Secukinumab is not associated with cancer recurrence or progression in patients with spondyloarthritis and history of neoplastic disease.

Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24 months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30 months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Antiphospholipid antibody positivity in early systemic lupus erythematosus is associated with subsequent vascular events.

OBJECTIVE: aPL are found in the blood of 20-30% of patients with SLE. Although aPL cause vascular thrombosis in the antiphospholipid syndrome, it is not clear whether positive aPL levels in early SLE increase risk of subsequent vascular events (VE). In a previous analysis of 276 patients with SLE, we found that early positivity for ≥2 of IgG anti-cardiolipin (anti-CL), IgG anti-ß2-glycoprotein I (anti-ß2GPI) and anti-domain I of ß2-glycoprotein I (anti-DI) showed a possible association with VE. Here we have extended that analysis. METHODS: Serum samples taken from 501 patients with SLE early in their disease had been tested for IgG anti-CL, anti-ß2GPI and anti-DI by ELISA. Complete VE history was available for 423 patients of whom 23 were excluded because VE occurred before the diagnosis of SLE. For the remaining 400 patients we carried out Kaplan-Meier survival analysis to define groups at higher risk of VE. RESULTS: Of 400 patients, 154 (38.5%) were positive for one or more aPL, 27 (6.8%) were double/triple-positive and 127 (31.8%) were single-positive. There were 91 VE in 77 patients, of whom 42 were aPL-positive in early disease. VE were significantly increased in aPL-positive vs aPL-negative patients (P = 0.041) and in double/triple-positive vs single-positive vs aPL-negative patients (P = 0.0057). Omission of the IgG anti-DI assay would have missed 14 double/triple-positive patients of whom six had VE. CONCLUSION: Double/triple-positivity for IgG anti-CL, anti-ß2GPI and anti-DI in early SLE identifies a population at higher risk of subsequent VE.

Post-traumatic stress disorder in patients with systemic lupus erythematosus heavily affects quality of life. A cross-sectional web survey-based study.

OBJECTIVES: Neuropsychiatric symptoms develop in up to 20% of the patients with Systemic Lupus Erythematosus (SLE). Growing evidence is accruing on the association of SLE with Post-traumatic Stress Disorder (PTSD), but little is known about its contribution on patient-reported outcomes. This study focuses on PTSD prevalence in our SLE cohort and on its impact on quality of life. METHODS: Trauma and Loss Spectrum - Self Reported (TALS-SR) and Lupus Quality of Life (Lupus QoL) questionnaires were administered via web to the patients with SLE in our cohort, along with questions on demographical and disease-related aspects. RESULTS: Among 99 patients who completed the questionnaire, fatigue prevalence was 75% and 31% scored TALS-SR test consistently with PTSD. Patients with PTSD achieved lower scores compared to those without PTSD in three Lupus QoL domains: planning (83.3 vs. 100, p = .035), body image (85.0 vs. 95.0, p = .031) and fatigue (66.7 vs. 91.7, p = .001). An inverse correlation was found between TALS-SR domains and Lupus QoL scores, particularly regarding fatigue with reaction to losses or upsetting events (ρ -0.458, p < .001). CONCLUSIONS: PTSD is possibly far more frequent in patients with SLE than in general population and exerts a detrimental influence on quality of life.

Impact of the COVID-19 pandemic in patients with systemic lupus erythematosus throughout one year.

Little is known about the impact of coronavirus disease 2019 (COVID-19) pandemic to the care of patients with systemic lupus erythematosus (SLE) in the long-term. By crossing population data with the results of a web-based survey focused on the timeframes January-April and May-December 2020, we found that among 334/518 responders, 28 had COVID-19 in 2020. Seventeen cases occurred in May-December, in parallel with trends in the general population and loosening of containment policy strength. Age > 40 years (p = 0.026), prednisone escalation (p = 0.008) and infected relatives (p < 0.001) were most significantly associated with COVID-19. Weaker associations were found with asthma, lymphadenopathy and azathioprine or cyclosporine treatment. Only 31% of patients with infected relatives developed COVID-19. Healthcare service disruptions were not associated with rising hospitalisations. Vaccination prospects were generally welcomed. Our data suggest that COVID-19 has a moderate impact on patients with SLE, which might be significantly modulated by public health policies, including vaccination.

Catastrophic antiphospholipid syndrome presenting with aortic barrage: case report and review of the literature.

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition characterized by multiple thromboembolic events occurring in a short period of time, frequently accompanied by significant systemic inflammation. Aortic involvement is rare in antiphospholipid syndrome and it had been never described in the context of its catastrophic variant. Here, we report an unusual case of aortic occlusion as a debut manifestation of CAPS and discuss its clinical features with an up-to-date review of the literature to identify risk factors and clues for clinical practice.

Beyond Neuropsychiatric Manifestations of Systemic Lupus Erythematosus: Focus on Post-traumatic Stress Disorder and Alexithymia.

PURPOSE OF REVIEW: To deepen the comprehension of the role of specific psychological conditions in the pathogenesis and in the treatment of systemic lupus erythematosus (SLE). Specifically, the present comprehensive review aims at examining the association between SLE, alexithymia (AT)-a personality construct referring to the inability to identify, describe, and express sensations, emotions, and physical state-and post-traumatic stress disorder (PTSD), to infer potential biological relationships between these psychopathological issues and disease course, and to draw up a research agenda on gray areas of these topics. RECENT FINDINGS: Whereas several studies document the presence of neuropsychiatric symptoms in patients with SLE, psychological distress, alexithymia, and post-traumatic manifestations are usually neglected by healthcare professionals and poorly investigated in research contexts. However, the interplay of these aspects, which affect physiologic stress coping mechanisms, potentially plays an important role in SLE pathogenesis. In particular, research documents that cytokine repertoire pattern alteration and hypothalamic-pituitary-adrenal axis impairment leading to inflammation and pain represent the main links between emotional health and immunity. AT and PTSD seem to be common in patients with SLE and account for multiple aspects of SLE-related morbidity. Furthermore, abnormal processing of stressful stimuli as hallmarks of PTSD and AT might promote neuroendocrine dysfunction and dysregulated immunity, thus contributing to the pathogenesis of SLE. A comprehensive, multidisciplinary clinical approach, based on a cooperation between immunologists, rheumatologists, neurologists, and mental health professionals, is crucial to promote patients' global health.

COVID-19: Pharmacology and kinetics of viral clearance.

Coronavirus Disease 2019 (COVID-19) is a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical spectrum of COVID-19 is broad and varies from mild to severe forms complicated by acute respiratory distress and death. This heterogeneity might reflect the ability of the host immune system to interact with SARS-CoV2 or the characteristics of the virus itself in terms of loads or persistence. Information on this issue might derive from interventional studies. However, results from high-quality trials are scarce. Here we evaluate the level of evidence of available published interventional studies, with a focus on randomised controlled trials and the efficacy of therapies on clinical outcomes. Moreover, we present data on a large cohort of well-characterized patients hospitalized at a single University Hospital in Milano (Italy), correlating viral clearance with clinical and biochemical features of patients.

Low prevalence of arrhythmias in clinically stable COVID-19 patients.

BACKGROUND: No studies investigated the prevalence of arrhythmias among clinically-stable patients affected by COVID-19 infection. METHODS: We assessed prevalence, type, and burden of arrhythmias, by a single-day snapshot in seven non-intensive COVID Units at a third-level center. RESULTS: We enrolled 132 inhospital patients (mean age 65±14y; 66% males) newly diagnosed with COVID-19 infection. Arrhythmic episodes were detected in 12 patients (9%). In detail, 8 had atrial fibrillation, and 4 self-limiting supraventricular tachyarrhythmias. There were no cases of ventricular arrhythmias or new-onset atrioventricular blocks. In addition, we report no patients with QTc interval >450 ms. CONCLUSIONS: Our single-day snapshot survey suggests that the prevalence of arrhythmias among clinically stable COVID-19 patients is low. In particular, no life-threatening arrhythmic events occurred.

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.

Giant cell arteritis: Update on clinical manifestations, diagnosis, and management.

Giant cell arteritis (GCA) is the most common vasculitis affecting people older than 50 years. The last decades have shed new light on the clinical paradigm of this condition, expanding its spectrum beyond cranial vessel inflammation. GCA can be now considered a multifaceted vasculitic syndrome encompassing inflammation of cranial and extra-cranial arteries and girdles, isolated or combined. Such heterogeneity often leads to diagnostic delays and increases the likelihood of acute and chronic GCA-related damage. On the other hand, the approach to suspected GCA patients has been revolutionized by the introduction of vascular ultrasound which allows a rapid, cost-effective, and non-invasive GCA diagnosis. Likewise, the use of tocilizumab is now part of the therapeutic algorithm of GCA and ensures a satisfactory disease control even in steroid-refractory patients. Nonetheless, some aspects of GCA still need to be clarified, including the clinical correlation of different histological patterns, and the prevention of long-term vascular complications. This narrative review depicts the diagnostic and therapeutic aspects of GCA most relevant in clinical practice, with a focus on clinical updates and novelties introduced over the last decade.

Factors associated with cardiovascular events in systemic lupus erythematosus in a monocentric cohort with up to 40 years of follow-up.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with an increased cardiovascular risk. Several traditional and disease-specific risk factors have been shown to correlate with the occurrence of cardiovascular events (CVE) in patients with SLE. However, results of previous studies are diverse. The objectives of this study were to report number, type and those factors associated with CVE in patients with SLE in a large, single-center, ethnically diverse cohort with a long follow-up duration. METHODS: Medical records of patients treated at the Lupus Clinic at University College London Hospital (UCLH) between 1979 and 2020 were retrospectively reviewed. Data about CVE, traditional cardiovascular risk factors, demographic and disease features, and treatment history were collected. Only patients with complete available information were included in the study. Regression analyses were performed to identify factors associated with CVE. RESULTS: Four hundred and nineteen patients were included in the study. Maximum follow-up length was 40 years. Seventy-one (17%) patients had at least one CVE. Multivariable analysis showed that only antiphospholipid antibody positivity (p-value<0.001) was associated with CVE. When analysing different types of CVE, antiphospholipid antibodies were specifically associated with both venous thromboembolic events (p-value<0.001) and cerebrovascular events (p-value=0.007). Dedicated subanalyses revealed that cumulative glucocorticoid dose (p-value=0.010) and a diagnosis of SLE before 2000 (p-value<0.001) were significantly associated with CVE. CONCLUSIONS: Cardiovascular disease is highly prevalent among patients with SLE and is associated with antiphospholipid antibodies, glucocorticoid therapy, and diagnosis before 2000.

Effectiveness of a two-year tapered course of tocilizumab in patients with giant cell arteritis: A single-centre prospective study.

OBJECTIVE: To evaluate the feasibility of tocilizumab tapering and withdrawal in patients with giant cell arteritis (GCA). METHODS: GCA patients eligible for tocilizumab were prospectively enrolled. Tocilizumab was administered weekly for the first 12 months, every-other-week for an additional 12 months, then discontinued. Relapses on tocilizumab were managed with temporary increases in systemic glucocorticoids or addition of methotrexate. Primary outcome was relapse-free survival at month 6 after tocilizumab suspension. Relapse-free survival on tocilizumab, imaging response, and adverse events were evaluated. RESULTS: 23 GCA patients were enrolled. Reasons for tocilizumab start were relapse (n = 14), persistence of activity (n = 5), or steroid-related adverse events (n = 4). At tocilizumab start, two patients were on methotrexate, which was maintained. Fourteen patients had extracranial vascular involvement on 18FDG-PET/CT. During the first 12 months, four patients (17%) had clinical relapse. At every-other-week tocilizumab start, all patients were in clinical remission, two patients had active vasculitis on 18FDG-PET/CT; two patients were on steroid therapy, and four patients were taking methotrexate. Two patients (9%) relapsed while on every-other-week tocilizumab. At tocilizumab suspension, no patient was on steroid therapy and no patient had signs of active vasculitis on 18FDG-PET/CT. In the 6 months after tocilizumab discontinuation, six patients (26%) relapsed. No new or unexpected safety findings were identified. CONCLUSION: Tocilizumab tapered over a two-year period was effective to induce and maintain remission in GCA. Relapses on tocilizumab were minor and responded to incremental changes in therapy. A significant proportion of patients relapsed in the 6 months after therapy suspension.

The Role of the Multidisciplinary Health Care Team in the Management of Patients with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterised by immune dysfunction, vascular damage and fibrosis affecting the skin and multiple internal organs. The clinical spectrum of SSc is wide and its manifestations may lead to severe morbidity and mortality, in addition to a great impact on patients' quality of life. Due to the multifaceted clinical manifestations of SSc, its management requires a combined expertise of different medical specialists to guarantee an adequate disease control and prevent organ complications. Multi-disciplinary teams (MDT), which are composed by physicians and other specialized health professionals, represent therefore a key element for the comprehensive management of SSc patients. Moreover, MTD can improve communication and patients' empowerment while the presence of dedicated nurses can help patients to ask questions about their condition. The scope of this narrative review is to analyse the available evidences regarding the role of MDT in the management of SSc patients, and how this holistic approach may improve different disease domains and the overall prognosis. MDT regarding the cardiovascular and lung complication are the more represented in literature, given the great impact in prognosis. Nonetheless, MDT have been shown to be fundamental also in other disease domains as they can intercept early manifestations, thus stratifying patients based on the individual risks in order to personalize patients' follow-up. MDTs may also minimize the treatment delay, enabling fast-track specialist referral. On the other hand, there are few trials specifically studying MDT in SSc and several authors have highlight the lack of standardization.

Autoantibody positivity predicts severity of rheumatic immune-related adverse events to immune-checkpoint inhibitors.

OBJECTIVE: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors are responsible for a considerable burden of morbidity and mortality. Predictors of severity of rheumatic irAEs have not been identified yet. The objective of this study was to test the hypothesis whether the presence of autoantibodies could be associated with a more severe and difficult-to-treat clinical phenotype of rheumatic irAEs. METHODS: Patients referred to our centre due to the onset of rheumatic irAEs were prospectively recruited between June 2018 and December 2020. A pre-specified panel of autoantibodies was tested in each patient at baseline visit. All patients were started on glucocorticoids and then followed-up. Conventional or biologic immunosuppressants were started in case of steroid-refractory or relapsing disease. Logistic regression analysis was performed to evaluate the association between the baseline positivity of at least one autoantibody and the necessity of an add-on therapy. RESULTS: Fourty-three patients with rheumatic irAEs were enrolled. Twenty-five (58%) patients had positivity of at least one of the tested autoantibodies. Twenty-two (51%) patients required the start of an additional immunosuppressant during follow-up. The only factor associated with the necessity of an add-on therapy was autoantibody positivity (OR=9.65, 95% CI:2.09-44.56; p-value 0.004). CONCLUSIONS: The presence of autoantibodies in patients with cancer who develop rheumatic irAEs could predict their progression to difficult-to-treat clinical manifestations. This finding might prompt a future therapeutic approach based on a tailored and earlier immunosuppressive treatment in selected cases.

Long-Term Clinical Outcome in Systemic Lupus Erythematosus Patients Followed for More Than 20 Years: The Milan Systemic Lupus Erythematosus Consortium (SMiLE) Cohort.

Tackling active disease to prevent damage accrual constitutes a major goal in the management of patients with systemic lupus erythematosus (SLE). Patients with early onset disease or in the early phase of the disease course are at increased risk of developing severe manifestations and subsequent damage accrual, while less is known about the course of the disease in the long term. To address this issue, we performed a multicentre retrospective observational study focused on patients living with SLE for at least 20 years and determined their disease status at 15 and 20 years after onset and at their last clinical evaluation. Disease activity was measured through the British Isles Lupus Assessment Group (BILAG) tool and late flares were defined as worsening in one or more BILAG domains after 20 years of disease. Remission was classified according to attainment of lupus low-disease-activity state (LLDAS) criteria or the Definitions Of Remission In SLE (DORIS) parameters. Damage was quantitated through the Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR-DI). LLAS/DORIS remission prevalence steadily increased over time. In total, 84 patients had a late flare and 88 had late damage accrual. Lack of LLDAS/DORIS remission status at the 20 year timepoint (p = 0.0026 and p = 0.0337, respectively), prednisone dose ≥ 7.5 mg (p = 9.17 × 10-5) or active serology (either dsDNA binding, low complement or both; p = 0.001) were all associated with increased late flare risk. Late flares, in turn, heralded the development of late damage (p = 2.7 × 10-5). These data suggest that patients with longstanding SLE are frequently in remission but still at risk of disease flares and eventual damage accrual, suggesting the need for tailored monitoring and therapeutic approaches aiming at effective immunomodulation besides immunosuppression, at least by means of steroids.

Biobanking for COVID-19 research.

BACKGROUND: Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick as possible to allow for implementation of science-based preventive, diagnostic, prognostic, and therapeutic strategies. METHODS: We established a COVID-19 biobank with the aim of collecting high-quality and well-annotated human biospecimens, in the effort to understand the pathogenic mechanisms underlying COVID-19 and identify therapeutic targets (COVID-BioB, NCT04318366). Here we describe our experience and briefly review the characteristics of the biobanks for COVID-19 that have been so far established. RESULTS: A total of 46,677 samples have been collected from 913 participants (63.3% males, median [IQR] age 62.2 [51.2-74.0] years) since the beginning of the program. Most patients (66.9%) had been admitted to hospital for COVID-19, with a median length of stay of 15.0 (9.0-27.0) days. A minority of patients (13.3% of the total) had been admitted for other reasons and subsequently tested positive for SARS-CoV-2. The remainder were managed at home after being seen at the Emergency Department. CONCLUSIONS: Having a solid research infrastructure already in place, along with flexibility and adaptability to new requirements, allowed for the quick building of a COVID-19 biobank that will help expand and share the knowledge of SARS-CoV-2.