Background: In systemic lupus erythematosus (SLE), there is not a standardized and validated definition of states of moderate and severe SLE activity. This is a major drawback both for research purposes and for the stratification of treatments according to severity. Objectives: To propose a definition for moderate disease activity state (MODAS) and severe disease activity state (SEDAS) in SLE and using the RELESSER-PROS cohort to describe the prevalence of both states of activity and to analyze the impact of this categorization on different outcomes. Methods: The study population belongs to the RELESSER-PROS prospective cohort with data from patients followed annually for 4 years. The MODAS and SEDAS definitions were generated by a panel of lupus experts, which may be differentiated depending on absolute score of clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI), certain clinical manifestations not considered in SLEDAI and the subjective assessment of the physician, through PGA. MODAS was defined as the presence of at least one of the following conditions: <4 cSLEDAI ≤ 8 or 1< PGA ≤ 2 (without severe clinical manifestations); and SEDAS: SLEDAIc >8 or PGA > 2 or the presence of severe SLEDAI and Non-SLEDAI manifestations. Low disease activity (No MODAS nor SEDAS): 1≤SLEDAIc ≤4 or 0

Background: Belimumab (BLM) is a monoclonal antibody targeting BAFF cytokine, which has shown efficacy and safety in the treatment of systemic lupus erythematosus (SLE). A pooled post-hoc analysis from randomized controlled trials BLISS-52 and BLISS-76 suggested that belimumab is effective reducing the risk of severe flare in patients with SLE [1]. However, data on flare prevention from controlled trials on the subject is lacking. Objectives: We aim to analyse the risk of flare in a multicentre SLE cohort treated with BLM as compared with a control cohort from RELESSER register, under standard of care (SoC). Methods: A longitudinal retrospective study, comparing a multicentre cohort of patients treated with BLM (BLMc) versus a control group of patients treated with standard of care from RELESSER-PROS cohort. We adjusted for a flare risk propensity score (PS) to properly balance covariates (i.e., age, sex, race, disease duration, previous flare, nephritis, serologic activity, baseline SLEDAI, damage index (SLICC/ACR/DI) (SDI) and concomitant treatments: glucocorticoids and antimalarials). Once homogeneous groups were achieved, the distribution of cumulative flares was compared using the Wilcoxon test. The significance level was set at 0.05. Results: Of a total of 1137 SLE Caucasian patients (ACR-97 criteria) (BLMc n = 274; RELESSER n = 853), 102 from BLMc and 134 from RELESSER were PS matched (overall, 236 patients). Differences between BLMc and RELESSER control group, both for covariates and for flares rates are displayed in Table 1. Only the follow-up duration turned out to be greater in BLMc than RELESSER group [4.67 (2.57) vs. 3.11 (0.339) years, respectively, p<0.001)]. Up to 75/134 (56%) patients in RELESSER group underwent ≥ 1 SLE flare during observation period, vs. 32/102 (33.3%) in BLMc. Regarding severe flares, 18/134 (13,4%) in RELESSER vs. 9/102 (8,8%) in BLMc were registered. The mean number of cumulative flares was significatively lower in BLMc (Figure 1); however, not statistically significant differences were found for severe flares comparations. Conclusion: According to risk factor of SLE-flare adjusted analysis, patients under BLM treatment in real world setting have a decreased risk of flare when comparing with standard of care. Funding: The RELESSER Registry was supported by the Spanish Society of Rheumatology and received financial support from GSK. REFERENCES: [1] van Vollenhoven RF et al, Ann Rheum Dis. 2012;71(8):1343-1349. Acknowledgements: Figure 1. Table 1Belimumab cohort (BLMc) vs RELESSER control group differencesBLMc(N=102)RELESSER(N=134)P-valueOverall(N=236)Sexfemale91 (89.2%)123 (91.8%)0.644214 (90.7%)Age at baselineMean (SD)46.4 (13.2)47.2 (12.3)0.64946.9 (12.7)Disease duration (years)Mean (SD)15.9 (9.86)14.7 (7.94)0.58815.2 (8.82)SLEDAIMean (SD)4.99 (3.72)4.50 (4.48)0.1184.71 (4.17)C3 or C4 lowN (%)50 (49.0%)71 (53.0%)0.046121 (51.3%)Positive anti-DNAN (%)63 (61.8%)76 (56.7%)0.517139 (58.9%)Previous severe flareN (%)23 (22.5%)32 (23.9%)0.93355 (23.3%)Proteinuria (any time)N (%)27 (26.5%)24 (17.9%)0.15551 (21.6%)HydroxychloroquineN (%)86 (84.3%)115 (85.8%)0.890201 (85.2%)GC dose at baseline≤5 mg50 (49.0%)46 (34.3%)0.085796 (40.7%)> 5 y < 10 mg13 (12.7%)20 (14.9%)33 (14.0%)≥10 y <30 mg16 (15.7%)19 (14.2%)35 (14.8%)≥30 mg1 (0.980%)1 (0.746%)2 (0.847%)Without GC22 (21.6%)48 (35.8%)70 (29.7%)Follow up duration (years)Mean (SD)4.67 (2.57)3.11 (0.339)<0.0013.78 (1.87)Cumulative flare (Global)Mean (SD)0.647 (1.26)1.32 (1.87)<0.0011.03 (1.67)Median [Q1,Q3]0 [0,1.00]1.00 [0,2.00]0 [0,1.25]Severe cumulative flareMean (SD)0.108 (0.370)0.172 (0.499)0.2760.144 (0.448)Median [Q1,Q3]0 [0,0]0 [0,0]0 [0,0]BLMc: Belimumab cohort; SLEDAI: Systemic lupus erythematosus disease activity index; GC: glucocorticoids (prednisone or equivalent).NIL. Disclosure of Interests: Íñigo Rúa-Figueroa GSK, GSK, Irene Altabás González: None declared, Karen Roberts: None declared, Ivette Casafont-Solé: None declared, Andrea Hernández: None declared, Marta De la Rubia Navarro: None declared, Maria Galindo: None declared, Tarek Carlos Salman-Monte: None declared, Paola Vidal-Montal: None declared, Sandra Garrote-Corral: None declared, M. Ángeles Blázquez: None declared, MARIA MERCEDES PIQUERAS GARCIA: None declared, Marina Sánchez Lucas: None declared, Josefina Cortés-Hernández: None declared, Juan Ramón De Dios: None declared, Eva Tomero Muriel: None declared, Paloma Vela Casasempere: None declared, Myriam Gandia Martinez: None declared, Beatriz Frade-Sosa: None declared, Consuelo Ramos Giráldez: None declared, Clara Moriano: None declared, Alejandro Muñoz Jimenez.: None declared, Jaime Calvo Alén: None declared, Raúl Menor-Almagro: None declared, Antonio Fernández Nebro: None declared, José M. Pego-Reigosa: None declared.

Background: Anifrolumab is a biological treatment with recent approval for systemic lupus erythematosus (SLE), supported by its efficacy in clinical trials. However, data from real clinical practice are lacking. Objectives: To describe the patient’s baseline clinical characteristics at the time of anifrolumab initiation and reasons for its prescription in patients with SLE under follow-up in Spanish Rheumatology Departments. Methods: Observational, uncontrolled, ambispective and multicenter study with medication of a cohort of patients with SLE (according to the 2019 EULAR/ACR criteria), treated in 19 Rheumatology departments. All patients who received at least one dose of anifrolumab and signed the informed consent were included. Sociodemographic, clinical, blood test variables and treatments, were collected. In addition, indexes or scales of activity (SLEDAI-2k, SFI, SLE-DAS, CLASI), damage (SLICC/ACR/DI), fatigue (FACIT), neuro-cognitive dysfunction (MoCA) and disease impact (LIT) of the baseline visit were calculated. A descriptive analysis of the sample was performed. Ethics Committee code: 2023/10814. Results: A total of 56 SLE patients were included. Table 1 shows the demographic, clinical characteristics and treatments of the patients. Graph 1 shows the main clinical manifestations that motivated the initiation of treatment with anifrolumab. Conclusion: To date, in this registry, anifrolumab was initiated in a real-life setting in patients with a long disease evolution and refractory to several synthetic and biological treatments. Even though patients presented with a whole array of clinical manifestations, there was a clear predominance of the mucocutaneous ones. It remains to be elucidated, through systematic follow-up and the analysis of prospective data, if anifrolumab is just as effective when used in real-life clinical practice as compared to clinical trials. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Graph 1Main cause of anifrolumab initiation Table 1Demographic and clinic characteristics of the patientsDEMOGRAPHICAge at anifrolumab initiation45.5 ± 12.9Years from SLE diagnosis to anifrolumab initiation14.2 ± 8.9Age at SLE diagnosis30.8 ± 13.6Sex (women)49 (87.5%)EthnicityCaucasian46 (82.1%)Hispanic6 (10.7%)Asian2 (3.6%)Arab2 (3.6%)Active workers27 (48.2%)SLEDAIRecent onset seizure2 (3.6%)Psychosis2 (3.6%)Organic brain syndrome1 (1.8%)Visual disturbance1 (1.8%)New onset sensory or motor neuropathy involving cranial nerves1 (1.8%)Lupus headache1 (1.8%)New onset stroke1 (1.8%)Vasculitis5 (8.9%)Arthritis31 (55.4%)Myositis1 (1.8%)Heme-granular or RBC urinary casts1 (1.8%)Hematuria1 (1.8%)Proteinuria2 (3.6%)Pyuria5 (8.9%)Inflammatory-type rash34 (60.7%)Alopecia22 (39.3%)Oral or nasal mucosal ulcers22 (39.3%)Pleuritis2 (3.6%)Pericarditis2 (3.6%)Low complement CH50, C3, or C421 (37.5%)High DNA binding20 (35.7%)Temp >38°C3 (5.4%)Platelets <100 x 109/L4 (7.1%)WBC <3 x 109/L14 (25%)OTHER MANIFESTATIONS (NOT SLEDAI)Diffuse interstitial lung disease2 (3.6%)Hands tremor1 (1.8%)Intense asthenia5 (8.9%)Raynaud2 (3.6%)SCALES AND ACTIVITYFlares47 (83.9%)Severe flare12 (21.4%)MoCA test24.2 ± 6LIT49.3 ± 31.9FACIT24.4 ± 13.4SLE-DAS9.7 ± 6.4SLICC/ACR DI0.82 ± 1.1SLEDAI8.9 ± 7.1PGA2.4 ± 2.3CLASI ACTIVITY9.6 ± 9.5CLASI DAMAGE2.3 ± 3.9TREATMENTSHydroxychloroquine46 (82.1%)Hydroxychloroquine dose204.6 ± 102.2Corticosteroids dose48 (85.7%)Median ± SD dose of corticosteroids9.5 ± 8.51 DMARDs at anifrolumab initiation52 (92.9%)2 DMARDs at anifrolumab initiation16 (28.6%)3 DMARDs at anifrolumab initiation5 (8.9%)Type of previous DMARDMethotrexate28 (50%)Leflunomide7 (12.5%)Azathioprine6 (10.7%)Mycophenolate17 (30.3%)Chloroquine sulfate3 (5.4%)Mepacrine5 (8.9%)Other5 (8.9%)Previous biologic treatment51 (91.1%)Type of previous biologicRituximab13 (23.2%)Belimumab34 (60.7%)Anti-TNFα3 (5.4%)Other1 (1.8%)

Background: No data on agreement between patient perception, DORIS 2021 remission, LLDAS, or physician assessment is currently available. Objectives: The aim is to compare the SLE activity perceived by the patient using the Patient Acceptable Symptom State (PASS) question with the global assessment of activity by the physician, and the definitions of LLDAS/DORIS2021. Methods: A cross-sectional multicenter study involving SLE patients from seven Spanish Rheumatology Departments was conducted. The study applied DORIS 2021 remission criteria and LLDAS. Rheumatologists classified disease activity into five categories: remission, SACQ, low, moderate, or high. The patients were asked about their clinical SLE condition through the PASS question: "Considering all the different ways your disease is affecting you, if you were to stay in this state for the next few months, do you consider your current state satisfactory?": PASS yes/PASS no. Statistical analysis included descriptive cross-sectional analysis and Cohen's kappa for agreement analysis. Results: Among the 503 patients in the study (Table 1), 386 (77.4%) reported an acceptable symptom state according to the PASS question. Mean patient global assessment (PtGA) was 29.62 (±24.38) on a scale of 0-100, while mean physician global assessment (PGA) was 0.46 (±0.59) on a scale of 0-3. A total of 236 (47.6%) patients met DORIS 2021 remission criteria, and 289 (59%) met LLDAS. According to the rheumatologists' categorical classification, 435 (86.8%) patients were in remission or low disease activity (Table 2). Among PASS-affirmative patients, 65.5% met LLDAS and 57.9% met DORIS 2021 remission criteria, with lower PtGA (19.7) and PGA (0.29) scores. In the non-PASS group, 62.8% were not in LLDAS, and 87.6% did not meet DORIS 2021 remission criteria, with higher PtGA (58) and PGA (1) scores (Table 3). The overall agreement between PASS and categorical classification was 82% with a Cohen's kappa of 0.43. Conclusion: The majority of SLE patients reported an acceptable symptom state according to the PASS question, which aligns with the PtGA scale. Physicians' assessments also showed similarities with patient perspectives. However, notable differences were observed regarding remission/LLDAS criteria, indicating that while patient and physician perspectives align on subjective classification, variations exist concerning LLDAS and DORIS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background Belimumab (BLM) is a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor. It is commonly used for treatment of systemic lupus erythematosus (SLE) patients with inadequate control to first-line treatments and inability to taper GC daily dose to acceptable levels. More recently it has been approved for patients with active lupus nephritis. Objectives To report baseline profile of SLE patients treated with BLM enrolled in a SLE Spanish registry. Methods Multicenter retrospective and longitudinal cohort study including SLE patients treated with BLM in 18 Spanish rheumatology units. Demographic, clinical data and treatments were collected at baseline, 6, 12 months and in the last visit available. Patients starting BLM in different periods (2010-2015 and 2016-2021) were compared regarding the reason of prescription of the drug. Results 324 patients (91% female, 84,8% caucasian) were enrolled. Mean (±SD) age at diagnosis: 31.8 years (±11.9); mean disease duration of 8.7 years (±9.07) and mean follow-up 3.8 (±2.7). A total of 319 (98.45%) subjects met SLE 1997 ACR or SLICC 2012 criteria; 217 (68.2%) were anti-dsDNA positive and 224 (69.8%) had low complement levels. At baseline, the mean SLEDAI-2K score was 10.4 (±5.25); 152 (47.5%) of patients had damage with a mean SDI score of 0.83 (±1.2). A total of 289 patients (89.2%) had received disease modifying anti-rheumatic drugs (DMARDs) before BLM: conventional (cDMARDS) in 282 patients (87%) and biologic DMARDs (bDMARDs) in 74 patients (22.8%); 164 (51.9%) had received more than one cDMARDs, methotrexate being the most frequently used (44.4%). Other cDMARDs used were: mycophenolate mofetil in 104 (37.01%), azathioprine in 91 (32.38%), leflunomide in 29 (10.32%), cyclophosphamide in 28 (9.92%) and calcineurin inhibitors in 13 (4.6%) of patients. The most frequent bDMARDs used was Rituximab in 80%. Most patients were receiving antimalarials (83,2%) and glucocorticoids (GC) (91.2%), with a mean dose of 12.3 mg/day. A total of 209 (67.9%) patients were receiving more than 5 mg/day and 180 (58.4%) more than 7.5 mg/day of prednisone.BLM was used in monotherapy in 99 (30.5%) subjects. It was initiated due to disease activity in 307 patients (95%) and/or as a GC sparing agent in 191 patients (59%). Most patients initiated BLM for several concurrent reason; only a few patients received BLM just for maintenance (4/322) or save GC (8/322). At baseline, only 6 patients (1.9%) were in DORIS-21-remission and LLDAS. The main reasons of prescription for ongoing activity were arthritis (65.4%), cutaneous (40.7 %) or both (81%). There were no statistically significant differences in any of the prescription reasons when comparing the periods 2010-2015 and 2016-2021. Conclusion In the majority of patients, belimumab was prescribed after the use of other DMARDs and more than 50% of patients had received at least 2 DMARDs and were receiving GC at medium doses. One third of patients received BLM as monotherapy. It was prescribed due to active disease in the vast majority of patients and/or as GC sparing agent. Activity in articular and cutaneous domains were the main reasons of indication. No changes in prescription habits were identified over time. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Type and reasons of prescription of BelimumabN (%) or mean (± SD) (n = 324 patients)Age at prescription of Belimumab (years)42.3 (± 12.9)Intravenous Belimumab215 (66.35%)Subcutaneous Belimumab110 (33%)Reasons of prescription* (multiple response allowed)Disease activity307 (95%)Maintenance197 (61%)Glucocorticoid sparing191 (59 %)ActivityCutaneous132 (40.7 %)Articular212 (65.4%)Renal58 (17,9%)Hematological60 (18.5%)Serosal47 (14.5%)Other29 (8.82%)

Background Belimumab (BLM) is a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor. It is approved for the treatment of systemic lupus erythematosus (SLE). It is effective in reducing disease activity, flares, damage prevention and also as a steroid-sparing agent. A treat to target (T2T) approach in the care of SLE patients is important in terms of improving short and long-term outcomes. Objectives To evaluate belimumab (BLM) effectiveness in SLE patients from a Spanish multicenter registry. Methods A longitudinal retrospective multicenter cohort including SLE patients treated with belimumab from 18 Spanish rheumatology departments. Demographic, clinical and serological data were collected at baseline, 6, 12 and in the last visit available. Changes in SLEDAI-2K; LLDAS and DORIS 2021 states and global response according to physician criteria were compared between visits, as well as changes in damage and glucocorticoids used. T-test was used for numerical variables and the Fisher's test for categorical variables. Results 324 patients were included: 295 (91%) females with a mean (±SD) age of 42.4 (±12.9) years. Mean follow-up was 3,8 (±2.7) years and mean time with BLM was 2.7 (±2.4) years. At baseline, mean SLEDAI-2K was 10.4 (±5.25), 68.2% had elevated anti-double-stranded DNA (anti-dsDNA) antibodies and 69.8% had complement consumption. BLM was initiated concomitant to other DMARD in 67.9% (n=220) of patients.Mean reduction in SLEDAI-2K score was 5.0 (± 5.1), 6.1 (± 5.5) and 7.13 (± 5.3) points at 6, 12 months and in the last visit, respectively (p<0.05 for all comparisons). Rates of achievement of LLDAS, DORIS and clinical response according to physician criteria, significantly increased from baseline to 6, 12 months, and to the last visit (Table 1). Anti-dsDNA antibodies and inflammatory markers (ESR, CRP), significantly decreased from baseline to 6, 12 months and in the last visit. Complements increased over the follow up but without statistical significance.A total of 107 (45,9%) patients discontinued GC. At 6 months, 58.9% (n=155) of patients reduced the dose of GC with respect to baseline and 72.8% (n=131) of patients did it at the last visit.Mean (±SD) prednisone dose was significantly reduce over the visits: 12.3 (±12.16); 7.42 (±5.36); 5.8 (±4.42) and 4.7 (±3.7) mg/day at baseline, 6 and 12 months and in the last visit, respectively. Median (IQR) SDI score at the end of the observation period did not change from baseline visit: 0 (0-1) and 0 (0-1), respectively (p=0.97). Neither were changes observed in the percentage of patients with damage between the beginning and the end of the observation period: at baseline 47.5% (n=152) patients presented damage and, in the last visit, 45.6% (n=99). Conclusion Real-world data of SLE patients confirm belimumab efficacy in real world, reducing clinical and serological activity in the short and medium-term. Add-on therapy with BLM leads to high rates of LLDAS and DORIS at 6 months, that continue increasing over time. BLM has an important GC sparing effect and prevents organ damage accrual. All these data shows that BLM is useful to achieve the therapeutic goals of a T2T strategy. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1Rates of therapeutic targets attained by patients in treatment with Belimumab.Table 1Clinical response and changes in GC dose.Disease activity Mean (±SD) or number (%); n=324Baseline6 months12 monthsLast visitSLEDAI reduction; mean (±SD)10 (± 5.25)5.0 (± 5.1) *6.1 (± 5.5) *7.13 (± 5.3) *LLDAS6 (1.9%)137(45.8%) *145 (62%) *177 (73.1%) *DORIS6 (1.9%)72 (24%) *85 (36.3%) *127 (52.5%) *Response according to physician212 (65.4%) *185 (57.1%) *165 (50.9%) *Number of swollen joints; mean (±SD)3.3 (±3.6)1.2 (±2.8) *0.69 (±1.95) *0.55 (±1.82) *Prednisone dose (mg/day); mean (±SD)12.3 (± 12.16) *7.4 (± 5,36) *5.8 (± 4,42) *4.75 (±3.74) *SLEDAI: Systemic Lupus Erythematosus Disease Activity Index. cSLEDAI: clinical SLEDAI; LLDAS: Lupus Low Disease Activity State. DORIS: Definition of remission in SLE. *p<0.056 months12 monthsLast visitDiscontinued4574130Ongoing279250194

OBJECTIVES To apply current definitions of Lupus Low Disease Activity State (LLDAS) to a large cohort and evaluate the concordance between LLDAS and the clinical status according to the expert opinion. Methods A cross-sectional analysis of a prospective multicenter study of SLE patients from seven Spanish Rheumatology Departments with high level of expertise in SLE. We applied the LLDAS definition and evaluated the agreement between the LLDAS and the clinical status according to the expert opinion. Modifications in LLDAS definition were also explored. Results 508 patients were included (92% women; mean age (±SD): 50.4 years (± 13.7). A total of 267 (54.4%) patients were in DORIS remission and 304 (62.7%) in LLDAS. Remission was the most frequent state considered by the rheumatologist (n=206, 41.6%). Agreement between expert opinion and LLDAS was 71.4%. Most cases (96.1%) in LLDAS, were classified as remission or low activity by the expert. Of the patients that did not fulfill LLDAS, 126 (70.4%) patients were classified as remission/low disease activity (Figure 1). The main reasons for discordance were the presence of new manifestations compared to previous visit and a SLEDAI 2-K >4 (Table 1). The modification of the LLDAS definition excluding the comparison with previous assessment increases the agreement to 82.6% (95% CI: 81.61–83.96%). Decreasing the cutoff point of prednisone dose to 5mg/daily did not change the agreement (Table 2). Conclusion Almost two thirds of SLE patients were in DORIS remission or in LLDAS. There is a good correlation between LLDAS and the physician's opinion, particularly for those patients who fulfill LLDAS definition. A modification in LLDAS definition excluding the comparison with previous assessment have an increase in the agreement with the expert opinion.

Introduction An accurate target in Systemic Lupus Erythematosus (SLE) Treat to Target strategies has been challenging over the past years. Recently, a new definition of remission was updated in 2021 by the international DORIS (Definition of Remission in SLE) taskforce. Objective To quantify the proportion of patients who achieve DORIS and evaluate the agreement between DORIS and the treating rheumatologist judgement. Methods Prospective multicenter study of SLE patients (ACR 1997 Classification Criteria or Clinical diagnosis by the Physician) from seven Spanish Rheumatology Departments. DORIS 2021 remission definition was applied and the rheumatologists were asked to classified the activity of the disease in 5 different categories: remission, serologically active clinically quiescent (SACQ), low, moderate or high activity. Statistical analysis: descriptive cross-sectional (at the time of recruitment) analysis was done. Analysis of the level of agreement between expert opinion and the definition of remission was evaluated using Cohen's kappa. The reasons of disagreement were evaluated. Results A total of 508 patients were included (92% women; mean age (±SD): 50.4 years (±SD 13.7)). Table 1 shows in detail the patients characteristics at baseline. Two hundred and sixty-seven (54.4%) patients were in DORIS 2021 remission. According to the rheumatologist judgement, 206 (41.6%) patients were considered in remission and 71 (14.3%) in a SACQ state (Figure 1). Overall agreement between rheumatologist opinion and DORIS was 81.28% (95% CI: 79.9, 82.9) with a Cohen's kappa of 0.62. We found disagreement in 46 patients, and the main reasons were a clinical SLEDAI>0 in 39 (84.8%) patients; Physician Global Assessment (PGA) >0.5 in 5 patients and a prednisone dose above 5 mg day in other five patients. Conclusion At a given point in time, more than half of SLE patients were in DORIS 2021 remission. The overall agreement between rheumatologist opinion and DORIS remission is accurate.

BackgroundTreat to Target strategies are necessary in Systemic Lupus Erythematosus (SLE). They are difficult to establish due to the heterogeneity of the disease. The current definitions of Lupus Low Disease Activity State (LLDAS) according to the Asia Pacific Lupus Collaboration (APLC) and remission according to Definition of Remission in SLE (DORIS) 2021 are difficult to achieve and maintain over time.ObjectivesTo evaluate the concordance between the LLDAS and the clinical status according to the rheumatologist opinion and reasons of disagreement. To explore modifications in LLDAS definition that best fit with the expert´s opinion.MethodsProspective multicenter study of SLE patients (ACR 1997 Classification Criteria or clinical diagnosis by the physician) from seven Spanish Rheumatology Departments. Statistical analysis: descriptive cross-sectional (at the time of recruitment) analysis of the demographic and clinical characteristics, treatments; remission and LLDAS and the subjective evaluations of SLE activity by the rheumatologist. Analysis of the level of agreement between expert opinion and the definition of LLDAS and its modification were evaluated using Cohen’s kappa.ResultsDEMOGRAPHIC, DISEASE CHARACTERISTICS AND TREATMENTS. Five hundred and eight were included (92% women; mean age (±SD): 50.4 years (±13.7)). Mean SLEDAI-2K (±SD) was 2.84 (±3.31). A total of 406 (79.9%) patients presented SLEDAI-2K≤4. A total of 317 (74.1%) patients were on antimalarial treatment. Two hundred and twenty-two (43.7%) patients were on some type of immunosuppressive or biological therapy. More than half of patients were not taking glucocorticoids (n=310, 61%). A total of 38 patients (7.5%) were taking doses of prednisone higher than 7.5mg/day.REMISSION/LLDAS 267 (54.4%) patients were in remission and 304 (62.7%) patients were in LLDAS. According to the expert opinion of the rheumatologist, remission was the most frequent state considered (n=206, 41.6%); followed by low activity (n=153, 30.9%); serologically active (n=71, 14.3%); moderate activity (n=55, 11.1%) and high activity (n=10, 2%).AGREEMENT Overall agreement between expert opinion and the definition of LLDAS was 71.4 % with a Cohen’s kappa of 0.3. The majority of the cases (96.1%) that fulfilled the definition of LLDAS, were classified by the expert as remission, serologically active or low activity. Only 12 (3,9%) patients were classified by the expert as moderate or high activity. Of the patients that did not fulfill the definition of LLDAS, 126 out of 179 (70.4%) patients were classified by the expert as remission/low disease activity (Figure 1). The main reasons for discordance in the group that did not fulfill the definition of LLDAS were the presence of new clinical features compared to previous visit and a SLEDAI 2-K >4, in 74 (58.7%) and 59 (46.8%) patients, respectively. The LLDAS adjustment that meant a significant increase in the agreement was the exclusion of the comparative features with the previous visit, with an increase in the agreement to 82.6% (95% CI: 81.61-83.96%). The modification of prednisone to 5mg/daily dose, did not represent a significant change in agreement from the original definition.Figure 1.Comparison of LLDAS and expert opinionConclusionAt a given point in time, almost two thirds of SLE patients were in remission or in LLDAS. There is a good correlation between LLDAS and the physician’s opinion, particularly for those patients who fulfill LLDAS definition. However, the agreement is not so good for patients who don’t, these being excessively classified by the physician as remission or low activity. The main LLDAS items causing this disagreement were a SLEDAI-2K >4 and the appearance of different clinical manifestations from the previous evaluation. On the contrary, physician assessment by the PGA adequately fits the LLDAS definition. The modification of the LLDAS definition excluding the comparison with previous assessment increases the agreement with the expert opinion to 82.6%.Disclosure of InterestsNone declared

Background: Despite great advances in the diagnosis and treatment of lupus, the scientific community does not know the perception of our patients regarding the knowledge of the disease and the relationship between patients and disease. Fatigue had the greatest impact on activities of daily living, yet the majority reported receiving no support or poor support in managing it 1 . Objectives: Through this initiative, it is intended to investigate about the knowledge of the disease and impact of the disease on quality of life of Lupus patients. Another objective is to give visibility to the current needs of people living with lupus. Methods: It was performed a national survey with 1,263 interviews with Lupus patients who reside in Spanish territory and belonging to lupus patient associations in Spain. The survey was carried out by the Spanish Lupus Federation (FELUPUS) in collaboration with GSK company. Online interview lasting approximately 25 minutes. The collection of information was anonymously carried out from May 21 to June 30, 2020. Results: 1.263 lupus patients were interviewed, 92% diagnosed with SLE and 8% with CLE. Survey sample is representative of the Lupus patient population in Spain [associated sampling error: 2.76%]. Questions about knowledge of the disease showed that 73% of patients considered that there is very little knowledge of the disease by society. Patient awareness of lupus increases as the disease progresses, so at the time of diagnosis, level of knowledge of the patient about Lupus is low in 92% of patients and at the moment of survey, 68% of patient had high knowledge. In terms of the perception of his illness, the affectation of the kidneys and heart (97%), fatigue and skin rashes (97%), are the statements that generate the greatest consensus. The survey about the relationship to disease demonstrated that 3 out of 4 patients have symptoms related to the disease, muscle and joint pain (75%) and fatigue (74%) are the symptoms that cause the greatest discomfort (Graph 1). Remarkable degree of agreement with the fact of not being able to sunbathe (78%), as well as the lack of energy (61%) and weakness in the body (60%). Flare-ups (86%), followed by fatigue (78%) and pain (77%) cause great concern. At diagnosis, 92% of patients have some organic involvement and regarding the diagnosis, at present, a greater number of patients present damage to the CNS (17%) and bones (21%). Many patients do not understand the concept of organ damage, wrongly relating it to fatigue (38%) or joint pain (47%). Graph 1. Conclusion: Among the conclusions of the survey, it stands out that society and the general population are unaware of what lupus is, while in the case of lupus patients, knowledge increases as the disease progresses. Citizen awareness campaigns about this disease are necessary, where patient associations together with health authorities have a crucial job. On the other hand, 92% of patients present organ damage at diagnosis. This means that we are arriving late to the diagnosis of many patients, which makes it necessary to promote a close collaboration between Primary Care and Hospitals, to refer patients as soon as they suspect SLE. References: [1]Sloan M, Harwood R, Sutton S, D’Cruz D, Howard P, Wincup C, Brimicombe J, Gordon C. Medically explained symptoms: a mixed methods study of diagnostic, symptom and support experiences of patients with lupus and related systemic autoimmune diseases. Rheumatol Adv Pract. 2020 Feb 26;4(1):rkaa006. What worries the most to Lupus patients? Question P12. Please indicate your level of concern with the following aspects of Lupus. Percentage of patients who have scored a 4 or 5 for each item (% T2B). Acknowledgements: GSK funded the study presented in the abstract. Disclosure of Interests: Patricia Fanlo Grant/research support from: GSK funded the study presented in the abstract.

Background: Oncohematological diseases have an increased incidence in Rheumatoid Arthritis (RA) patients. However, their trend in RA in Spain is unknown Objectives: To analyze the incidence and trend of hospital admissions for lymphomas and leukemias in RA patients in Spain from 1999–2015 Methods: We performed an observational retrospective population study analyzing the spanish administrative database that includes a Minimun Basic Data Set (MBDS) of hospital admissions of RA patients from 1999–2015. We selected MBDSs for lymphomas and leukemias. Cases were identified by the presence in primary/secondary diagnosis of ICD9 codes. The population at risk was estimated with a prevalence of RA of 0,5% (0,8% women and 0,2% men). Crude and adjusted rates were calculated, and the trend was analyzed using the Generalized Linear Model with the year as the analysis variable. SPSS version 20 (Chicago, IL) was used Results: 338.343 RA hospital admissions were detected, being 3561(1,1%) lymphomas (61,5% women, 38,5% men) and 1664(0,5%) leukemias (52,3% women, 47,7% men). Mean age 68,94(SD 11,38) in lymphomas and 71,46(SD 11,24) in leukemias. Age-adjusted rate during the period for lymphoma was 152,19/105 inhab/year (92,05 women and 240,14 men). Lymphoma age-adjusted rate increased from 52,46/105 inha/year in 1999 to 187,57 in 2015, both women (from 42,74 to 142,95) and men (from 280,77 to 326,63). An annual increase in lymphoma rate of 6,9% is estimated (RRI 1,069; CI 95% 1,054–1,085). Age-adjusted rate during the period for leukemia was 90,87/105 inhab/year (37,09 women and 144,65 men). Leukemia age-adjusted rate increased from 18,86/105 inhab/year in 1999 to 94,05 in 2015, both women (13,80 in 1999 to 65,93 in 2015) and men (38,70 in 1999 to 204,84 in 2015). An annual increase in leukemia rate of 8,2% is estimated (RRI 1,083; CI 95% 1,069–1,097). Conclusions: In Spain from 1999–2015 lymphoma and leukemia hospital admissions in RA patients increased, with an estimation of 6,9% and 8,2% annual increase respectively. Disclosure of Interest: None declared

Background Treatment and evolution of Rheumatoid Arthritis (RA) have had an important change in the last years. However the trend of amyloidosis, habitually related to long-standing and active RA, in Spain is unknown. Objectives To analyse the incidence and trend of hospital admissions for amyloidosis in RA patients in Spain from 1999 to 2015. Methods We performed an observational retrospective population study analysing the spanish administrative database that includes a Minimun Basic Data Set (MBDS) of hospital admissions of RA patients from 1999 to 2015. We selected the MBDSs for amyloidosis. Cases were identified by the presence in primary and secondary diagnosis of its ICD9 code. The population at risk was estimated with an estimated prevalence of RA of 0,5% (0,8% women and 0,2% men). Crude and adjusted rates were calculated, and the trend was analysed using the Generalised Linear Model (GLM) with the year as the analysis variable. SPSS version 20 (SPSS Inc, Chicago, IL) was used. Results 338.343 RA hospital admissions were detected, being 3085 (0,9%) due to amyloidosis with 2298 (74,5%) women and 787 (25,5%) men. Mean age 65,42 (SD 13,08). There were 366 (11,9%) deaths. Age-adjusted rate during the period was 122,87/105 inhab. per year (98,96 women and 146,79 men). Amyloidosis age-adjusted rate decreased from 138,88/105 inhab. per year in 1999 to 71,47 in 2015, both women (128,18 in 1999 to 61,35 in 2015) and men (162,36 in 1999 to 107,95 in 2015). An annual decrease in the amyloidosis rate of 4,6% is estimated (RRI 0,953; CI 95% 0,939–0,968). Conclusions In Spain from 1999 to 2015 amyloidosis hospital admissions in patients with RA decreased, with an estimation of 4,6% annual reduction. This finding concurs with a greater knowledge of RA and its treatment advances with ”treat-to-target” strategies. Disclosure of Interest None declared

Objective: To evaluate the usefulness of the uterine artery mean pulsatility index (mPI-UtA) and the sFlt-1/PlGF ratio in women with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS) for the prediction of placental dysfunction-related adverse outcomes (AO), namely pre-eclampsia (PE) and intrauterine growth restriction (IUGR), and for differential diagnosis between PE and SLE flares. Study design: Observational prospective cohort study of 57 pregnant women with SLE or APS. Main outcome measures: mPI-UtA and sFlt-1/PlGF ratio in maternal serum were obtained at four gestational age periods (11-14, 19-22, 24-29 and 32-34 weeks). Comparisons among pregnancies with normal outcome, SLE flare and AO were performed. Results: Overall, we had 44 ongoing pregnancies (36 with SLE and 8 with APS) of which most (n = 35, 80%) were uncomplicated. The overall rate of AO was 9% (n = 4), that was diagnosed at a mean (SD) gestational age of 34.1 (7.5) weeks. Five SLE patients (14%) suffered a SLE flare. No differences for these markers were found between normal pregnancies and those affected by SLE flare. mUtA-PI values were significantly higher in the AO group when compared with normal and SLE flare groups, at 19-22 weeks (1.52, 0.95 and 0.76) and 32-34 weeks (1.13, 0.68 and 0.65), respectively. The sFlt-1/PlGF ratio was significantly higher in the AO group at 24-29 weeks (191.1, 3.1 and 9.2), respectively. Conclusion: Our preliminary results indicate that mPI-UtA and sFlt1/PlGF ratio may be useful to predict AO in women with SLE, and to make the differential diagnosis with a lupus flare.

Background There have been important changes in the management of rheumatoid arthritis (RA) in the last 20 years, due to the incorporation of new drugs. An increase in the incidence of tuberculosis infection (TB) has been observed because of reactivation of latent TB with the use of new treatments. Adequate prevention measures have been implemented. Objectives To analyse the incidence and trend of hospital admissions for TB in patients with RA in Spain during the period between 1999 and 2015. Methods This is a retrospective population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of patients with RA. Period: 1999 to 2015. The TB cases were identified by the presence in primary and secondary diagnosis of ICD 9 codes. The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence of RA of 0.5%. The crude and adjusted rates of TB were calculated. The trend was analysed using Generalised Linear Models (GLM) using the year variable as the analysis variable. Results Among all the admissions of patients with AR (338.343), 1209 (0.35%) were due to TB, 665 (55%) in women and 544 (44,9%) in men. The mean age was 63.25 (SD 13.7). The mean of the Charlson index was 1.84 (SD 1.45), in women 1.63 (SD 1.3) and in men 2.09 (SD 1.59) (p<0.001). There were a total of 94 (7.8%) deaths during admission (6.9% in women, 8.8% in men, p=0.231). The TB age-adjusted rate during the study period was 42.78/100.000 inhabitants RA-year (28.2 in women and 100.74 in men). The TB age-adjusted rate in both sexes remains without significant changes between 1999 and 2015 (IRR 0.225; CI95% 0.985–1.025). During the period 1999–2011 an increase of the incidence is observed, while in the period 2011–2015 it is observed a decrease of the same (fig 1). Conclusions Conclusion: In Spain, in patients with RA, the income rate in relation to tuberculosis increased from 1999 to 2010 and subsequently decreased in the period from 2011 to 2015. Disclosure of Interest None declared

Background Felty’s syndrome (FS) is an unfrequent entity realted to Rheumatoid Arthritis (RA) but it’s unknown the trend of FS in Spain. Objectives To analyse the incidence and trend of hospital admissions for FS in RA patients in Spain from 1999 to 2015. Methods We performed an observational retrospective population study analysing the spanish administrative database that includes a Minimun Basic Data Set (MBDS) of hospital admissions of RA patients from 1999 to 2015. We selected the MBDSs for FS. Cases were identified by the presence in primary and secondary diagnosis of its ICD9 code. The population at risk was estimated with an estimated prevalence of RA of 0,5% (0,8% women and 0,2% men). Crude and adjusted rates were calculated, and the trend was analysed using the Generalised Linear Model (GLM) with the year as the analysis variable. SPSS version 20 (SPSS Inc, Chicago, IL) was used. Results 338.343 RA hospital admissions were detected, being 802 (0,2%) due to FS, 455 (56,7%) women and 347 (43,3%) men. Mean age was 67,94(SD 13,76). There were 61 (7,6%) deaths. Age-adjusted rate during the period was 42,19/105 inhab. per year (19,76 women and 64,61 men). FS age-adjusted rate decreased from 25,90/105 inhab. per year in 1999 to 17,20 in 2015, both women (12,85 in 1999 to 11,75 in 2015) and men (80,15 in 1999 to 38,75 in 2015). An annual decrease in the FS rate of 0,5% is estimated (RRI 0,995; CI 95% 0,976–1,014). Conclusions In Spain FS hospital admissions in patients with RA decreased between 1999–2015 with an estimation of 0,5% annual reduction not statistically significative. Disclosure of Interest None declared

Background Several changes have appeard in the last years in the management of Rheumatoid Arhritis (RA), and also a greater awareness about cardiovascular risk has emerged. However, the trend of CVDs in RA in Spain is unknown. Objectives To analyze the incidence and trend of hospital admissions for CVDs in patients with RA in Spain during the period between 1999 and 2015. Methods We performed an observational retrospective population study analyzing the spanish administrative database that includes a Minimun Basic Data Set (MBDS) of hospital admissions of patients with RA 1999-2015. We selected the MBDSs for CVDs, myocardial infarction (MI), ischemic heart disease (IHD), congestiveheart failure (CHF), cerebrovascular disease (CeVD) and aortic aneurysm (AA). Cases were identified by the presence in primary and secondary diagnosis of ICD9 codes. The population at risk was estimated through the population censuswith an estimated prevalence of RA of 0,5% (0,8% women, 0,2% men). Crude and adjusted rates were calculated, and the trend was analyzed using the Generalized Linear Model (GLM) with the year as the analysis variable. SPSS statistical package version 20 (SPSS Inc, Chicago, IL) was used. Results 338.343 RA hospital admissions were detected in the period, being 207.597 (61,3%) due to CVDs. table1 summarizes the data of the six subgroups of CVDs. Conclusions CVDs were the first cause of hospital admissions in Spain in RA patients during the period 1999-2015. Moreover, in that period there was an increasing incidence of hospital admissions due to CVDs in all the studied subgroups, being strikingly higher inmen after age-adjusted rates. An annual rate increase is estimated in all the different studied subgroups oscilating between 5 and 9% annual increasing. Disclosure of Interest: None declared

Background The clinical coexistence of Systemic Lupus Erythematosus (SLE) and Sjögren’s Syndrome (SS) was recognised in 1959. The prevalence of SS among patients with SLE varies considerably among the published studies (10%–30%). There is still controversy as to whether or not SLE patients with overlapping SS have a distinct and significantly milder lupus. Objectives To address the clinical and serologic features of SLE and differences from SLE that occurs in overlap with SS. Methods A retrospective cohort of 3575 unselected SLE patients from 45 Rheumatology Units across Spain was evaluated for the presence of overlapping SS using the American-European consensus criteria. Cumulative clinical data were collected at the moment of the last assessment. Clinical and laboratory parameters in SLE patients with SS (SLEwSS) were compared with those in SLE patients without SS (SLEwoSS). Results SS was identified in 516 SLE patients (14.4%). Compared with the SLEwoSS group, patients with SLEwSS were significantly older, had a higher frequency of mucocutaneous manifestations, Raynaud’s phenomenon, peripheral neuropathy, anti-Ro/SSA, anti-La/SSB, neoplasia, and older age at death, but had a significantly lower frequency of renal involvement, thrombocytopenia, anti-DNA, anti-β2-GPI IgM and complement consumption. Both groups displayed a clinically similar presentation of lymphadenopathy, systemic vasculitis, serositis, damage accrual, mortality, musculoskeletal and CNS manifestations. Conclusions SLEwSS appears to constitute a subgroup of SLE patients with distinct clinical and serologic features, in whom SS is expressed as an overlapping entity. A particular cluster of clinical variables, namely, mucocutaneous manifestations, Raynaud’s phenomenon, peripheral neuropathy, renal involvement and thrombocytopenia, was found to be important overall for discriminating SLE patients with or without SS. SLEwSS patients constitute a subgroup of patients with SLE characterised by milder lupus: older age at death, similar rates of mortality and SLICC-ACR damage index, less renal and immunological manifestations. Disclosure of Interest None declared

Background The need of orthopaedic surgery (OS) is a marker of disease severity in RA. During the last 20 years, the treatment in RA has changed, incorporating strategies based on ”treat-to-target” and biological therapies. But, have these new strategies modified the incidence of OS in RA? Objectives To analyse the incidence and trend of hospital admissions for OS in patients with RA, in Spain, during the period between 1999 and 2015. Methods This is a national retrospective population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of all hospital admissions of patients with RA. Period: 1999 to 2015. The OS were identified by the presence of ICD9 codes for arthrodesis, Total Hip Arthroplasty -THA-, Total Knee Arthroplasty -TKA-, Total Superior Limb Arthroplasty -TSLA. The population at risk was estimated through the population census of the National Institute of Statistics. The adjusted rates of hip fracture were calculated, by sex and age. The trend was analysed by Generalised Linear Models (GLM). Results Of a total of 338.343 hospital admissions, 21.088 (6,62%) were for OS. The main clinical-demographic characteristics are shown in the next table 1. The mean age of OS increased 6 years during the study period (p<0,001). The OS age-adjusted rate during the study period was 752,9/105 inhab-year. The global fracture age-adjusted remained stable during de study period (IRR 1,002; IC95% 0,9–1,01). In RA patients>60 the rate increase while in RA <60 years the rate decrease (figure 1). Conclusions In Spain, during the period from 1999 to 2015, the global incidence rate of orthopaedic surgery in patients with RA has remained stable. In RA patients>60 years the rate increase while in RA <60 years the rate decrease. The mean age of OS increased 6 years. Disclosure of Interest None declared

Background During the last 20 years there have been significant changes in the treatment of patients with rheumatoid arthritis (RA) and in the prevention and treatment of osteoporosis. The potential impact of these strategies on important outcomes as the incidence of hip fracture in RA is unknown. Objectives To analyse the incidence and trend of hospital admissions for hip fracture in patients with RA, in Spain, during the period between 1999 and 2015. Methods This is a retrospective population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of patients with RA. Period: 1999 to 2015. The hip fracture cases were identified by the presence in primary and secondary diagnosis of ICD 9 codes. The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence of RA of 0.5%. The crude and adjusted rates of hip fracture were calculated. The trend was analysed using Generalised Linear Models (GLM) using the year variable as the analysis variable. Results Of a total of 338.343 admissions of patients with RA, 6.656 (2%) was due to hip fracture, 5.608 (84.2%) in women and 1.048 (15.7%) in men. The mean age was 77.54 (SD 9.6). Mean age increased linearly during the study period (from 75,3 years in 1999 to 79,9 in 2015). There was a total of 326 (4.9%) deaths during admission. The fracture age-adjusted rate during the study period was 243,66/100.000 RA-patients*year (245,24 in women and 198,05 in men). The fracture age-adjusted rate increased from 150.11/100.000*year in 1999, to 303.12 in 2015 (in both sex). In women from 134.71 in 1999 to 304.83 in 2015) and in men from 99.63 in 1999 to 268.5 in 2015). An annual increase in the fracture rate of 3.1% is estimated. Conclusions In Spain, during the period from 1999 to 2015, although the mean age has increased, the incidence of hip fracture has not been reduced. We estimate an annual increase of 3.1%. Disclosure of Interest None declared

Background There have been significant changes in the management of rheumatoid arthritis (RA) during the past 20 years. The potential impact of these strategies on hospitalisation trend is unknown. Objectives To analyse the incidence and trend of hospital admissions in patients with RA in Spain from 1999 to 2015. Methods This is a population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of patients with RA during the period 1999–2015. The admission cases in patients with RA were identified by the presence in primary and secondary diagnosis of the ICD9 codes (714.0–714.9). The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence for RA of 0.5%, with crudes and adjusted admission rates being calculated. The trend was analysed using Generalised Linear Models (GLM). Results There were a total of 3 38 343 hospital admissions in RA patients during the study period, accounting for a total of 1 76 097 patients (1 17 985 women and 58 112 men). The mean age at admission was 68 years (67.8 in women and 68.5 in men), with a linear increase throughout the study period from 65.3 in 1999 until 70.5 in 2015 (p<0.001). The main admission code was for Osteoarticular and connective tissue diseases (20%) followed by Circulatory system diseases (16.8%). There were a total of 18 641 intrahospital deaths (5.5% of all the admissions). The age-adjusted admission rate was 12.03/100 RA patients*yr (9,12 for women and 1.88 for men). The age-adjusted admission rate increased from 1999 to 2015 (in both genders). An annual increase of admission rate of 3.7% is estimated. When adjusting by age, the largest increase is observed in patients older than 80 years, with an estimated annual increase of 7.5%. Conclusions In Spain, despite the improvement in RA management, there is a global tendency to the increase of admissions during the period of 1999–2015, mainly in >60 year, especially in >80 year. Disclosure of Interest None declared