Long-term retention rate, adverse event temporal patterns and rescue treatment strategies of mycophenolate mofetil in systemic sclerosis: insights from real-life.

BACKGROUND: Mycophenolate mofetil (MMF) is a mainstay for the treatment of systemic sclerosis (SSc). The occurrence and implications of MMF-related adverse events on drug retention rates in real life remain poorly defined. We aimed to determine the MMF retention rate and to investigate the causes and patterns of discontinuation, adverse events (AEs) and treatment options used after discontinuation. METHODS: SSc patients who started MMF treatment underwent a retrospective longitudinal assessment for up to 5 years. We documented the incidence, predictors, and impacts of MMF treatment on gastrointestinal intolerance, infections, laboratory abnormalities, and cancer. Rescue strategies implemented after MMF discontinuation were recorded. RESULTS: The 5-year MMF retention rate of 554 patients stood at 70.7% and 19.6% of them stopped MMF due to AEs. One out of every four patients experienced a dose reduction or discontinuation of MMF due to AEs, with gastrointestinal intolerance being the predominant cause. The 5-year cumulative incidence rates for gastrointestinal intolerance, cancer, severe infections, and laboratory toxicity leading to MMF discontinuation were 6.4%, 4.1%, 3.1%, and 2.1%, respectively. Lower respiratory tract was the most affected, with bacteria being the predominant causative agent. Intestinal and pulmonary circulation involvement were tied to elevated AE rates and MMF discontinuation. The most common approaches post-MMF cessation were "watch and wait" and switch to rituximab. CONCLUSIONS: MMF use in SSc appears to be limited by the occurrence of AEs, both in terms of persistence and dosing of the drug. Rescue options after MMF discontinuation are limited and many patients remain without immunosuppressant.

Therapeutic strategies for primary heart involvement in systemic sclerosis.

Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), even though often underdiagnosed. SSc-pHI has been recently defined as cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications. SSc-pHI represents a major determinant of mortality in SSc, accounting alone for about 12% of disease-related deaths; its early recognition and promptly therapeutic interventions are therefore crucial. Both perfusion defects and myocardial inflammation contribute to the occurrence of myocardial fibrosis that precipitates myocardial remodeling, potentially leading to heart failure and arrhythmic complications. To date, clear evidence and guidelines for effectively managing SSc pHI are not established yet, resulting in a lack of a defined therapeutic algorithm. In this review we summarize the most recent scientific literature on the prevailing therapeutic strategies and interventions to manage SSc-pHI, with particular focus on therapeutic strategies to counteract the 3 major pathogenic events of the disease, i.e. microvascular damage, myocardial inflammation and myocardial fibrosis.

Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.

Introduction: Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia. Methods: We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. Results: Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). Discussion: This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

Increased prevalence of malignancies in patients with IgG4-related disease: implications for clinical care.

OBJECTIVES: The association between cancer and IgG4-related disease (IgG4-RD) is evolving. The primary aim of this study was to investigate the prevalence of malignancies in IgG4-RD. The secondary aim was to describe the epidemiological and clinical characteristics of IgG4-RD patients with a history of cancer. METHODS: Two hundred and ten patients with IgG4-RD were included in this retrospective study. IgG4-RD phenotypes, clinical and serological variables were analyzed. The prevalence of cancer in IgG4-RD was compared with that in the Italian population using the registry of the Global Cancer Observatory (GCO) of the World Health Organization. The Standardized Incidence Ratio (SIR) for cancer in IgG4-RD was obtained based on the 5-years Limited Duration Prevalence (2015-2020) of tumors in the Italian population. RESULTS: Thirty-seven/210 patients (18%) developed cancer before or after the diagnosis of IgG4-RD. Solid and hematologic tumors were more frequently observed in pancreato-biliary IgG4-RD. The SIR for malignancy in IgG4-RD patients was 2.54 higher than the general Italian population (p= 0.007). The SIR was 2.78 higher for males (p= 0.005) and 1.15 higher for females (p> 0.05). Thirty-two malignancies were diagnosed before and 16 after IgG4-RD diagnosis. Interval "from IgG4-RD to cancer" was shorter than that "from cancer to IgG4-RD". Most tumors occurring after IgG4-RD developed within 36 months from diagnosis of IgG4-RD. CONCLUSIONS: The prevalence of cancer in patients with IgG4-RD is increased compared with the Italian population and mechanistically suggests a possible paraneoplastic association. Close surveillance is warranted for the first 36 months after IgG4-RD diagnosis.

Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.

OBJECTIVES: to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients. METHODS: SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation. RESULTS: One-hundred-fifty-two SSc-patients (mean age 47.3 ± 12.3 years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%) were evaluated over a median(IQR) time of 3.3(1.7-5.0) years. The primary indication for rituximab were interstitial lung disease (ILD)(38.8%), worsening skin fibrosis(36.8%), and arthritis(13.8%); 138 patients(90.8%) received more than one rituximab course. The 5-years rituximab retention rate was 59.9%(44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation[5.7(3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration[sHR 0.8(0.7-0.9)], anti-topoisomerase-I negativity[sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis[sHR 0.3 (0.1-0.8)]. Treatment failure was the second cause of rituximab discontinuation[3.7(2.2-6.0) per 100 patient-year] and was associated with anti-centromere antibody positivity[sHR 2.8(1.1-7.4)] and anti-topoisomerase-I negativity[sHR 0.2(0.1-0.6)]. Adverse events(AEs) were the less common cause of discontinuation[3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset[sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment[sHR 4.5(1.2-16.3)]. CONCLUSION: rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.

Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies.

INTRODUCTION: Idiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM. METHODS: Patients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period. RESULTS: Among the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed. CONCLUSION: Our data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.

Association of IgG4-related disease and systemic rheumatic disorders.

PURPOSE: Autoimmune disorders can occur together especially in genetically predisposed individuals. We here aimed to assess the occurrence of IgG4-related disease (IgG4-RD) in association with other systemic immune-mediated conditions. METHODS: We retrospectively analyzed the clinical records of patients with IgG4-RD followed at the IgG4-RD Clinic of San Raffaele Hospital (Milan, Italy) for pre-existing or concomitant immune-mediated disorders. IgG4-RD was diagnosed based on histological findings and on the 2011 Comprehensive Diagnostic criteria. Associated immune-mediated disorders were diagnosed based on available classification and/or diagnostic criteria. RESULTS: Two-hundred and thirty-four patients with a definitive diagnosis of IgG4-RD were included in this study. A pre-existing immune-mediated connective tissue disease was reported in 6/234 patients (3%): one case each of sarcoidosis, Takayasu arteritis (TA), eosinophilic granulomatosis with polyangitis (EGPA), and rheumatoid arthritis; and two cases of granulomatosis with polyangitis (GPA). Organs involved by IgG4-RD included the lungs, the pancreas, the peritoneum, lacrimal glands, meninges and orbits. Sarcoidosis, EGPA, and TA preceded the onset of IgG4-RD. GPA preceded IgG4-RD onset in one case and occurred simultaneously in the other case. Rheumatoid arthritis occurred together with IgG4-RD in one case. CONCLUSION: Our observation suggests that "secondary" IgG4-RD can present in the context of pre-existing systemic immune-mediated disorders and complicate systemic autoimmune diseases as well as chronic granulomatous conditions. Further studies are needed to define whether this peculiar clinical scenario is associated with different genetic backgrounds, pathological bases, and long-term outcomes.

Cardiac Safety of mRNA-Based Vaccines in Patients with Systemic Lupus Erythematosus and Lupus-like Disorders with a History of Myocarditis.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger immune-mediated adverse events, including myocarditis. Evidence of vaccine safety in patients with rheumatic disorders and underlying autoimmune myocarditis is scarce. To address this issue, we studied 13 patients with systemic lupus erythematosus (SLE) and allied conditions with a history of myocarditis and receiving mRNA-based vaccines. Data about general and cardiac laboratory tests, treatment, and disease status were collected during routine consultations before and after the primary vaccination course and after each vaccine dose administration, while myocarditis symptoms were closely monitored. A significant increase in troponin levels from baseline was found after 13 (6-20) days from the first (p = 0.046) and 17 (4-29) days after the second dose (p = 0.013). Troponin levels progressively decreased within 3 (1-6) months in the absence of typical symptoms or signs of myocarditis. A significant increase in the constitutional domain of the British Isles Lupus Assessment Group (BILAG) index (p = 0.046) was observed in SLE patients. However, no patient needed any treatment change. mRNA-based anti-SARS-CoV-2 vaccines can apparently be safely administered to patients with SLE and lupus-like disorders with previous myocarditis despite potential subclinical and transient rises in cardiac damage markers.

Clinical response to biologicals for severe asthma: any relevance for sex in different age ranges?

Background: Whether sex can influence the clinical response to biological treatment in patients with severe asthma has not been fully addressed. Aims and methods: The aim of this study was to investigate in patients with severe asthma undergoing biological treatment the individual evolution of lung function measurements and patient-reported asthma control scores over a 12-month follow-up period, in relation to patients' sex, in different age ranges. Second, the change in the administered dose of oral corticosteroids (OCS) before and after 12 months of treatment was investigated. Results: 64 patients (58% female and 42% male) with a median age of 52 years were enrolled in the study. There were no relevant differences between sexes in terms of lung function, patient-reported asthma control, exacerbation rate and daily OCS dose within the study timeframe. A separate sub-analysis by biological treatment confirmed the same finding. Stratifying individuals by age, we showed that older men had lower lung function parameter values (forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity index) than older women, whereas an opposite trend was observed in terms of Asthma Control Test score. No other relevant differences were detected after age stratification. Conclusion: According to our findings, sex does not act as a determinant of treatment response to biologicals in people with severe asthma. Although to be confirmed in larger studies, our data suggest that neither sex nor age should limit biological treatment prescription, once the eligibility criteria for that therapy are satisfied.

Relationship between hair shedding and systemic inflammation in COVID-19 pneumonia.

Background: A higher risk for COVID-19 infection and severity for men compared to women has been described since the beginning of the pandemic. The role of androgens has been recently highlighted as they control two key steps of coronavirus infection mediated through the transmembrane protease serin 2 (TMPRRS2) and the angiotensin-converting enzyme 2 (ACE2) receptor in the lung tissue. Furthermore, a high incidence of androgenic alopecia among males with COVID-19 disease have been reported.Objective: This study aims to evaluate the telogen effluvium (TE) prevalence and its relationship with clinical and immunologic parameters in a sample of patients consecutively evaluated after recovery from COVID-19 pneumonia in Northern Italy.Methods: Overall 104 patients were recruited within three months from COVID-19 pneumonia recovery; 80 (77%) had been hospitalized in a Respiratory Intensive Care Unit and the remaining ones had been treated at home. The extent of TE was assessed with a visual analogic scale for thick bundle of hairs. Demographic and clinical data and systemic inflammation biomarkers were also evaluated.Results. Thirty-two patients reported a history of TE and their mean TE-VAS score was 5.78 ± 1.72 (range 3-9). Women had about a 5-fold higher risk (odds) of complaining of TE compared to males (OR = 4.69, 95%CI: 1.91, 11.49; p = .001), and the association became stronger when adjusted for COVID-19 severity (hospital admission vs home care: OR = 6.09, 95%CI: 2.34, 15.88; p < .001). Levels of C-reactive protein >1.90 mg/l (ORadj: 2.43, 95%CI 0.85, 7.05, p = 0.096) or IL 1ß > 5 ng/l (ORadj 4.72, 95%CI: 1.31, 23.19, p = .03) were also significantly associated with TE.Conclusion: This exploratory study raises the hypothesis that hair shedding is more strictly related to the severity of COVID-19 disease and the underlying inflammation rather than to patients' hormonal status. KEY MESSAGESThe presence of Telogen effluvium (TE) was significantly more common in women.Higher severity of the Covid-19 disease seems to play a critical role, more important than the hormonal influence, in the development of TE.The severity of inflammation related to TE and Covid-19 could also play a role as suggested by the higher levels of CRP and platelets and IL1ß.

Is mild asthma truly mild? The patients' real-life setting.

OBJECTIVES: Asthma exacerbations and, more rarely, fatal asthma attacks have been reported in mild asthma patients, suggesting poor disease control and awareness of its potential burden. Our study aimed to explore outside the hospital/specialist setting the perspective and disease treatment behavior of patients self-reporting a mild asthma diagnosis. METHODS: Computer-Assisted Personal Interviewing (CAPI) technique was used to investigate the identified study population. Questions about diagnosis, symptoms, comorbidities, treatment strategy, ongoing assessments, and quality of life were administered. RESULTS: Overall, 258 patients were considered for the analysis. As the most relevant results, 22% of them reported severe respiratory symptoms, 52% experienced at least one exacerbation/year, and 7% needed Emergency Room care. Sixty-six percent of the respondents assumed as needing short-acting bronchodilators only. Of note, 22% of patients were using oral steroids (OCS) intermittently and 72% of them considered their quality of life unsatisfying. CONCLUSION: Outside the hospital/specialist setting, mild asthma burden is still not negligible and the treatment approach is not correct. In particular, the reported OCS use is disproportionate. Our data suggest that mild asthma, especially when self-assessed might be other than mild, suggesting that efforts to increase disease awareness, improve the disease control limiting the OCS abuse are required.

COVID-19 Vaccination in Patients with Severe Asthma on Biologic Treatment: Safety, Tolerability, and Impact on Disease Control.

BACKGROUND: COVID-19 vaccination has been recommended for severe asthmatics. We aimed to evaluate the safety, tolerability, and impact on disease control and patient's quality of life of the mRNA SARS-CoV-2/COVID-19 vaccine in severe asthma patients regarding biologic treatment. METHODS: Severe asthmatic patients regularly managed by two big allergy and respiratory referral centers were offered to undergo Pfizer COVID 19 vaccination at the hospital site. Patients filled in an adverse events questionnaire after the first and second dose, as well as the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ). RESULTS: Overall, 253 patients were vaccinated; only 16 patients refused. No serious events were detected. Less than 20% of patients reported side effects, most of which were classified as very common side effects. No differences were reported according to the ongoing biologic drug. A significant improvement in both ACT and AQLQ was observed between the first and the second dose administration. CONCLUSIONS: Our data confirm the optimal safety and tolerability profile of mRNA SARS- CoV-2/COVID-19 in severe asthma patients on biologic treatment, as well as their positive attitude towards COVID-19 vaccination. The negligible proportion of patients reporting side effects and the absence of asthma exacerbations are relevant to support the COVID-19 vaccination campaign in severe asthma patients worldwide.

Oral health in asthmatic patients: a review : Asthma and its therapy may impact on oral health.

Different drugs used to treat asthma, such as beta 2 agonists and inhaled steroids, may promote a higher risk of caries, dental erosion, periodontal disease and oral candidiasis. This article reviews the evidences of mechanisms involved in oral diseases in patients affected by asthma. The main mechanism involved is the reduction of salivary flow. Other mechanisms include: acid pH in oral cavity induced by inhaled drugs (particularly dry powder inhaled), lifestyle (bad oral hygiene and higher consumption of sweet and acidic drinks), gastroesophageal reflux, and the impairment of local immunity. In conclusion asthma is involved in the genesis of oral pathologies both directly and indirectly due to the effect of the drugs used to treat them. Other cofactors such as poor oral hygiene increase the risk of developing oral diseases in these patients. Preventive oral measures, therefore, should be part of a global care for patients suffering from asthma.

Baricitinib restrains the immune dysregulation in patients with severe COVID-19.

BACKGROUNDPatients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules.METHODSWe treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome-coronavirus 2 (anti-SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1ß, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio.CONCLUSIONThese data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients' immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.

Factors related to alexithymia in patients with systemic sclerosis: a tight relationship with facial image dissatisfaction.

To assess clinical and psychosocial factors related to alexithymia in systemic sclerosis (SSc). We enrolled 40 consecutive SSc patients in a cross-sectional study evaluating alexithymia with Toronto Alexithymia scale (TAS-20). We measured Beck Depression inventory (BDI), Hamilton Anxiety rating scale (HAM-H), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Visual Analog Scale (VAS) pain, Pittsburgh Sleep Quality Index (PSQI), Satisfaction with Appearance Scale (SWAP), and Mouth Handicap in Systemic Sclerosis (MHISS). The prevalence of alexithymia was 42%. Alexithymic patients presented increased depressive (p = ≤ 0.001) and anxiety symptoms (p = ≤ 0.001), sleep disorders (p = 0.03), pain (p = 0.02), esthetic concerns (p = 0.03), disability in activities (p = 0.03) and reduced scores of SF-36 in mental components summary (MCS) (p = ≤ 0.001) and physical components summary (PCS) (p = 0.01). We found significant correlations with sleep disorders (r = 0.41, p = ≤ 0.001), BID (r = 0.35, p = 0.04), facial image dissatisfaction (r = 0.35, p = 0.04), mouth disability (r = 0.51, p = 0.005), depressive (r = 0.6, p = ≤ 0.001), and anxiety symptoms (r = 0.48, p = ≤ 0.001), fatigue (r = - 0.45 p = 0.005), SF-36 PCS (r = - 0.51, p = ≤ 0.001) and MCS (r = - 0.65, p = ≤ 0.001). In multiple linear regression analysis, SWAP facial was the only variable associated with TAS-20 [0.99 (0.48) p = 0.05]. Alexithymia correlates with several psychosocial factors but seems strongly related to facial image dissatisfaction.

Belimumab and low-doses of mycophenolate mofetil as induction therapy of class IV lupus nephritis: case series and literature review.

BACKGROUND: The treatment of Lupus Nephritis (LN) is an unmet need in the management of patients with Systemic Lupus Erythematosus (SLE). CASE PRESENTATION : We report two cases of women affected by Lupus Nephritis (LN) ISN/RNP Class IV with serological active disease, high disease activity and marked fatigue. In both cases, Mycophenolate mofetil (MMF), as induction therapy, was poorly tolerated because of gastrointestinal toxicity. Belimumab, together with low-doses of MMF, was effective as induction treatment leading to early achievement of complete renal response in these two selected cases of LN. CONCLUSIONS: We also report a literature review concerning the efficacy and safety of Belimumab in Lupus Nephritis. Further studies are needed to evaluate the use of Belimumab to manage the renal involvement in patients with Systemic Lupus Erythematosus, waiting for the results of ongoing randomized clinical trials.

Physical activity and sedentary behavior in patients with Systemic Lupus Erythematosus.

INTRODUCTION: The aim of this study was to evaluate the proportion of patients with Systemic Lupus Erythematosus (SLE) who did not met the WHO recommendations for physical activity and to evaluate the amount of time spent in sedentary behavior. METHODS: SLE patients were consecutively enrolled in a cross sectional study. The type and the time spent in physical activity and sedentary behavior were evaluated using the IPAQ short form questionnaire. The adequate physical activity was defined according to the 2010 WHO recommendations for health and the sedentary behavior according to the 2017 SBRN consensus. We also assessed quality of life using SF-36, mood disorders using BDI and HAM-H, fatigue using Facit-Fatigue and sleep disorders using PSQI scores. RESULTS: Physical activity was not sufficient to meet WHO recommendations in 56 of 93 SLE patients (60%). SLE patients spent a median (95% range) of 180 (0-600) minutes everyday in sedentary activities. The length of daily sedentary time was more than 6 hours in 25% of SLE patients. In multivariable analysis, the factors associated to the probability of not meeting WHO criteria was only the time of exposure to antimalarials (OR 0.88, p 0.03) and the factors related to the probability of being in the upper tertile of sedentary time (more than 270 minutes) were age (OR 1.04, p 0.02), disease activity expressed by SELENA-SLEDAI score (OR 1.2, p 0.01) and Facit-fatigue score (OR 0.94, p 0.04). CONCLUSION: A relevant proportion of SLE patients were inadequately physically active. It is essential to improve the awareness of the importance of increase physical activity and reduce sedentary time. A better control of disease activity and fatigue and a prolonged use of antimalarials could help to reach this notable goal.

The relation between, metabolic syndrome and quality of life in patients with Systemic Lupus Erythematosus.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is associated to an increased prevalence of Metabolic Syndrome (MeS) and to a reduction of Quality of Life (QoL). The aim of this study is to evaluate the association between MeS and QoL in SLE. METHODS: SLE patients were consecutively enrolled in a cross sectional study. MeS was defined according to IFD definition. Therapy with glucocorticoids (GC) and antimalarial was analyzed as cumulative years of exposure. We used a cut off of 7.5 mg of prednisone to define high daily dose of GC. QoL was quantified using SF-36. We used BDI and HAM-H to assess symptoms of mood disorders. Fatigue was evaluated using Facit-Fatigue, physical activity using IPAQ, sleep quality using PSQI and alexithymia using TAS-20. RESULTS: We enrolled 100 SLE patients. MeS prevalence was 34%. Patients with MeS presented reduced scores in SF-36 MCS and PCS compared to patients without MeS (p 0.03 and p 0.004). BDI and HAM-H score were significantly higher in patients meeting MeS criteria compared to subjects without MeS (p 0.004, p 0.02). These results were confirmed after adjustment for confounders. Compared to patients without MeS, those with MeS presented higher age, lower education level, higher recent SELENA-SLEDAI, higher number of flares, increased SDI, longer cumulative exposure to high dose GC and shorter duration of antimalarial therapy. In the multiple logistic regression model, the variable associated to the Odds Ratio of having MeS were: the average of recent SELENA-SLEDAI (OR 1.15 p 0.04), the years of exposure to high dose of GC (OR 1.18 p 0.004), the years of exposure to antimalarials (OR 0.82 p 0.03) and the BDI score (OR 1.1 p 0.005). CONCLUSION: A modern management of SLE should not miss to take all the possible measures to ensure an adequate QoL to SLE patients, with particular attention to those affected by MeS.