Lina Martínez-Estupiñán

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.

Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis

Objective Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features. Methods Two case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc. Results Four out of five analysed SNPs were significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: pFDR=6.14 × 10−4, OR=0.78; rs4963128: pFDR=6.14 × 10−4, OR=0.79; rs702966: pFDR=3.83 × 10−3, OR=0.82; and rs2246614: pFDR=3.83 × 10−3, OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant. Conclusions The results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases.

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.

Multiobserver Reliability of Ultrasound Assessment of Salivary Glands in Patients with Established Primary Sjögren Syndrome

Objective. To evaluate the multiobserver reliability of salivary gland ultrasonography (SGUS) for scoring greyscale (GS) parenchymal inhomogeneity and parenchymal color Doppler (CD) signal in patients with established primary Sjögren syndrome (pSS). Methods. The study comprised 2 multiobserver reliability assessments in patients with pSS in 2 European centers. The first reliability exercise was performed on 24 patients with pSS and 8 controls who were independently evaluated with GS and CD US by 5 observers at the Institute of Rheumatology, Belgrade, Serbia. The second reliability exercise was carried out on 10 patients with pSS who were independently assessed with GS and CD US by 8 observers at the Hospital G.U. Gregorio Marañón, Madrid, Spain. SGUS parenchymal inhomogeneity and parenchymal CD signal were semiquantitatively scored using a 4-grade scoring system. The multiobserver agreement was calculated by the overall agreement and Light’s κ statistics. Results. A total of 640 SGUS examinations were performed in the first reliability exercise and a total of 320 examinations in the second reliability exercise. Multiobserver reliability was good (κ = 0.71–0.79) to excellent (κ = 0.81–0.82) for GS parenchymal inhomogeneity in both exercises. There was a moderate (κ = 0.53–0.58) to good (κ = 0.70) multiobserver reliability for parenchymal CD signal in the first exercise. However, there was no agreement or only a fair agreement (κ = 0.03–0.29) for parenchymal CD signal in the second exercise. Conclusion. US may be a reliable technique in the multiobserver scoring of GS parenchymal inhomogeneity of major SG in patients with established pSS. CD scoring of SG needs further standardization to be used in multicenter studies.

AB0253 To What Extent is Foot Pain Attributable to Disease Activity in RA Patients

Background A high prevalence of foot pain (70-90%) has been widely described in rheumatoid arthritis (RA) (1-4). Foot inflammation in RA usually starts in the metarsophalangeal (MTP) joints, extends to other joints with consequent pain, deformities and functional impairment (5, 6). The foot disorders and complaints it might have their origins in inflammatory disease activity or biomechanical abnormalities. Objectives The objective of this cross-sectional prospective study was to establish what extend foot complaints in RA patients in remission or low disease activity may originate in subclinical inflammatory disease activity as opposed to podiatric biomechanical abnormalities. Methods We recruited 136 patients with foot complaints. Sixty-two were bDMARD-treated RA patients presenting DAS-determined remission or low disease activity while the remaining 74 were gender matched controls without rheumatic or muskoskeletal disorders. In an effort to identify the root cause of pain, we subjected both groups to a comprehensive podiatric and biomechanical assessment followed by an ultrasound (US) scan. Results Most RA patients and controls were female (77.4% and 83.8%, respectively). There was no statistical difference in the proportion of obese subjects in either group (p=0.792). Inappropriate shoes were used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia, particularly heel pain, was more frequent in the control group, with associated talalgia and metatarsalgia being more prevalent in the RA group (p<0.05). The RA patient group was also more likely to present greater foot deformity, more limited joint movement and foot pathologies than the controls. US inflammatory and structural changes were significantly more frequent in RA patients than in controls (p<0.05). US structural involvement was significantly associated with limited joint mobility and pathologic biomechanical tests only in RA patients (p<0.05).Figure 1. Transverse (A) and longitudinal (B) ultrasound image of tibialis posterior B-mode tenosynovitis and damage that shows hypoechoic sheath widening (s) and a peripherial tendon defect (d). mm, medial malleolus. Conclusions RA foot pathologies often seem to be linked to disease activity and ultrasound can be useful to help the clinician differentiate disease-related foot pain from other possible biomechanical causes. References Hooper L, et al. Arthritis Care Res.2012;64(8):1116-24. Rome K, et al. J Foot Ankle Res.2009;2:16. Rao S, Best Pract Res Clin Rheumatol 2012;26(3):345-68. Fuchs HA, et al. Arthritis Rheumatol.1989;32(5):531-7. van der Leeden M, et al. Rheumatology.2006;45(4):465-9. van der Leeden M, et al. Arthritis Res Ther.2010;12(1):R3. Disclosure of Interest None declared

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

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