Search

Objective To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients. Methods The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P Results Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage. Conclusion We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG). We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission. We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.

The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: (i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (p value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (p value = 0.61 for males, p value = 0.09 for females), monotherapy (p value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank p value = 0.63), and different lines of biologic therapy (p value = 0.79 for biologic-naïve patients; p value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness.

Introduction: Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and uveitis. Methods: A Delphi consensus-based approach was used to identify a core set of statements. The process included development of initial questions by a steering committee, an exhaustive search of the literature using complementary approaches to identify potential statements and two Delphi voting rounds for finalization of the statements. Results: Consensus was achieved on the related nature of IMIDs, the existence of a high prevalence of multiple IMIDs in a single patient and the fact that a multidisciplinary approach can result in a more extensive evaluation and comprehensive approach to treatment. The goals of a multidisciplinary team should be to increase diagnosis of concomitant IMIDs, improve the decision-making process, and increase patient satisfaction and adherence. Early referral and diagnosis, early recognition of concomitant IMIDs and optimizing treatment to improve patient quality of life are some of the advantages of using multidisciplinary teams. To be effective, a multidisciplinary team should be equipped with the appropriate tools for diagnosis and follow-up, and at a minimum the multidisciplinary team should include a dermatologist, gastroenterologist and rheumatologist; providing psychologic support via a psychologist and involving an ophthalmologist, general practitioners and nurses in multidisciplinary care is also important. Conclusion: The present Delphi consensus identified a set of overarching principles that may be useful for implementation of a multidisciplinary approach for the management of SpA-related IMIDs. Funding: Aristea and Hippocrates.

Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA.

Our aim was to prospectively investigate the impact of Behcet's disease (BD), disease activity, and clinical and demographic characteristics on different aspects of quality of life (QoL) measured by the short-form (SF)-36 QoL scale. We administered the SF-36 to 37 consecutive BD patients in different moments of disease activity, and to 23 healthy controls (HC). The eight subcategories of the SF-36 underwent statistical analysis for identifying differences and correlations. Compared to HC, BD patients showed significantly lower mean scores in all SF-36 QoL subscales except mental health and role-emotional. Females showed a poorer QoL compared to males. Disease activity evaluated by the BD Current Activity Form inversely correlated with physical functioning (ρ = -0.68, p

The study aims are to describe the activity of our Unit on the diagnostics of monogenic autoinflammatory diseases (AIDs), and to apply the clinical classification criteria for periodic fevers from the Eurofever Registry to our cohort of patients, thus evaluating their usefulness in the real life. We retrospectively analyzed data from patients referring to our Center for recurrent fever attacks, and undergoing genetic analysis between April 2014 and July 2016, and we applied the classification criteria to both genetically positive and -negative patients. We visited 195 patients (101 females, 94 males); 126 (64.6%) were adults and 192 (98.5%) Caucasians; 12.3% carried mutations and 12.7% of adults were genetically positive. No statistically significant differences were identified in the frequency of genetic diagnosis between adults and children (p = 0.82) as well as in the frequency of genetic diagnosis, based on the number of genes evaluated (p = 0.57). When we applied the Eurofever criteria, 126/195 (64.6%) patients were classified for at least one among the four main monogenic AIDs; 22 (11.3%) patients fulfilled criteria for 2 diseases and 4 (2.1%) for 3 diseases. Among patients carrying mutations, 12/24 (50%) correctly fulfilled the score, 3/24 (12.5%) fulfilled criteria differently from their genetic diagnosis; 9/22 (40.9%) recieved no classification. An expanded genetic testing does not seem useful, while a correct interpretation of patients' clinical picture may allow performing specific genetic testing. The classification criteria from the Eurofever Registry have shown to be a beneficial tool in the evaluation of patients with a suspected monogenic AID.

This study aimed to evaluate the role of interleukin (IL)-1 inhibitors anakinra (ANA) and canakinumab (CAN) in the treatment of Behcet’s disease (BD)-related uveitis. Multicenter retrospective observational study includes 19 consecutive BD patients (31 affected eyes) received treatment with anti-IL-1 agents. Data were analyzed at baseline and at 3 and 12 months. The primary endpoint is the reduction of ocular inflammatory flares (OIF). The secondary endpoints are improvement of best corrected visual acuity (BCVA); reduction of macular thickness defined by optical coherence tomography (OCT) and of vasculitis identified with fluorescein angiography (FA); evaluation of statistically significant differences between patients treated with IL-1 inhibitors as monotherapy, subjects also administered with disease modifying anti-rheumatic drugs (DMARDs) and/or corticosteroids as well as between patients administered with IL-1 inhibitors as first line biologic treatment and those previously treated with TNF-α inhibitors. At 12 months, OIF significantly decreased from 200 episodes/100 patients/year to 48.87 episodes/100 patients/year (p

Biological therapies have represented a cornerstone in the treatment of immune-mediated inflammatory diseases. Their advent combined with implementation of a treat-to-target approach has meant that remission or low disease activity are now realistic targets for treatment achieved by a significant number of patients. However, biologicals are not risk free and their elevated costs continue to present an important economic burden to national healthcare services. "Can we wean patients with inflammatory arthritis from biological therapies?" Over the last decade this question has become increasingly important as to define the best management strategies in terms of efficacy, safety and economic outcomes. Not surprisingly this has generated an interesting debate as to whether reasons to taper biologics outweigh reasons not to taper and evidence in support of either of these schools of thought is persistently growing. AIM: In this article we reviewed the contents of the relevant session from the 2019 Controversies in Rheumatology and Autoimmunity meeting in Florence.

The article listed above was initially published with incorrect copyright information. Upon publication of this Correction, the copyright of this article changed to "The Author(s)". The original article has been corrected.

AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was a 2-year international observational study of patients with moderate to severe rheumatoid arthritis. Baseline characteristics, abatacept retention rates, and clinical outcomes were compared by treatment line in the Austrian cohort of ACTION. Of 100 patients enrolled in Austria, 98 (98.0%) were evaluable: 33/98 (33.7%) biologic naive and 65/98 (66.3%) with ≥1 prior biologic failure. At baseline, biologic-naive patients had shorter disease duration and lower concomitant corticosteroid use than biologic-failure patients. Overall crude abatacept retention rate was 60.5% and retention rate was higher in biologic-naive (65.1%) versus biologic-failure (58.0%) patients. Good/moderate EULAR (European League Against Rheumatism) response rates were 85.7% in biologic-naive and 100% in biologic-failure patients. In the Austrian cohort of ACTION, overall abatacept retention at 2 years was high, with higher retention rates in patients receiving abatacept as an earlier treatment line. Good/moderate EULAR response rate was higher in biologic-failure than in biologic-naive patients.

Studies on last genetic and epigenetic predisposition to APS are summarized. It is well known that genetic predisposition is in HLA system (DR4 and DRw53) and that lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are both associated with the same HLA antigens. Other genes, outside the MHC, give their contribution to the development of this autoimmune syndrome, such as IRF5, STAT4 and those related to inherited thrombophilia - factor V Leiden and G20210A prothrombin polymorphisms. Finally, post-transcriptional modifications of anti-beta2GPI antibodies could be implicated too. The most important discovery of last years is that altered microRNAs' expression is linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in APS.

Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Immune checkpoint inhibitors (ICPIs) are new cancer drugs that target self-tolerance pathways exploited by tumors to escape immune destruction, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand (PD-L1). Several ICPIs have been approved by Food and Drug Administration, increasing overall survival with different cancers. However, their use can determine development of many different inflammatory side effects, that are defined immune-related adverse effects (irAEs); among others, rheumatological irAEs can develop in these patients. Currently, we have limited data about these adverse effects; particularly, few evidence come from clinical trials about patients with pre-existing autoimmune diseases because they were excluded from them. Therefore we analysed the existing scientific literature dealing with this issue, in order to answer to different clinical questions. According to all reviewed data, rheumatological irAEs are not infrequent, in both previously diseased and undiseased patients, but they are often mild and reversible. Close monitoring and interdisciplinary management and monitoring is necessary in order to ensure best care. Many questions remain unanswered or not completely answered; further data are necessary to implement our knowledge in this field and to standardize and optimize clinical practice.

Active sacroiliitis based on magnetic resonance imaging (MRI) without intravenous (I.V.) contrast material injection is considered sufficient for the diagnosis of spondyloarthritis (SpA), according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. This work shows the added value of administering I.V. contrast material when evaluating the response to tumor necrosis factor (TNF) antagonists therapy, on the extension of bone marrow oedema (BMO) and pathological enhancement (osteitis/synovitis) in the sacroiliac joints (SIJs) on MRI. Forty-three patients (25 females and 18 males, mean age of 54 ± 16.60 years, range 22–75 years) with a clinical diagnosis of SpA and active sacroiliitis at MRI with I.V. contrast material, were considered for a follow-up MRI after 6 months of TNF antagonists therapy. Disease activity was monitored by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. Descriptive statistics, Student’s t test and Cohen’s kappa were used. P

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes. info:eu-repo/semantics/publishedVersion

Increasing evidence indicates that patients with chronic inflammatory arthritis (CIA), including rheumatoid arthritis and spondyloarthropathies, have an increased risk of arrhythmic events, significantly contributing to the higher cardiovascular disease (CVD) morbidity and mortality observed in these subjects compared to the general population. Although the mechanisms accounting for such an arrhythmogenic substrate are not fully understood, the main role is probably played by chronic systemic inflammation, able to accelerate the development of structural CVD, as well as to directly affect cardiac electrophysiology. In the past decade, biologic therapies have revolutionized the treatment of CIA by highly enhancing the probability to effectively control disease activity and its systemic consequences, including cardiovascular involvement. Accordingly, accumulating data demonstrated that by potently inhibiting systemic inflammation, biologic drugs can reduce CVD progression and ameliorate arrhythmic risk parameters, with a putative beneficial impact on arrhythmia incidence. Nevertheless, a significant number of reports from clinical trials and postmarketing experience suggest that some of these medications, particularly TNF inhibitor monoclonal antibodies and rituximab, may in some circumstances precipitate arrhythmia occurrence, probably by acutely amplifying myocardial electric instability intrinsically associated with these diseases. In this review, we analyze the intricate link between biologic drugs and arrhythmias in CIA in the effort to identify which factors are involved in the fine-tuning of antiarrhythmic/pro-arrhythmic balance, and understand how this knowledge should be translated in the clinical practice to obtain the most favorable benefit-to-risk profile when biologic drugs are used in these patients.

The purpose of the study was to estimate the clinical profile of naive biological patients with rheumatoid arthritis (RA) starting adalimumab through 3-year calendar periods and their clinical outcomes such as drug survival and global clinical disease control (GCDC). RA patients starting adalimumab as first biological drug between 2003 and 2012 were subdivided in 3-year calendar periods. Survival on therapy was estimated using the Kaplan-Meier analysis. One and 2-year clinical response was assessed by calculating percentage of patients attaining GCDC (28-joint Disease Activity Score (DAS28) ≤ 2.6 + Health Assessment Questionnaire (HAQ) ≤ 0.5), low disease activity (DAS28 ≤ 3.2), remission (DAS28 ≤ 2.6) and good European League Against Rheumatism (EULAR) response. Multivariate regression models were used to assess baseline predictors of drug discontinuation or achievement of clinical remission. We recruited 1695 RA patients. Overall drug persistence at 3 years was 40.6 %, while the global rate of nonswitching patients was 54.7 %. Compared to 2003–2005, initiators in more recent years had a significantly lower 3-year crude drug retention rate (log rank, p

Behçet's syndrome (BS) is a systemic inflammatory disorder characterized by a wide range of potential clinical manifestations with no gold-standard therapy. However, the recent classification of BS at a crossroads between autoimmune and autoinflammatory syndromes has paved the way to new further therapeutic opportunities in addition to anti-tumor necrosis factor agents.This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast.IL-1 inhibitors currently represent the most studied agents among the latest treatment options for BS, proving to be effective, safe and with an acceptable retention on treatment. However, since BS is a peculiar disorder with clinical features responding to certain treatments that in turn can worsen other manifestations, identifying new treatment options for patients unresponsive to the current drug armamentarium is of great relevance. A number of agents have been studied in the last decade showing changing fortunes in some cases and promising results in others. The latter will potentially provide their contribution for better clinical management of BS, improving patients' quality of life and long-term outcome.

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. © 2015 Elsevier Inc.

Background:SIRENA is an Italian, prospective Registry in Spondyloarthritis (SpA) patients, naïve to conventional, targeted and biological DMARDs. Patients are diagnosed, newly or confirmed, according to ASAS criteria and classified in subjects with predominant axial(AX) or with mainly peripheral manifestations(PER).Objectives:To compare descriptively AX vs PER subgroups of patients.Methods:Demographic data, diagnostic delay and subtypes of SpA as well as clinical features and comorbidities are collected.Results:282 patients were enrolled: 101 (35.8%) AX and 181 (64.2%) PER. Baseline data are shown in Table 1. There were more obese patients in AX (21.4% AX vs 16.1% PER) and more overweight ones in PER (19.4% AX vs 23.8% PER). The % of subjects with diagnostic delay was higher in AX (65.7% vs 53.9% PER) and the delay longer (mean of 73.1 months vs 47.8). In both groups, main reason of the delay was incorrect referrals (41.5% for AX and 45.3% for PER). Noteworthy the fact that in PER, the 75.7% of patients had a newly diagnosed SpA. In PER, the most frequent SpA type was PsA (82.3%), followed by undifferentiated SpA (8.8%) and enteropathic SpA (7.5%), while in AX, 49.5% were ankylosing spondylitis, 21.8% nr-ax-SpA and only 4% PsA. The majority of PER patients reported as first symptom peripheral arthritis (80/181), psoriasis (57/181) and enthesitis while in AX referred inflammatory back pain (80/101). High percentages of comorbidities were reported: psoriasis (65.8%) and cardiometabolic diseases (34.8%) were higher in PER while depression/anxiety and GI diseases were higher in AX (Table 2). At the baseline, the mean PhGA score (0-100) was 51.5 for AX and 43.8 for PER.Conclusion:SIRENA study highlights relevant differences in AX vs PER patients, expecially in terms of diagnostic delay, clinical presentation and comorbidities.Table 1.MeanAX n=101MeanPER n=181Age (years)47.352.8Sex (female/male - %)50.5/49.547.5/52.5Weight (Kg)73.073.9BMI25.325.4Diagnostic Delay (yes - %)65.7%53.9%Time of delay (mean - months)71.347.8Newly SpA diagnosis (%)55.5%75.7%Table 2.A) First Symptom(more than 1 symptom referred)AX n=101N. PatientsPER n=181N. PatientsArthritis23122Enthesitis1654Dactylitis728Inflammatory Back Pain8034Psoriasis skin1057Psoriasis nails219Uveitis41IBD79B) Comorbidities(more than 1 comorbidity referred)% Patients% PatientsCardiometabolic20.8%34.8% -Hypertension19.8%30.9% -Dyslipidemia17.8%11.6% -Diabetes6.0%7.7% -MetS5.0%6.6%Psoriasis22.8%65.8%Gastrointestinal20.8 (16.9% CD)12.8 (4.4% CD)Depression/Anxiety11.9%2.2%Endocrine6.9%11.1%Osteoporosis3%5.5%Hepatic4% (3% NAFLD)4.4% (2.2% NAFLD)Infections3%3.9%Malignancies0%4.4%Acknowledgments:This study was sponsored by Janssen Italy.We thank the Investigators and their staff at all of the study sites.Disclosure of Interests:Rosario Foti Speakers bureau: Abbvie, BMS, ROCHE, Janssen, Celgene, Gabriella Cardinale: None declared, Luisa Costa: None declared, Franco Franceschini Consultant of: Eli-Lilly, Janssen, Pfizer, Sanofi-Genzyme, UCB Pharma, GSK, Francesco Ciccia Grant/research support from: Pfizer, Novartis, Celgene, Janssen, Consultant of: Lilly, Novartis, Pfizer, Janssen, Roche, Celgene, Speakers bureau: Pfizer, Novartis, Celgene, Janssen, Roche, Abiogen, BMS, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Maurizio Rossini Speakers bureau: AbbVie, Abiogen, Amgen, BMS, Eli-Lilly, Novartis, Pfizer, Sanofi, Sandoz and UCB, Ennio Lubrano: None declared, Mauro Galeazzi: None declared, Mariasole Chimenti: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Giuseppe Galfo: None declared, Silvia Marelli Employee of: Janssen, Ennio Favalli Speakers bureau: BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis and Abbvie

Evaluate abatacept retention over 2 years in the AbataCepT In rOutiNe clinical practice (ACTION) study.ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. Crude abatacept retention rates over 2 years were estimated using Kaplan-Meier analyses in biologic-naive and -failure patients. Clinically relevant risk factors and significant prognostic factors for retention were evaluated using a Cox proportional hazards multivariable model.Overall, 2350/2364 enrolled patients were evaluable; 673 (28.6%) were biologic naive and 1677 (71.4%) had prior biologic failure (1 biologic, 728/1677 [43.4%]; ≥ 2 biologics, 949/1677 [56.6%]). Abatacept retention rate (95% confidence interval [CI]) at 2 years was 47.9% (45.7, 50.0): 54.5% (50.4, 58.3) for biologic-naive vs 45.2% (42.7, 47.7) for biologic-failure patients (log-rank P 0.001). For patients with 1 and ≥ 2 prior biologic failures, respectively, retention rates (95% CI) were 50.2% (46.3, 53.9) vs 41.3% (38.0, 44.6; log-rank P 0.001). Main reasons for discontinuation (biologic-naive vs biologic-failure, respectively) were lack of efficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) double positivity versus negativity were predictive of higher retention in both biologic-naive (hazard ratio [HR] [95% CI] 0.71 [0.53, 0.96]; P = 0.019) and biologic-failure patients (HR [95% CI] 0.76 [0.62, 0.94]; P = 0.035).Abatacept initiation as earlier vs later line of therapy in RA may achieve higher 2-year retention rates. RF and anti-CCP seropositivity could predict increased abatacept retention, irrespective of treatment line.NCT02109666.

Biological drugs have revolutionised the treatment of rheumatic diseases, and the recent expiry of the patents for many biological agents has generated considerable interest among pharmaceutical companies and regulatory agencies, and led to the marketing of highly similar, low-cost versions known as biosimilars. The increasing trend of switching patients from effective but expensive drugs to their biosimilar counterparts will have a considerable economic impact in the coming years. However, although this will greatly extend patient access the latest treatments, clinicians, scientific societies and the patients themselves have expressed a number of concerns about their long-term efficacy and safety, as well as the consequences of potentially multiple switches being dictated by economic pressure rather than medical needs. Thee aim of this review is to evaluate the pros and cons of choosing biosimilars, and whether and when they can really be considered clinically equivalent to the original drugs.

Background Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism due to a deficient activity of homogentisate 1,2-dioxygenase. Patients suffer from a severe arthropathy. Evidence was provided on the presence of a secondary serum amyloid A (SAA)-based amyloidosis[.1Here a complete microscopic and ultrastructural analysis of different AKU tissues, taken from six differently aged patients, is presented. Objectives SAA amyloidosis is a complication in AKU[,2 making the detection of amyloid deposits at an early phase,important for treatment[.3 We present a study of tissues from patients of different age and relevance of symptoms, providing a detailed overview of AKU amyloidosis. Methods Different tissues were obtained from a cohort of 6 AKU patients: 4 M (63,68,42,44 y) and 2 F (66,71 y) with different severity of symptoms. Histology and amyloid were investigated. A complete microscopic and ultrastructural analysis is presented and patient features as radiological examination, mild-to-severe degenerative changes as joint space narrowing, cartilage irregularities, sub-chondral sclerosis or peripheral osteophytes and linear intervertebral disk calcifications were reported. SAAserum levels and other serological markers were measured too.Specimens were analysed by Congo Red, Immunofluorescence, Transmission Electron Microscopy. Results The analysis of all AKU specimens confirmed the massive presence of amyloid fibrils even in young patients. Alterations in collagen composition, strictly associated to amyloid bundles deposition, were observed especially in labial salivary gland, cartilage, tendons and infrapatellar fat pad. Histological analysis showed depletion of glycosaminoglycans in young patients, whereas, at light microscopy, calcification and fibrillation were observed only in elderly patients. Immunofluorescence assessed undoubtedly the presence of SAA in amyloid deposits in AKU, and we reported for the first timethe finding of amyloid deposition in young AKU patients and in less common regions. Conclusions We provide the first detailed overview of amyloidosis in AKU. Overall, our findings depicted a novel biological framework underlining the pathological role of amyloidosis in several AKU tissues. Furthermore, we found that degradation of extra-cellular matrixin AKU is not limited to elderly.The clinical burden of AKU may notably increase, since amyloidosis was foundeven in young AKU patients, whereas degeneration of cartilage and tendons was limited to older subjects. References [1] Millucci L, et al. J Inherit Metab Dis2015Sep;38(5):797–805. [2] Braconi D, et al. Free RadicBiol Med2015Nov;88(Pt A):70–80. [3] Millucci L, et al. DiagnPathol. 2014Sep 26;9:185. Disclosure of Interest None declared

Background To date, a few studies have reported the long-term efficacy of Infliximab (IFX) in Behcet’s disease (BD)-related uveitis.1,2 Nevertheless, it is known that TNF-α inhibitor drugs may lose their efficacy over time due to the formation of anti-drug antibodies, causing secondary failure and influencing the retention rate of these agents.3 In this regard no previous study has specifically investigated IFX retention-rate in BD-related uveitis. Objectives To evaluate the 10 year drug retention rate of IFX in BD-related uveitis, the effect of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on drug survival and differences according to the lines of biologic treatment. Methods Cumulative survival rates were studied using the Kaplan-Meier plot, while the Log-rank (Mantel-Cox) test was used to compare survival curves. Results Forty patients (70 eyes) were eligible for analysis. The drug retention rates at 12-, 24-, 60- and 120 month follow-up were 89.03%, 86.16%, 75.66% and 47.11% respectively. No differences were identified according to the use of concomitant DMARDs (p=0.20), while a statistically significant difference was observed in relation to the different lines of IFX treatment (p=0.014). Visual acuity improved from baseline to the last follow-up visit (p=0.047) and corticosteroids-sparing effect was observed (p Conclusions IFX retention rate in BD-uveitis is excellent and is not affected by concomitant DMARDs References [1] Keino H, Okada AA, Watanabe T, et al. Long-term efficacy of infliximab on background vascular leakage in patients with Behcet’s disease. Eye (Lond)2014;28(9):1100–6. [2] Keino H, Okada AA, Watanabe T, et al. Efficacy of Infliximab for Early Remission Induction in Refractory Uveoretinitis Associated with Behcet Disease: A 2-year Follow-up Study. Ocul Immunol Inflamm2017;25(1):46–51. [3] Fabbroni M, Cantarini L, Caso F, et al. Drug retention rates and treatment discontinuation among anti-TNF-α agents in psoriatic arthritis and ankylosing spondylitis in clinical practice. Mediators Inflamm2014;2014:862969. Disclosure of Interest None declared

Background The pathogenesis of Ochronosis, the musculoskeletal manifestation of alcaptonuria (AKU) is still unclear. The joint damage usually described is similar to osteoarthritis, but in some cases the spinal involvement could resemble spondiloarthritis (SpA). These findings suggest that inflammatory changes could be prevalent in some cases while degenerative aspects could be dominant in others. Objectives To evaluate the prevalence of inflammatory changes in peripheral joints and enthesis of a cohort of patients affected by AKU. Methods Consecutive patients with definite diagnosis of AKU referred to our clinic from 2014 to 2017 were enrolled. All patients underwent an ultrasound (US) exam of the metacarpo-phalangeal joints (MCP), proximal interphalangeal joints (PIP), radiocarpal/mid carpal joints, elbow, gleno-humeral, hip, knee, ankle and metatarso-phalangeal (MTP) joints bilaterally; flexor and extensor tendons of fingers and wrists and the ankle tendons were also examined. Further, the enthesis of the rotator cuff of the shoulder, triceps, quadriceps, patellar and Achilles tendons were assessed. Joints and tendons with a synovial sheath were assessed for effusion, synovial hypertrophy and power Doppler (PD) signal while enthesis were evaluated for the presence of PD signal, enthesophytes and calcifications. All the US lesions were scored using a dichotomous scale (presence/absence). All US exams were performed by an expert sonographer blind to clinical history, using an Esaote MyLab70 scanner equipped with high resolution linear probes. Results We enrolled 19 patients (11 women) with a mean age of 53 yo (SD ±14,69). Only 2 patients didn’t show inflammation at any joint or tendon. The most involved joint was the knee (11/19), while regarding enthesis, the Achilles tendon (4/19) and the distal patellar tendon insertion were the most frequently involved (6/19). The mean number of joints with effusion or synovial hypertrophy was respectively equal to 2,47 (median 2, range 1–8) and 1,84 (median 2, range 1–7), while 0,21 joints (median 0, range 0–2) presented also PD. The mean of the exudative tenosynovitis was 0,47 (median 0, range 0–3), while for proliferative tenosynovitis was 0,42 (median 0, range 0–2). The PD signal in tendons with sheaths was rare (mean 0,16, median 0, range 0–2). Finally, the mean number of enthesis with PD was 0,95 (median 0, range 0–7) while the mean value was 0,37 (median 0, range 0–3) for enthesophytes and 2,63 (median 1, range 0–9) for calcifications. Conclusions The pathological processes that lead to the typical joint damage in ochronosis are not yet completely clarified. The results of this study showed that articular inflammation is common in these patients, sometimes associated with enthesis involvement. The role of inflammation should be further addressed as could be a new therapeutic target for this disease. Disclosure of Interest None declared

Background In recent times IL-1 inhibition has been proposed as an intriguing therapeutic option in Behcet disease (BD) patients with multi-drug resistant manifestations.1 However, despite the good clinical results obtained during the last years, cases of BD nonresponsive to anakinra (ANA) and canakinumab (CAN) have also been identified. This evidence has induced to suspect the existence of specific subsets of patients characterised by a more pronounced IL-1 driven pathogenesis.2,3 Objectives To identify predictive factors of response to interleukin (IL)−1 inhibition among demographic, clinical and therapeutic data in patients with (BD). Methods BD patients treated with ANA or CAN were enrolled. Patients were divided into 2 groups according to the clinical response: group 1 included subjects showing a treatment duration of at least 52 weeks and no secondary inefficacy during the first follow-up year; the remaining patients were included in the group 2. Demographic, clinical and therapeutic data were analysed to identify significant differences between groups. Results Eighteen patients (50%) were included in group 1 and 18 (50%) in group 2. A better response to IL-1 inhibitors was significantly more common among patients with BD-related uveitis (p=0.006) and patients with a longer disease duration (p=0.03). Conclusions IL-1 blockade is effective in BD, especially in the subset of patients presenting ocular involvement and in those with long-lasting disease. References [1] Vitale A, Rigante D, Lopalco G, Selmi C, Galeazzi M, Iannone F, Cantarini L. Interleukin-1 inhibition in Behcet’s disease. Isr Med Assoc J2016;18(3–4):171–6. [2] Vitale A, Rigante D, Caso F, Brizi MG, Galeazzi M, Costa L, et al. Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory Behcet’s disease: a case series. Dermatology2014;228(3):211–4. doi:10.1159/000358125 [3] Cantarini L, Vitale A, Scalini P, Dinarello CA, Rigante D, Franceschini R, et al. Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol2015;34(7):1293–301. doi:10.1007/s10067-013-2443-8 Disclosure of Interest None declared

Background The targeted pharmacodelivery of cytokines by means of antibody-fusion proteins aims at selective accumulation of the active compound at the site of disease while sparing healthy tissues. Dekavil (F8IL10) is a fully human fusion protein composed of the vascular targeting antibody F8 fused to the cytokine interleukin-10. A phase 1 dose escalation study in patients with rheumatoid arthritis (RA) has recently been completed. Dekavil is currently under investigation in a phase 2 clinical study for the treatment of RA. Objectives The phase 1 study investigated safety, tolerability and the maximum tolerated dose of Dekavil when administered in combination with methotrexate (MTX). The currently ongoing phase 2 (in patients with active RA despite MTX therapy who had failed anti-TNF treatment) measures the mean change from baseline in DAS28-CRP between F8IL10 and placebo arms as primary endpoint. Methods The target population of both RA studies comprises patients with active RA despite MTX therapy who had failed anti-TNF treatment. Dekavil is administered once weekly for 8 consecutive weeks by s.c. injection in combination with a fixed dose of MTX (10–25 mg). The recently completed phase 1 study investigated escalating doses of Dekavil (6–600 µg/kg +MTX). The ongoing randomised multicenter, double-blind, placebo-controlled phase 2 trial assesses therapeutic activity in two treatment groups (Dekavil 30 or 160 µg/kg plus MTX) and one placebo group (placebo plus MTX). Results Dekavil was well tolerated up to the highest investigated dose (600 µg/kg) and an MTD was not reached. In 34 out of 35 patients treated in the phase 1 study no SAEs and no SUSARs were reported. One subject (cohort 9, 450 µg/kg) experienced a DLT (G2 purpura), which was accompanied by an SAE (G2 dyspnea, not drug related). The patient fully recovered within one week following corticosteroid administration. The most frequently observed adverse event was mild (G1) injection site reaction and occurred in 60% of the patients. Furthermore, two cases of drug related anaemia (G3 and G2; 160 µg/kg and 450 µg/kg, respectively) were reported in this study. All adverse reactions resolved completely. After 4 cycles of treatment, 36.4% of patients (12/33) exhibited ACR responses. The fraction of responses increased to 45.8% (11/24) after 8 cycles. Two patients achievedan ACR70 for more than 12 months after the last drug administration. As of January 2018, 25 patients have been treated in the phase 2 clinical study and neither SUSARs nor treatment-related deaths were recorded. Immunogenicity assessment is completed for the first 20 study subjects did not reveal an antibody response specific to F8IL10. An interim read-out after 45 patients will provide a more thorough understanding of the therapeutic activity of F8IL10. Conclusions The data obtained in the population studied to date suggest that Dekavil may be a safe and well tolerated novel therapeutic for the potential treatment of RA. Disclosure of Interest M. Galeazzi: None declared, G. Sebastiani: None declared, R. Voll: None declared, O. Viapiana: None declared, J. Dudler: None declared, P. Zufferey: None declared, E. Selvi: None declared, S. Finzel: None declared, F. Bootz Employee of: Philogen Group (Sponsor of the study), D. Neri Shareholder of: Philogen Group (Sponsor of the study)

Background Preventing organ damage is a major challenge in Systemic Lupus Erythematosus (SLE). Objectives To evaluate factors associated with development of damage in a prospectively followed cohort of early diagnosed SLE patients. Methods The Early Lupus Project1 encompasses 9 Italian centres recruiting, from the 1 st January 2012, an inception cohort of consecutive patients diagnosed with SLE within 12 months from appearance of four or more 1997 ACR classification criteria. At study entry and then every 6 months a large panel of data was recorded. Here, we report on factors associated with the development of damage assessed by the SLICC/ACR Damage Index (SDI). Using univariate analysis, we assessed the contribution of covariates collected at baseline (demographic, comorbidities, serological, clinical by BILAG2004 domains, disease activity by ECLAM, HRQoL by visual analogic scale) in the development of damage (SDI from 0 to ≥1). Forward-Backward Cox-regression models were fitted with covariates with p Results Overall, 279 patients were enrolled in the Early Lupus Project inception cohort up to the 31th of December 2017; 230 patients (89.6% Caucasians, 13.4% males) were eligible for this study having SDI=0 at enrolment and at least 6 months of follow-up. Mean (±SD) age at recognition of 4 ACR criteria was 36.5 (±14.4) years, median disease duration at recruitment was 1.1 months (interquartile range 0.0–4.8) and median follow-up duration was 27.4 months (interquartile range 7.2–48.0). At last follow-up visit 84 patients (36.5%) had an SDI score ≥1 (median=0; interquartile range 0–1); see figure 1A for overall SDI domains involved. Baseline dyslipidemia (p 35 year) at baseline (p=0.001; HR 2.3 95% CI 1.4–4.0) together with total dose of corticosteroids (p=0.015; HR 1.06 per gram of prednisone equivalent; 95% CI 1.01–1.11) during follow-up were the factors independently associated with increased risk of developing damage in this cohort (figure 1B). Their effect was confirmed after stratification for antimalarials (yes/no) and immunosuppressants (yes/no) use. Conclusions The early development of organ damage in this SLE patients cohort was associated with modifiable risk factors as baseline dyslipidemia and higher corticosteroid dose. Addressing them since the very early stages of the disease, and treating disease activity to target remission or minimal disease activity, may reduce damage and improve patients outcome. Reference [1] Sebastiani GD, et al. Early Lupus Project – A multicentre Italian study on systemic lupus erythematosus of recent onset. Lupus2015Oct;24(12):1276–82. Disclosure of Interest None declared

Background Behcet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications: no laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available in the clinical practice. Objectives To search for a correlation between serum amyloid-A (SAA) levels and disease activity evaluated via BD current activity form (BDCAF), to assess disease activity in relationship with different SAA thresholds, to examine the association between single organ involvements and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels. Methods Ninety-five serum samples were collected from 64 BD patients, and their related demographic, clinical and therapeutic data were retrospectively collected. Results No correlation was identified between SAA levels and BD disease activity (Spearman rho=0.085; p=0.411), while a significant difference was found in the mean BDCAF score between patients presenting SAA levels 200 mg/L (p=0.027). SAA levels higher than 200 mg/L were significantly associated with major organ involvement (p=0.008). A significant association was found between SAA levels>150 mg/dl and ocular (p=0.008), skin (p=0.002) and mucosal manifestations (p=0.012). Patients undergoing biologic therapies were significantly associated with SAA levels Conclusions SAA level does not represent per se a biomarker of disease activity, but might be useful as a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD. Disclosure of Interest None declared

Background Infliximab (IFX) has been proved to be effective in several organ involvement of Behcet’s Disease (BD). A recent report 1 describing rapid loss of efficacy of biosimilar IFX after switching from originator IFX suggests the necessity to exercise caution regarding the automatic substitution of originator IFX with biosimilar IFX in patients achieving remission with originator IFX. Objectives The purpose of the present study was to describe our experience with biosimilar IFX CT-P13 in patients affected with BD, who were switched from originator IFX. Methods Retrieved data including demographic characteristics, clinical manifestations and previous treatments were collected. All patients met the ISG and/or ICBD classification criteria for Behcet’s Disease. In order to evaluate disease activity, the BD Current Activity Form (BDCAF) has been evaluated before starting biosimilar, at three, six and nine months after switching to CT-P13. The occurrence of adverse events was also recorded. Wilcoxon matched-pairs signed-ranks test was carried out to evaluate differences between BDCAF distributions pre-switch and either at three, at six and at nine months after switching. Results Thirteen caucasian adult BD patients (mean age 39.77±7.46 years) with a mean disease duration of 12.54±4.21 years, underwent IFX treatment at licensed dosage for a period of 117.66±48.01 months. After 106.92±46.37 months of treatment with originator IFX, all of them were switched to CT-P13 biosimilar IFX. At 3 months after switching, none of them had discontinued CT-P13 biosimilar IFX treatment. No significant difference was noticed between BDCAF mean score assessed at switch and 3 months after switching (p=0.15). At 6 months follow up, 2/13 patients (15.38%) discontinued CT-P13 biosimilar IFX treatment, both for recurrence of mucocutaneous involvement. One out of 2 patients who discontinued CT-P13 IFX had previously experienced a disease flare under originator IFX therapy, requiring a modification of ongoing therapy. BDCAF mean score assessed before and 6 months after switching were not significantly different (p=0.81). Nine months after switching 2 out of the remaining 11 patients were lost at follow up. Once more, no difference was shown between BDCAF mean score assessed at switch and at 9 months follow up (p=0.85). No adverse events occurred during the observed period. Conclusions Despite the short follow up period, these data suggest that switching BD patients from originator IFX to CT-P13 seems to be effective and safe; only a small percentage of patients experienced relapse of symptoms, whereas a significant modification of BDCAF pre-switch and post-switch was not noticed. Although encouraging, these results need to be confirmed over a longer follow up period and on larger cohorts of patients. Reference [1] Cantini F, et al. (2017) Rapid loss of efficacy of biosimilar infliximab in three patients with Behcet’s disease after switching from infliximab originator. Eur J Rheumatol4 (4):288–290 Disclosure of Interest None declared