I. Rúa-Figueroa

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study

Objective: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. Methods: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI scoreu2009≤u2009two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. Results: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0u2009±u200915.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100u2009mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0–8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. Conclusion: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

Classification of Systemic Lupus Erythematosus: Systemic Lupus International Collaborating Clinics Versus American College of Rheumatology Criteria. A Comparative Study of 2,055 Patients From a Real-Life, International Systemic Lupus Erythematosus Cohort.

The new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria aimed to improve the performance of systemic lupus erythematosus (SLE) classification over the American College of Rheumatology (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external validation. Our objective was to compare the sensitivity for SLE classification between the ACR 1997 and the SLICC 2012 criteria sets in a real‐life, multicenter, international SLE population.

The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB)

Introduction Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. Methods The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. Results Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100u2009mg/dl (34%) and a high-density lipoprotein (HDL) level of <50u2009mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (pu2009=u20090.001) and with TC (pu2009=u20090.005) and TGs (pu2009<u20090.001) at the end of the follow-up period. Conclusion Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity.

Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry

OBJECTIVESnTo identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality.nnnMETHODSnThis is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years.nnnRESULTSnThree damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well.nnnCONCLUSIONnIn a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

OBJECTIVESnTo identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality.nnnMETHODSnThis is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared.nnnRESULTSnMean age (years)u202f±u202fS.D. at diagnosis was 14.2u202f±u202f2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DIu202f±u202fS.D. was 1.27u202f±u202f1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, Pu202f<u202f0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (Pu202f<u202f0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (Pu202f<u202f0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (Pu202f<u202f0.017 for both comparisons).nnnCONCLUSIONSnIn a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

AB0173 Mycobacterial infection in systemic lupus erythematosus: clinical significance and associated factors. data from the registry of patients with sle of the spanish society of rheumatology (RELESSER)

Objectives To study the prevalence of mycobacterial infection (MI), the associated factors and their clinical significance in patients included in a large SLE cohort. Methods Retrospective descriptive study of RELESSER patients with a history of MI and analysis of the factors associated with this infection. Results In RELESSER 3,658 patients with ≥4 ACR SLE criteria were included. 90% are women with a mean age of 32.9 years. 93% are Caucasians. The mean follow-up time (± SD) was 120.2 (± 87.6) months. 705 (19.3%) patients had ≥1 severe infection (defined as requiring admission); 1,227 severe infections occurred. MI were diagnosed in 42 patients (1.2% of all RELESSER patients, 3.4% of all severe infections), 85.7% women. The incidence rate of MI was 1 per 1,000 patients/year (95% CI:0.7–1.4). MI presentation was pulmonary in 18 (42.9%) patients and extrapulmonary in 24 (57.1%) patients [joints in 8 (19.0%) patients, soft tissue in 6 (14.3%) and other sites in 10 (23.8%)]. The extrapulmonary form was associated with immunosuppressants use: 84.6% of the 13 patients treated with immunosuppressive drugs versus 44.4% of the 27 patients without (p=0.01). We did not observe this association with the use of corticosteroids. To study the factors associated with MI, we performed a bivariate analysis including the variables associated with severe infection in RELESSER (age, sex, ethnicity, corticosteroids, immunosuppressants, antimalarials, previous admission by SLE activity, rituximab and anti-TNF use, Katz severity index, SDI index, SLEDAI index and Charlson comorbidity index). There is a statistically significant association with previous admission by SLE activity (RR:2.9, 95–95%:1.3–6.2, p=0.007), renal impairment (RR:2.0, CI 95%:1,1–3,7, p=0,04), the Katz score (RR:2.1, 95% CI:1.1- 4.0, p=0.04) and the Charlson index (RR: 2.5; 95% CI: 1.3–4.8, p=0.009). Damage (SDI>0) was closely associated with significance:RR: 2.0; 95% CI: 1.0–4.0, p=0.07. Iimmunosuppressants use was associated with an important increase in the risk of MI: RR:4.3; 95% CI:2.2–8.3, p=0.31. Two patients (4.8%) died (1 respiratory and 1 extrapulmonary). Mean survival after MI diagnosis in these cases was 21 days. Conclusions MI in RELESSER affects 1.15% of patients. Its incidence rate is 1 per 1,000 patients/year (95% CI:0.7–1.4). Extrapulmonary localization affects more than half of the patients and is associated with immunosuppressants use. Previous admission by SLE activity, renal involvement, SLE severity and increased number of comorbidities are factors associated with MI. Acknowledgements Work supported by Spanish Society of Rheumatology, FIS/ISCIII/FEDER (PI11/02857), BIOCAPS from the European Union 7th Framework Programme/REGPOT-2012–2013.1(316265), GSK, Roche, Novartis, UCB. Disclosure of Interest None declared

AB0429 Pure Red Cell Aplasia in Patients from SLE Registry from The spanish Society of Rheumatology (RELESSER)

Background Systemic Lupus Erythematosus (SLE) is an autoimmune systemic rheumatic disease that, in our area, presents hematologic manifestations in approximately 70% of cases1. Some of them are very rare, there are no large series whose analysis could provide relevant information. Objectives To study the characteristics of patients with Pure Red Cell Aplasia (PRCA) in a large sample of SLE patients. Methods SLE patients from RELESSER database were studied. We analysed the clinical and analytical SLE manifestations at 12 different domains (mucocutaneous, renal, musculoskeletal, constitutional, haematologic, vascular, cardiac, respiratory, neuropsychiatric, gastrointestinal, ophthalmic and serological) before, during and after PRCA diagnosis and until the last available assessment. We also studied activity (SELENA-SLEDAI) and damage (SLICC/ACR DI)indices at each of those times. We evaluated the treatment received, PRCA recurrences and the number of deaths by this entity. Results 3,656 patients from 45Rheumatology Units across Spain were studied. 5 cases of PRCA were found (<0.5%of total) There were not viral infections in relation with the PRCA. All patients had a good response to treatment, reaching complete remission without relapses or deaths. The mean number of treatment lines (± SD)that were necessary was 2.2 (±1.01)and the mean (± SD)number of treatments used was 2.8 (±1.92). Except for the patient diagnosed with PRCA before SLE, all of them received glucocorticoids as initial treatment. Of these 4patients only 1achieved complete remission without requiring immunosuppressive therapy. The following table shows the characteristics of each patient:Table 1 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Number of organ systems affected by SLE before PRCA diagnosis Not applicable 6 6 4 7 Number of organ systems affected by SLE at PRCA diagnosis Not applicable 1 1 1 6 Number of organ systems affected by SLE until last assessment 3 3 5 1 2 Haemoglobin levels at PRCA diagnosis (g/dl) 7 4.9 4.9 4.5 6.3 Bone Marrow biopsy or aspirate Selective aplasia/hypoplasia of the red series, without changes in other series SLEDAI / SLICC-ACR DI at PRCA diagnosis Not applicable 4 / 1 2 / 1 0 / 0 20 / 0 SLEDAI / SLICC-ACR DI 1 year after PRCA Not applicable 0 / 1 2 / 1 2 / 0 4 / 0 SLEDAI / SLICC ACR DI at last assessment 0 / 0 6 / 3 0 / 2 0 / 0 0 / 0 Number of treatment lines 2 2 2 1 4 Treatments administered 1st: Oxitosona 1st: Glucocorticoids 1st: Glucocorticoids Glucocorticoids 1st: Glucocorticoids hydroxicloroquine 2nd: Belimumab erythropoietin 2nd: Inmunoglobulins 2nd: Inmunoglobulins & RBC transfusion 2nd: Ciclosporin A 3rd: Rituximab 4th: Darbepoetin α Total number of treatments administered 2 3 2 1 6 Relapse No Death No Conclusions PRCA is a very rare cause of anemia in SLE. In most cases it appears several years after the diagnosis of SLE. It is a serious manifestation but in our series, with a proper management showed a favourable response. References Pego-Reigosa JM et al. Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus. Lupus 2015;24:720–9. Disclosure of Interest A. Lois-Iglesias: None declared, I. Rúa-Figueroa: None declared, C. Erausquin: None declared, D. Grados: None declared, A. Olivé: None declared, V. Quevedo: None declared, J. Alegre: None declared, J. Calvo: None declared, F. Lόpez-Longo: None declared, M. Galindo: None declared, F. deToro: None declared, C. Mouriño: None declared, J. Pego-Reigosa Grant/research support from: Work supported by Spanish Society of Rheumatology, FIS/ISCIII (PI11/02857), BIOCAPS from the EU 7th Framework Programme/REGPOT-2012–2013.1 (316265), GSK, Roche, Novartis, UCB.

FRI0424 Cardiovascular Events in Systemic Lupus Erythematosus (Sle): A Nationwide Study in Spain (Relesser Registry)

Objectives To examine the frequency of cardiovascular events (CVE) and to investigate the main risk factors for atherosclerosis in a large cohort of patients with SLE from Spain (RELESSER Registry) Methods Design: A national multicenter retrospective study. Patients with SLE (ACR 1997 criteria) from 45 Rheumatology university centers (RELESSER Registry) were enrolled. Protocol: A specific protocol was designed to collect variables. Data were extracted from clinical records. Variables:demographic, comorbidity, clinical, laboratory and treatment information. Outcome: Cardiovascular event after SLE diagnosis. It was defined as the presence of ≥1: 1) ischemic heart disease (myocardial infarction and/or angina pectoris based on clinical and/or electrocardiogram and/or changes in cardiac enzymes and/or coronary angiography diagnosis); 2) cerebral vascular accident (CVA) based on a previous diagnosis or clinical manifestations and/or a image specific procedure and 3)peripheral artery disease supported on a previous diagnosis or clinical manifestations confirmed by image procedure. Statistical analysis: Descriptive. Differences between groups were compared using χ2 test, t-test or Mann-Whitney-U-test. Multiple logistic regression (MLR) analysis of potential CV risk factors was performed. Results Of the 3,658 SLE patients enrolled in RELESSER, 3,649 (99.7%) had sufficient CVE information available. 269 patients (7.4% [95% CI,6.6-8.3]) suffered 318 CVE after SLE diagnosis. The main characteristics of these patients are shown in table. The average (SD) of age at first CVE from SLE diagnosis was 48.6 (17.1) years and occurred after a median disease duration of 10.4 years after diagnosis. The probability of suffers a first CVE after SLE diagnosis was 1.2% at 1st year, 3.4% at 5th year, 5.7% at 10th, and 9.8% at 15th years. CVA were the most frequent CVE after SLE diagnosis (5.7% [95% CI, 5.0-6.5]) followed by ischemic heart disease (3.8% [95% CI, 3.2-4.4]). Univariate analysis found no association of CVE with a family history of CV disease, methotrexate, hematologic disorders, discoid rash, photosensitivity, oral ulcers, arthritis or positivity of Anti-Sm, anti-Ro, anti-La and anti-RNP. MLR analysis shown a strong association (HR [95% CI], p-value) between CVE and age (1.06[1.04-1.08], p<0.001), hypertension (1.66[1.14-2.42], p=0.009), smoking (1.52[1.07-2.15], p=0.019), diabetes (2.42[1.37-4.28], p=0.002), SELENA-SLEDAI at the last visit (1.07[1.03-1.11], p<0.001), neuropsychiatric lupus (2.12[1.33-3.40], p=0.002), Valvular disease (2.10[1.20-3.72], p=0.011), antiphospholipid antibodies (APA) (1.55[1.23-2.56], p=0.012) and high doses of glucocorticoids (GC): >60mg/d (3.11[1.53-6.29], p=0.012). Conclusions SLE patients suffer a high prevalence of premature CVE associated with traditional CV risk factors and related to SLE, particularly with activity SLEDAI, neuropsychiatric lupus, valvular disease, APA and high doses of GC. Acknowledgements This work has been supported by FIS (ISCIII) PI11/02857.Partially supported by GSK, UCB, Roche and Novartis. Dr. Pego-Reigosa receives support from Biocaps (grant 316265) of the 7th Framework Programme of the European Union. Disclosure of Interest S. Manrique-Arija: None declared, A. Fernandez-Nebro: None declared, Í. Rua-Figueroa: None declared, J. Lopez-Longo: None declared, J. Calvo-Alén: None declared, M. Galindo: None declared, J. Pego-Reigosa Grant/research support from: Biocaps

FRI0427 Characterization of Patients with Lupus Nephritis Included in A Large Cohort from the Spanish Society of Rheumatology Registry of Patients with Systemic Lupus Erythematosus (RELESSER)

Objectives To describe the profile of patients included in RELESSER with histologically confirmed lupus nephritis (LN). Methods RELESSER is a multicentre cross-sectional study with an analytical component.Information was retrospectively collected from the medical records of patients with SLE who were followed up at participant rheumatology units.A total amount of 359 variables including demographic data,clinical manifestations,activity,severity,comorbidities,treatments and mortality were recorded. Specifically, the following renal data were included: WHO histological type of LN, the presence of proteinuria, haematuria, leukocyturia, cellular casts and creatinine clearance. Data regarding recurrence, treatment response, development of end-stage renal disease (ESRD) and/or the need for dialysis or renal transplantation were collected. We performed a descriptive analysis by calculating means and standard deviations for numerical variables and frequencies for qualitative variables. Chi -square or t- Student tests were applied according to the type of variable to analyse its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. Statistical significance was p<0.05. Results LN was histologically confirmed in 1092 patients (30.5%).Most patients were female (85.7%),Caucasian (90.2%),and the mean age at LN diagnosis was 28±12 years.Most had LN proliferative forms (70.2%),and there were only 15 cases of thrombotic microangiopathy (TMA).The development of NL was more frequent in women (p<0.001),at younger age (p<0.001) and in Caucasians (p=0.03).Complete response to treatment was achieved in 2.2% of patients,8.6% developed ESRD,and 9.7% and 5.3% ended in dialysis and kidney transplantation, respectively.The rate of patients with complete response was lower in the case of proliferative forms,but the difference did not reach statistical significance.The higher the age of LN the greater the likelihood of complete response (p<0.001).This likelihood was lower in Asians (p=0.036).326 recurrences were recorded, with a mean individual event of 1 and a mean time to first recurrence of 47 months (0-28), regardless of histology.The lower was the serum creatinine and the older was the age at LN onset, the lower was the recurrence risk. TMA was a risk factor for recurrence (p=0.016),whereas recurrences were related with persistent lupus activity at the last visit (p<0.001) and with ESRD (p<0.001).During the follow up, the LN development associations are described in Figure 1. LN was related to an increased risk for avascular bone necrosis [OR 2.61, (CI 1.84-3.69)] and premature gonadal failure [OR 12.32, (CI 7.34-20.71), p<0.001]. LN itself was a poor prognostic factor associated with increased mortality risk [OR 2.4 (1.81-3.22), p<0.001]. Conclusions LN, mainly proliferative forms, affects almost one third of patients with SLE, and is often associated with the occurrence of other severe lupus manifestations, being a poor prognostic factor. TMA and relapses are associated with worse outcome in renal function. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3180

THU0021 Differences between Defined and Incomplete SLE Patients Included in RELESSER Registry

Background Patients with incomplete Systemic Lupus Erythematosus may represent a group of patients who will later develop SLE or they may form a subset of SLE patients with mild disease. Objectives To study the differences in clinical manifestations, damage, co-morbidity and disease severity between patients with defined SLE (dSLE) and those with incomplete SLE (iSLE), included in RELESSER registry. Methods All patients included in the transversal phase of RELESSER were studied. The registry includes demographic data, clinical manifestations, information about activity, damage, severity, comorbidity, treatments and mortality, collecting 359 variables per patient, with highly standardized definitions. SELENA-SLEDAI (S-SLEDAI) and SLICC/ACR/DI (SDI) scores and Katz index (IK) were calculated. To compare both groups an analysis based on the estimation of simple and adjusted odds ratios (OR) by means of logistic regression, with 95% confidence intervals (95%CI) was done. Results 4,024 SLE patients were included (91% females; mean age at diagnosis:35.4 years; disease duration: median 11.0 years). 3,679 (91.4%) were dSLE and 345 (8.6%) iSLE. dSLE were younger than iSLE at diagnosis (34.6 vs 42.9 years) (OR:0.92; CI95%: 0.90-0.96; p<0.001), with a longer disease duration (12 vs 8 years) (OR:1.05; CI95%: 1.03-1.07; p<0.001). As it was supposed, most clinical manifestations were more frequent in dSLE patients. Every one of the ACR criteria was associated with dSLE condition and this association was extremely high in the cases of malar rash (OR:9.14; CI95%:6.20-13.46; p<0.001), oral ulcers (OR:9.37; CI95%:6.08-14.45; p<0.001) and renal disorder (OR:9.12; CI95%:5.18-16.07; p<0.001). The analysis adjusted by gender, age at onset and disease duration showed higher S-SLEDAI (OR:1.14;CI95%:1.08-1.20;p<0.001), SDI (OR:1.29; CI95%:1.15-1.44; p<0.001), KI (OR:2.10; CI95%:1.83-2.42; p<0.001), number of hospitalizations due to SLE activity (OR:2.79; CI95%:2.15-3.63; p<0.001) and mortality (OR:2.25; CI95%:1.24-4.48; p=0.008) in dSLE patients than in iSLE ones. Higher number of dSLE received glucocorticoids (OR:3.22; CI95%:2.43-4.25; p<0.001), cyclophosphamide (OR:3.47; CI95%:2.12-5.67; p<0.001), mycophenolate mofetil (OR: 3.45; CI95%:1.91-6.25; p<0.001) and rituximab (OR:3.34; CI95%:1.36-8.23; p=0.009). Refractoriness were associated with the dSLE condition (OR:3.04; CI95%:1.98-4.68; p<0.001). Although there were differences in certain risk factors between both groups, it was not the case in cardiovascular events. Conclusions These results, obtained from the largest iSLE patients cohort reported up to now, support the hypothesis that iSLE behaves as a relative stable and mild disease, with lower activity, severity and refractoriness than dSLE. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4580