M. Hinojosa

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.

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.

AbstractAnti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.

Patient self-assessment and physician’s assessment of rheumatoid arthritis activity: which is more realistic in remission status? A comparison with ultrasonography

OBJECTIVE The objective of this study was to compare disease activity assessed by the patient, the physician and musculoskeletal US in patients with RA in clinical remission. METHODS We evaluated 69 patients with RA in clinical remission according to their attending rheumatologist. Tenderness and swelling in 28 joints were blindly assessed by patients and physicians. The presence of B-mode and Doppler synovitis was blindly investigated in the above joints. The DAS28 and Simplified Disease Activity Index (SDAI) were calculated. RESULTS The percentage of patients in remission according to the self-derived DAS28 (26.1%) was significantly less than that according to the physician-derived DAS28 (52.2%) (P < 0.0005). There was no significant difference in the percentage of patients in remission according to the self-derived SDAI (14.5%) and the physician-derived SDAI (11.6%) (P = 0.172). We found moderate agreement between the patient-derived and physician-derived DAS28 and SDAI [intraclass correlation coefficient (ICC) = 0.620 and ICC = 0.678, respectively]. Agreement between patient and physician was better for the tender joint count (TJC; ICC = 0.509) than for the swollen joint count (SJC; ICC = 0.279). The mean (S.D.) count for B-mode synovitis [4.09 (3.25)] was significantly greater than the SJC assessed by both the patient and physician [2 (3.71) and 1.42 (2.03), respectively] (P < 0.0005 and P = 0.033, respectively). We found moderate agreement between the physician-assessed SJC and the joint count for Doppler synovitis (ICC = 0.528). CONCLUSION Patient-assessed and physician-assessed overall RA activity showed acceptable agreement. Patient self-assessment overestimated disease activity determined by the DAS28. At the patient level, physician-assessed joint swelling showed an acceptable concordance with Doppler US synovitis.

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.

Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous anti-TNF agents in patients with rheumatoid arthritis?

OBJECTIVE The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. METHODS Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly 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 power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. RESULTS There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters 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). CONCLUSION Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis 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

FRI0619-HPR Joint Prostheses and Biologic Therapies in a Rheumatologic Clinic

Background Biologic therapies (BT) have been changed considerably the treatment of autoimmune and autoinflammatory rheumatic diseases. However, patients with joint prostheses may present adverse effects due to these therapies. Objectives To describe clinical features, treatment and complications of patients with joint prosthesis treated with BT. Methods We included all patients treated in our BT Unit from January 2010 to December 2014. For each patient we analysed demographic, diagnosis, treatments, number of prostheses and complications. Results Eight hundred patients were treated with TB in our TB Unit during the study period of which 77 (9.6%) patients needed joint prosthesis. The diagnosis of patients with joint prosthesis was as follows: 51 (66.2%) rheumatoid arthritis (RA), 16 (20.7%) ankylosing spondylitis (AS), 5 (6.5%) lupus erythematosus, 3 (3.9%) psoriatic arthritis and 2 (2.6%) juvenile idiopathic arthritis. We found 129 prostheses placed in the 77 patients, of which 56 (43.4%) were hip prostheses, 50 (38.7%) were knee prostheses, 5 (3.9%) were MCF prostheses, 4 (3.1%) were ankle prostheses, 3 (2.3%) were wrist prostheses, 2 (1.5%) were IF prostheses, 2 (1.5%) were elbow prostheses and 2 (1.5%) were shoulder prostheses. The mean age of prosthesis placing was 60 years (range 28-85) and the mean disease duration at the moment of prosthesis placing was 20 years. The most used BT were as follows: 28 (36.4%) infliximab, 20 (26%) rituximab, 16 (20.7%) tocilizumab, 9 (11.6%) abatacept and 4 (5.2%) etanercept. Thirty four (44.1%) patients had received more than one biological drug, 44 (57.1%) patients had concomitant synthetic disease-modifying anti-rheumatic drugs (sDMARDs) treatments and 41 (53.2%) patients had steroid treatment associated. We recorded 7 (5.4%) prosthetic infections in 7 (9.1%) patients of which 6 were diagnosed with RA and one with AS. From all infections, 2 occurred in prosthesis placed before the beginning of BT treatment and 5 occurred in prostheses placed during BT treatment. All patients with prosthesis infections were treated with concomitant sDMARDs and steroid treatment. Five patients needed prosthesis replacement for other reasons. Conclusions Most frequent prostheses were hip and knee prostheses. The majority of prosthetic infection occurred in patients with prosthetic placement during the BT treatment. All patients with prosthesis infections received also sDMARS and steroid treatments. Disclosure of Interest None declared

AB0983 Contribution of Knee Involvement Evaluated by Doppler Ultrasound and Synovial Fluid Analysis in Rheumatoid Arthritis Disease Activity Assessment

Objectives The objective of this prospective, cross-sectional study was to determinate the contribution of concomitant non-inflammatory knee involvement evaluated by Doppler ultrasound (DUS) in rheumatoid arthritis (RA) disease activity assessment and when indicated, by synovial fluid (SF) analysis in a Rheumatology Clinic of a University Hospital Methods We evaluated 106 patients with RA who consecutively attended. Patients with a history of other musculoskeletal diseases were excluded. RA activity was evaluated by the Disease Activity Score (DAS28). Tenderness and swelling at the knees were recorded separate. Clinical assessment was performed by the same rheumatologist before US assessment. A B-mode (BM) and power Doppler (PD) US assessment was performed by the same rheumatologist, blinded to clinical and laboratory results. For each knee we evaluated and scored synovitis components in BM and PD [synovial effusion (SE), synovial hypertrophy (SH), PD signal] according to Outcome Measurement in Rheumatology (OMERACT) definition and scoring system (0-3). After DUS evaluation the knees were classified in two groups: 1) knee involvement probably due to RA [i.e. SH grade 2-3, with or without PD signal, or SH grade 1 with PD signal (1-3), independently of SE]; 2) knee involvement probably not due to RA: [i.e. SH grade 0 or SH grade 1 without PD signal, independently of SE]. If SE grade 2-3 was detected an arthrocentesis was performed. The SF analysis included a macroscopic and microscopic examination (i.e. cellular count, crystals) and bacterial culture. After SF evaluation knees were re-classified in three groups: 1) knee involvement probably due to RA: inflammatory SF (≥500 cells) and crystals absence; 2) knee involvement probably not due to RA: mechanical SF, with or without crystals; 3) uncertain: inflammatory SF (≥500 cells) with crystals. This last group was included in the group of knee involvement probably due to RA for the final analysis Results We evaluated 212 knees. Pain and/or swelling were present in 174 (72%) knees. Table 1 shows the results of DUS evaluation in clinically affected knees. After DUS evaluation 48 (27.59%) knees were classified in probably due to RA and 126 (72.41%) in not-probably due to RA. DAS 28 was re-calculated excluding the knees classified as probably not due to RA from swollen and pain joint counts. In addition, after SF analysis the knees were re-classified and DAS28 was re-calculated. All patients in remission according to initial DAS28 were also in remission according to both re-calculated DAS 28. The number of patients in remission significantly increased after DUS and DUS+SF assessments (23%, 31.7% and 33.7% respectly; p=0.004 and p=0.001 respectly) Table 1 Grade 0 Grade 1 Grade 2 Grade 3 Synovial hypertrofy 33.29% (58) 56.82% (99) 9.2% (16) 0.57% (1) PD signal 73.6% (128) 17.83% (31) 8.63% (15) 0% (0) Conclusions Knee involvement was common in our RA patients. Knee involvement not due to RA might overestimate RA activity measured by DAS28. DUS and SF analysis may contribute to an accurate diagnosis of knee involvement in RA patients, which should be relevant for better therapeutic management Disclosure of Interest M. Montoro: None declared, I. Janta: None declared, R. Irace: None declared, M. Medina: None declared, B. Serrano: None declared, C. Mata: None declared, L. Martinez: None declared, J. Martinez: None declared, M. Hinojosa: None declared, N. Bello: None declared, J. Ovalles: None declared, J. Nieto: None declared, L. Valor: None declared, F. Lopez: None declared, I. Monteagudo Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, MSD and Esaote, C. Gonzalez: None declared, E. Naredo Grant/research support: Grant/research support: UCB and MSD Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, L. Carreño: None declared DOI 10.1136/annrheumdis-2014-eular.3895

AB0434 Relation of Subclinical Ultrasound Detected Synovitis and Peripheral B-Cell Counts in Rheumatoid Arthritis Patients Treated with Rituximab

Background The clinical response in patients with Rheumatoid Arthritis (RA) to rituximab (RTX) has been shown to be related with the presence of B-cells in the synovi. To date this has not been proved for peripheral B-cell counts. Ultrasound (US) has proven higher sensitivity for detecting synovitis than clinical assessment. The relation of subclinical US-detected synovitis and peripheral B-cell counts in RA patients treated with RTX has not been addressed. Objectives the aim of study was to assess the association between the presence of absolute B- cell count in peripheral blood and subclinical synovitis measured by US [B-Mode (BM) and power Doppler (PD)] in RA patients treated with RTX in clinical remission according to the attending physician. Methods In this cross sectional study we evaluated 37 RA patients treated with RTX in clinical remission according to clinical judgment. Inclusion criteria were having received at least two cycles of RTX and having had no change in therapy in the previous 3 months. All patients underwent a blind clinical, laboratory and US assessment (BM and PD of 12 joints). A global index for B-mode synovitis (BMI; range 0–36) and a global index for synovial PD signal (PDI; range 0–36), obtained by the sum of the B-mode synovitis and synovial PD signal scores for each joint region was calculated for each patient. B-cell absolute count was determined in our routine laboratory by flow cytometry. Results Thirty (81%) patients were female with a mean (SD) age of 60 (12) years. Sixteen (43.2%) patients were rheumatoid factor (RF) positive and 29 (78.4%) had antibodies to citrullinated peptides (ACPA). The mean (SD) disease duration was 16 years (8). Fifteen patients (40.5%) satisfied the DAS28 criteria for remission, the mean (SD) DAS28 was 3.04 (1.2). All patients had evidence of BM synovitis and 16 (43.2%) patients had synovial PD signal. There was no correlation between DAS28 and BMI and PDI (r =0.13, p=0.45; r =0.27, p=0.09, respectively). Twenty six (67.5%) patients had peripheral B-cells (>1 cell/mm3). There was no difference in the B-cell count according to DAS28 (DAS28 <2.6=34.53, DAS28>2.6=49.45, p=0.52) or PDI score (PDI<1=49.48, PDI>1=35.44, p=0.54). There was no correlation between B-cell count and DAS28, BMI or PDI score (r =0.020, p=0.907; r =-0.151, p=0.371; r = -0.099, p=0.558). Conclusions in our study we did not find any relation between subclinical synovitis measured by US and peripheral B-cell count in RA patients treated with RTX. References Buch MH, Smolen JS, Betteridge N, Breedveld FC, Burmester G, Dörner T,Ferraccioli G, Gottenberg JE, Isaacs J, Kvien TK, Mariette X, Martin-Mola E,Pavelka K, Tak PP, van der Heijde D, van Vollenhoven RF, Emery P; Rituximab Consensus Expert Committee. Updated consensus statement on the use of rituximabin patients with rheumatoid arthritis. Ann Rheum Dis. 2011 Jun;70(6):909-20. Disclosure of Interest L. Martinez Estupiñan: None declared, E. Naredo Grant/research support: UCB and MSD, Consultant for: Abbvie, Roche Farma, Bristol- Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, L. Valor: None declared, I. Janta: None declared, M. Montoro: None declared, T. Del Rio: None declared, J. C. Nieto-González: None declared, M. Hinojosa: None declared, N. Bello: None declared, J. Martínez: None declared, C. González-Fernández: None declared, J. Lόpez-Longo: None declared, I. Monteagudo Consultant for: Abbvie, Roche Farma, Bristol- Myers Squibb, Pfizer, UCB, L. Carreño-Pérez: None declared DOI 10.1136/annrheumdis-2014-eular.4136

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