I. Farina

Factors and comorbidities associated with first neuropsychiatric event in systemic lupus erythematosus: does a risk profile exist? A large multicentre retrospective cross-sectional study on 959 Italian patients

OBJECTIVE To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE. METHODS A number of generic (not strictly SLE related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated. RESULTS Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors [mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001] were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement. CONCLUSIONS In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus.

HLA-G may predict the disease course in patients with early rheumatoid arthritis.

The current management of early rheumatoid arthritis (ERA) is to start an intensive treatment as soon as possible. To avoid under/overtreatment, it is important to identify reliable ERA evolution biomarkers. HLA-G molecules has been associated with rheumatoid arthritis, suggesting a role in disease regulation. HLA-G antigens are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that act as ligand for immune-inhibitory receptors (ILT2, ILT4, KIR2DL4). Expression of HLA-G is influenced by a 14 bp insertion/deletion polymorphism in exon 8 of the gene, where the deletion is associated with mRNA stability. We analyzed 23 ERA patients during a 12 months follow-up disease treatment for sHLA-G, IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma samples by ELISA, mHLA-G and ILT2 expression on peripheral blood CD14 positive cells by flow cytometry and typed HLA-G 14 bp deletion/insertion polymorphism by Real-Time PCR. Disease status (DAS28), ultrasonography with power Doppler and laboratory data were checked. Cytokine levels confirmed the anti-inflammatory effect of the treatment. sHLA-G, mHLA-G and ILT2 expression inversely correlated with DAS28 disease scores. The frequency of 14 bp deletion allele increased in patients with disease remission. Based on these results, HLA-G may be a candidate biomarker to evaluate early prognosis and disease activity in ERA patients.

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register

INTRODUCTION Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). OBJECTIVES To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. METHODS We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. RESULTS We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX+MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX+MTX and RTX, respectively; while 12 patients (4.5% in RTX+MTX, and 2.5% in RTX group) suspended therapy for AE. CONCLUSIONS RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

Ultrasound-detected tenosynovitis independently associates with patient-reported flare in patients with rheumatoid arthritis in clinical remission: results from the observational study STARTER of the Italian Society for Rheumatology

OBJECTIVES This study aimed to estimate the prevalence of US-detected tenosynovitis in RA patients in clinical remission and to explore its clinical correlates. METHODS A total of 427 RA patients in clinical remission were consecutively enrolled from 25 Italian rheumatology centres. Tenosynovitis and synovitis were scored by US grey scale (GS) and power Doppler (PD) semi-quantitative scoring systems at wrist and hand joints. Complete clinical assessment was performed by rheumatologists blinded to the US results. A flare questionnaire was used to assess unstable remission (primary outcome), HAQ for functional disability and radiographic erosions for damage (secondary outcomes). Cross-sectional relationships between the presence of each US finding and outcome variables are presented as odds ratios (ORs) and 95% CIs, both crude and adjusted for pre-specified confounders. RESULTS The prevalence of tenosynovitis in clinical remission was 52.5% (95% CI 0.48, 0.57) for GS and 22.7% (95% CI 0.19, 0.27) for PD, while the prevalence of synovitis was 71.6% (95% CI 0.67, 0.76) for GS and 42% (95% CI 0.37, 0.47) for PD. Among clinical correlates, PD tenosynovitis associated with lower remission duration and morning stiffness while PD synovitis did not. Only PD tenosynovitis showed a significant association with the flare questionnaire [OR 1.95 (95% CI 1.17, 3.26)]. No cross-sectional associations were found with the HAQ. The presence of radiographic erosions associated with GS and PD synovitis but not with tenosynovitis. CONCLUSIONS US-detected tenosynovitis is a frequent finding in RA patients in clinical remission and associates with unstable remission.

Involvement of the Inconstant Bursa of the Fifth Metatarsophalangeal Joint in Psoriatic Arthritis: A Clinical and Ultrasonographic Study

Objective. To evaluate the involvement of the bursa located next to the head of the 5th metatarsal bone in patients with psoriatic arthritis (PsA) in comparison with the other seronegative spondyloarthritis (SpA). Methods. All patients with PsA seen during a period of 24 months were enrolled. The control group included healthy subjects and patients with the other SpA. All subjects underwent clinical and ultrasound (US) examination of the lateral surface of the 5th metatarsal. Results. 150 PsA patients (88 M; 62 F), 172 SpA (107 M; 65 F), and 95 healthy controls (58 M; 37 F) were evaluated. Based on clinical and US evaluation, bursitis was diagnosed in 17/150 (11.3%) PsA patients but in none of the SpA (P < 0.0001) and healthy (P = 0.0002) controls. In detecting bursitis, US was more sensitive than clinical examination, although the difference did not reach statistical significance (P = 0.09). Conclusion. The bursa of the 5th metatarsophalangeal joint appears to be involved in PsA more frequently than by chance. If confirmed by other studies, this finding could be considered as a distinctive clinical sign of PsA, useful for differential diagnosis with the other SpA. In asymptomatic patients, US proved to be more sensitive in the detection of bursitis.

SAT0061 Concurrent Ultrasound-Detected Synovitis and Tenosynovitis Predict Flare in Patients with Rheumatoid Arthritis in Clinical Remission

Background Subclinical synovial inflammation detected by ultrasonography (US) in patients with rheumatoid arthritis (RA) in clinical remission relates to disease flare. The impact of tenosynovitis in this context is not known. Objectives To evaluate the association between US-detected tenosynovitis and synovitis in RA patients in clinical remission and flare over 12-months. Methods STARTER is a multicentre cohort study of the US Study Group of the Italian Society for Rheumatology. Participants were selected on the basis of a reliability exercise and the availability of high-end equipment. Patients with RA in clinical remission underwent clinical evaluation and US synovitis (-S) and tenosynovitis (-T) were assessed categorically for Grey Scale (GS) and power Doppler (PD) at 11 joints, extensor and flexor tendons in both hands and wrists. Patients were seen at 6 and 12 months. Flare within 12 months was defined as increase of >1.2 or >0.6 if final DAS28>3.2. The relationship between the presence of GS-T/-S, PD-T/-S was evaluated by logistic models, presented as odds ratios (OR) and 95% confidence interval (CI), adjusted for pre-specified confounders. Results 361 patients (72.3% f, mean age (sd) 56.1 (13.3), median disease duration (IQR) 7.1 years (3.6–13.5)) were included. 98/326 (30.6%) patients had a flare within 12 months. Considering US variables separately, only PD-S significantly predicted flare (OR 1.87 (1.12,3.14)). When the model included both –T and –S, only the concurrent presence of –T and –S predicted flare (PD-T+-S: OR 2.06 (1.04, 4.07); GS-T+-S: OR 2.27, (1.01,5.10)), while isolated –S and –T did not. Conclusions In patients with RA in clinical remission, US-detected synovial and tenosynovial inflammation identifies patients at risk of flare. US might help decisions on management in this population. Disclosure of Interest None declared

The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study

Objective To define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation. Methods A multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models. Results 361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months. Conclusions PD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.

THU0090 Influence of age at disease onset on clinical, functional, and ultrasonographic outcomes in a monocentric early rheumatoid arthritis cohort

Background Rheumatoid Arthritis (RA) onset may occur at any age and peaks in the fifth decade. Because the mean age of general population is continually increasing and since older age could impact on outcomes, late-onset RA (LORA) will probably become a relevant issue for health care system in the next future. A better characterization of LORA could help rheumatologist in the therapeutic decision-making process tailored on the individual patient. Objectives To investigate the relationship between age at disease onset and clinical, ultrasonographic and functional outcomes. Methods Early RA (ERA) patients fulfilling 2010 ACR/EULAR, with available clinical ad ultrasonographic follow-up of at least 1 year, who consecutively attended our Early Arthritis Clinic between 2009–2014, were retrospectively analyzed. Patients were pooled into 3 groups by age at RA onset: <45 years (young-onset RA [YORA] group 1), 45 to 60 years (intermediate-onset RA [IORA] group 2), and >60 years (late-onset RA [LORA] group 3). At baseline biological, functional and ultrasonographic data were recorded. The following items were compared at baseline and after 12 months from diagnosis: DAS28CRP remission rate, functional disability using the Health Assessment Questionnaire (HAQ), power doppler (PWD) score, Methotrexate (MTX) treatment, use of glucocorticoids (GCs). Results The main baseline demographic and disease characteristics of the whole sample of ERA (n=223) and the 3 age groups- YORA (46), IORA (81) and LORA (96)- are summarised in Table 1. Age at RA-onset was independently associated with DAS28CRP remission at 1 year (Table 2). Conclusions In a cohort of ERA, older age at disease onset is associated with a more active pattern disease at the beginning but with a greater probability of DAS28CRP remission at 1 year. Disclosure of Interest None declared

AB0227 Impact of early arthritis clinic on the rate of treatment with biologics in rheumatoid arthritis: interrupted time series analysis

Background Early diagnosis is one of the mainstay of rheumatoid arthritis (RA) management. Early diagnosis reflects on early treatment, better response with reduction of long-term detrimental disease outcomes. Early arthritis clinics (EAC) are the healthcare services devoted to facilitate early diagnosis and optimize treatment of early onset inflammatory arthritis. Despite the a priori beneficial potential of EAC, no strong experimental data support EAC efficacy. Interrupted time series analysis is one of the “next best” approaches for dealing with interventions when randomisation is not possible or clinical trial data are not available. Objectives To evaluate the impact of the implementation of an EAC in terms of probability of starting second-line biologic DMARDs, using a quasi-experimental approach. Methods RA patients fulfilling 1987 ACR criteria who attended the outpatient rheumatology clinic (RC) between 2002 and 2008 and the Early Arthritis Clinic between 2009 and 2014 were retrospectively analyzed. The EAC was developed as a healthcare service integrating primary care with tertiary rheumatology care to provide early referral of suspected inflammatory arthritis and tight monitoring and standardized therapeutic approach according to “treat to target” (T2T) strategy and EULAR guidelines to early RA. The two sub-cohorts were compared in terms of: 1) lag time from symptoms onset to RA treatment with DMARDs; and 2) risk of treatment with bDMARDs at 24 months. Interrupted time analysis was performed to compare lag time from onset to treatment and log-transformed 24-month risk of biologics periods before the implementation of the EAC with subsequent periods. Results A total of 353 RA patients were included: 208 (mean±SD age 58.7±12.6 years, 164 F, baseline DAS28 4.76±1–23) followed in RC and 145 (mean±SD age 58.8±14.9 years, 106 F, DAS28 5.09±1.31) in EAC. Lag time from symptoms onset to treatment resulted significantly lower (median [IQR] months 4 [2–7] vs 12 [5–24]; p<0.0001) in patients managed in EAC compared with RC. Within 24 months a biologic therapy was started in 62/208 (29.8%) of patients followed in RC, and 21/145 (14.5%) in EAC group (p=0.001), along with an increased remission rate at 24 months (43% vs 62%, p<0.001). Analyzing the time series “interrupted” by the implementation of the EAC, comparing before and after intervention periods, a significant change in slope was observed for both lag time (coefficient -8.85 [95% CI -17.25, -0.44], p=0.04) and risk of treatment with biologics (coefficient -1.17 [95% CI -2.09, -0.24], p=0.01). As expected in more recent years - according to a T2T approach - a monotonous positive trend in percentage of patients treated with biologics is also observed in EAC (coefficient 0.31 [95% CI 0.05, 0.58]). Conclusions The implementation of an EAC that integrates care and applies tight control and standard of care, leads to early diagnosis and treatment and may lower the need – overtime - of second-line biologic drugs, with a significant impact both on individuals and health care systems. Disclosure of Interest None declared

SAT0170 Bdmards Mono vs Combo Therapy in Rheumatoid Arthritis. Analysis of A Rheumatological Single Tertiary Center Real-Life Experience

Background Despite adavantages of biological combo therapy over biological mono for RA treatement and the limited approval of biologics as monotherapy (etanercept, adalimumab, certolizumab, tocilizumab), real life registries data revealed that approximately one-third of patients taking biologic agents are using them as monotherapy. Objectives To assess the prevalence of bDMARDs use as monotherapy (bDMARDs-mono) in a cohort of RA patients treated with bDMARDs attending a tertiary rheumatological center.To characterize the clinical profile of these patients, and to investigate factors related to monotherapy. Methods All patients with Rheumatoid Arthritis attending our center and receiving bDMARDs up to 31th january 2015 were retrospectively analyzed. Demographic, and clinical characteristics of each patient were recorded: age, gender, disease duration, drugs history and clinical disease activity (DAS28) at last visit. Results 341 RA patients receiving bDMARDS were included. F 160, M 123, mean age 59.98 ±12.54, disease duration 178.69±101.81 months. 197 patients were taking bDMARD as first line bio-therapy, 144 had been previously treated with one or more bDMARDs. 52% (n=179) of patients were receving bDMARD-mono with a mean disease duration 187.4±125.1 month; 48% (n=162) were bDMARDs-combo, 65% of them with MTX; mean disease duration 168.9±42.4 m. Biologic agents used as mono or combo are shown in table 1. 32% of bDMARDs-mono had discontinued csDMARDs before starting biological therapy, 68% after an average 50,4 months after starting bDMARDs (p<0.001). The most common reasons for discontinuing csDMARDs were toxicity (55% of cases), with significant difference between those who stopped before and after starting bDMARDs (66% vs 48% respectively, p<0,02). 11% of patients discontinue csDMARDs because of nonspecific bad tolerance, 9% for inefficacy, 11% for others unspecified reasons. 25 patients (14%) on bDMARDs-mono stopped csDMARDs for clinical remission. Overall, 57% of RA patients were in clinical remission (DAS28 PCR <2.6) at the time of the inclusion in the study, without significant differece between the two groups (bDMARDs-mono vs combo). The use of bDMARDs-mono was more frequently observed in those patients with disease duration longer than 10 years (p<0,0001). Conclusions Biologic monotherapy for managing RA is widely used in our clinical practice especially in patients with long term disease. The proportion of patients (1/3) who start bDMARD-mono is quite similar to that reported in literature. On the other hand, most of patients arrive to bDMARDs-mono after starting biologic agent as the result of csDMARD witdrawal due to AE or intollerance to DMARDs and to a lesser extent because achieving good control of the disease since patients preference is strongly oriented to csDMARD discontinuation rather than bDMARDs withdrawal or tapering. References Emery P, et al. Ann Rheum Dis 2013:Dec:72 (12):1897–904. Disclosure of Interest None declared