Natalia Mena-Vázquez

Eficiencia de diferentes dosis de rituximab en la artritis reumatoide

OBJECTIVE Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. MATERIAL AND METHODS Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. RESULTS Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). CONCLUSIONS The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option.

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

AB0113 Efficacy of treatment with probiotics in the inflammatory activity of patients with rheumatoid arthritis. systematic review of the literature

Objectives To study the effectiveness of the use of probiotics in the control of inflammatory activity of patients with rheumatoid arthritis and analyse its effect on their metabolic profile. Methods A bibliographic search was carried out in Medline and Embase. The search strategy included the terms MeSH and the free text of ”lactobacillus”, ”bacillus”, ”probiotics” and ”rheumatoid arthritis.” The search strategies were carried out by two authors, which were included according to the type of studies: meta-analysis, systematic reviews and clinical trials, depending on the type of participant: adults with RA who have received probiotics, the main outcome measures: changes in the Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)), as well as each of the parameters that constitute them: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analogue scale of the doctor and the patient (EVA), number of painful joints (NAD) and inflamed (NAI) and functional status by Health Assessment Questionnaire (HAQ) Secondary variables: number of adverse events and parameters of metabolic activity. The quality of the evidence was analysed following the guidelines of the Scottish Network of Intercollegiate Guidelines (SIGN). Results After the selection of 34 articles, 9 articles were finally included. All were randomised, double-blind, placebo-controlled clinical trials (RCTs) with a level of evidence between 1+and 1++and a recommendation grade of A and B. Seven CDs showed improvement in arthritis measurements. In Peltonen et al. observed a high rate of improvement in the experimental group than in the control group (3.1 vs 2, p=0.027). Mandel et al. they described improvement of the EVA in the experimental group (p=0.046). Zamani the al. they described an improvement in DAS28 (−0.3±0.4 versus −0.1±0.4, p=0.01). Vaghef-Mehrabany et al defined this improvement (p<0.01). Pineda et al. showed an improvement in HAQ at 3 months in the experimental group (from 0.97 to 0.80, p=0.02), although not in ACR20 (p=0.33). Allipour et al. found improvements in CRP between the two groups (mean [95% CI]=2.03 [0.54–3.51], p=0.009); NAD: (mean [95% CI]=0.72 [0.25, 1.19], p=0.003); NAI: (mean [95% CI]=0.351 [0.13, 0.58], p=0.003); EVA: (mean [95% CI]=16.71 [8.91, 24.50] p<0.001; DAS-28: (average [CI] 95%]=0.31 [0.02, 0.61], p=0.039) and in cytokine levels, Hatakka et al observed no significant improvement in the experimental group in HAQ, NAD and NAI, and Nenonent et al. Did not observe differences in DAS28. In the last, EC of Vaghef-Mehrabany of 2017 metabolic measures were evaluated without finding significant improvements If an improvement in insulin resistance was observed as measured by the HOMA B index in the study by Zamani et al. Conclusions Treatment with probiotics seems to be effective in controlling the inflammatory activity of rheumatoid arthritis. 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

THU0160 Disease modifying antirheumatic drugs in rheumatoid arthritis with interstitial lung disease: a prospective study

Objectives To describe the evolution of interstitial lung disease (ILD) in RA patients treated with disease modifying antirheumatic drugs (DMARDs) for 1 year in real clinical practice conditions. Methods Design: Prospective observational case-series. Patients: Patients with RA (ACR/EULAR 2010 criteria) and ILD (American Thoracic Society/European Respiratory criteria) from two centres (Regional Hospital of Málaga and Valme Hospital of Sevilla) were included. Protocol: All patients with RA and ILD who visited outpatient clinic from January to December 2015. They were reviewed according to a predetermined protocol for systematic data collection. Resolution Computed Tomography (HRCT),Pulmonary function test (PFT) and echocardiogram were requested for all patients.This visit was marked as v0 (index date). At 12 months (v12) the joint assessment (DAS28), echocardiogram, PTF and HRCT were again evaluated. HRCTs were assessed by the same radiologist with expertise in chest radiology. Outcomes: At v12:(1)improvement (ie improvement in FVC≥10% or DLCO≥15% and no radiological progression),(2)non-progression (stabilization or improvement in FVC≤10% or DLCO<15% and no radiological progression),(3)progression (worsening of FVC>10% or DLCO>15% and radiological progression), or (4) death due to ILD. Variables: Description of ILD type (Nonspecific interstitial pneumonia/Usual interstitial pneumonia) and lung function by PTF, HRCT.Presence of PTH by echocardiogram and dyspnoea.Collection of adverse events. Statistical analysis: Descriptive analysis and Wilcoxon or T test between the v0 and v12. One factor ANOVA between sDMARD,bDMARD and combination therapy groups. Results The main characteristics at V0 of the patients (n=22) are shown in the table. Seven patients (31.8%) received a sDMARDs with a bDMARDs; 12 patients (54.5%) in monotherapy with sDMARD, with MTX being the most frequent (34.7%); 3 (13.6%) in monotherapy with bDMARDs (Table 1). Three patients (13.6%) had improvement (1 with MTX, 1 with RTX and 1 with HCX + RTX), 15 patients (68.2%) remained stable (4 with MTX, 3 with LFN, 1 with HCQ, 1 AZA, 1 ABT, 1ABT + SSZ, 2 MTX + ETN, 1 HCQ + RTX, and 1 HCQ + ADA);and 3 (13.0%) got worse of ILD (1 with MTX developed unknown lung mass, 1 with LFN and 1 with LFN + IFX). One patient died during follow-up due to respiratory infection (under treatment with RTX). No patient developed PPH. We did not find significant differences between v0 DAS28 and at 12 months (2.55 [0.75] vs 2.42 [1.22], p=0.567) or in HAQ 1.15 [0.93] vs 1.25 [0.78], p=0.450). There were no significant differences in PTF, HRCT or DAS28 at v12 between sDMARD, bDMARD and combination therapy groups. Four patients (18.2%) had adverse effects: 2 respiratory infections, 1 oral herpes simplex and 1 tooth infection. Conclusions Most patients with RA and ILD who are receiving treatment with DMARD (82%)remained stable or improved after at least 1 year of both synthetic and biological DMARD treatment. However, a significant percentage of patients had an adverse outcome. More prospective studies with a greater number of patients are necessary to identify the influence of DMARDs in this evolution. Disclosure of Interest None declared

SAT0295 Measuring Microarchitecture Bone in Patients with Systemic Lupus Erythematosus. Pilot Study

Objectives To evaluate the trabecular bone score (TBS) in patients with systemic lupus erythematosus (SLE). Methods Design: Cross sectional study. Patients: we recruited 37 patients with SLE who had at least one DXA and one analysis of the trabecular microarchitecture during the follow-up. Protocol: we analysed the most recent DXA, TBS and clinical data collected from the clinical records using a predesigned questionnaire. Variables: demographic, therapeutic (including use of glucocorticoids and antiresorptives), clinical and laboratory features of SLE (including cumulative number of ACR criteria of LES, SLICC damage and SELENA-SLEDAI average of the two years prior at protocol date). Also were collected: personal and family history of fragility fractures, densitometric diagnosis (OMS) and FRAX index. Outcome variables: (1) Measurement of microarchitecture using software “Trabecular bone score -MedIMaps®” (TBS) and (2) Measurement of BMD (g/cm2) of the lumbar spine (L1 L4), proximal femur and total hip, using DXA (GE Lunar Prodigy Advance). Definitions: The cutoff points for TBS used in the study were the same proposed by the International working group of TBS users: (1) Normal microarchitecture, score>1.350; (2) microarchitecture partially degraded, score <1.350 and >1.200; and (3) microarchitecture degraded<1.200. Bone densitometry scores were classified according to OMS criteria as normal bone, osteopenia and osteoporosis at the lumbar spine (LS), femoral neck (FN) and total hip (TH). Statistical analysis: Descriptive analysis of the main variables, T-student test for the comparison of quantitative variables of groups, Fisher exact test to compare qualitative and correlation of Pearson/Spearman Rho for the quantitative variables. Results The main characteristics of the patients (n=37) are shown in the Table. Almost all of them had received hydroxychloroquine, calcium supplements and vitamin D. The majority had lumbar osteopenia (43.9%) and trabecular bone microarchitecture partially degraded (46.3%). A trend towards association between densitometric diagnosis (OMS) and the TBS LS (p=0.096) was observed, but not in the case of the BMD FN (p=0.335) or BMD TH (p=0.447).) A negative correlation between the FRAX index and the LS T-score (p=0005 r= -0.5) and FN (r= -0.7; p<0.001 was observed, but not with the TBS (Rho = -0, 3; p=0.1). No correlation between FRAX, TBS, SLEDAI and SLICC was observed. No association was observed between the uses of hydroxychloroquine, oral or intravenous glucocorticoids and the T-score or TBS.Table 1. Main characteristics of the patients (n=37). Conclusions Most patients with SLE studied in this small pilot study have some moderate bone disorder that affects both the amount of bone mass and quality of their lumbar trabecular microarchitecture. Acknowledgements SEIOMM Disclosure of Interest None declared

AB1144-HPR Case Management on Frail Patients in the Rheumatology Department at the Regional University Hospital in Malaga

Objectives To determine the features of patients referred to case management and from the case management process at the Regional University Hospital in Malaga. Methods Design: Descriptive cross-sectional study. Patients: patients treated in the Rheumatology service at the Regional University Hospital in Malaga and referred to case management from April to November 2013. The case management model is created as a response to the need for greater efficiency in care management due to the new Socio-medical Syndrome situation caused by the ageing of the population, the increase of frail patients and the need for home care. The case management process begins with the rheumatologist identifying a problem to be referred to case management. The rheumatologist contacts the rheumatology nurse specialist who prepares a report and hands it over to the case management nurse of the hospital. The case management nurse of the hospital contacts the primary care center of the patient that manages the petition from the Rheumatology unit. Variables include the basic characteristics of the patients, the Barthel index that measures the dependence in activities of daily living, the main reasons for referral to case management and professionals involved in primary care. Statistical Analysis: Basic descriptive of the results, the Kolmogorov-Smirnov test for the normality of the variables. Results From April to November 2013, 16 patients (75% women) with an average age 66.5±13.35 years were referred to case management. Rheumatic diseases in patients were: rheumatoid arthritis (n=10), systemic lupus erythematosus (n=3), scleroderma (n=1), severe osteoporosis (n=1) and psoriatic arthritis (n=1). 87.5% Frail patients with a Barthel index score of severe dependence in 62.5% of cases and of total dependence in 25% of cases. 43.8% lived with relatives, 25% with a professional caregiver and 25% lived alone. The reasons for referral to case management were: domiciliary nursing (50%), professional in-home caregiving (37.5%), help from the primary care center (PCC) staff (25%), information from the primary care physician (PCP) (25%), social problems (18.8%), nursing-home PCP (6.3%). Primary care professionals involved in the care of these patients were: nurses (62.5%), PCPs (37.5%), social workers (50%), community case manager nurses (50%). In 75% of cases the PCC belonged to the districts of Malaga. Conclusions Case management is a management tool that integrates primary care and specialty care professionals optimizing resources and improving the quality of health care provided to patients in situations of dependency. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4555