodsPeripheral blood was drawn from seropositive RA patients with an incomplete response to csDMARDS (n=41) who initiated biological therapy, according to routine clinical practice, with TNFb (n= 19) (10 Etanercept, 3 Adalimumab, 3 Certolizumab, 2 Golimumab, 1 Infliximab) or ABT (n= 22). cTfh cell frequencies were determined by flow cytometry of freshly isolated PBMCs at the basal visit and 12 months (12M) after starting treatment escalation. For each patient, an age and gender-matched healthy control (HC) was also studied at both time points (n=41).Resultsa). Effect of treatment escalation on the cTfh cell frequency. As compared with HC, RA patients receiving csDMARDs demonstrated an increased frequency of cTfh and also of activated ICOS+ cTfh cells (a-cTfh), and this was observed in both treatment escalation groups. A significant improvement of disease activity (ΔDAS28 >2.0) was apparent in all of the patients at 12M. Nevertheless, the cTfh cell frequency did not vary in patients receiving TNFb; conversely, in subjects receiving ABT it significanly decreased to HC levels. At the same time, the frequency of a-cTfh cells was significantly reduced in both groups; however, in the TNFb group it remained above HC whereas in the ABT group it reached magnitudes comparable to HC. b). Relation of the baseline cTfh cell frequency with the clinical response. In the ABT group, the baseline frequencies of cTfh and a-cTfh had been higher for patients who went on to achieve remission at 12M (12Mr), as compared with those who remained active (12Ma) [Tfh logistic regression OR for remission 25.3, 95% CI (12.2-39.8); ROC AUC 0.94(0.83-1), p<0.0005]; as stated above, the 12M frequencies were no longer elevated; in addition there were no differences between the 12Ma and 12Mr subjects. Conversely, in the TNFb group, the baseline frequencies of cTfh and a-cTfh had been lower for 12Mr as compared with 12Ma patients [Tfh OR for not achieving remission 8.5 (4.3-15.5); ROC AUC 0.77(0.54-0.99), p<0.05]; furthermore, the 12M frequencies showed the same pattern: they had not significantly changed, persisted elevated above HC and remained lower in 12Mr as compared with 12Ma patients. The baseline cTfh cutoff frequency for achieving remission in the ABT group was >0.35% (sensitivity 92.7%, specificity 90%). The baseline cTfh cutoff frequency for not achieving remission in the TNFb group was >0.44% (sensitivity 67.7%, specificity 90%).ConclusionABT but not TNFb, is able to curtail cTfh cell numbers in RA, suggesting that costimulation blockade can restrain germinal center overactivity. Higher baseline cTfh cell frequencies predict a good response to ABT and at the same time, a poor response to TNFb. Therefore, immunophenotyping of patients with an incomplete response to csDMARDs can facilitate a personalized therapeutic strategy for treatment escalation.References[1]Vinuesa CG, Cook MC. Immunity. 2011[2]Craft J, Nat Rev Rheumatol 2012[3]Arroyo-Villa I et al., Arthritis Res Ther 2014[4]Aldridge J, et al. Rheumatology (Oxford) 2022.Acknowledgements:NIL.Disclosure of InterestsIrene Monjo: None declared, Beatriz Nieto-Carvalhal: None declared, Mariela del Carmen Uyaguari: None declared, Alejandro Villalba: None declared, Laura Nuño: None declared, Diana Peiteado: None declared, Elisa Fernandez: None declared, Sara Garcia-Carazo: None declared, Alejandro Balsa Grant/research support from: BMS, Gebro Pharma, Maria-Eugenia Miranda-Carus Grant/research support from: BMS, Gebro Pharma.

BackgroundObesity has been associated with the response to biologic disease modifying anti-rheumatic drugs (bDMARDs). Obese patients have lower response to anti-TNF drugs than to other cytokine-targeted drugs, such as anti-IL6[1]. IL6 receptor inhibition is effective in the treatment of rheumatoid arthritis (RA), and there are two ways of administration: intravenous (IV) weight-adjusted tocilizumab and subcutaneous (SC) fixed-dose tocilizumab or sarilumab. However, evidence regarding the influence of body mass index (BMI) and these different routes of administration is still scarce.ObjectivesTo analyze the role of BMI in the clinical response to antiIL6 therapy in its different routes of administration in patients with RA. To perform an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment.MethodsThis study involved 65 patients with RA starting IV tocilizumab at 8mg/kg every 4 weeks or SC antiIL6: tocilizumab 162mg/week or sarilumab 200mg/14days. Demographic and clinical characteristics before antiIL6 initiation (age, sex, smoking habit, age at diagnosis, concomitant and previous treatments and BMI) were collected. Laboratory parameters such as rheumatoid factor and anti-citrullinated peptide antibody were also assessed. Adipokine serum levels (leptin and adiponectin) were measured at baseline and after 6 months (6M) of treatment. Clinical response to treatment was assessed by Clinical Disease Activity Index (CDAI) 6M after initiation of the bDMARD. Differences between variables were assessed using the X2 test and Mann-Whitney test. Correlations between BMI, adipokines and other quantitative variables were assessed using the Pearson or Spearman coefficients. P-values <0.05 were considered statistically significant.ResultsForty seven patients started IV antiIL6 (72.3%) and 18 SC (27.7%). Thirty six (55.4%) achieved low disease activity (LDA)/remission by CDAI: 24 patients from the IV group (51.4%) and 12 (66.7%) from the SC group without significant differences (p=0.19). No differences between BMI or serum adipokine levels were associated with the achievement of LDA/remission when patients were stratified according to the route of antiIL6 administration.Leptin levels in both groups (SC and IV) were very similar at baseline and 6M and regarding changes on adipokine profile between baseline and 6M, we observed a decrease in leptin and an increase in adiponectin levels both in SC and IV (Table 1).Serum adipokine levels (ng/mL)Route of administrationbaseline6 monthspivLeptin18.6 (10.4-30.9)16.9 (7.2-29.2)0.22Adiponectin18310(13250-33890)20610 (12690-33650)0.39scLeptin17.9 (10.1-27.4)16.3 (7.6-30.7)0.22Adiponectin28750 (20570-4394)33350 (24157-49862)0.35BMI showed a significant positive correlation with leptin, overall and stratifying by route of administration, both at baseline and 6M. Adiponectin did not show a significant correlation with BMI.Figure 1.ConclusionObesity and serum adipokines did not show association with the achievement of LDA/remission in patients treated with antiIL6 regardless the route of administration. Furthermore, IV and SC treatments could be used both in obese and normal-weight RA patients expecting the same efficacy.Reference[1]Novella-Navarro et al. Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines. Clin Exp Rheumatol. 2022 Sep;40(9):1726-1732.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Rituximab (RTX) is a chimeric monoclonal antibody against CD20 receptor, used in the treatment of rheumatic diseases. Hypogammaglobulinemia has been described as an adverse event. It has been reported that hypogammaglobulinemia is more frequent in patients with ANCA-associated vasculitis (AAV).Objectives:To study the basal characteristics of patients with AAV and rheumatoid arthritis (RA) in treatment with RTX and to analyze the risk factors of hypogammaglobulinemia.Methods:Retrospective observational study of patients treated with RTX. Patients diagnosed with AAV and RA with immunoglobulin levels prior to treatment and after each cycle were included. Clinical and demographic variables were analyzed. Both populations were compared using t-Student for continuous and chi-squared for categorical variables. The influence of the basal characteristics of the patients was analyzed using univariate and multivariate logistic regression models.Results:Among the 86 included patients, 10 (11.6%) had AAV and 76 (88.4%) RA. Patient’s characteristics stratified by disease are included in Table 1.Table 1.Characteristics of patients treated with RTX, according to their underlying disease.Overall sample n=86ARn=76VAAn=10pAge at diagnosis, years m±SD57 ± 1256 ± 1263 ± 110,11Disease progression, years m±SD11,5 ± 913 ± 91 ± 1< 0,001Female n/N (%)66/86 (76,6)60/76 (78,9)6/10 (60)0,18IGG <725 prior to initiation of treatment n/N (%)10/86 (11,6)4/76 (5,3)6/10 (60)< 0,001IgG < 600 n/N (%)12/86 (14)4/76 (5,3)8/10 (80)<0,001IgG <400 n/N (%)2/86 (2,3)02/10 (20)<0,001IgM Hipogamaglobulinemia n/N (%)26/86 (30,2)17/76 (22,4)9/10 (90)<0,001Pretreatment with non-antiTNF biologics n/N (%)25/86 (29,1)24/76 (31,6)1/10 (10)0,15Pretreatment with antiTNF n/N (%)60/86 (69,8)59/76 (77,6)1/10 (10)<0,001Pretreatment with FAMES n/N (%)80/86 (93)72/74 (94,7)8/10 (80)0,08Pre-treatment with JAK inhibitors n/N (%)11/86 (12,8)11/76 (14,5)00,19Cyclophosphamide pretreatment n/N (%)3/86 (3,5)03/10 (30)< 0,001Infections n/N (%)21/86 (24,4)15/76 (19,7)6/10 (60)0,02Severe infection n/N (%)7/86 (4,6)1/76 (1,3)3/10 (30)< 0,001Cumulative dose of steroids one year prior m±SD2923 ± 30032227 ± 18986199 ± 4621< 0,001Cumulative dose of steroids during treatment m±SD2626 ± 23532303 ± 19135668 ± 39970,002The overall sample was divided into two groups, patients who developed hypogammaglobulinemia and patients who did not. Of the 12 patients who developed hypogammaglobulinemia, 4 had RA and 8 AAV (p<0.001). In the univariate analysis, patients who developed hypogammaglobulinemia presented higher age at diagnosis (61 ± 15 vs 43 ± 11 years, OR=1.14 p<0.001), shorter time of disease progression (4.9 ± 8 vs 12.6 ± 9 years, OR=0.86 p0.02) and lower gammaglobulin rates at baseline (744 ± 504 vs 1145 ± 295 OR=0.16 p0.006). There were more severe infections in the group of patients with hypogammaglobulinemia than in the group without it (1/4 [25%] vs 1/74 [1.4%], OR=0.42 p<0.001). Patients with hypogammaglobulinemia received a higher cumulative dose of steroids during treatment (OR=1,000 p 0.019). Within the RA group, patients with hypogammaglobulinemia also received a higher cumulative dose of steroids (p 0.009).In the multivariate study, only age at the beginning of treatment (OR=1.1 p=0.020) remained a risk factor for the appearance of hypogammaglobulinemia.Conclusion:A significantly higher percentage of hypogammaglobulinemia is observed in patients with AAV treated with Rituximab, compared to patients with RA. The development of hypogammaglobulinemia seems to be influenced by age at diagnosis, years of disease progression, IgG levels prior to initiation of treatment and a higher cumulative dose of glucocorticoids (targeted in both the overall sample and the RA group). In addition, there is a higher frequency of severe infections in the hypogammaglobulinemia group. Studies with larger sample sizes are needed to confirm these results.Disclosure of Interests:María Sanz: None declared, Gemma Bonilla: None declared, Diana Peiteado: None declared, Diego Benavent: None declared, Chamaida Plasencia: None declared, Laura Nuño: None declared, Irene Monjo: None declared, Alejandro Villalva: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz

Methotrexate (MTX) remains the first line of treatment in Rheumatoid Arthritis (RA)1,2. Inhibition of AICAR transformylase by MTX results in augmented release of adenine nucleotides to the extracellular space1; these are rapidly hydrolysed by the combined action of ectonucleotidases CD39 and CD79 rendering the antiinflammatory agent adenosine1. CD39, the rate-limiting enzyme in this cascade, is highly expressed by a subset of human FoxP3+CD4+ regulatory T cells (Treg39+)2-4 and MTX may act synergistically with Tregs in the control of inflammation. To study the expression of CD39 on circulating Treg cells of untreated early Rheumatoid Arthritis (ERA) patients and its relation with the ex vivo effect of MTX. Peripheral blood was drawn from 22 DMARD- and steroid- naïve ERA patients with a disease duration < 24 weeks, 15 longstanding RA patients (LRA, disease duration > 2 years) and 37 age and gender-matched healthy controls (HC). LRA patients were receiving low-dose weekly MTX and were naïve for biologicals. 10 ERA patients who had achieved remission 12 months after initiating MTX donated blood for a second time (ERA-R). The frequency of Treg and Treg cell subsets was assessed by flow cytometry. CD4+CD25+CD127- (total T reg), CD4+CD27+CD127-CD39+ Treg (Treg39+) and CD4+CD25-CD39- responder T (Tresp39-) cells were isolated by Ficoll-Hypaque, followed by sorting. The suppressor potency of Tregs was assessed in cocultures of isolated Tregs with Tresp, established at different Treg/Tresp ratios. Proliferation was determined by CFSE dilution; cytokine secretion was measured by ELISA of culture supernatants. As previously described5, ERA but not LRA patients demonstrated a superior frequency of circulating Treg (CD4+CD25+CD127-FoxP3+) cells. In addition, the proportion of Tregs that expressed CD39 (Treg39+) was significantly increased in ERA but not LRA. Total ERA Tregs were significantly more potent suppressors of proliferation, TNFα and IFNγ secretion when compared with HC or LRA Tregs, and this difference was partially and significantly abrogated in the presence of adenosine deaminase, or the adenosine A2A receptor (A2AR) antagonists DMPX (3,7-dimethyl-1-propargylxanthine) or ZM 241385, but not in the presence of the adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-dipropylxanthine). When MTX was added to the culture medium, the suppressor potency of total Tregs was further enhanced in all 3 groups of patients, and this enhancement was significantly higher in ERA total Treg/Tresp39- cocultures as compared with HC or LRA total Treg/Tresp39- cocultures. The effect of MTX was also partially and significantly abrogated by adenosine deaminase, DMPX or ZM 241385 but not by DPCPX. We then tested the suppressor potency of isolated Treg39+ together with the enhancer effect of MTX on this potency, and observed that there were no longer differences among ERA, LRA and HC; this further suggests that the differences observed in assays using total Tregs can be attributable to the increased Treg39+ proportions present in ERA. The frequency and function of ERA-R Treg cells were not different from HC or LRA Tregs. The suppressor action of CD39+Tregs is mediated at least in part by adenosine trough A2AR ligation, and the superior suppressive potency of total ERA Tregs is associated with their higher proportion of TregCD39+ cells as compared with HC or LRA. In addition, the augmented suppressor effect observed in the presence of MTX is partly mediated by an increased adenosine production acting on A2AR and is more marked in ERA patients reflecting again their higher proportion of Treg39+ cells. This indicates that MTX cooperates with Treg39+ cells in the control of inflammation. [1]Montesinos MC, et al. Arthritis Rheum. 2007. [2]Peres RS, et al. Proc Natl Acad Sci U S A. 2015. [3]Deaglio S, et al. J Exp Med. 2007. [4]Borsellino G, et al. Blood. 2007. [5]Benito-Miguel M, et al. J Immunol. 2009. FIS PI 20/00141; FIS RD16/0012/0012; Fondo Europeo de Desarrollo Regional (FEDER), unrestricted research grant from Gebro Pharma Laura Nuño: None declared, Alejandro Villalva: None declared, Marta Novella-Navarro: None declared, Irene Monjo: None declared, Diana Peiteado: None declared, Sara García-Carazo: None declared, Amaya Puig-Kröger: None declared, Alejandro Balsa Grant/research support from: BMS, Gebro Pharma, Maria-Eugenia Miranda-Carus Grant/research support from: BMS, Gebro Pharma

BackgroundAs a result of the development of the ASAS criteria for axial spondyloarthritis (axSpA), a new entity (non-radiographic axSpA –nr-axSpA) was created. In some countries major concerns have been raised with regard to this entity because this could imply administrating TNF inhibitors (TNFi) to non-SpA patients. Especially the possibility of treating women with fibromyalgia has been mentioned.ObjectivesTo evaluate if the gender distribution and the pattern of patients have changed in clinical practice since TNFi were approved for nr-axSpA.MethodsDataset from a prospective cohort including all patients with axSpA treated with biological therapy (BT) since 2000 till August-2017 in a tertiary hospital was analysed. Patients’ and disease’ characteristics and disease activity parameters were collected at baseline. Based on the starting date for the first BT, patients were classified in two groups: i) before 2013 and ii) during or after 2013, since the nr-axSpA approval-date for TNFi in the country was July 2012. Gender distribution and other characteristics were compared between both groups using Chi-square and Student-t tests.ResultsIn total, 385 axSpA patients initiated BT. Out of these, 266 initiated BT in period i) and 119 in period ii). The characteristics of patients in both groups are depicted in table 1. Importantly, no differences between period i) and ii) were observed regarding gender distribution (38% and 39% of women; p=0.8, respectively). Additionally, during period ii), the percentage of patients with nr-axSpA was similar for both genders and out of all patients with nr-axSpA, the majority (60%) were men. Overall, disease duration was shorter in period ii for both genders. Women in period ii) had significantly higher ASDAS, BASMI and CRP than women in period i) and higher ASDAS, BASDAI and BASFI than men in period ii).Abstract OP0322 – Table 1Patients characteristics stratified for starting first TNFi period and genderConclusionsIn clinical practice, the frequency of women initiating BT have not increased since its approval for nr-axSpA. Additionally, women treated nowadays with BT have more objective parameters of disease activity than they used to do. This supports that when treating axSpA women (including nr-axSpA) with BT, we are currently treating axSpA -and not fibromyalgia- patients.Disclosure of InterestNone declared