Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered

Editorial: Chronic autoimmune arthritis, infections and vaccines

The link between autoimmunity and infection continues to represent an intriguing immunologic conundrum for scientist and a frequent clinical challenge for patients and physicians. Patients with chronic autoimmune arthritis indeed have an increased risk of infections, mainly due to the dysregulation of their immune system and the use of immunosuppressive therapy. Infections in these patients are more frequent, have a more severe clinical course, eventually with prolonged viral persistence, compared to the general population and represent a frequent cause of death. Besides, infections can trigger autoimmune diseases via different immunologic mechanisms such as molecular mimicry, epitope spreading, by-stander activation and can also induce disease relapses. SARS-CoV-2 infection represents a dramatic example of this complex connection. It is known, indeed, that different autoimmune manifestations can complicate SARS-CoV-2 infection such as uncontrolled host-immune response leading to life-threatening condition known as cytokine release syndrome, or autoimmune hemolytic anemia, immune thrombocytopenic purpura, Guillain-Barre syndrome, and the detection of different autoantibodies. This Research Topic includes seventeen contributions, fifteen original articles and two review articles, providing several new insights into the efficacy and safety of SARS-CoV-2 vaccine in autoimmune patients, immunologic biomarkers for diagnosis and therapeutic outcome of autoimmune arthritis

Review Article Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered

Analysis of gut microbiota in rheumatoid arthritis patients. Disease-related dysbiosis and modifications induced by etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota

Immunogenicity of viral vaccines in the italian military

Military personnel of all armed forces receive multiple vaccinations and have been doing so since long ago, but relatively few studies have investigated the possible negative or positive interference of simultaneous vaccinations. As a contribution to fill this gap, we analyzed the response to the live trivalent measles/mumps/rubella (MMR), the inactivated hepatitis A virus (HAV), the inactivated trivalent polio, and the trivalent subunits influenza vaccines in two cohorts of Italian military personnel. The first cohort was represented by 108 students from military schools and the second by 72 soldiers engaged in a nine-month mission abroad. MMR and HAV vaccines had never been administered before, whereas inactivated polio was administered to adults primed at infancy with a live trivalent oral polio vaccine. Accordingly, nearly all subjects had baseline antibodies to polio types 1 and 3, but unexpectedly, anti-measles/-mumps/-rubella antibodies were present in 82%, 82%, and 73.5% of subjects, respectively (43% for all of the antigens). Finally, anti-HAV antibodies were detectable in 14% and anti-influenza (H1/H3/B) in 18% of the study population. At mine months post-vaccination, 92% of subjects had protective antibody levels for all MMR antigens, 96% for HAV, 69% for the three influenza antigens, and 100% for polio types 1 and 3. An inverse relationship between baseline and post-vaccination antibody levels was noticed with all the vaccines. An excellent vaccine immunogenicity, a calculated long antibody persistence, and apparent lack of vaccine interference were observed

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Profile of patients with rheumatic diseases undergoing treatment with anti-TNF agents in the Brazilian Public Health System (SUS), Belo Horizonte - MG

The aim of this study was to describe the baseline demographic and clinical characteristics as well as the functional status of a prospective cohort of patients with rheumatic diseases assisted by the Brazilian Public Health System (SUS). Data for 302 patients receiving tumor necrosis factor α inhibitors (anti-TNF agents) was collected through a standard form. Among patients, 229 (75.8%) were female and 155 (51.3%) were Caucasian; the mean age was 50.3 ± 12.8 years, and the mean disease duration was 9.9 ± 8.7 years. Among them 214 patients (70.9%) received adalimumab, 72 (23.8%) etanercept, and 16 (5.3%) infliximab. Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) was 1.37 ± 0.67 for all participants. Poor functional response was associated with female gender, married patients and with a score of < 0.6 on the EuroQoL-5 dimensions (EQ-5D). Significant correlation was found between the HAQ-DI values, disease activity and quality of life (QOL). The results obtained in this study contribute to a better understanding of the clinical and demographic characteristics of patients with rheumatic diseases at the beginning of anti-TNF-agent treatment by SUS. Furthermore, our findings are consistent with another Brazilian and foreign cross-sectional investigations. This knowledge can be of great importance for further studies evaluating the effectiveness of biological agents, as well as, to contribute to improve the well-being of the patients with rheumatic diseases