M.V. Irigoyen

Long-term TNF-α Blockade in Patients with Amyloid A Amyloidosis Complicating Rheumatic Diseases

OBJECTIVE To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. METHODS Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. RESULTS At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. CONCLUSION Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection.

AB1078-HPR Telephone Follow-Up, Standardized To The Initiation of Biologic Therapy of Patients with Rheumatoid Arthritis (RA) in A Specific Unit of Biologic Therapy. Pilot Study

Objectives To know the usefulness of follow-up call legalized at the beginning of biologic therapy and patient contact with consultation of nursing after the start of treatment. Methods Observational study cross.Patients: We collected 120 patients who began treatment with biologic therapy, intravenous or subcutaneous from December 2013 to November 2015. Protocol: Protocol is education for self-management of subcutaneous biological therapy at the beginning of the treatment. This Protocol includes a follow-up call from the consultation of nursing that matches the first administration of the treatment at home or within 3–5 days after the first infusion. This call is made in the case of the biological subcutaneous as per guideline: etanercept (7 days), adalimumab (14 days), golimumab (28 days), tocilizumab (7days), certolizumab (14 days), abatacept (7days) either guideline prescribed in case of dose reduction. Offers the possibility of contact (telephone and e-mail) with the consultation of nurses in case of doubt or incidence during treatment and is analytical control to the month of the beginning of nurse telephone consultation. Statistical analysis: a descriptive analysis of the main variables. Results 120 patients with RA initiated treatments were: etanercept 33,3% (n40), adalimumab 8,3% (10), tocilizumab sc 20% (24), abatacept sc 12,5% (15), golimumab 13,3% (16), rituximab 6,7% (8), certolizumab pegol 3,3% (4), biosimilar 2,5% (3). In terms of the associated FAME: none 38,3% (46), methotrexate 49,2% (59), Leflunomide 8.3% (10), sulfasalazine 1,7% (2), hydroxychloroquine 2,5% (3).They were detected in the Protocol call patients with incidences 14,16% (17): local reaction3.3% (4), pruritus 5.8% (7), upset general 0.8% (1), diarrhea 0.8% (1), constipation 0.8% (1), headache 1.7% (2). The patients called the nursing consultation to communicate incidences 10.83% (13): anemia 0.8% (1), hypertransaminasemia 1,7% (2), implant dental 0.8% (1), bruising 0,8% (1), inefficiency 6.7% (8). Also communicated to the consultation of nursing infections during 16.6% (20): urinary tract infection 5,8% (7), upper respiratory tract infection 1,7% (2), upper respiratory tract infection+herpes simplex 0,8% (1), lower respiratory tract infection 3,3% (4), surgical wound infection 0.8% (1), dental infection 0,8% (1), herpes simplex 0,8% (1), gastroenteritis 0,8% (1), not frightening infection 1,7% (2).Patients who started biologic therapy in the period studied only 8.3% (10) changed treatment.The emergence of new comorbidities were detected during treatment with biologic therapy 4,16% (5): hypertension 0,8% (1), hypertension + diabetes mellitus II 1,7% (2), nonspecific Interstitial pneumonia 0,8% (1), psoriasis 0,8% (1). Conclusions The follow-up call is a useful tool for the control of security of the new beginnings of biological agents. It could foster adherence to treatment monitoring at home and offering the possibility to communicate with the nursing. Disclosure of Interest None declared

AB1109 Dose de-escalation in a specialized outpatient clinic on biological therapy: cost minimization observational study

Objectives To estimate the annual cost in the use of biological therapy (BT) in patients with different rheumatic diseases when dose modifications are undertaken in daily clinical practice in a specialized outpatient clinic during 2016 and to compare the results with data obtained in 2013. Methods Design: Cost minimization observational study under conditions of clinical practice. Patients: Patients with different rheumatic diseases who come to a specialized outpatient clinic on BT in the Rheumatologic department at a tertiary Spanish hospital (with a tight follow-up) that had been treated with BT under reduced doses during 2016 were collected. Protocol: Reductions in treatment dose or dose frequency were established empirically and were carried out by their rheumatologist in those patients who were in remission (DAS 28 <2,6) for at least 6 months without steroids. Main outcome: Reduction of annual average cost in euros in BT used in patients who are in dose reduction in clinical practice in 2016. Secondary outcome:Differences in annual costs reduction in 2016 compared with 2013. The cost reduction was calculated by comparing the actual expenditure (after modifying treatment dose in clinical practice) with the theoretical costs (official price) in case you had not made the adjustment. Statistical analysis: Sample descriptive analysis. Reducing annual absolute costs and by treatment after tapering down doses in clinical practice in 2016 and the differences found between 2013 were calculated. Results During 2016, the dose of the BT of 168 patients (94 Subcutaneous BT and 74 intravenous BT) were modified in clinical practice after reaching clinical remission:mean of DAS 28 (mean±SD)=2.31±0.76 or BASDAI (mean±SD)=2.15±1.39 without radiographic progression. Most patients were women (n=113;67%)and had rheumatoid arthritis (n=103;62%) and the rest were distributed among: spondyloarthritis (n=28;17%), psoriatic arthritis (n=22;13%), juvenile idiopathic arthritis (n=10;5%) and Systemic Lupus Erithematosus (n=5;3%). No patients treated with certolizumab or anakinra was modified treatment doses. During this period, 5 patients discontinued BT (3 remissions and 2 minor adverse events). Table 1 shows the number of patients by type of BT and costs. The BT dose reduction in clinical practice during 2016 represented a saving of 676,501.67€ and a greater efficiency of treatments while in 2013, only 86 patients (30 etanercept, 15 adalimumab, 16 Infliximab (Remicade), 15 Tocilizumab IV and 55 Rituximab) had a modified dose of BT in clinical practice assuming a saving of 396,995.46€. The difference in the annual cost reductions in 2016 compared to 2013 meant a saving of 279.506,21€ more in the last year. Table 1. Conclusions In rheumatic diseases we may do a dose de-escalation of BT in patients who go into remission and therefore we could reduce the associated costs of BT and being more efficient with the treatments. We believe that it is important to create specialized outpatient clinics on BT where a tight-control management of these patients and an individualized treatment are carried out. Disclosure of Interest None declared

SAT0089 Cost Minimization Observational Study after Dose Optimization in A Specialized Outpatient Clinic on Subcutaneous Biological Therapy

Objectives To estimate annual cost in the use of subcutaneous BT (scBT) in patients with rheumatic diseases when dose modifications are undertaken in daily practice in a specialized outpatient clinic of a tertiary hospital during 2013 and to compare the results with data obtained in 2012. Methods Cost minimization, cross-sectional observational study.Patients with different rheumatic diseases who are following a tight control care in a specialized scBT outpatient clinic of a tertiary Spanish hospital who have been treated with BT under conventional and modified doses during 2013 were collected.Reductions in treatment dose were made at the discretion of their physician in patients who were in remission for at least 6 months.Main outcome:Reduction of annual average cost in euros in scBT used in clinical practice in 2013. Secondary variables:demographics, type of rheumatic disease, clinical and laboratory data. The cost reduction was calculated by comparing the real expenditure (after modifying treatment dose) with the theoretical costs if he had not made the adjustment. Statistical analysis:Descriptive analysis was performed. Reducing annual absolute costs and by treatment after the adequacy of dose in 2013 and the differences found between 2012-2013 were calculated. Results A total of 204 patients were followed in the monographic scBT clinic in 2013, with 333 visits [1.58 visits/patient (min.1-max.5)]. Most patients had RA (n=123, 60.3%) and the rest were distributed among: spondyloarthritis (n=37, 17.6%), psoriatic arthritis (n=33; 16.2%), juvenile idiopathic arthritis (n=11; 5.4%) and one SAPHO (0.5%) treatments received in the outpatient clinic were:etanercept, adalimumab, golimumab, abatacept, certolizumab and anakinra. During 2013, the dose of the scBT of 43 (21.1%) patients (19 RA,6 SpA,16 PsA,2 JIA) were modified in clinical practice because they reached clinical remission:DAS28[(mean (±SD)]=2.57 (0.85) or BASDAI [(mean (±SD)]=2.67 (1.59), without radiographic progression. No patients treated with golimumab, abatacept, certolizumab or anakinra was modified treatment doses. Among the 43 patients, 28 patients were treated with Etanercept and 15 with Adalimumab. The BT dose reduction in clinical practice during 2013 represented a saving of €205,947.68 and a greater efficiency of treatments while in 2012, only 28 patients (18 etanercept and 10 adalimumab) had a modified dose of scBT in clinical practice assuming a saving of €124,120.79. Conclusions In rheumatic diseases we may adjust the dose of treatment in patients who go into remission reducing the associated costs of scBT and being more efficient with the treatments. A largest number of patients in dose reduction, during 2013, could be attributed to a tight-control management carried out since the creation of a specialized BT outpatient clinic. We believe it is important to create outpatient clinics specialized in BT where periodic assessments with close monitoring of these patients and an individualized treatment are carried out. Disclosure of Interest S. Manrique-Arija Grant/research support: Pfizer, C. Romero-Barco: None declared, M. Ordoñez-Cañizares: None declared, I. Ureña: None declared, L. Cano: None declared, F. Jimenez-Nuñez: None declared, L. Nieves-Martin: None declared, N. Mena-Vazquez: None declared, M. Irigoyen: None declared, A. Ponce: None declared, V. Coret: None declared, M. Belmonte-Lopez: None declared, M. Rodriguez: None declared, A. Fernandez-Nebro Grant/research support: Pfizer, Roche, Speakers bureau: Pfizer, Roche, Abbvie, MSD, BMS DOI 10.1136/annrheumdis-2014-eular.4525

AB0583 Effectiveness and safety of short-term treatment of active rheumatoid arthritis (RA) moderate to severe with tocilizumab

Objectives To evaluate the effectiveness and safety of tocilizumab (TCZ) for the treatment of active RA in our department. Methods Type of study: Prospective cohort. Inclusion criteria: RA-patients (new ACR-EULAR criteria) who have failed to at least one anti-TNF drug. Variables and Statistic: We evaluated the monthly changes of DAS28 and HAQ during the first year of treatment with TCZ using repeated measures ANOVA and survival of TCZ over the first 2 years with survival curves of Kaplan-Meier. Safety was assessed collecting adverse events, withdrawals due to safety and deaths. Results We included 35 patients, 19 of them from clinical trials (88.6% women with a mean age of 55.3±11.1 years) with a total follow-up for 29.7 person-years, a median duration of disease of 10.0±7.3 years. Anti-CCP was positive in 22 patients (64%) and the rheumatoid factor in 31 (89%). Thirty-one (89%) had radiographic erosions and 1 patient had previous orthopedic surgery (arthroplasty of both knees). The number of previous DMARDs: 6 (17%) had received one, 11 (31%) two, 11 (31%) three, 1 (3%) four, 2 (5.7%) five, and one (3%) six DMARDs. The mean of DMARDs was 2.4±1.3 per patient. Twenty (60%) patients had taken MTX (mean dose 16.4±4.8 mg/week), 6 (17%) had received LF (mean dose 20mg/24 h) and 1 (3%) hydroxychloroquine (mean dose of 400mg/24 h). The number of previous biological therapies used was: 8 (22.9%) patients had received one, 13 (37%) two, 7 (20%) three and 6 (17%) four, which represented an average of 2, 3±1.0 per patient biologics. The DAS28 improved progressively during the first year with TCZ (F =17.8; Trace Pilai p=0.008). Although the most significant change occurred in the first month (mean difference 1.9 (95% CI =0.4 to 3.3, p=0.002, Bonferroni adjustment p=0.010) after 1 year reached an estimated mean difference of 3.1 (95% CI =1.3 to 4.8, Bonferroni adjustment p=0.002).The HAQ also improved progressively with TCZ the first 3 months (F =3.5; Trace Pilai p=0.043), but in a much slower than the DAS28 [mean difference from baseline to third month in 0.436 (95% CI = - 0056 to -0929; Bonferroni adjustment p=0.103). Twenty (57.1%) patients continued with treatment after a median of 18 months (CI 95% 11.7 to 24.2 months) which resulted in the suspension rates of 14%, 17% and 26% at 3, 6 and 12 months, respectively. The causes of withdrawal or abandonment of treatment with TCZ were: 2 (6%), infections (severe cellulitis, and conjunctivitis), 2 (6%) due to failure of efficacy, 3 (9%) for infusional reaction, 1 (3%) by asymptomatic neutropenia, 3 (9%) patient’s decision, 2 (6%) due to gastrointestinal intolerance and 1 (3%) for protocol violation. Of all dropouts, only 8 patients were withdrawn due to adverse effects (including the only serious case was a right lower limb cellulitis). Conclusions In patients with RA who have previously failed other biologic therapies, TCZ produced a rapid improvement of inflammatory activity and physical function. The rate of discontinuation due to adverse events was relatively low for this subgroup of patients (23%), and serious adverse events were unusuals. Disclosure of Interest None Declared

AB0731 Risk factors and prevalence of osteoporosis in patients with systemic lupus erythematosus

Objectives To determine the prevalence and risk factors of osteoporosis in patients with Systemic Lupus Erythematosus (SLE) in our hospital. Methods Design: Retrospective study. 101 SLE-patients were studied in the Rheumatology Department in Carlos Haya Hospital in Malaga. Patients’ disease and demographic data (including SLEDAI) were collected. Bone mineral density (BMD) was measured at the lumbar spine (LS) and femoral neck (FN) with a DEXA-LUNAR- PRODIGY. The results were classified according to WHO criteria. Thoracic and lumbar spine radiographies were assessed using the Genant method. Results Data from 98 SLE-patients were available for analysis (94% women, mean age 42±14 years). Only 61 patients (62%) had a DEXA. Patients with DEXA were similar to others in terms of gender, race, history of fracture, alcohol, tobacco, sedentary, photosensitivity or use of corticosteroids. However, patients with DEXA were older (42.3±14 years vs. 40.6±13.5 years, T-test p=0.002), had a longer duration of lupus (120.7±103.3 months vs. 89.6±68.4, U of MW p no significant differences were found in the prolonged steroids taking (>6 months) [4 (44.4%) vs. 30 (66.7%), Fisher’s exact test p=0.266] and SLICC (0.9±0.9 VS. 0.9±1.5, T-test p=0.937). Conclusions The prevalence of osteopenia and osteoporosis in our SLE-patients is greater than in general population and it is more frequent in older age, menopausal status and history of fracture. The profile of patients with DEXA reflects that this test is not request systematically in clinical practice but only to those patients with more osteoporosis risk, this is a considerable bias in our study. The small sample size and the systematic use of prophylactic treatmentin patients treated with corticosteroids may be also explained why it was not found relationship between glucocorticoids and low mineral bone density Disclosure of Interest None Declared

SAT0080 Early Rheumatoid Arthritis Patients without Treatment: Baseline Asessment of Insulin Resistance and Cytokines

Objectives To analyze insulin resistance (IR), inflammatory cytokines, adipokines and clinical and laboratory characteristics in patients with early rheumatoid arthritis (ERA) who have not received any treatment for their disease. Methods This is a cross-sectional study based on cases and controls. Forty six consecutively adults (age ≥16 years old) with ERA (disease duration <1 year) according to 2010 ACR/EULAR criteria, and 45 sex and age matched controls were included. Patients with Diabetes (2010 ADA Criteria) or in treatment with glucocorticoids or DMARDs (current or previous) were excluded. All participants signed an informed consent. Glucose, lipid profile, RF, antiCCP and ESR were measured; insulin, ultrasensitive CRP, IL6, TNFα, Resistin, adiponectin, and leptin were determined in frozen serum stored at -80°C. Insulin Resistance (IR) was estimated by the Homeostasis model assesment for insulin resistance (HOMA-IR), by HOMA β, by McAuley and by QUICKI index. A cardiovascular risk factors (CVRF) questionnaire was also completed. Measurement of waist and hip circumference was performed. Statistical analysis: Comparisons between groups were performed using Chi-square, T-test or Mann Whitney test. Pearson or Spearman´s correlation analysis was used for estimating correlation between quantitative variables. Results 103 subjects were investigated. 12 were excluded (6 were other types of arthritis, 6 were Diabetics) and finally, 91 subjects were included in the study; 46 were patients with RA and 45 were healthy controls. Most of them were women (76.1% in RA). Cases and controls were similar in age, sex and BMI. Regarding characteristics of patients with RA, the mean time duration of RA was 5,9 (SD± 3,5) months, and more than 70% of patients had positive RF and/or AntiCCP. CRP and ESR were higher in RA patients than in controls (p<0,001). Differences were found in values of total cholesterol, which were higher in controls [215 mg/dl Vs 195 mg/dl (p=0,024)], HDL levels were lower in RA patients [52 mg/dl Vs 59 mg/dl (p=0,044)], hypertension was observed in a larger number of patients with RA [30.4% vs. 13.3% (p=0,049)]. Cytokines levels, such as IL6, TNF-alpha were higher in RA patients too. Serum Resistin levels were higher in RA patients but no differences were found in leptin, adiponectin or atherogenic index, HOMA-RI, HOMA β, QUICKI or MCauley index. Bivariate analysis revealed a statistically significant correlation between the different indices of IR and parameters of inflammatory activity (PCR, TNF), leptina and body composition. In multiple linear regression noted a positive correlation between HOMA IR and AR evolution time to diagnosis in months. Conclusions The patients with untreated very early RA still do not show insulin resistant observed in patients with established RA despite having high levels of DAS28, CRP, ESR, IL6, TNF-alpha, and resistin. Lack of association between AR and IR indexes might be due to the short course of the disease Disclosure of Interest None Declared

AB1247 Application of a triage approach reduces the requirement for central DXA

Objectives To analyse if using risk indices and PIXI scans jointly would reduce requirement for central DEXA to diagnose postmenopausal OP. Methods A stratified sample of postmenopausal women was selected: a random sample of 305 postmenopausal women from Primary care, and 200 consecutive postmenopausal women referred for central DXA measurement from tertiary care. Inclusion criteria: Caucasian female, age ≥50 yrs, and full menopause (amenorrhea ≥12 mo.). Exclusion criteria: previous diagnose of OP, previous treatment with OP drugs (calcium and/or vitamin D and/or estrogens for menopausal symptoms treatment were allowed) or steroids and other drugs related with low BMD, and institutionalized persons OR Steinbrocker’s functional grade 4. Informed consent was obtained. Four risk indices were calculated: SCORE, ORAI, OSIRIS, and OST. All participants underwent two different BMD measurements: a non-dominant heel BMD (PIXI Lunar, Software #50699, GE Corp.), and a central DXA of the hip and lumbar spine (Lunar Prodigy Advance, Software ENCORE 2006, PA+300274, GE Corporation). OP definition according to the WHO was used. Statistical analyses: The diagnostic utility was measured by ROC curves. We calculated the sensitivity and specificity for risk indices, PIXI, and all possible combinations. Logistic regression was performed to build a risk model with the presence or absence of osteoporosis at the central DEXA as dependent variable. The thresholds was established in 2 ways: 1) a cutoff point where the sensitivity and specificity are maximized, and 2) with two cutoff points, where both it sensitivity and specificity reached 90%. Results 505 Caucasian women with a mean (SD) 61 (8) yrs, were recruited. Median (p25-p75) scores for each risk index were: OST 1 (0-3), ORAI 10 (7-14), and SCORE 8 (6-11). The mean (SD) PIXI T-score of the calcaneus was -0.33 (1.14). The mean (SD) femoral neck T-score was -1.01 (1.05), total femur was -0.59 (1.19) and lumbar T-score was -1.18 (1.36). The prevalence of osteoporosis by central DXA was 20% (n=102), 19% (57) in primary care and 23% (45) in tertiary care. The combined algorithm PIXI + OST + SCORE was the greatest area under the curve obtained: 75% (95% CI, 71 to 79). Most favorable threshold for this algorithm stratified subjects into high, medium, and low risk according to 2 cutoff (-20 and -5, respectively), and the most favorable subsequent decision was referral for central DXA if the medium or high risk categories were reached. According to this algorithm (table) 11 (2.2%) false negatives were obtained, but 257 (52%) central DEXA were avoided and a 20 – 35% in costs could have been saved. Table 1. Distribution of population by disease status and dichotomous test result (DEXA diagnosis columns and algorithm triage in rows) Osteoporosis – + Prueba  bajo 226 11 237  medio 129 39 168  alto 38 51 89 Total 393 101 494 Conclusions A triage based on a combined algorithm composed of PIXI + OST + SCORE reduces reduce the requirements of central DEXA a 52%, and may savings cost. Disclosure of Interest None Declared