V. Grosso

Atherosclerosis and rheumatoid arthritis: more than a simple association.

In the last decades a large amount of evidence linked rheumatoid arthritis (RA) to atherosclerosis. In fact, RA patients have an increased risk of cardiovascular events that is not fully explained by other classic cardiovascular risk factors. RA and atherosclerosis may share several common pathomechanisms and inflammation undoubtedly plays a primary role. The proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD). In RA, inflammation alters HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, induces atherosclerosis. Interestingly, some genetic polymorphisms associated with RA occurrence enhance atherosclerosis, however, other polymorphisms associated with RA susceptibility do not increase CVD risk. Several other mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular are really wide and different. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of CVD occurrence.

The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainly focused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing data concerning HBV reactivation in RA patients treated with newer biological drugs like tocilizumab and abatacept have cumulated. In this review, epidemiology, pathogenesis and natural history of HBV infection have been revised first, mainly focusing on the role that specific therapeutic targets of current biotechnological drugs play in HBV pathobiology; finally we have summarized current evidences from scientific literature, including either observational studies and case reports as well, concerning HBV reactivation under different classes of biological drugs in RA patients. Taking all these evidences into account, some practical guidelines for screening, vaccination, prophylaxis and treatment of HBV reactivation have been proposed.

Switching from Intravenous to Subcutaneous Formulation of Abatacept: Different Results in a Series of 21 Patients

To the Editor: We read with interest the article by Reggia, et al 1, a monocentric study analyzing the efficacy and safety of switching from intravenous (IV) to subcutaneous (SC) formulation of abatacept (ABA) in patients with rheumatoid arthritis. The authors report a relatively high risk of disease relapse (27%) occurring in a mean of 11 weeks after switching to SC administration. The study did not find any significant predictive factor for a switch failure. The concern that patients with a higher body mass index could receive lower cumulative doses compared to weight-tiered monthly infusions, leading to a significant influence on treatment efficacy, was not confirmed by this study, or by previous dose-finding trials and … Address correspondence to Dr. S. Monti; E-mail: sara.saramonti{at}gmail.com

Randomized controlled trials and real-world data: differences and similarities to untangle literature data

Randomized controlled trials (RCTs) represent the gold-standard of medical evidence to assess the efficacy and safety of therapeutic interventions. However, the need to minimize bias and ensure the correct design to explore the study aims often affects the generalizability of results. As a consequence, the evidence derived from the most rigorous research strategy available is not always representative of the real-world settings for which this evidence is ultimately intended. Observational studies, in contrast, although affected by a number of potential confounders, can more effectively capture treatment characteristics and safety issues that had not been identified by previous RCTs, owing to the short duration of follow-up or highly selective inclusion criteria. The aim of this review is to provide a comparative summary of the main advantages and pitfalls of RCTs and real-world data, emphasizing the need for a constant integration of all available levels of evidence to provide the best care for patients.

AB0332 Golimumab Efficacy in Rheumatoid Arthritis after Conventional and Biological Treatment: Data from The Italian Lorhen Registry

Background The efficacy of Golimumab (GLM) treatment in rheumatoid arthritis (RA) has been widely documented in clinical trials. Data are still needed to assess its efficacy and tolerability in everyday clinical practice. Objectives To assess the efficacy of the treatment with GLM in RA previously treated with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs) from a multicentric observational cohort (the LORHEN Registry). Methods All patients with a diagnosis of RA in the LORHEN database who started GLM from october 2010 up to september 2015, with at least one reported visit, were included. We reviewed the data regarding the first 24 months of treatment, focusing on clinical efficacy. The efficacy of GLM was assessed with DAS28, DAS28(CRP), SDAI and EULAR response criteria. We executed intention-to-treat (ITT) and per-protocol analysis (PP). We repeated the analysis for the subgroups of patients who received GLM as first or second bDMARD. Results We retrieved the data regarding 180 patients, with a mean (sd) age of 54,57 (13,62) years and a mean (sd) disease duration of 9,52 (9,32) years. Methotrexate was the concomitant csDMARD for 123 (68,3%) patients, while leflunomide, sulfasalazine and cyclosporine were given to 13 (7,2%), 5 (2,8%) and 4 (2,2%) patients respectively. 35 (19,4%) patients were treated with GLM monotherapy. 137 (76,1%) and 5 (2,8%) patients were given low dose (≤10mg prednisone equivalent a day) and medium dose (≥10 and ≤25) corticosteroid at baseline, with following tapering. A total of 79 patients stopped the treatment with GLM due to inefficacy or adverse events before 24 months of treatment. With the ITT design 55 (30,6%) and 44 (24,4%) patients achieved good or moderate EULAR response respectively at 6 months. The mean (sd) DAS28, DAS28(CRP) and SDAI progressively reduced, reaching 2,61 (1,11), 2,41 (0,72) and 4,62 (3,80) respectively at 24 months. Within the PP scenario, 32 (66,7%) and 9 (18,8%) patients reached and maintained good or moderate EULAR response respectively to the end of the follow-up. The clinical response to GLM therapy resulted slightly reduced when given as a second line bDMARD treatment, but the data did not met statistical significance. Conclusions GLM is effective in treating RA in everyday clinical practice. The efficacy increases significantly over the first 6 months and slightly during the following 18 months. Interestingly enough, patients treated with GLM after a first bDMARD can still achieve low disease activity and clinical remission, with an overall efficacy of the treatment not statistically different to the first line. Disclosure of Interest None declared

AB0226 One Year Experience of A Bdmard Spacing Protocol in Real Life Rheumatoid Arthritis Patients

Background Current guidelines about rheumatoid arthritis (RA) management might admit tapering schedules of biologic disease modifiying drugs (bDMARDs) when disease activity control has been achieved and maintained, in line with growing scientific evidences [1]. Great heterogeneity in target populations, end-points, study designs, therapeutic protocols, criteria for bDMARD discontinuation and resumption globally prevents from univocal interpretation of study results [2]. Real life data might provide additional information on the topic, which could be better extended to routine care. Objectives To analyze the impact of a bDMARD down-titration strategy (spacing) on clinical and sub-clinical disease activity control over time (12 months) in real life RA patients attending a single Italian Rheumatologic Unit. Methods RA patients with at least 1 year of bDMARDs treatment and a well-controlled disease (at least low disease activity/LDA according to DAS28 criteria for at least 6 months) were offered to undergo a spacing (doubling the inter-administration period) of their ongoing bDMARD (anti-TNF, Abatacept/ABA, Tocilizumab/TCZ) medication. When present, concomitant conventional synthetic DMARDs (csDMARDs) and/or low dosage (less than 7,5 mg/d prednisone-equivalent) oral corticosteroid (CS) were admitted and maintained: Group A= CS-on patients; Group B= CS-off patients. Disease activity was monitored every 2 months through DAS28 in order to detect any clinical relapse (>LDA): relapsing Group A patients immediately resumed original bDMARD schedule, relapsing Group B patients started firstly low dose CS (5 mg/d) while keeping on bDMARD spacing. At the same time-points, ultrasonographic (US) assessment (Gray Scale/GS and power Doppler/PD scores) was performed on dorsal view of bilateral hands and wrists. Clinical and US results were analyzed either globally and by CS-co-medication, as to detect any bDMARD sparing effect. Results Thirty-seven RA patients consented to the bDMARD spacing. Most patients were on anti-TNF agents (4 TCZ, 1 ABA) in association with csDMARDs (7/37 csDMARD free), and without CS co-medication (30/37 CS free). At time of spacing overall clinical (mean DAS28±sd 1,92±0,59), lab (median ESR [IQR] 10,50 [7–16] mm/h, median CRP [IQR] 0,14 [0,10–0,49] mg/dL) and US parameters (median GS score [IQR] 9 [6–13,5], median PD score [IQR] 0 [0–0]) were consistent with disease control; more than half patients had negative prognostic factors. Globally, trends over time of either clinical and US parameters did not significantly differ between groups, regardless of CS co-administration. Nevertheless, over the first year of observation more CS-off than CS-on patients experienced disease relapse (12 versus 4 patients, respectively, p=0,99); this occurred sooner in CS-off patients, too (mainly in the first 6 months of follow up). Conclusions The feasibility of bDMARDs step-down schedules in RA patients should be clarified in real life setting, as well as in clinical trials. bDMARD spacing might be a possible choice, especially when low dosage CS are co-administered: their eventual bDMARD sparing effect should be confirmed with larger and longer observations, together with complete evaluations about cost-effectiveness and risk-to-benefit profiles. References Smolen JS, et al. Ann Rheum Dis 2014;73:492–509. Yoshida K, et al. AnnRheumDis 2014;73:595–599. Disclosure of Interest None declared

SAT0225 Screening for Pulmonary Arterial Hypertension in Systemic Sclerosis Patients: Single Center Real-Life Performance of The Detect Algorithm

Background A new algorithm for early detection of PAH in Systemic Sclerosis (SSc) patients has been recently developed (1). However, the cost-effectiveness of this strategy has not yet been defined in a real-life setting. Objectives The aim of this study was to compare two methods of PAH screening among SSc patients for the referral to invasive tests (right heart catheterization (RHC)) in a single PH referral center. Methods Patients with SSc according to the ACR/EULAR 2013 classification criteria were enrolled in the study and prospectively followed in a Scleroderma Unit of a University Hospital which is also a PH referral center between Jan 2015 and Jan 2016 with at least 6-monthly visits. According to the ESC/ERS 2015 guidelines (2), annual screening with echocardiography, DLCO, ECG and serum biomarkers (including urate and NT-proBNP) was performed. Patients satisfying the two-steps DETECT score and/or with echocardiographically estimated Pulmonary Arterial Systolic Pressure (PASP) ≥45 mmHg or between 35–45 mmHg with unexplained dyspnea (3) were referred to an expert cardiologist to undergo RHC. Results Three-hundred patients with a diagnosis of SSc were screened and 39 patients (13%) met the criteria for the application of the DETECT algorithm (disease duration >3 years, DLCO <60%). The male:female ratio was 1:12; 16 patients (41%) were positive for anticentromere antibodies; 14 patients showed cutaneous teleangectasias (26%); 33 patients (85%) were classified as limited SSc, 4 (10%) as diffuse SSc and 2 as SSc without skin involvement (5%). For 2 of them (5%), STEP 1 score was not calculated due to missing serum biomarkers. Among the remaining 37 patients, 2 (5%) had a STEP 1 score <300; and 35 (95%) showed a STEP 1 score ≥300. Among the latter, for 11 (31%) echocardiographic measures for the calculation of the STEP 2 score could not be derived. In 7/24 (29%) the STEP 2 score was <35 while in 17/24 (71%) ≥35, thus needing referral to RHC according to the DETECT algorithm. In the same 39-patients group, 12 (31%) satisfied the ItinerAir criteria for RHC (p=0,0019, chi-squared). Conclusions Our results indicate that the feasibility in clinical practice of both PAH screening methods strongly depends on the performance of a correct echocardiographic screening, with a complete assessment and quantification of right heart parameters, which often lacks in outpatient practice. In addition, applying the DETECT algorithm, a larger number of patients should be sent to RHC than those identified by solely echocardiographic parameters. Further observational studies are needed to define the real-life sensivity and cost-effectiveness of this new algorithm. References Coghlan JG et al, Ann Rheum Dis 2014. Galiè N et al, Eur Respir J 2015. Hachulla E et al, Arthritis Rheum 2005. Disclosure of Interest None declared

AB0788 Treating Axial-Spa to Target: Prevalence of Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease in a Cohort of Patients Treated with Anti-TNFα Agents

Background Treating disease to target is emerging as the recommended strategy also in the management of axial-SpA (axSpA) (1). Reaching remission, defined as inactive disease (ID), constitutes the ideal target in clinical practice. Objectives Using the new composite disease activity index “Ankylosing Spondylitis Disease Activity Score” (ASDAS) (2) we assessed the prevalence of ID in a cohort of patients with axSpA treated with anti-TNFα agents. Potential patient- and disease-related factors influencing the status of ID were analyzed. Methods The study population was selected from outpatients with axSpA treated with anti-TNFα attending our Rheumatology Department. Disease activity was evaluated in terms of BASDAI and ASDAS-CRP during the latest follow up visit. ID was defined as ASDAS-CRP<1.3 (2). Statistical analysis was performed with STATA. Results General characteristics of the 53 enrolled patients are presented in Table 1. A BASDAI <4 was recorded for 70% of the study population, while only 31% showed ID according to ASDAS-CRP (Figure 1). As expected, a strict correlation between the two disease activity indices was confirmed (Spearmans r =0.76; p<0.0001). Multivariate logistic regression demonstrated an inverse correlation of ID status with NSAIDs intake (OR 0.15; CI95% 0.45-0.54). ID achievement resulted independent from sex, disease duration, BASMI,DMARDs, type of anti-TNFα agent. Conclusions In our cohort of axSpA treated with biological agents, only one third achieved ID according to ASDAS-CRP. Even with the limitations of the small sample size, ID does not correlate with the principle patient- and disease-related features but is inversely associated with NSAIDs intake. Further studies are needed to optimize the targeted treatment of axSpA and to identify potential predictive factors of ID. References Smolen JS, et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 2014; 73:6–16. Machado P, et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis 2011; 70:47–53. Disclosure of Interest None declared

THU0232 Golimumab Therapy Retention Rates in Patients with Rheumatoid Arthritis and Seronegative Spondyloarthritis: Data from the Italian Lorhen Registry

Background The efficacy of Golimumab (GLM) treatment in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has been widely documented. In everyday clinical practice, however, many patients discontinue therapy due to adverse events (AE), lack of efficacy or other reasons. [1] Objectives To compare first year retention rates of GLM treatment among RA, PsA and AS, using the first one as reference standard, in a multicentric observational cohort (the LORHEN Registry). Methods All patients in the LORHEN database who started GLM were included. All patients were treated according to current EULAR recommendations for the management of RA and spondyloarthritis. Drug survival during the first year of treatment was measured, along with specific reasons for discontinuation (inefficacy or adverse events). We compared drug retention rates using the Kaplan-Meier method. Cox regression analyses, using RA as reference category, were used to adjust for age, sex, disease duration, number of previous csDMARDs and treatment with low dose prednisone. Results One hundred and thirty-four RA patients, 84 PsA patients and 108 AS patients were included. 49 (37%) RA patients, 29 (35%) PsA patients and 22 (20%) AS patients discontinued treatment during the first year. Thirty-six (27%) and 12 (9%) RA patients, 17 (20%) and 11 (13%) PsA patients, 14 (13%) and 7 (6%) AS patients discontinued GLM due to lack of efficacy or AE, respectively.Patients with a diagnosis of AS showed a lower, but not significant, risk of discontinuation, with an adjHR (95%CI) of 0.35 (0.10 – 1.17).Patients treated with low dose prednisone showed a reduced risk of discontinuation with an adjHR (95%CI) of 0.35 (0.14 – 0.86). Age, sex, disease duration and number of previous csDMARDs did not significantly influence the risk of discontinuation. Conclusions AS patients seem to have better GLM retentions rates with respect to RA and PsA patients; however this difference is significantly reduced after adjusting for confounders. The significantly lower adjHR observed for low dose prednisone therapy might reflect a beneficial effect even in patients treated with bDMARDs. References Scirè CA et al. Clin Exp Rheumatol. 2013;31:857-63. Disclosure of Interest None declared