J.G. Ovalles-Bonilla

Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed?

To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission.

Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis

OBJECTIVE To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.

Structural damage in rheumatoid arthritis: comparison between tendon damage evaluated by ultrasound and radiographic damage

OBJECTIVE To compare structural damage assessed by conventional radiography and tendon damage assessed by musculoskeletal US (MSUS) at wrist and ankle in RA patients. METHODS We evaluated 72 consecutive patients [56 (77.8%) females] with RA. The MSUS evaluation consisted in a B-mode examination of bilateral extensor carpi ulnaris and tibialis posterior tendons. Tendon damage was defined and scored according to OMERACT. A total score for the tendon damage score (TDS) was calculated by summing the grades for each tendon. For the radiographic evaluations we used the van der Heijde score; a total radiographic score (RTS) was calculated by summing a bone erosion score (ERS) and a joint space narrowing score (JSNS). RESULTS We evaluated 288 tendons. The mean (s.d.) of TDS was 2.3 (1.8). Fifty-four (75%) patients presented tendon damage of at least one tendon. From all evaluated tendons, 134 (46.5%) had no tendon damage, 146 (50.7%) had grade 1 and 8 (2.8%) had grade 2 tendon damage. The mean (s.d.) for RTS was 91.4 (97), for ERS was 47.3 (61.9) and for JSNS was 44.1 (37.2). We found a significant correlation between disease duration and both TDS and RTS (r = 0.413 and r = 0.560, respectively; P < 0.0001). We found a good significant correlation between TDS and all variables of radiographic structural damage (RTS, r = 0.65; ERS, r = 0.637; JSNS, r = 0.618; P < 0.001). CONCLUSION The MSUS assessment of only four tendons can be an additional feasible method to assess structural damage in RA patients.

SAT0509 Clinical and Serological Profile of Children with Positive SSA-Ro/SSB-La Antibodies

Background Several studies have shown the relationship between anti-SSA-Ro/SSB-La antibodies and Systemic Lupus Erythematosus (SLE), Sjögren Syndrome (SS) and other autoimmune diseases in adult population. However, the expression of these autoantibodies and clinical correlation in juvenile patients is poorly described. Objectives To characterize the clinical and serological profile and primary rheumatic diseases in pediatric patients with positive anti-SSA-Ro and/or anti-SSB-La antibodies. Methods The data was obtained from a long term prospective cohort of patients under age 18 diagnosed with rheumatic diseases in a tertiary hospital in Spain. Demographic, clinical, and laboratory data were collected from 1986 to 2010. Patients were divided into 2 groups: anti-SSA-Ro/SSB-La positive and anti-SSA-Ro/SSB-La negative. Results A total of 187 patients were tested for anti Extractable Nuclear Antigens (ENA), with a following mean time of 11 years. Mean age at disease onset was 12.6 years and 77% were female. Fifty-four (28.9%) anti-SSA-Ro/SSB-La positive subjects were compared against 133 (71.1%) anti-SSA-Ro/SSB-La negative subjects. Among positive cases, 13 (24.1%) patients were double-positive for anti-SSA-Ro and anti-SSB-La, 51 (94.4%) were positive for anti-SSA-Ro and 3 (5.5%) were single-positive for anti-SSB-La. The anti-SSA-Ro/SSB-La antibodies were found less frequently (p=0.003) in the overlapping syndromes, and more frequently in SLE (p=0.007). In addition rheumatoid factor (p<0.001), anti-Sm (p<0.001) and anti-RNP (p<0.001) were frequently co-expressed with anti-SSA-Ro/SSB-La antibodies. Finally the anti-SSA-Ro/SSB-La positive group presented more hematological and skin manifestations than the negative group (p<0.05). Conclusions Similarly to adults, we observed a relationship between anti-SSA-Ro/SSB-La antibodies and SLE in pediatric patients. However a low proportion of childhood primary SS exists in our anti-SSA-Ro/SSB-La positive cases. This could be explained by underdiagnoses related to the atypical clinical presentation of SS in pediatric population. Single-positive anti-SSB-La patients are uncommon, the clinical significance of this serological result remains uncertain in children. References Rheumatol Int (2014) 34:1123–1127. Disclosure of Interest None declared

Salivary gland ultrasound is linked to the autoimmunity profile in patients with primary Sjögren’s syndrome:

Objective Salivary gland ultrasound (SGU) is a reliable technique for assessing the salivary glands in patients with primary Sjögren’s syndrome (pSS). The aim of this study was to elucidate the relationship between SGU findings and autoimmunity in patients with pSS. Methods Patients with pSS underwent an SGU assessment. The patients were classified into three groups according to their autoimmunity profile: the complete positive group (positive rheumatoid factor, antinuclear antibodies, and anti-Ro/anti-La antibodies), the partial seropositive group (positivity of at least one autoantibody but not all), and the seronegative group. Results In total, 93 patients were evaluated. Eighty-six (92.5%) were female, and their median age was 49.5 years. The median disease duration was 12.3 years. Pathological SGU findings were present in 32 (34.4%) patients [25 of 36 (78.1%) in the complete positive group and 7 of 44 (21.9%) in the partial positive group]. Patients with pathological SGU findings had a shorter disease duration and slightly higher European League Against Rheumatism Sjögren’s syndrome disease activity index. Conclusions The autoimmunity profile and pathological SGU findings are strongly associated with each other in patients with pSS. However, the disease duration does not seem to be related to pathological SGU findings.

AB0899 Impact of Musculoskeletal Ultrasound in Routine Clinical Practice in Pediatric Rheumatology Unit

Background Musculoskeletal ultrasound (MSU) is a useful, non-invasive, nonionizing, quick and well-tolerated imagine technique, appropriate for assessing children. In the last years, MSU has been increasingly used in pediatric rheumatology. Most studies have been on juvenile idiopathic arthritis (JIA) patients, showing more sensitivity of MSU for detecting synovitis than clinical examination. The impact of MSU in adult patients with rheumatic diseases have been studied, but there is a lack of studies on the impact of MSU in pediatric rheumatology. Objectives To investigate the impact of MSU in diagnosis and therapeutic decisions in a pediatric rheumatology outpatient clinic. Methods We included patients who attended consecutively our pediatric rheumatology unit in 11 random days during a 4-month period (September-December 2013). A consultant rheumatologist with 25 years of experience in pediatric rheumatology decided whether MSU was indicated or not, and completed a standard questionaire. This questionnaire was composed of clinical data, previous diagnosis, current global and local diagnosis, global and local treatment decisions and disease activity assessment. The level of Indication of MSU was measure by a Likert scale from 0 (not neccesary) to 5 (very neccesary). MSU of selected joints was performed by a rheumatologist ultrasonographer. MSU findings were provided to the consultant rheumatologist immediately after the MSU examination. The consultant rheumatologist completed a second questionaire with global and local changes in diagnosis and treatment decisions, and changes in disease activity. Results The study included 111 patients (38 (34,2%) male and 73 (65,8%) female). Fifteen (13,5%) were new patients and 96 (86,5%) were follow-up patients. Fifty-one (45,8%) patients had already been diagnosed with JIA. The consultant rheumatologist asked for a MSU in 66 patients (59,5%) with a mean indication level of 3,48 (SD 1,25) (range 1-5). A clinical joint examination was performed in 67 patients with a total of 107 joints assessed. From these joints, in 92 (86%) a MSU examination was also performed. Table 1 shows number and percentage of changes in diagnosis and treatment decisions, and changes in disease activity. From 51 patients with JIA diagnosis, 42 (82,4%) were assessed with MSU for disease activity with changes in 19 (45,2%) patients. Table 1. Patients with MSUS, number and percentage of changes in global/local diagnosis and treatment changes, and changes in disease activity Patients N Disease activity change (n: 50) Diagnosis change Treatment change Total pat. AIJ (n: 42) Total pat. Global Local Total pat. Global Local Total 66 20 (40%) 19/42 (45,2%) 30 (45,5%) 1 (43,9%) 30 (43,9%) 45 (68,2%) 12 (18,2%) 11 (16,7%) New 10 0 0/4 3 (30%) 0 3 (30%) 3 (30%) 3 (30%) 1 (10%) Follow-up 56 20 (35,7%) 19/38 (50%) 27 (48,2%) 1 (1,8%) 26 (46,4%) 18 (32,1%) 9 (16,1%) 10 (17,9%) Conclusions MSU changed global and local diagnosis, treatment decisions, and disease activity in a relevant number of patients in our pediatric rheumatology unit. References Micu MC, Alcalde M, Sáenz JI, Crespo M, Collado P, Bolboacă SD, Naredo E. Impact of musculoskeletal ultrasound in an outpatient rheumatology clinic. Arthritis Care Res 2013;65:615-21. Disclosure of Interest J. C. Nieto-Gonzalez: None declared, I. Monteagudo Consultant for: Abbvie, Roche Farma, Bristol- Myers Squibb, Pfizer, UCBL, E. Naredo Consultant for: Abbvie, Roche Farma, Bristol- Myers Squibb, Pfizer, UCB, General Electric Healthcare, and EsaoteL, L. Vargas-Henny: None declared, I. Janta: None declared, M. Hinojosa-Davila: None declared, L. Martinez-Estupiñan: None declared, M. Montoro: None declared, J. G. Ovalles-Bonilla: None declared, L. Carreño: None declared DOI 10.1136/annrheumdis-2014-eular.4206

THU0187 Does Ultrasound-Scored Synovitis Depend on the Pharmacokinetics of Subcutaneous Anti-TNF Agents in Patients with Rheumatoid Arthritis?

Background Many observational studies have shown responsiveness of ultrasound (US)-detected synovitis in rheumatoid arthritis (RA) patients, most of them using biologic therapies. However, these studies have not taken into consideration in their design the pharmacokinetic characteristics of the drug administered. Objectives To investigate whether the pharmacokinetics (i.e. time point of US assessment) of subcutaneous anti-Tumour Necrosis Factor (anti-TNF) agents influences the grade of US-detected synovitis in RA patients treated with these drugs. Methods Fifty consecutive RA patients (31 women, 18 men) were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria consisted of being in treatment with subcutaneous anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory and US assessment at two time points, i.e., at peak plasma drug concentration and at trough plasma drug concentration. Patients were assessed at both time points for disease activity according to the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI) by the same investigator. US assessments were performed by a rheumatologist expert in musculoskeletal US who was blinded to the anti-TNF agent, the administration time, and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial PD signal (i.e. Doppler synovitis). A global index for B-mode synovitis (BSI), joint count for B-mode synovitis (BSC), a global index for Doppler synovitis (DSI), and joint count for Doppler synovitis (DSC) were calculated for a 12-joint US scoring model (31) and a wrist-hand-ankle-foot US scoring model. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. Results Twenty (40.8%) patients were treated with etanercept, 19 (38.8%) with adalimumab, 6 (12.2%) with golimumab, and 4 (8.2%) with certolizumab. There were no significant differences between the clinical, laboratory and B-mode and Doppler US indices and joint counts for both the 12-joint US model and the wrist-hand-ankle-foot model at peak time and trough time (p=0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US, and Doppler US at peak time and trough time assessments (p=0.070-1). DAS28, Disease Activity Score in 28 joints; SDAI, Simplified Disease Activity Index; B-mode synovitis index; BSC, B-mode synovitis count; DSI, Doppler synovitis index; DSC, Doppler synovitis count; W, wrist; A, ankle; Diff, values at peak time–values at trough time. Table 1. Clinical and US assessments at peak and trough time Conclusions Our results suggested that subcutaneous anti-TNF pharmacokinetics does not significantly influence US-scored synovitis in RA patients. Disclosure of Interest : M. Hinojosa-Dávila: None declared, E. Naredo Grant/research support: Esperanza Naredo has received speaker fees from Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote. Esperanza Naredo has received research funding from UCB and MSD., L. Valor: None declared, D. Hernández: None declared, C. Mata-Martínez: None declared, B. Serrano-Benavente: None declared, N. Bello: None declared, J. G. Ovalles-Bonilla: None declared, J. Martínez-B.: None declared, L. Martínez-E.: None declared, J. C. Nieto: None declared, T. Del Río: None declared, C. González: None declared, J. Lόpez-Longo: None declared, M. Montoro: None declared, I. Monteagudo: None declared, L. Carreño: None declared DOI 10.1136/annrheumdis-2014-eular.2966

FRI0260 Survival, causes of death and mortality risk factors in systemic sclerosis

Background Among the rheumatic diseases, Systemic Sclerosis (SSc) stands out as a severely incapacitating and life-threatening disease. Objectives To analize the causes of death, survival and risk factors for mortality in SSc patients. Methods Demographic, clinical, immunological and mortality data were obtained from a long term prospective cohort of SSc patients recruited between 1986 and 2011 in the Rheumatology Department of Gregorio Marañon Hospital in Madrid, Spain. Patients were divided into 4 groups: limited SSc, diffuse SSc, SSc in overlap and SSc in mixed connective tissue disease (SSc-MCTD). ANOVA, Kruskal-Wallis or χ2 tests were used to identify differences among groups; Kaplan-Meier and Mantel-Haenszel (log-rank) analysis were used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality. Results A total of 137 patients were included, of whom 122 (89%) were women. Mean age at diagnosis was 43±17.7 years, and the mean follow-up time was 15.2 years. A global mortality of 34 (24.8%) cases was observed: 8 related to cardiac involvement, 8 to serious infections, 7 to pulmonary involvement, 6 to neoplasms, 2 to renal involvement and 3 to other causes. Survival rates from disease onset were 96, 90, 75 and 50% at 5, 10, 20 and 30 years, respectively. Limited SSc and SSc-MCTD show a significantly (p=0.002) higher survival mean time (33.7 years) when compared to diffuse and overlap variants (22.4 years). Poorer survival is associated with interstitial lung disease, pulmonary arterial hypertension, severe infections, cardiac involvement, chronic kidney disease, and Anti-Ro antibodies (see table 1). Independent prognostic factors for mortality were interstitial lung disease (HR 6.8, CI 95% 1.5-30, p=0.012), pulmonary arterial hypertension (HR 5.6, CI 95% 1.2-26.9, p=0.032), and Anti-Ro antibodies (HR 3.9, CI 95% 1.5-9.8, p=0.004). Table 1. Risk factors related to mortality. Univariate and multivariate analysis Factors Dead (%) Alive (%) HR (95% CI) p* Diffuse SSc 47.1 26.2 3.4 (1.1-10.2) 0.031 SSc in Overlap 20.6 6.8 3.9 (1.1-14.2) 0.032 Severe Infections 64.7 21.4 3.6 (1.7-7.4) <0.001 Interstitial lung disease‡ 84.4 50 3.3 (1.2-8.5) 0.016 Pulmonary arterial hypertension‡ 17.6 4.9 3.1 (1.2-7.5) 0.014 Cardiac Involvement 61.8 16.5 2.8 (1.4-5.9) 0.004 Chronic kidney disease 20.6 2.9 3.2 (1.3-7.9) 0.011 Anti-Ro‡ 39.3 16.3 3.2 (1.5-7.2) 0.004 Anti-Ro 52KDa 28.6 15.1 2.5 (1.1-5.9) 0.03 Anti-Ro 60KDa 14.3 5.8 2.4 (0.8-7.1) 0.118 SSc: Systemic Sclerosis. *Univariant Cox proportional hazards regression analysis. ‡Independent risk factors for mortality. Conclusions A 20-year survival was seen in more than 70% of SSc patients. The main causes of death are cardiac involvement, severe infections and pulmonary manifestations. Diffuse SSc, SSc-MCTD, interstitial lung disease, pulmonary arterial hypertension, severe infections, cardiac involvement, chronic kidney disease, and Anti-Ro antibodies are the main risk factors for mortality. Disclosure of Interest None Declared