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Background:In 2017, TOCILIZUMAB (TCZ) obtained marketing authorization for treatment of giant cell arteritis (GCA); however, this doesn’t extend to polymyalgia rheumatica (PMR) therapy. Based on efficacy data for TCZ in GCA, TCZ is sometimes used as a glucocorticoid (GC) sparing agent when PMR is GC dependent or when a rapid steroid withdraw is needed. Currently, there are no available recommendations on the use of this therapeutic class in for this particular indication.Objectives:Here, we present the results of an observational French multicentric study of patients with PMR treated with TCZ.Methods:Thirteen medical centers were included in this study. The data was collected retrospectively between 2015 and 2020. The minimum duration of treatment was 3 months. Patients were included when receiving TCZ for isolated PMR or associated with a non-active GCA (asymptomatic, no vascular fixation on PET scanner).Results:Overall, 34 patients were included (24 women; mean age 70.1 years (+/-10.3)). At TCZ introduction, patients had been treated with GC for a mean duration of 27,9 months (+/-25.9) and the mean GC dose was 16,8mg/d (+/-10). Fifteen patients (44%) had one or more complications from GC therapy. Another immunosuppressant was added before TCZ treatment for 25 (74%); mostly METHOTREXATE (24/25).TCZ was initiated intravenously at 8mg/kg every 4 weeks for 27 patients (79%) and subcutaneously at 162mg/week for 7 patients (21%).The reasons for TCZ introduction included GC dependence (n=30, 88%), and necessity of quick GC sparing (n=4 patients,12%).Of all patients, 76% (26 patients) had stopped GC treatment definitively, with a mean time of 9,4 (0-32) months.The mean TCZ treatment period was 19,2 months (3-66). Fifteen patients (44%) permanently stopped TCZ at the end of the observation period (8 prolonged remissions;1 myocardial infarction; 1 cutaneous lymphoma; 1 primary failure, 3 lost to follow up).Eighteen patients (60%) benefited from an attempted tapering of TCZ (infusion spacing or dose reduction), 6 attempts (1/3) led to a relapse. 1/2 patients had side effects mostly benign (cytopenia n=6, infections n=5).Conclusion:This is the largest cohort presenting results of the use of TCZ in PMR. Despite the small number of participants, our study suggests TCZ is effective as a GC sparing agent in PMR. As there are no official recommendations of use, indications for TCZ use within this population are no defined. Randomized Controlled Trial would be beneficial to validate these first results.References:[1]Toussirot, « Biothérapies, pseudo- polyarthrite rhizomélique et artérite à cellules géantes État des lieux en 2018 ».[2]Devauchelle-Pensec et al., « Efficacy of First-Line Tocilizumab Therapy in Early Polymyalgia Rheumatica ».[3]Genovese et al., « Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis ».[4]Stone et al., « Trial of Tocilizumab in Giant-Cell Arteritis ».Disclosure of Interests:None declared

Background:IL17 inhibitors (IL17i) are an alternative for patients with axial spondyloarthritis (axSpA) who did not respond to TNF inhibitors (TNFi). Secukinumab (SEC) is the first human monoclonal antibody that binds to the protein interleukin-17A.Objectives:The objectives of this study were to describe the characteristics of axSpA patients treated with IL17i and TNFi and to assess the persistence with IL17i and TNFi in a real world cohort.Methods:A retrospective multicenter observational study was conducted. axSpA patients (pts) according to ASAS criteria initiating a IL17i or TNFi between June 2016 and December 2019 were included. Demographic features, current and previous use of biologic Disease-modifying antirheumatic drugs (bDMARDs) were collected. Date and reasons of discontinuation – i.e., lack of efficacy, safety issue, sustained remission or others – were collected. Kaplan-Meyer analysis were performed.Results:370 pts were included. Among the 202 patients who received TNFi, 90 (44.6%) were female, mean age was 43.2 +/- 13.2 years, mean body mass index was 26.1 kg/m2 +/- 5.4, 49 pts (46.7%) were smokers. The most common SpA phenotype was axial radiographic (n = 89, 54,9%) and 114 (68.3%) pts were HLA B27 positive, mean BASDAI was 57.5 +/- 14.6, median disease duration was 8.6 years [3.0-10.5]. Among the 168 patients who received SEC, 78 (46.4%) were female, mean age was 47.7 +/- 11.8 years, mean body mass index was 27.2 kg/m2 +/- 5.8, 45 pts (44.1%) were smokers. The most common SpA phenotype was axial radiographic (n = 106, 76,3%) and 114 (78.1%) pts were HLA B27 positive, mean BASDAI was 62.8 +/- 14.8, median disease duration was 9 years [5.0-19.0]. TNFi was the first line bDMARD in 116/202 pts (57.4%) and SEC was the first line bDMARD in 15/168 pts (8.9%). SEC was prescribed at 150mg every month in 121/168 (73.3%) pts. The median persistence with TNFi and SEC were 18.0 months [11.0-27.0] and 12.0 months [6.0-22.0], respectively. During the 3-year follow-up, 130 pts (42 with TNFi and 88 with SEC) discontinued treatment: 80 (22 with TNFi and 58 with SEC) for lack of effectiveness, 41 (16 with TNFi and 25 with SEC) for adverse events. No patient treated with SEC presented a new-onset inflammatory bowel disease.Figure 1.Persistence with SEC after 3 years of follow-upConclusion:In this real world cohort of AxSpA pts, SEC was mostly prescribed at second and third-line, contrary to axSpA pts treated with TNFi. Most reason of discontinuation were related to lack of effectiveness with both therapeutic classes.Disclosure of Interests:Thibaut DELEPINE: None declared., Peggy Philippe Speakers bureau: Abbvie, MSD, Fresenius, Pfizer, UCB Pharma, Novartis, Consultant of: Abbvie, MSD, Fresenius, Pfizer, UCB Pharma, Novartis, Emeline Cailliau: None declared., Eric Houvenagel: None declared., Xavier Deprez Speakers bureau: Pfizer, UCB, Abbvie, Novartis, MSD, Consultant of: Pfizer, UCB, René-Marc Flipo Speakers bureau: Novartis, Lilly, Abbvie, Pfizer, MSD, Consultant of: Novartis, Lilly, Abbvie, Pfizer, MSD, Jean-Guillaume Letarouilly Grant/research support from: Pfizer (research grant).

Background:The reasons explaining why some patients exhibit higher monosodium urate (MSU) crystal burdens than others remain largely unknown. While MSU crystal formation is enhanced by certain factors in vitro such as pH, temperature, and other ion concentrations, it is currently unknown whether comorbidities and clinical features are associated with increased MSU deposition in vivo.Objectives:To determine which factors are associated with the burden of MSU crystal deposition quantified by dual-energy CT (DECT) in urate lowering therapy (ULT)-naive gout patients.Methods:In this multicenter cross-sectional study, DECT scans of knees and feet were prospectively obtained from ULT-naive, or not taking any ULT for more than a year, gout patients. Demographic, clinical (including gout history and comorbidities), and biological data were collected, and their association with DECT MSU crystal volume was analyzed using bivariate and multivariate analyses. A second bivariate analysis was performed by splitting the dataset depending on an arbitrary threshold of DECT MSU volume (1 cm3).Results:A total of 125 gout patients were included, of whom 91 underwent both DECT scans of knees and feet. In bivariate analysis, age (p=0.03), symptom duration (p=0.003), subcutaneous tophi (p=0.004), hypertension (p=0.02), diabetes mellitus (p=0.05), and chronic heart failure (p=0.03) were associated with the total DECT volume of MSU crystal deposition. In multivariate analysis, factors associated with DECT MSU volumes ≥1 cm3 were gout duration (OR for each 10-year increase 3.15 [1.60;7.63]), diabetes mellitus (OR 4.75 [1.58;15.63]), and chronic heart failure (OR 7.82 [2.29;31.38]). The model performance was good with an AUC of 0.816.Conclusion:Specific comorbidities, particularly chronic heart failure, diabetes mellitus, and hypertension, are more strongly associated with increased MSU crystal deposition in knees and feet than gout duration, regardless of serum urate level.Disclosure of Interests: :Tristan Pascart Grant/research support from: Research Grant Horizon Pharma, Consultant of: Novartis, BMS, Sanofi, Pfizer,, Speakers bureau: Novartis, BMS, André Ramon: None declared, Sebastien Ottaviani: None declared, Julie Legrand: None declared, Vincent Ducoulombier: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Laurène Norberciak: None declared, Pascal Richette: None declared, Fabio Becce: None declared, Paul Ornetti: None declared, Jean-François Budzik: None declared

Objectives:Secukinumab (SEC) is an interleukin-17 inhibitor used to treat patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Drug maintenance is often used as a proxy for treatment effectiveness and safety in real life settings. We aim to assess SEC maintenance in routine clinical practice and to identify survival predictors associated.Methods:We conducted a retrospective, longitudinal, observational, multicenter study including all patients (pts) with axSpA or PsA who received at least 1 injection of SEC between July 2016 and October 2019. We collected patient’s demographics and clinic characteristics, SEC date of initiation and dosage and dosage modification of SEC, previous biologic Disease-modifying antirheumatic drugs (bDMARDs) and concomitant treatments. Date and reasons of discontinuation – i.e., lack of efficacy, safety issue, sustained remission or others – were collected. Several potential maintenance predictors were tested: age, gender, disease (axSpA or PsA), smoking status, bDMARDs history and concomitant treatment. Among patients with non-radiographic axSpA (nr-axSpA), evidence of MRI sacroiliitis or elevated CRP were also assessed as potential maintenance predictors. Drug maintenance was analyzed by the Kaplan-Meier method and adjusted for baseline factors were estimated by log rank analysis.Results:The main characteristics of the 561 pts included were the following: 363 (64.7%) axSpA, 198 (35.3%) PsA, 329 (58.6%) female, mean age 45,6 +/- 12 years, 221 (39.4%) smokers, 175 (31.2%) radiographic sacroiliitis, 259 (46.2%) MRI sacroiliitis, 198 (35.3%) elevated CRP, 247 (44.0%) HLA B27 positive, mean BASDAI 48,3 +/- 26.8%. SEC was associated to methotrexate (MTX) in 139 pts (24.8%) and was the first line bDMARD in 55 pts (9.8%). The median drug maintenance (MDM) of SEC was 79 weeks (wk) [73-84]. At 52 wk, 245 pts (60%) SpA were still treated with SEC. During the 3-year follow-up, 264 pts discontinued SEC: 180 (68.2%) pts for lack of effectiveness, 47 (17.8%) for adverse events, 14 (5.3%) for others and 23 (8.7%). SEC prescription as first line bDMARD was associated with longer survival versus second line or more: 111 wk [83-138] vs. 69 wk [57-80] (p=0. 017) (figure 1). MDM was not significantly different depending on gender, MTX combo, elevated CRP, axSpA vs PsA and smoking status. Among the nr-axSpA pts, MRI sacroiliitis or elevated CRP did not modify SEC maintenance (p=0.68) (figure 2).Figure 1.Secukinumab maintenance according to therapeutic lineFigure 2.Secukinumab maintenance in nr-axSpA populationConclusion:In routine clinical practice, SEC median maintenance was 79 weeks. Fist line administration was the only independent factor associated with improved SEC retention. Lack of effectiveness was the most common reason of discontinuation.Disclosure of Interests:Benoît Flachaire: None declared, Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Vincent Pradel: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Guy Baudens: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Corinne Miceli Richard: None declared, Philippe Dieudé: None declared, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Jérémie SELLAM: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Marie-Hélène Guyot: None declared, Chi Duc Nguyen: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Thao Pham Speakers bureau: Novartis, Janssen, Lilly

Background:Real-world data are missing for Ustekinumab (UST) and secukinumab (SEK) in psoriatic arthritis (PsA).Objectives:To evaluate the characteristics of the patients (pts) with PsA treated by UST or SEK and to assess real world persistence of UST and SEK in PsA.Methods:This is a retrospective, multicenter study of pts with PsA (CASPAR criteria or diagnosis confirmed by a rheumatologist) initiating UST or SEK with a follow-up ≥ 6 months from January 2011 to April 2019. The comparison of persistence between UST and SEK was analysed using a Cox model with an inverse probability of treatment weighting propensity score including 11 confounding factors. Subgroup analyses (age>65 years, gender, Body Mass Index (BMI), Charlson score>2, psoriasis, CRP>5mg/L, number (nb) of prior biotherapies, proportion of pts on maximum dose of UST or SEK, combination with methotrexate (MTX), enthesitic and axial forms of PsA) were also performed to test the heterogeneity of UST and SEK persistence. Finally, 2 sensitivity analyses were performed, first excluding the pts treated before the marketing authorization of SEK, and then excluding the pts that underwent a molecule switch. Causes of discontinuation were also collected.Results:406 pts were included: 245 with UST and 161 with SEK. At baseline before propensity score-matching, the UST group has a higher BMI (28.9 ± 6.4 kg/m2vs. 27.4 ± 6.0 kg/m2), more peripheral forms (98% vs. 90.8%), a higher nb of active smokers (27.1% vs. 19.9%), a higher frequency of psoriasis (96.3% vs. 83.2%), less MTX users (38.9% vs. 44.2%), a higher nb of pts with CRP >5mg/L (54.3% vs. 47%), a higher nb of pts naïve to biotherapies (22% vs. 13%) and a higher nb of pts with recommended dosing (97.3% vs 50.9%). The median persistence was 9.4 months and 14.7 months for UST and SEK, respectively. The persistence rate was lower in the UST group compared to the SEK group (40.9% vs. 59.1% % at 1 year; 26.4% vs. 38.0% at 2 years; weighted HR=1.42; 95% CI 1.07 to 1.92; p=0.015) (Fig 1). In subgroup analysis, combination with MTX was associated with a higher persistence rate in the patients with SEK compared to those receiving UST: 43.6% vs. 23.2% (HR=2.20; 95% CI 1.30 to 3.51; p=0.001), whereas no difference was observed in SEK and UST monotherapy: 33.8% vs 28.4%, respectively (HR=1.06; 95% CI 0.74 to 1.53; p=0.75) (Fig 2). A similar difference was found in the sensitivity analyses, with however a difference at the limit of significance for the analysis excluding pts with a molecule switch (adjusted HR=1.35; IC95% 0.96 to 1.92; p=0.085). The causes of discontinuation were due to inefficacy in 85% of cases and an adverse event in 12% of cases (19% in the SEK group and 9% in the UST group).Conclusion:In this first real-world study comparing UST and SEK persistence in PsA, the persistence of SEK was longer than that of UST. Subgroup analysis revealed this difference of persistence was restricted to patients treated in combination with MTX.Disclosure of Interests:Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Benoît Flachaire: None declared, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Maeva Kyheng: None declared, Jérémie SELLAM: None declared, Pascal Richette: None declared, Philippe Dieudé: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Eric Houvenagel Speakers bureau: Janssen, Novartis, Chi Duc Nguyen: None declared, Marie-Hélène Guyot: None declared, Nicolas Segaud: None declared, Frederic Maury: None declared, Laurent Marguerie: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Guy Baudens: None declared, Corinne Miceli Richard: None declared, Elisabeth Gervais Speakers bureau: Novartis, Janssen, Roche, Pfizer, BMS, Abbvie, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thao Pham Speakers bureau: Novartis, Janssen, Lilly, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly

Background:The close relationship between gout and cardiovascular diseases is well established. A growing hypothesis explaining this association would be that monosodium urate (MSU) crystals are deposited within vessel walls. Dual-energy computed tomography (DECT) can identify and quantify MSU crystal deposition in soft tissues. It remains unclear whether vascular spots exhibiting DECT attenuation characteristics of MSU are artefacts or true MSU crystal deposits.Objectives:The objectives of this study were to determine whether the presence of peripheral vascular MSU crystal deposition identified with DECT is associated with the extent of MSU deposits in joint soft tissues, and if this association persists over time under urate-lowering therapy.Methods:Patients with a clinical suspicion or established gout diagnosis prospectively underwent DECT for identification and quantification of the MSU crystal burden in their knees and feet. Some of these patients were also enrolled in the GOUT-DECTUS longitudinal study, and thus underwent follow-up DECT scans of their knees and feet at 6, 12 and 24 months. DECT scans were examined for the presence of vascular spots ≥0.01 cm3 classified as MSU crystal deposits according to the default post-processing settings. Multiple linear regressions adjusting on serum urate levels and gout diagnosis were implemented to determine the association between DECT MSU crystal volume in joint soft tissues, and the presence of vascular MSU deposits. Mixed linear models were used to compare DECT volumes of MSU crystal deposition in soft tissues between vascular MSU positive and negative patients during follow-up.Results:A total of 169 patients were included, of which 140 had a final diagnosis of gout, including 15 also included in the longitudinal study. Patients were mostly male (78.8%) and were 65.5 ± 14.6 years old. Among gout patients, disease duration was 9.3 ± 9.9 years and 56.5% were urate lowering therapy-naive. A total of 11/29 (37.9%) controls and 40/140 (28.6%) gout patients presented with a least one vascular spot of DECT MSU deposition, with an average volume of 0.02 ± 0.02 cm3, and all subjects also presented at least one vascular calcification. In the feet, patients positive for vascular DECT MSU crystal deposition had an MSU volume of 3.81 ± 10.06 cm3 in joint soft tissues, compared with 1.85 ± 7.72 cm3 for those without vascular MSU deposition (p=0.018). In the knees, patients with vascular MSU deposition had an MSU crystal volume of 6.03 ± 24.13 cm3 in joint soft tissues, compared with 0.83 ± 2.88 cm3 for those without vascular evidence of MSU deposition. In the longitudinal subgroup analysis, coefficients of the fixed effects for the presence of vascular MSU deposits on the MSU crystal volume in joint soft tissues was 0.4 (p=0.35) in the feet and 1.21 (p=0.03) in the knees. The presence of vascular DECT MSU deposits was associated with a 3.4-fold increase in MSU crystal volume in knee joint soft tissues throughout follow-up.Conclusion:This study suggests that some vascular spots identified with DECT as MSU crystal deposition may be real and not artefacts. This correlation remains throughout follow-up in the knees. However, the comparable prevalence of vascular DECT MSU deposits between gout patients and controls, the systematic co-existence of vascular calcifications and the uneven regression under urate-lowering therapy requires further analysis to determine which DECT spots are artefacts and which are not.References:[1]Dual-Energy Computed Tomography Detection of Cardiovascular Monosodium Urate Deposits in Patients With Gout. Klauser AS, Halpern EJ, Strobl S, Gruber J, Feuchtner G, Bellmann-Weiler R, Weiss G, Stofferin H, Jaschke W.Disclosure of Interests:Tristan Pascart Grant/research support from: Research Grant Horizon Pharma, Consultant of: Novartis, BMS, Sanofi, Pfizer,, Speakers bureau: Novartis, BMS, Paul Carpentier: None declared, Laurène Norberciak: None declared, Julie Legrand: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Fabio Becce: None declared, Jean-François Budzik: None declared

Background The adipose tissue belongs to the endocrine metabolic system which impacts inflammatory events in rheumatoid arthritis (RA). Recently a few studies have demonstrated that the body weight and Body Mass Index (BMI) are predictive factors of the clinical response of patients treated for RA by Infliximab. Moreover others studies proved that Obesity has also been associated with the increased incidence and a worse outcome of RA. Objectives The purpose of this study was to assess the influence of the body weight on the therapeutic response and the remission rate after one year of treatment with TOCILIZUMAB in RA. Methods This retrospective multicenter longitudinal study included patients treated by TOCILIZUMAB (8mg/kg per 4 weeks) for RA for at least one year from 2006 onwards. Patients for whom the body height was known were specifically analysed to test the influence of BMI and categories of BMI (normal 30kg/m2 ). After one year, of treatment the therapeutic response was estimated by the variation of the DAS 28 score. Linear regression of the delta DAS 28 according to initial body weight and secondarily to the BMI was performed. EULAR response and remission rates were assessed according to body weight and to the BMI. Two definitions of remission were admitted: DAS 28 score Results A total of 129 patients were included. At treatment initiation, patients had an average weight of 71,6±17,6 kg and an average DAS 28 5,4±1,3. At the endpoint, the DAS 28 score was 2,1±1,2. Linear regression showed a positive impact of body weight on DAS 28 improvement (p=0,0261, Fig. 1). According to EULAR classification 4 patients were in good therapeutic response, 120 in moderate response and 5 had no response without statistically correlation with body weight (p=0,7). Of the 101 patients in remission with a DAS 28 score When comparing the patients in the group above the median of weight (70kg) and those below the median, Delta Das 28 showed a strong tendency to be higher for the heaviest patients, respectively 3,6±1,6 and 3,1±1,4 (p=0,0519). No statistical difference was found regarding remission. With regard to the 104 patients of whom body height was known, the average BMI was 26,9±6,3 kg/m2 with an initial DAS 28 5,5±1,3 and final DAS 28 3,4±1,5. Linear regression of Delta Das 28 positively correlated with the initial BMI (p=0,0144). 96 patients presented a good response, 4 patients were in moderate response and 4 had no response. 80 patients obtained a final DAS 28 A total of 44 patients were in the normal BMI group, 34 were overweight and 26 were in the obese group. Patients in the obese group improved their Das 28 by 4,1±1,3 versus 3,0±1,2 for normal BMI and 3,2±1,7 and overweight (p=0,0087/Fig. 2). There was no statistically difference for remission. Conclusions This study suggests a positive influence of the high initial body weight and high BMI on the improvement of the DAS 28 in patients treated with TCZ in RA. Acknowledgements Grant to Roche-Chugai Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3855