P. Nero

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.

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patients disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

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.

AB0608 Greater Organ Involvement and Disease Activity in Childhood-Onset than Adult-Onset With SLE (DATA from Reuma.Pt/Les)

Background Systemic lupus erythematosus (SLE) is a multi-organ immune-mediated disease that affects predominantly women at reproductive age but may present itself at any age. Age at disease onset has a strong modulating effect on clinical presentation and course of disease. Although young patients may have a more aggressive disease, controversies persist regarding the impact of age at disease onset on SLE outcome. Objectives Characterize childhood-onset, adult-onset and late-onset SLE and assess whether disease outcome differs in these three patient groups. Methods Patients with childhood-onset (diagnosis ≤18 years) SLE fulfilling ACR 1997 criteria were identified in the Portuguese registry Reuma.pt/SLE and compared with adult-onset (≥19y and ≤49 years) and late-onset (≥50 years) SLE patients paired for disease duration. Results Two hundred and sixty seven SLE patients with mean disease duration of 11.9±9.3 years were analyzed (Table 1). The number of fulfilled ACR criteria was significantly higher in childhood-onset SLE. A greater proportion of women, higher prevalence of arthritis and anti-SSA antibodies were noted in the adult-onset group. Hypertension, diabetes and thyroid disease were significantly more prevalent in late-onset SLE. Disease activity at last visit evaluated using the SLEDAI-2K was significantly higher in childhood-onset group than in the late-onset counterparts. SLICC/ACR damage index was numerically higher in late-onset SLE and significantly more patients in this group had irreversible damage. Cyclophosphamide and mycophenolate mophetil were used more frequently in childhood-onset SLE patients.Table 1. Demographic and clinical characteristics of childhood-onset, adult-onset and late-onset SLE Childhood-onset Adult-onset Late-onset P N=89 N=89 N=89 Female n (%) 77 (87) 85 (96) 78 (88) 0.039 Current mean age (years) 25.1±9.1 40.0±13.1 68.3±7.3 <0.001 Number of ACR criteria fulfilled 5.8±1.3 5.3±1.3 5.2±1.1 0.005  Malar rash (%) 55 (62) 32 (36) 33 (37) <0.001  Arthritis (%) 62 (70) 79 (89) 71 (80) 0.005  Renal involvement (%) 52 (58) 28 (31) 14 (16) <0.001  Neurologic disorder (%) 10 (11) 5 (6) 2 (2) 0.039  Hematologic disorder (%) 68 (76) 53 (62) 67 (75) 0.029 Anti-SSA positivity (%) 13 (15) 30 (34) 19 (21) 0.006 Low complement (%) 74 (83) 60 (67) 46 (52) <0.001 SLEDAI-2K at last visit 3.4±3.8 2.2±2.7 1.6±2.8 0.004 SLICC-DI 0.5±0.9 0.7±1.3 0.9±1.3 0.116 SLICC-DI ≥1 (%) 18 (20) 23 (26) 36 (40) <0.001 Hypertension (%) 17 (19) 16 (18) 43 (48) <0.001 Diabetes (%) 0 (0) 7 (8) 15 (17) 0.008 Thyroid disease (%) 3 (3) 13 (26) 20 (23) 0.004 Conclusions The skin, kidney and neurological involvement are most common in childhood-onset, as well as the use of immunosuppressants, supporting the concept of a more severe disease. In contrast, patients with late-onset SLE have more comorbidities and irreversible damage. The age of SLE onset has a significant impact not only on the clinical characteristics and disease activity, but is also important for disease outcome. Disclosure of Interest None declared

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

THU0312 Microcirculation Comparative Study in Fibromyalgia Patients with and without Raynaud's Phenomenon

Background Previous studies demonstrated functional and morphological microcirculatory abnormalities that may be relevant to the pathophysiology and clinical manifestations of fibromyalgia (FM). Objectives To ascertain and compare capillary morphology of FM patients with and without Raynauds phenomenon (RP) using nailfold videocapillaroscopy (NVC). Methods Patients fulfilling the 2010 American College of Rheumatology Diagnostic Criteria for FM were allocated in 2 groups according to the presence or absence of RP (RP+ or RP-, respectively). All patients with secondary causes of RP other than FM were excluded. One blinded operator performed all the NVC using a 200x amplification digital microscope and analytical software. Capillary parameters evaluated in fingers II-V of both hands included: tortuosity, apex enlargement, branch enlargement, microhemorrhages, giant capillaries, capillary density, capillary branching and architectural derangements. Each parameter was rated 0-3 (0= no changes; 1= <33% abnormalities; 2=33-66% abnormalities; 3= >66% abnormalities) and the mean scores were calculated. The association of RP with the capillary parameters was assessed using multivariate linear regression adjusted for age, FM duration and occupation. Results Twenty FM patients were enrolled, 10 in each group, however 2 patients RP+ were excluded due to thyroid disease. Included patients were all female, had a mean age of 50.4 years and a mean duration of disease of 12.8 years. In both RP+ and RP- groups, the most frequently found abnormalities were minor dysmorphies, namely tortuosities, apex enlargement and branch enlargement. However, scoring of these parameters showed no significant difference between the 2 groups. More than half of RP+ and RP- patients presented slight focal decreases in capillary density, once again with no difference between groups. The only giant capillaries were found in a RP+ patient with an “early scleroderma pattern” as proposed by Cutolo et al. Hemorrhages were scarce and had a traumatic appearance, except in the previously mentioned patient. Interestingly, RP associated negatively with the capillary branching score. Table 1 summarizes the results. Table 1. Microcirculatory parameters assessed in fibromyalgia patients with and without Raynauds phenomenon Parameters RP+, n=8 RP−, n=10 Adjusted p-value n (%) Score, median (IQR) n (%) Score, median (IQR) Tortuosity 8 (100) 1.17 (0.66) 10 (100) 1.25 (0.53) 0.99 Apex enlargement 7 (87.5) 0.31 (0.50) 10 (100) 0.14 (0.06) 0.26 Branch enlargement 7 (87.5) 0.13 (0.33) 10 (100) 0.03 (0.06) 0.06 Microhemorrhages 2 (25) 0 (0.06) 2 (20) 0 (0) 0.20 Giant capillaries 1 (12.5) 0 (0) 0 (0) 0 (0) 0.24 Capillary density 5 (62.5) 0.03 (0.09) 6 (60) 0.08 (0.19) 0.98 Capillary branching 3 (37.5) 0 (0.03) 5 (50) 0.03 (0.13) 0.04 Architectural derangements 2 (25) 0 (0.08) 3 (30) 0 (0.03) 0.27 IQR, interquartile range; RP, Raynauds phenomenon. Conclusions No association was established between RP and microcirculatory abnormalities in FM patients. However, capillary tortuosity and enlargement were present in almost all subjects, supporting previous findings that FM may associate with minor NVC dysmorphies. Some authors suggest that tissue hypoxia arising from repeated autonomic-mediated vasoconstriction might explain these changes, as well as the apparent reduction in capillary density. Studies with a larger sample of FM patients are needed to confirm these results. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2157