Efficacy and safety of tocilizumab in adult-onset Still's disease: Real-life experience from the international AIDA registry.

BACKGROUND/OBJECTIVES: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. METHODS: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. RESULTS: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). CONCLUSIONS: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.

Update on Malignancy in Myositis-Well-Established Association with Unmet Needs.

Idiopathic inflammatory myopathies are a group of rare connective tissue diseases with a well-documented association with malignancy. The mechanisms underlying the increased risk of neoplasms in the course of myositis are not fully understood. The Pubmed database has been thoroughly screened for articles concerning cancer-associated myositis (CAM). The article summarizes the current state of knowledge on the epidemiology and pathogenesis of CAM. Furthermore, it analyses potential risk and protective factors for developing CAM, with particular emphasis on the association with distinct serological profiles. The review summarizes recommendations proposed so far for the management of CAM and presents a novel scheme for cancer screening proposed by the authors. Moreover, promising areas requiring further research were indicated.

Underdiagnosis of cardiopulmonary involvement in patients with idiopathic inflammatory myopathies.

OBJECTIVES: In the course of idiopathic inflammatory myopathies internal organs, including heart and lungs, can be involved. Cardiopulmonary complications significantly alter the course of the disease, leading to poorer prognosis. A lack of clear guidelines on the assessment of internal organ involvement in the course of myositis increases the risk of underdiagnosis. The aim of the study was to evaluate the incidence of clinical symptoms indicative of cardiovascular and pulmonary involvement in patients with myositis, and the impact of these ailments on daily living. MATERIAL AND METHODS: A self-designed online survey was distributed via online support groups and community forums for patients with idiopathic inflammatory myopathies. The questionnaire contained inquiries about demographical data, clinical symptoms, including symptoms indicative of cardiopulmonary involvement, as well as the standardised Health Assessment Questionnaire. Respondents were divided according to concomitant diseases into a subgroup diagnosed with cardiopulmonary diseases and a subgroup without such comorbidities. The prevalence of cardiopulmonary symptoms was compared between the subgroups. The impact of cardiopulmonary symptoms on the degree of disability and daily functioning was assessed. RESULTS: In total, 370 patients were included in the study group. The most commonly symptoms included dyspnoea during exercise, palpitations and ankle oedema during daily activities. Cardiopulmonary symptoms were frequent in respondents diagnosed with cardiopulmonary diseases and in patients declaring no comorbidities of the heart and lungs. Intensity of chest pain, tolerance of physical activity, and fatigue were comparable in both of the study subgroups. The degree of disability was higher in respondents with concomitant cardiovascular and/or pulmonary comorbidities, but only dry cough and ankle oedema impacted the results. CONCLUSIONS: Clinical symptoms indicative of heart and lung involvement occur frequently in patients with idiopathic inflammatory myopathies; however, cardiopulmonary complications seem to be relatively rarely detected. Active screening for cardiopulmonary involvement is recommended.

The impact of COVID-19 and healthcare system changes on the well-being of rheumatic patients.

OBJECTIVES: The COVID-19 pandemic has significantly impacted the healthcare systems. Many Polish outpatient clinics have been implementing telemedical consultations as a tool to ensure the continuity of care for patients with chronic diseases. The aim of the study was to evaluate patients' satisfaction with telemedical appointments, as well as availability of the various medical services and patients' well-being during the pandemic. MATERIAL AND METHODS: An online-based questionnaire on the experience with telemedical consultations, availability of medical services and current state of health was conducted among Polish rheumatology patients approximately 6 months after the outbreak of the COVID-19 pandemic. RESULTS: The survey was completed by 107 respondents with a mean age of 41.52 ±14.33 years. The overall level of satisfaction from telemedical consultations, evaluated with a VAS 1-10 scale, was assessed as 6.23 ±3.04 for teleconsultations in primary healthcare units and 6.00 ±2.80 for rheumatology outpatient units. 42.99% of the respondents were in favour of maintaining telemedical appointments even after the pandemic. Incidences of reduced access to medical services during the COVID-19 pandemic were reported by 77.57% of the patients. Almost half of the respondents reported reduced accessibility to rheumatological care. An alarming decline in health self-esteem, evaluated with a VAS 1-10 scale, was noted from the average 6.37 ±1.92 before COVID-19 to the current rating of 5.78 ±1.91 (p = 0.0087). CONCLUSIONS: Polish rheumatology patients are moderately satisfied with the medical teleconsultations in primary health care units and rheumatology outpatient clinics. A substantial number of patients experienced deterioration of well-being as well as limited access to traditional healthcare services, including rheumatology care.

Antisynthetase syndrome - much more than just a myopathy.

The aim of the study was to summarize current knowledge on antisynthetase syndrome (ASS), including its epidemiology, pathogenesis, proposed so far diagnostic criteria, heterogeneity of clinical manifestations, prognostic factors and therapeutic possibilities. PubMed database was screened for "antisynthetase syndrome" OR "antisynthetase antibodies" between February and April 2020. Aminoacyl-tRNA synthetases participate in the immune system activation as antigens, but also serve chemoattractive and cytokine-resembling roles, initiating innate and adaptive pathways. Exposure to various inhaled antigens may induce the autoimmune cascade leading to ASS. NK cells with its impaired INF-y production as well as formation of NETs by neutrophils contribute to pathogenesis. The prevalence of symptoms vary significantly depending on the study with muscular, articular and pulmonary involvement being the most frequently observed. Although classified as subtype of idiopathic inflammatory myopathies, myositis may not necessarily be the prominent manifestation. Since clinical presentation is heterogeneous and symptoms can emerge gradually, ASS could be considered as a heterogeneous spectrum rather than a homogenous disease entity. The currently available classification criteria do not fully correspond with the clinical patterns of the disease. Therapy is based on glucocorticosteroids and other immunosuppressive agents. Randomized controlled trials, dedicated for patients with ASS, are needed to form treatment algorithms.

Cardiovascular complications in patients with idiopathic inflammatory myopathies: does heart matter in idiopathic inflammatory myopathies?

This review presents a detailed study of original researches and previously published reviews concerning cardiovascular involvement in idiopathic inflammatory myopathies (IIM). We aimed to summarize the current knowledge on the cardiac involvement in IIM, evaluate its impact on mortality and indicate areas still awaiting to be investigated. We searched MEDLINE database (until January 2019) and the reference lists of articles. Selection criteria included only published data, available in English, both original researches and reviews. Articles related to cardiovascular involvement in IIM were selected and analysed. The references were also screened, and relevant articles were included. Cardiovascular involvement is frequent in IIM but typically remains subclinical. Among far less prevalent symptomatic forms, congestive heart failure is the most common. Myocardium and conduction system seems to be predominantly affected. High rate of left ventricular diastolic dysfunction was observed. Non-specific changes of ST-T segment were the most common abnormalities in electrocardiography. Patients with IIM were more frequently affected by atrial fibrillation as compared with other autoimmune diseases. Increased risk of myocardial infarction was observed; furthermore, patients often develop comorbidities that enhance cardiovascular risk. Since cardiovascular disorders remain one of the major causes of death and subclinical involvement is frequent, active screening is justified. Growing availability of the novel imaging techniques may facilitate diagnosis. Correlation between myocardial involvement and the type of autoantibodies and impact of different therapeutic options on the progression of cardiovascular lesions require further studies.

The attitude of Polish rheumatology patients towards telemedicine in the age of the COVID-19 pandemic.

OBJECTIVES: In response to the outbreak of the SARS-CoV-2 coronavirus pandemic, the Polish government has enabled specialist teleconsultations. Due to this, Polish patients have gained access to continuation of outpatient specialist healthcare using information and communication technologies. The goal of the study was to recognize the needs and expectations as well as the main concerns of Polish rheumatology patients in regard to teleconsultations. MATERIAL AND METHODS: An online-based questionnaire comprising 17 single choice and multiple choice, open-end questions was collected among Polish rheumatology patients directly after the introduction of specialist teleconsultations. RESULTS: 244 respondents completed the survey. Mean age of the respondents was 40.6 ±10.5 and 92.6% of them were female. 48% of the respondents lived not further than 20 kilometres from their outpatient rheumatology clinic. The mean severity of current symptoms, assessed by patients on a visual-analogue scale, was 4.9 ±2.4. 82% of the respondents selected telephone consultations as the most convenient form of receiving rheumatology advice. The patients highlighted the lack of physical examination (43%) and additional tests (43.9%) as the factors discouraging them from teleconsultations; 8.2% of respondents were against maintaining rheumatology teleconsultations after the SARS-CoV-2 pandemic; 3.7% of the respondents received information on teleconsultations from a medical professional. CONCLUSIONS: The community of Polish rheumatology patients is eager to benefit from specialist teleconsultations. Telephone consultations are the most eagerly chosen form of remote consultations. Medical professionals should actively promote this form of patient in order to reach the patients who do not use the computer readily.

Interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) axis in idiopathic inflammatory myopathies and its association with laboratory and clinical parameters: a pilot study.

Idiopathic inflammatory myopathies (IIM) are rare connective tissue diseases, which can lead to internal organ involvement. IL-33/ST2 pathway is involved in the pathogenesis of numerous diseases including autoimmune disorders. IL-33 fulfils cardioprotective function, while soluble ST2 (sST2) is a decoy receptor that reduces protective impact of IL-33. The aim of the study was to evaluate the concentrations of sST2 and IL-33 in sera of patients with IIM and evaluate its associations with the clinical course of the disease. Patients with IIM as well as age- and sex-matched healthy controls were recruited. Concentrations of sST2 and IL-33 were assessed with ELISA in sera of both patients and controls. Patients were asked to fill in the questionnaires concerning clinical symptoms and physical functioning. Concentrations of sST2 and IL-33 were correlated with the results of laboratory tests and clinical symptoms. Concentrations of sST2 were significantly higher in IIM group than in healthy subjects (median sST2 in IIM 26.51 vs in healthy controls 21.39; p = 0.03). In the majority of patients, IL-33 concentrations did not exceed the detection limit. Anti-SRP-positive patients presented significantly higher concentrations of sST2 as compared to anti-SRP-negative patients (p = 0.04). In patients with anti-Ro52 antibodies, sST2 concentrations were significantly lower than in anti-Ro52-negative patients (p = 0.02). Concentrations of sST2 correlated with the degree of disability evaluated with Health Assessment Questionnaire. sST2 is increased in patients with IIM and its concentration correlates with the degree of disability. In patients with anti-SRP antibodies, levels of sST2 are exceptionally high.

Disability in idiopathic inflammatory myopathies: questionnaire-based study.

Idiopathic inflammatory myopathies (IIM) are progressive, debilitating diseases that can lead to severe impairment. The aim of the study was to evaluate the level of disability and compare it between different subtypes of IIM as well as to estimate clinical symptoms associated with greater risk of disability and distinguish the most troublesome activities in this group of patients. A online form concerning clinical symptoms, comorbidities and limitations in daily living was created and distributed to online support groups for patients with IIM. Health Assessment Questionnaire was used to estimate disability and physical limitations while visual analogue scales enabled to assess the intensity of clinical symptoms. 361 out of 377 responders were included for further evaluation. High prevalence of disability was observed in each subtype yet predominantly in patients with inclusion body myositis (IBM) as 51.43% of them fulfilled the criteria of severe to very severe disability. Level of disability correlated with muscle weakness, tolerance of physical activity and level of fatigue. 45.62% of responders in general required walking devices and 43.50% of participants declared using facilitating devices for maintaining hygiene. Patients with IIM encounter multitude physical limitations that can be partially compensated by usage of facilitating devices or aid of the caregivers. IBM seems to be the most disabling subtype.