Serena Fasano

Rituximab in the treatment of inflammatory myopathies: a review.

Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015. The following terms were assessed: inflammatory myopathies OR anti-synthetase syndrome OR polymyositis OR dermatomyositis AND RTX. A total of 48 studies were included. We identified 458 patients with myositis treated with RTX. We found a rate of response to RTX of 78.3%. RTX can play a role in the management of patients with myositis, at least in those with positive myositis-specific autoantibodies.

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Methods. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. Results. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Conclusion. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

Primary prevention of cardiovascular disease in patients with systemic lupus erythematosus: case series and literature review:

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000–2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.

Low-dose aspirin as primary prophylaxis for cardiovascular events in systemic lupus erythematosus: a long-term retrospective cohort study

OBJECTIVES Cardiovascular (CV) morbidity and mortality are significantly greater in SLE patients than in the general population. ASA is known to be associated with a decrease in the incidence of CV events in high-risk patients from the general population, but its efficacy as primary prophylaxis in SLE patients has not yet been investigated. METHODS The clinical charts of SLE patients consecutively admitted to a tertiary centre who, at admission, satisfied 1992 ACR and/or 2012 SLICC classification criteria for SLE and had not experienced any CV event, were reviewed. The occurrence of any CV event was recorded at each visit. ASA was prescribed to all patients at first visit. The rate and reasons for ASA discontinuation were also recorded at each visit. RESULTS One hundred and sixty-seven consecutive SLE patients were enrolled and followed up for a median of 8 years (range 1-14 years). Among them, 146 regularly took the medication (ASA-treated patients) and 21 refused to take or discontinued it (non-ASA-treated patients). Five CV events occurred in the 146 ASA-treated patients (4.2 per 1000 person-years) and four in the 21 non-ASA-treated patients (30 per 1000 person-years; P = 0.0007). The CV event-free rate was higher in ASA-treated than in non-ASA-treated patients (log-rank test χ(2) = 15.74; P = 0.0001). No relevant side-effect related to ASA was recorded. CONCLUSION Low-dose ASA is a safe treatment and may be beneficial in the primary prophylaxis of CV events in SLE patients. Controlled, prospective studies are needed to provide a better definition of its role in these patients.

Autoimmune gastrointestinal complications in patients with systemic lupus erythematosus: case series and literature review.

The association of systemic lupus erythematosus (SLE) with gastrointestinal autoimmune diseases is rare, but has been described in the literature, mostly as case reports. However, some of these diseases may be very severe, thus a correct and early diagnosis with appropriate management are fundamental. We have analysed our data from the SLE patient cohort at University College Hospital London, established in 1978, identifying those patients with an associated autoimmune gastrointestinal disease. We have also undertaken a review of the literature describing the major autoimmune gastrointestinal pathologies which may be coincident with SLE, focusing on the incidence, clinical and laboratory (particularly antibody) findings, common aetiopathogenesis and complications.

Current pharmacological treatment of idiopathic inflammatory myopathies

ABSTRACT The idiopathic inflammatory myopathies are uncommon and heterogeneous disorders. Their classification is based on distinct clinicopathologic features. Although idiopathic inflammatory myopathies share some similarities, different subtypes may have variable responses to therapy, so it is very important to distinguish the correct subtype. There are few randomised, double blind placebo controlled studies to support the current treatment. High dose corticosteroids continue to be the first-line therapy and other immunosupressive drugs are used in refractory cases, as well as steroid-sparing agents. Some novel therapeutic approaches have emerged as potential treatment including tacrolimus, intravenous immunoglobulin and rituximab, following good outcomes reported in case studies. However, more randomised controlled trials are needed. This review considers the current and the potential future therapies for inflammatory myopathies.

The incidence of cardiovascular events in Italian patients with systemic lupus erythematosus is lower than in North European and American cohorts: implication of disease-associated and traditional risk factors as emerged by a 16-year retrospective GIRRCS study: GIRRCS=Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale.

Abstract Previous study from our group has pointed out a lower number of cardiovascular (CV) events in Italian patients with systemic lupus erythematosus (SLE) than in North European and American ones. This study aims to assess the incidence of the first CV event in a large, multicenter, Italian cohort of patients with SLE and search for differences in disease and traditional risk factors among distinct cohorts. Clinical charts of SLE patients consecutively admitted to 5 Italian rheumatologic centers from November 1st 2000 to December 31st 2015 and free of CV events at baseline were retrospectively studied. CV cumulative incidence (ie, the proportion of patients who experienced a new CV event over the follow-up period) and CV incidence rate (ie, the number of events in the cohort divided by the total number of years at risk) were evaluated. The detected incidences were compared with those reported in SLE cohorts from other countries. The median duration of follow-up was 6 years (IQR = 3–11). During the observational period, 37 (cumulative incidence = 7.2%) patients had a first episode of CV event with an incidence rate of 10.1/1000 person-years. The CV cumulative incidence and incidence rate detected in our Italian cohort were lower than those from most North European and American cohorts, characterized by a high impact of traditional risk factors. Nevertheless, the cumulative incidence was similar to that reported in a Spanish cohort with a high frequency of traditional risk factors (geographic impact), while the incidence rate was only slightly higher than that in the Baltimore cohort, which is characterized by a strict follow-up of patients (medical impact). Our results confirmed that Italian lupus patients have a low incidence of CV events. Moreover, the geographic origin, traditional risk factors, and medical approach appear to have an impact on CV disease in SLE.

Lung involvement in “stable” undifferentiated connective tissue diseases: a rheumatology perspective

Previous studies of the occurrence of interstitial lung disease (ILD) in undifferentiated connective tissue diseases (UCTD) were conducted in patients admitted to Respiratory Medicine Units. The aim of the present prospective study was to investigate lung involvement in UCTD patients admitted to a Rheumatology Unit. Eighty-one consecutive UCTD patients were enrolled in the study. Each patient underwent history and physical examination, routine laboratory investigations, antinuclear antibody (ANA) profiling, B-mode echocardiography, and lung function study according to previously reported methods. Lung high resolution computed tomography (HRCT) was performed in patients who provided informed consent. Six patients (7.4%) had a history of grade II dyspnea. Three of them had a DLCO ranging from 42 to 55% of the predicted value; and a HRCT-documented ILD with a non-specific interstitial pneumonia (NSIP) pattern. Symptoms in the other three patients were due to cardiac disease. None of the 75 asymptomatic patients, had relevant findings at physical examination, 26/75 had a DLCO <80% (<70% in 10 cases). Of these, 3 of the 30 patients who underwent lung HRCT were affected by NSIP-ILD. Six of the 81 enrolled were affected by ILD, which was symptomatic in three patients. A higher percentage of patients had a reduced DLCO. The latter finding may reflect a preradiographic ILD or a preechocardiographic pulmonary vascular disease.

Low mortality rate in Italian rheumatoid arthritis patients from a tertiary center: putative implication of a low anti-carbamylated protein antibodies prevalence

Background and objective Anti-carbamylated protein antibodies (anti-CarP Ab) represent a novel kind of autoantibodies specificity detectable in the sera of patients with rheumatoid arthritis (RA). They have been recently reported to be associated with increased mortality in Spanish patients with RA. The aim of our study was to compare the incidence mortality rates (IMRs) detected in RA patients from a tertiary Italian center with those reported in other European tertiary centers and to evaluate the putative role of anti-CarP Ab in modulating the low IMR detected in our patients. Methods Clinical charts of patients consecutively admitted to our center, from January 1, 2008, to December 31, 2014, were retrospectively reviewed. The mortality rate (expressed as the number of deaths in the cohort divided by the number of years of IMR follow-up) and causes of death were assessed at December 31, 2015. Sera of 61 patients, representative of the whole cohort, collected at the time of admission to our center were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab in our series were compared with those reported in other European cohorts. Results We observed 608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy and the Spanish cohort, while only all-cause and cardiovascular IMRs were significantly lower in our series with respect to the Leiden Early Arthritis Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than in any other European cohorts. Conclusion We confirm that the mortality rate is lower in our Italian RA cohort with respect to other European cohorts. Whether the low prevalence of anti-CarP Ab might be responsible for this result awaits to be furtherly investigated.

SAT0482 Undifferentiated connective tissue disease at risk for systemic sclerosis: predictive role of anti-topoisomerase and avascular areas

Background Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc) is a condition characterised by Raynaud’s phenomenon and either SSc marker autoantibodies or typical capillaroscopic findings or both, unsatisfying classification criteria for SSc1 and reported to evolve into definite SSc in about 50% of 60 cases over a 12–102 months follow-up time.2 We found marker autoantibody positivity to predict the evolution into SSc satisfying 2013 ACR criteria for the disease.3 Objectives To investigate in patients followed-up for a longer time if distinct marker autoantibody specificities have a different predictive value. Methods Sixty-five patients consecutively admitted to a tertiary Rheumatology Unit from November 1 st 2000 to December 31 st 2016 and diagnosed as UCTD-risk-SSc were enrolled in the study. Patients were monitored for a median of 27 months (range 6–144) and were evaluated twice yearly to assess disease progression. Kaplan-Meier curves and the log-rank test were used to analyse differences in fulfilling the criteria for SSc between subsets. Risk prediction was assessed by univariate Cox regression analysis. Results During follow-up 40/53 marker autoantibody-positive patients (75.5%) versus 3/12 (25%) marker autoantibody negative ones satisfied SSc criteria (p=0.006). Out of them, 11/12 (91.7%) anti-topoisomerase (Scl70) positive versus 29/40 (72.5%) anti-centromere (ACA) positive patients evolved into definite SSc (p=0.04). In univariate analysis, anti-Scl70 positivity increased by 2-fold the risk of a definite SSc outcome (HR 2.1 95% CI 0.9–4.4) with respect to ACA positivity (HR 0.5 95% CI 0.2–1.0) (p=0.05). In addition 3/3 (100%) patients with avascular areas at baseline versus 40/62 (64.5%) with megacapillaries only or no capillaroscopic abnormalities satisfied SSc criteria over a 12–38 months follow-up time (p=0.06). Conclusions We confirm that autoantibody positivity patients presents a faster evolution. Moreover we first detected an increased HR of Scl-70 versus ACA positivity and a potential role of baseline detected avascular areas. References [1] Valentini G. Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc). Autoimmun Rev2015. [2] Valentini G, et al. Early Systemic Sclerosis: Analysis of the Disease Course in Patients With Marker Autoantibody and/or Capillaroscopic Positivity. Arthritis Care Res2014. [3] van den Hoogen F, et al. 2013classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis2013. Disclosure of Interest None declared