E. Galuppi

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.

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

THU0022 Replication analysis of gene-gene interaction between HLA-DQA2 and HLA-DQB2 variants in italian rheumatoid arthritis patients

Background Rheumatoid Arthritis (RA) is a complex and multifactorial disease, caused by multiple interactions between genetics and environmental factors. In the context of RA genetics, the Human Leukocyte Antigen (HLA) exerts a primary role. Approximately 90% of RA patients show alleles at the HLA-DRB1 locus, codifying for 5 Amino Acids, known as “shared epitope” (SE). SE is associated with increased risk to develop RA and more severe phenotype, but it does not entirely explain HLA contribution to disease risk. Moreover, it is generally accepted that occurrence risk could be determined by specific gene-gene interactions. A study carried out in USA (NARAC) reported a particular interaction between SNPs in the HLA class II region: HLA-DQA2 (rs9275595) and HLA-DQB2 (rs10807113). Results showed 11 fold increased risk to develop RA in patients carrying both variants (Liu et al., 2011), while single variants did not significant contribute to the RA risk (Odds ratio, OR, respectively, 1.6 and 1.0). Gene-gene interaction between HLA-DQA2 and HLA-DQB2 SNPs is remarkable, considering that glycoproteins codified by these genes combined each other and create a quaternary structure. Objectives To replicate NARAC study evidence in Italian population, we genotyped rs9275595 (HLA-DQA2) and rs10807113 (HLA-DQB2) variants using a case/control model. Methods The study included a cohort of 316 Italian RA patients and a matched group of 443 healthy control individuals. All subjects were genotyped for HLA-DQA2 T>C (rs9275595) and HLA-DQB2 A>C (rs10807113) using TaqMan technology and Real-Time PCR. Results Replication test performed in our Italian RA cohort did not identify significant interaction between two variants analyzed. However, considering the single variant rs9275595, the results showed a significantly increased risk to develop RA. Taking T/T genotype as the reference, C/C homozygotes showed significant association with a 3.82 fold increased risk of RA (OR=3.821 95% CI (2.017–8.351) p-value=0.00063). The SNP acted under an additive model: T/C heterozygotes showed significant OR=1.988 (95% CI 1.458–2.711, p-value=0.00002). Conclusions The results of this study do not confirm the gene-gene interaction previous reported in the NARAC cohort (Liu et al., 2011). However, outcomes suggest that HLA-DQA2 rs9275595 could contribute to RA pathogenesis in the Italian population. References Liu C, Ackerman HH, Carulli JP. A genome-wide screen gene-gene interactions for rheumatoid arthritis susceptibility. Hum Genet. 2011 May;129(5):473–85. 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

Hypertrophic osteoarthropathy: classification, diagnostic features, and treatment options

ABSTRACT Introduction: Hypertrophic osteoarthropathy (HOA) is an orphan disease characterized by digital clubbing, periostitis of tubular bones and arthralgia/arthritis. The disease may be classified as primary or secondary. Pulmonary and other intra-thoracic diseases are the cause of more than 90% of the secondary forms. Areas covered: The diagnosis is generally based on the presence of a triad of symptoms including digital clubbing, periostitis of the distal end of the tubular bones and painful swelling of the limbs, associated with bilateral and symmetrical arthritis in the large joints. Radiographic evaluation is the assessment reference for the diagnosis. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) seem to be the key mediators in the pathogenesis of this disorder. Treatment and prognosis depend on the HOA underlying cause. In some cases, treatment of associated malignancy can solve or improve clubbing. Bisphosphonates may have a role for the symptomatic treatment of HOA. Expert opinion: In clinical practice primary HOA is rare while secondary form is relatively frequent and may mimic other rheumatologic conditions. Notably HOA should be considered in the differential diagnosis of painful arthritis with periosteal bone involvement and if clubbing or periostitis become evident in a previously healthy individual a comprehensive search for an underlying illness should be undertaken.

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

THU0095 Difference in Physical Function Between Remission and Low Disease Activity in Early Rheumatoid Arthritis

Background Remission is the optimal therapeutic goal in treating rheumatoid arthritis to target but low disease activity could constitute a valuable alternative goal especially in patients with long standing disease. Few data exist about the different clinical and functional implications of the two disease activity conditions especially in Early Rheumatoid Arthritis (ERA). Objectives To investigate whether aiming a state of remission yields some benefit when compared with low disease activity as regard to functional outcomes in an Early Rheumatoid Arthritis cohort of patients. Methods ERA patients fulfilling 2010 ACR/EULAR who consecutively attended our Early Arthritis Clinic between 2009-2014 were retrospectively analyzed. Patients with available follow-up of at least 1 year were included. Disease activity and functional disability has been evaluated using DAS28 and HAQ after 6 (T6) and 12 (T12) months from diagnosis. Standardized therapeutic approach has been performed according to EULAR guidelines. At T6 and T12 HAQ was compared between patients with different levels of disease activity according to the DAS28: remission (REM-DAS28<2.6) and low disease activity (LDA-DAS28≤3.2). Data were analysed by using t student test. Results One hundred and thirty-nine patients completed the 1-year follow up. At baseline DAS28 and HAQ were respectively 4.59±1.1 and 0.95±0,7. At T6 81 (58%) patients achieved DAS28 remission and had an HAQ of 0.27±0.41, 22 (16%) patients were in DAS28 LDA with an HAQ of 0.49±0.5. At T12 83 (60%) patients achieved DAS28 REM and 27 (19%) DAS28 LDA with an HAQ respectively of 0.22±0.35 and 0.75±0.61. At both time points, HAQ resulted significally lower (p<0.05) in REM groups compared to that in LDA. Within the period of observation (from T6 to T12) 11 patients changed from LDA to REM. When investigating the change in physical function in these patients we saw improvement of HAQ from 0.48±0.55 to 0.21±0.29. 13 patients moved from REM to LDA and HAQ deteriorated significantly (REM 0.33±0.3, LDA 0.74±0.49, p=0.01). Conclusions Even though LDA constitutes an alternative goal especially in patients with long standing disease, our analyses revealed that aiming a state of clinical REM within the first months of the disease, is much better also in term of physical function. Reaching early a good physical function not only will benefit the patient but also will improved major socioeconomic consequences of Rheumatoid Arthritis. References H Radner, JS Smolen, D Aletaha. Remission in rheumatoid arthritis: benefit over low disease activity in patient-reported outcomes and costs. Arthritis Research & Therapy 2014;16:R56. Disclosure of Interest None declared