Alejandro Muñoz

A10.24 Switching Infliximab for New Alternatives: A Correspondence Analysis of Biologics, Reasons to Stop, and Time Periods

Background The reason to stop the first biologic may vary from agent to agent and also from the earlier times to the more recent ones. Issues like the availability of newer alternatives or a better knowledge of the effectiveness and safety profile of individual biologics may influence treatment decisions, including the discontinuation of the biologic. Objective To visually assess the relationship between the reason for stopping the first biologic and the period of time when the biologic was started. Methods All patients with rheumatoid arthritis undergoing treatment with a biologic are registered in the clinical database of a single centre with seven treating rheumatologists. The biologic used, as well as the reason to stop it is recorded, as well as all dates regarding the start and the last dose. We performed a multiple correspondence analysis with the Burt method of adjusted inertias and standard normalisation with the variables: first biologic, time period (1998–2001, 2002–2005, 2006–2009), and reason to stop (adverse event, inefficacy, others). Correspondence analysis provides a means of displaying or summarising a set of data with categorical variables in two-dimensional graphical form. Results The total inertia of the exploratory analysis was 0.10. The first two dimensions added to 57% of the inertia, so that all dimensions were accounted for. The major drives of the relationship between the three variables were “infliximab” and the time period “1998–2001” (% inertia 0.146 and 0.177, respectively). The distance between other categories of the three variables was not relevant enough to make any suggestions of an association. The figure shows the correspondence map of the relationship. Abstract A10.24 Figure 1 Conclusions If to any biologic at all, time has affected the decision to start infliximab, with more treatments started in the earlier times than in the later ones. The reason to stop any first biologic does not clearly relate to the time neither to the biologic itself in this single centre dataset.

Effectiveness of dose reduction of etanercept and adalimumab in patients with rheumatoid arthritis

Methods A retrospective study on a cohort of 13 patients diagnosed rheumatoid artritis treated with anti-TNF (10 patients with etanercept, and 3 with adalimumab) and clinical remission (DAS28 < 2.6) in the last 6 mounths, in which reducing the dosing. Clinical activity was evaluated by clinical activity index (DAS28), for functional capacity was used HAQ (Health Assessment Questionnaire). Others variables studied was visual analog scale (VAS). Analyzing before starting dose reduction, at 3 and 6 months.

Eficacia y seguridad de los glucocorticoides en la artritis reumatoide: revisión sistemática de la literatura

OBJECTIVES 1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); 2) to generate practical recommendations. METHODS A systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus. RESULTS A total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS. CONCLUSIONS These recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA.

SAT0003 Relationship Between Anticitrullinated Protein Antibodies and Clinical Remission in Arthritis

Background The relationship between anticitrullinated protein antibodies (ACPA) and the clinical outcome of rheumatoid arthritis (RA) under treatment has been evaluated in clinical trials with conflicting results. Thus, an analysis of the BeSt study(1) indicated that response to treatment was similar in ACPA-positive and ACPA-negative patients However, ACPA-positive patients showed more frequently radiological damage progression. On the contrary, in the IMPROVED study(2), ACPA-negative patients achieved less remissions on treatment than ACPA-positive patients Objectives We evaluated the clinical response of patients with RA receiving treatment according to ACPA titers. Methods This was a retrospective longitudinal observational study. We included all patients seen at our Unit who fulfilled the following criteria: 1) Diagnosis of RA by a rheumatologist meeting the 1987 criteria for RA; 2) Available determinations of ACPA; 3) Treatment for AR (whether or not biological therapy) with a minimum follow up of 6 months. The outcome variable was clinical regression defined as reaching DAS28 <=2.6. Predictors of the outcome variable were evaluated using logistic regression models adjusted by gender and age. Results 71 patients were included, 79% of them women. Clinical regression was observed in 42 (59%) patients during the first 12 months of follow-up. Baseline median (IQR) ACPA levels were 363 (27.7-500) for individuals without clinical regression and 91.7 (7-458) for those with regression (p=0.045). 19 (66%) patients without regression vs. 15 (36%) with regression showed ACPA levels ≥200 (p=0.013). 6 (20%) patients without clinical response vs. 18 (42%) individuals with response showed negative ACPA titers (p= 0.050). Factors independently associated with clinical regression were: Recent onset RA [adjusted odds ratio (AOR) 5; 95% confidence interval (95%CI) 1.01-25; p=0.049], baseline ACPA levels ≥200 [AOR 0.13; 95%CI 0.03-0.5; p=0.004], baseline CRP levels [per unit increase; AOR 0.94; 95%CI 0.91-0.99; p=0.024], baseline DAS28 [per unit increase; AOR 0.47; 95%CI 0.25-0.89; p=0.021]. Conclusions ACPA levels can predict clinical regression of patients with RA receiving treatment in real life conditions. Individuals with high ACPA levels may benefit from a more aggressive treatment approach. ACPA titers may be useful to monitor the clinical activity of RA. References The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study. M van den Broek,1 L Dirven,1 NB Klarenbeek,1 THE Molenaar,2 Ann Rehum Dis 2012;71:245-248. Remission induction therapy with MTX and predinisone in patients with early rheumatoid and indifferentiated arthritis (yhe IMPROVED study)Ann Rheum Rheum Dis 2012 ;March 8 Disclosure of Interest None Declared

AB0784 Two no-invasive methods to evaluate liver fibrosis in systemic sclerosis patients: Transient elastography (fibroscan) and APRI score

Background Systemic sclerosis (SSc) is a complex and rare autoimmune disease characterized by vascular damage as well as skin and internal organs sclerosis. The occurrence and extent of primary liver damage in SSc patients has not been adequately studied. In a review of 727 patients with scleroderma only 8 (1.1%) had hepatic involvement. If this very uncommon complication occurs, it usually happens 10 to 15 years after the onset of scleroderma. Transient elastography (Fibroscan) has been validated for the diagnosis of hepatic fibrosis. Objectives Our aim was to study the frequency of liver stiffness detected with Fibroscan in patients with SSc and the association of liver stiffness with liver disease severity measured by the AST platelet ratio index (APRI). Methods All consecutive patients with a diagnosis of SSc according to the American College of Rheumatology attending a single clinic during a one-year period were included. The APRI was calculated in all patients as follows: AST/upper limit of normal × 100/platelet count (109/l). An APRI≥0.5 has acceptable accuracy for excluding significant fibrosis. Transient elastography (TE) was performed with the Fibroscan Echosens 502 model (XL). Liver stiffness scores were expressed as kilopascals (Kpa). For the diagnosis of fibrosis, a cut-off value of TE >7.5 kpa has been proposed. Prevalence was obtained with 95% confidence intervals (CI). Correlation was tested with Spearman’s rho. Results The study included 40 patients (M/F 6/34) with a median age of 59 years (range: 34-79), HBV, HVC, and anti-mitochondrial antibodies were all negative, alcohol consumption was less than 20 g/day in all cases. Median liver stiffness score was 5.32 Kpa (range: 3.1-9.4). One patient had a TE ≥7.5 Kpa (prevalence 5%; 95% CI 0.1 – 24.8). This patient had a value of 9.4 Kpa with an ultrasound pattern compatible with fatty liver and an APRI value of 0.18. The median APRI value was 0.29 (range: 0.16-0.58). The patient with the highest APRI value had a liver stiffness score of 0.31 Kpa. There was no correlation between the APRI score and liver stiffness by Fibroscan (rho =0.11). Conclusions The prevalence of significant liver fibrosis is moderate to low in SSc patients with no clinical evidence of hepatic disease, as liver could be less prone to SSc-specific pathophysiologic events. Fibroscan, a non-invasive method, detected a prevalence of liver stiffness similar to expected. Liver enzymes levels do not correlate well with liver stiffness. Disclosure of Interest None Declared

A5.9 Values of B Lymphocyte Subpopulations (Healthy Population) using flow Cytometry a Starting Point for any study

Background Flow cytometry is a widely used technique nowadays for the determination of cell subpopulations in the study of autoimmune, infectious and tumoral diseases. Our goal is to study the means and medians of B lymphocyte subpopulations in healthy population, to thereby have reference limits with which being able to compare when carrying out studies in population with autoimmune diseases. Methods We studied 50 healthy patients. Male/female: 25/25. Age: 18–65 years. Previously, it was checked that none of these patients had any autoimmune diseases nor any other disease or condition causing lymphopenia or lymphocytosis. The fluorochromes used were: CD3, CD19, CD38, CD27 and IgD. Results Abstract A5.9 Table 1 Subpopulations Mean Typical deviation Median Naive 70.46 8.06 73.70 DN 4.05 2.08 4.66 Unswitched Memory 9.65 5.33 10.05 switched Memory 11.38 4.62 11.00 Bm1 7.82 9.29 5.10 Bm2 73.14 10.71 73.05 PreGC 2.90 1.61 2.89 Bm3 + 4 0.56 0.53 0.44 Late Bm5 3.17 2.74 2.50 Early Bm5 9.12 4.93 9.21 Conclusions Knowing the mean, medians and standard deviations of the B lymphocyte subpopulations subsets is important in helping to compare these results with those obtained in studies of patients with autoimmune diseases. In most cases, conclusions drawn after the study with flow cytometry are based on knowing how these subpopulations vary with respect to healthy people in order to draw conclusions about what subpopulations are involved the most in the pathogenesis of the disease. We believe, therefore, important to deepen in studies of this kind in order to clarify more situations of normality in the world of flow cytometry: a technique that is increasingly taking more importance in the understanding of autoimmune diseases.

Clinical and economic efficiency to reduce dose etanercept and adalimumab in patients with rheumatoid arthritis

Methods A retrospective study on a cohort of 13 patients diagnosed rheumatoid artritis (RA) treated with anti-TNF (10 patients with etanercept, and 3 with adalimumab) and clinical remission (DAS28 < 2.6) in the last 6 months, in which reducing the dosing. This reduction was about 30% in both groups (etanercept passed from 25 mg twice a week to 25 mg every 5 days. In the case of Adalimumab it went from 40 mg to 40 mg every 2 weeks every 20 days. Clinical activity was evaluated by clinical activity index (DAS28), for functional capacity was used HAQ (Health Assessment Questionnaire). Others variables studied was visual analog scale (VAS). Analyzing before starting dose reduction, at 3 and 6 months.

Wegener granulomatosis: type of presentation and initial treatment in a series of 23 cases.

Granulomatosis with poliangeitis (Wegener) is a necrotizing granulomatous vasculitis characterized by damage in the respiratory tract, kidney, skin, nervous system ... The onset of the disease is usually indolent, with nonspecific symptoms. The most frequent initial clinical presentation is the upper respiratory tract involvement (90%). The presence of pulmonary infiltrates is 70% and bilateral and cavitary nodules in about 60%.

Prediction of treatment response by anticitrullinated protein antibodies (ACPA) levels among patients with rheumatoid arthritis

Background The relationship between ACPA and the clinical outcome of rheumatoid arthritis (RA) under treatment has been evaluated in clinical trials with conflicting results. Thus, the response to treatment was influenced by ACPA in the BeSt study. However, radiological damage progression was more likely among ACPA-positive patients. Conversely, ACPA-negative patients achieved less remissions in the IMPROVED study. Because of these, we evaluated the clinical response (CR) of patients with RA receiving treatment according to ACPA titers. Patients and methods All patients seen at our Unit who fulfilled the following criteria were included in this retrospective study: 1) Diagnosis of RA by a rheumatologist meeting the 1987 criteria for RA; 2) Available determinations of ACPA; 3) Treatment for AR (whether or not biological therapy) with a minimum follow up of 6 months. The outcome variable was CR defined as reaching DAS28 <1.6. Predictors of CR were evaluated using logistic regression. Results 71 patients were included, 79% of them women. CR was observed in 19 (27%) patients during the first 12 months of follow-up. Baseline median (IQR) ACPA levels were 306 (7-500) for individuals without CR and 76 (7-153) for those with CR (p=0.022). 29 (56%) patients without CR vs. 5 (26%) with CR showed ACPA levels ≥200 (p=0.028). ACPA levels decreased significantly among patients with CR (p=0.019), but they did not change in those without CR (p=0.330). Factors independently associated with CR were: recent onset RA [adjusted odds ratio (AOR) 0.19; 95% confidence interval (95%CI) 0.41-0.90; p=0.036], baseline ACPA levels ≥200 [AOR 6.48; 95%CI 1.12-37.3; p=0.037], baseline CRP levels [per unit increase; AOR 1.06; 95%CI 1.001-1.12; p=0.048], baseline DAS28 [per unit increase; AOR 3.04; 95%CI 1.3-7.4; p=0.014]. Conclusions ACPA levels can predict CR of patients with RA receiving treatment in real life conditions. Individuals with high ACPA levels may benefit from a more aggressive treatment approach. Titers of ACPA may be useful to monitor the clinical activity of RA.

The reason to stop infliximab is clearly related to the existence of new alternatives: a correspondence analysis of biologics, reasons to stop, and time periods

Background The reason to stop the first biologic may vary from agent to agent and also from the earlier times to the more recent ones. Issues like the availability of newer alternatives or a better knowledge of the effectiveness and safety profile of individual biologics may influence treatment decisions, including the discontinuation of the biologic.