Filipe Barcelos

Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Reuma.pt.

Objectives. To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. Methods. We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. Results. Tocilizumab-treated patients (n = 95) presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (n = 429). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6–21.6/3.2–12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2–6.5/1.3–5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5–8.7/1.1–5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4–12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8–4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8–4.5). Conclusions. Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups.

Predictors of damage progression in Portuguese patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have a longer life expectancy. The occurrence of irreversible damage has become a major concern. The present study assessed damage progression in patients with SLE over a 2‐year period and identified baseline features associated with damage accrual. Two hundred and twenty‐one patients that fulfilled criteria for SLE and had a follow‐up longer than 6 months were enrolled. Demographic, clinical, and immunological data were collected at baseline. Accumulated organ damage was scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Patients were prospectively followed and SDI assessment repeated at 2 years. At baseline 72 patients (33%) presented some irreversible damage, and after 2 years 53 had accrued new damage. The mean SDI for the whole cohort increased from 0.582 to 0.980. Damage progression was higher in ocular, cardiovascular, and musculoskeletal systems. Older age [OR = 1.045; 95% confidence interval (CI) 1.021–1.069; P= 0.03], presence of antiphospholipid antibodies (OR = 3.047; 95% CI 1.169–7.941; P= 0.02), steroid use (OR = 6.401; 95% CI 1.601–25.210; P= 0.008), azathioprine use (OR = 3.501; CI 1.224–10.012; P= 0.01), and hypertension (OR = 3.825; 95% CI 1.490–9.820; P= 0.005) were predictors of damage progression in multivariate analysis. Overall SDI increased over time, with some systems being affected more frequently. Demographic and clinical characteristics, co‐morbidity, and treatment options may contribute to irreversible damage. It is necessary to determine whether the control of modifiable factors (e.g., hypertension and judicious use of medications) might prevent damage progression in SLE patients.

Gene expression profiling and association studies implicate the neuregulin signaling pathway in Behçet's disease susceptibility

Behçets disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BDs genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene–gene interactions. These association findings support a role for the EGF/ErbB signaling pathway in BD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.

IL10 low-frequency variants in Behçet's disease patients

To explain the missing heritability after the genome‐wide association studies era, sequencing studies allow the identification of low‐frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçets disease (BD) and the goal of this study is to investigate the role of low‐frequency IL10 variants in BD susceptibility.

AB1071 The Use of Visual Analogue Scale in Rheumatic Disease: Validation of an Electronic Version

Background VAS scales are very useful and easy to perform scales that rheumatologists use on a daily basis. There are several ways to perform this evaluation, on paper through a ruler that includes a slider indicator among others. With the use of more electronic patients records it is useful to determine if the use of a computer assisted VAS could perform the same as the paper. Objectives To evaluate and validate an electronic based VAS in a touch-screen platform. Methods Patients followed in our biologic clinic were evaluated with a paper version of several visual analogue scale (disease activity, pain intensity, back pain in the night, back pain anytime and how the disease disturbs) and after with the electronic version according to their diagnosis. The touch-screen was specially developed for our patients, integrating software that recognized the patient by disease through a bar code and presented the questionnaires according to the disease. Concordance between paper rand touch-screen questionnaire was done through Intraclass Correlation Coefficients. Internal consistency was evaluated by Cronbachs alpha coefficient. Results A total of 88 patients were included in the global disease scale (80.7% rheumatoid arthritis and 19,3% psoriatic arthritis) 85.2% were female, mean age was 54.34±11.05 years and mean disease duration was 11.83±9.32 years. Several other VAS used in spondyloarthropathies was compared in a group of 56 patients the majority were man (58.9%), 30.4% had psoriatic arthritis, 69,6% had ankylosing spondylitis mean age was 46.69±11.78 years and mean disease duration was 10.4±8.77years. Table 1. Results Touch-screen Paper ICC (Touch-screen vs Paper) VAS (last week) How the disease disturbs (n=88) Mean (standard deviation) 36.08 (25.56) 40.28 (27.19) 0.906 Pain intensity (n=87) Mean (standard deviation) 36.15 (25.87) 38.06 (25.63) 0.921 Spondylitis: VAS (last week) (n=56) Back pain during the night Mean (standard deviation) 25.61 (26.23) 25.55 (28.73) 0.943 Back pain at any time (day and night) Mean (standard deviation) 27.96 (25.09) 28.30 (26.37) 0.924 How the disease disturbs Mean (standard deviation) 30.57 (26.34) 29.66 (27.30) 0.867 ICC: Intraclass Correlation Coefficients. Conclusions We found no relevant difference between paper and touch-screen version of all the used VAS scales, with high correlation coefficients validating this platform. This is a useful instrument in our clinical practice, and could be a valid alternative to VAS on paper or rulers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5384

OP0031 Tocilizumab is Associated with Higher CDai/Sdai Remission in Biologic-Naïve Rheumatoid Arthritis Patients – Data from Reuma.Pt

Background Tocilizumab (TCZ), an interleukin-6 receptor blocker, and anti-tumor necrosis factor (TNF) biologic agents are key therapies in the management of rheumatoid arthritis (RA). They are considered to be equally effective and very few head-to-head comparisons have been published. Objectives To compare remission rates in RA patients treated with anti-TNF agents and TCZ and assess the impact of previous biologic therapies in treatment response. Methods We included RA patients registered in the Rheumatic Diseases Portuguese Register, Reuma.pt, who started anti-TNF or TCZ after January 1, 2008, were treated for at least 6 months and had available DAS28 scores at baseline and at 6 months. Our primary outcome was the proportion of patients who achieved remission at 6 months by DAS28, CDAI, SDAI and Boolean remission criteria. Logistic regressions were performed to compare the groups and subgroup analyses of biologic-naïve patients were conducted. Results 524 RA patients were enrolled, (106 adalimumab, 202 etanercept, 43 golimumab, 78 infliximab, 95 TCZ). At baseline, the groups were similar except for proportion of biologic-naïve patients (lower in TCZ group, p<0.0001) and mean DAS28, CDAI and swollen joint count, all higher in the TCZ group (respectively: p=0.0005, p=0.037 and p<0.0001). At 6 months, more TCZ-treated patients were in DAS28 remission, with no differences for CDAI, SDAI or Boolean remission. Considering only naïve patients, DAS28, CDAI and SDAI remission were significantly higher in the TCZ group compared to anti-TNF, with similar rates of Boolean remission. This was confirmed in the multivariate logistic regression, adjusting for age, gender, number of previous biologics and baseline disease activity: DAS28 OR 10.8 (5.9-19.7), CDAI OR 2.9 (1.3-6.5), SDAI OR 4.1 (1.8-9.5), Boolean OR 1.9 (0.88-4.3). Table 1. Proportion of patients in remission according to different criteria and biologic class Anti-TNF Tocilizumab OR (95% CI) Overall Population  DAS28 (n=524) 102/429 (23.8) 55/95 (57.9) 4.4 (2.8–7.0)  CDAI (n=327) 36/260 (13.9) 14/67 (20.9) 1.6 (0.8–3.2)  SDAI (n=298) 33/239 (13.8) 14/59 (23.7) 1.9 (0.97–3.9)  Boolean (n=468) 42/358 (11.7) 11/83 (13.3) 1.1 (0.6–2.3) Biologic-naïve patients  DAS28 (n=417) 89/365 (24.4) 37/52 (71.2) 7.7 (4.0–14.5)  CDAI (n=258) 33/223 (14.8) 11/35 (31.4) 2.6 (1.2–5.8)  SDAI (n=237) 32/206 (15.5) 11/31 (35.5) 2.99 (1.33–6.76)  Boolean (n=348) 36/302 (11.9) 8/46 (17.4) 1.6 (0.7–3.5) Conclusions TCZ treatment was associated with higher rate of DAS28 remission at 6 months and previous biologic therapy significantly affected CDAI/SDAI remission. Naïve patients treated with TCZ had better DAS28, CDAI and SDAI remission rates compared to those treated with TNF inhibitors, whereas the more stringent Boolean remission was similar among all groups. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2668

AB0451 Changes in DAS28, CDAI and SDAI are Associated with Biologic Class, Gender, Previous Biologic Therapy and ACPA/RF Status – Results from Reuma.PT

Background Tocilizumab (TCZ) and anti-tumor necrosis factor (TNF) biologic agents are key therapies in the management of rheumatoid arthritis (RA). They are considered to be equally effective and very few head-to-head comparisons have been published. Objectives To compare response to therapy in RA patients treated with anti-TNF agents and TCZ according to different response measures and determine the factors influencing it. Methods We included RA patients registered in the Rheumatic Diseases Portuguese Register, Reuma.pt, who started anti-TNF or TCZ after January 1, 2008, were treated for at least 6 months and had available DAS28 scores at baseline and at 6 months. Our primary outcome was the change in DAS28, CDAI and SDAI at 6 months. We performed linear regressions to compare the groups and determined the best model predicting change in disease activity for each index. Results 524 RA patients were enrolled, (106 adalimumab, 202 etanercept, 43 golimumab, 78 infliximab, 95 TCZ). At baseline, TCZ users were less frequently naïve to biologic therapies (54.7% vs. 85%, p<0.0001), had more swollen and tender joint counts (p<0.0001 and p=0.02, respectively) and higher disease activity according to all indexes: DAS28 6.1±1.1 vs. 5.4±1.3 (n=524, p<0.0001), CDAI 33.3±13.2 vs. 28.1±13.6 (n=376, p=0.005), SDAI.35.6±13.1 vs. 29.1±30.4 (n=361, p=0.004). At 6 months, change in DAS28, CDAI, SDAI and joint counts was significantly higher in the TCZ group (Table 1). Multivariate linear regression models best predicting change in disease activity included biologic class, number of previous biologics, baseline activity, gender and ACPA/RF status (Table 2). Compared to anti-TNF, TCZ was associated with a larger difference in ΔDAS28, ΔCDAI and ΔSDAI of, respectively, 1.45, 4.25 and 5.41. Table 1. Baseline and change in disease activity according to biologic class (Mann-Whitney test) Change at 6 months Anti-TNF (n=429) Tocilizumab (n=95) p-value ΔDAS28 1.8 (1.4) 3.3 (1.6) <0.0001 ΔCDAI (n=327) 16.0 (13.6) 22.7 (15.7) 0.0003 ΔSDAI (n=298) 17.1 (14.8) 25.2 (16.5) 0.0001 ΔSJC 4.7 (4.8) 7.8 (6.6) <0.0001 ΔTJC 6.4 (7.2) 8.7 (7.7) 0.005 Table 2. Multivariate linear regression models predicting 6-months change in disease activity ΔDAS28 (n=524) ΔCDAI (n=286) ΔSDAI (n=260) Adjusted-R2 0.391 0.613 0.559 Covariables β-coefficient (p) β-coefficient (p) β-coefficient (p) Biologic class (TCZ) 1.45 (<0.0001) 4.25 (0.004) 5.41 (0.003) No. previous biologics −0.41 (<0.0001) −2.47 (0.002) −2.78 (0.004) Baseline activity 0.54 (<0.0001) 0.79 (<0.0001) 0.77 (<0.0001) Female gender −0.40 (0.02) −1.74 (0.29) −1.64 (0.41) ACPA/RF positivity −0.45 (0.004) −3.65 (0.01) −4.77 (0.008) Conclusions TCZ treatment was associated with greater change in DAS28, CDAI, SDAI and joint counts at 6 months. Biologic class, number of previous biologics, baseline activity, gender and ACPA/RF status predicted change in disease activity. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3414

AB1070 SF-36: is There A Difference between Paper and Touch-Screen Evaluation?

Background Patient reported outcomes are a relevant aspect in the follow-up of our patients. The use of computer assisted platforms is being introduced rapidly in our daily clinical practice. We should be comfortable in using new technologies as long as they are validated and reflect the same outcome as older forms of patient reported outcomes. Objectives To evaluate and validate an electronic based SF-36 questionnaire in a touch-screen platform Methods Patients followed in our biologic clinic were evaluated with a paper version of SF-36 and after with the electronic version. The touch-screen was specially developed for our patients, integrating software that recognized the patient by disease through a bar code and presented the questionnaires according to the disease. Concordance between paper rand touch-screen questionnaire was done through Intraclass Correlation Coefficients. Internal consistency was evaluated by Cronbachs alpha coefficient. For categorical variables Cohen Kappa concordance coeficent was used. Results A total of 120 patients were included 75.8% were female, mean age was 50.78±11.88 and mean disease duration was 11.43±9.02, 69.9% had less than the complete secondary school level. 14.2% had psoriatic arthritis, 30% ankylosing spondylitis, and 55.8% had rheumatoid arthritis. The ICC: Intraclass correlation coefficients between touch-screen versus paper were respectively for the different dimensions of SF-36 Physical function – 0.928, Physical role – 0.870, Pain – 0.858, General health – 0.925, Vitality – 0.905, Social function – 0.899, Emotional role – 0.781, Mental health – 0.944, Cronbachs Alpha (8 domains) for touchscreen – 0.891 and for paper – 0.907. Conclusions We found no relevant difference between paper and touch-screen version of the SF-36, with high correlation coefficients validating this platform. This is a useful instrument in our clinical practice, helping clinicians to have more data on their patients with less time expended. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5094