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Seminars in Arthritis and Rheumatism Aug 2022Glucocorticoids (GCs) have been the cornerstone of treating dozens of inflammatory conditions for more than seven decades. GC toxicity is ubiquitous in both clinical... (Review)
Review
Glucocorticoids (GCs) have been the cornerstone of treating dozens of inflammatory conditions for more than seven decades. GC toxicity is ubiquitous in both clinical trials and clinical practice, and toxicities associated with GC use are central to the experience of most patients being treated for immune-mediated conditions. These conditions span the full range of medical specialties, including rheumatology, nephrology, gastroenterology, neurology, pulmonology, ophthalmology, and others. One of the goals of novel therapies for inflammatory disease must be to diminish the effects of GC toxicity in clinically important ways, thereby differentiating these new treatments from existing approaches. Despite the importance of glucocorticoids in the treatment of inflammatory disease for more than 70 years, no reliable means of calculating the degree to which GC toxicity has worsened or improved over the course of treatment has been available. The Glucocorticoid Toxicity Index (GTI), developed by an international group of subspecialty physician experts as a clinician-facing clinical trials outcome measure, is a standardized, validated measure of the phenomenon known as GC toxicity. The purpose of the instrument is to measure change in GC toxicity between two points in time: for example, between the baseline visit and the time of the primary efficacy outcome assessment. The instrument is designed to quantify both worsening and improvement in GC toxicity. The GTI has been validated in both real-world experiences and clinical trials, including a phase 3, label-enabling trial in ANCA associated vasculitis. This article reviews the history and rationale for the development of the GTI, describes key data from validation studies, considers the minimum clinically important difference, and provides instructions for use of the instrument.
Topics: Glucocorticoids; Humans; Neurology; Outcome Assessment, Health Care; Rheumatology
PubMed: 35486995
DOI: 10.1016/j.semarthrit.2022.152010 -
EClinicalMedicine Feb 2023There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this...
BACKGROUND
There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants.
METHODS
This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models.
FINDINGS
Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet's disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24).
INTERPRETATION
COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms.
FUNDING
Kaohsiung Veterans General Hospital (KSVGH111-113).
PubMed: 36643619
DOI: 10.1016/j.eclinm.2022.101783 -
Annals of the Rheumatic Diseases Jan 2024To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
OBJECTIVES
To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
METHODS
A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously.
RESULTS
Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment.
CONCLUSION
These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Quality of Life; Comorbidity
PubMed: 36828585
DOI: 10.1136/ard-2022-223429 -
Journal For Immunotherapy of Cancer Jun 2023Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune...
BACKGROUND
Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.
METHODS
We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.
RESULTS
We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04).
CONCLUSION
Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).
Topics: Female; Humans; Male; Middle Aged; Adrenal Cortex Hormones; Antirheumatic Agents; Lung Neoplasms; Melanoma; Retrospective Studies; Receptors, Interleukin-6
PubMed: 37328287
DOI: 10.1136/jitc-2023-006814 -
Experimental and Therapeutic Medicine Dec 2023Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness,...
Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, and novelties since the development of the currently used 2012 European League Against Rheumatism and American College of Rheumatology provisional classification criteria. PMR is a prevalent disease that can occasionally prove difficult to diagnose and treat. Possibly, the most abundant type of evidence and data revealed over the past decade have been acquired through musculoskeletal imaging, with implications in diagnosis, disease monitoring and relapse, prognosis and changes with treatment. Further research on pathophysiology is required to gain a deeper understanding of the underlying processes, which will serve as the foundation for future personalized treatments. In addition, there is an increasing demand for improved diagnostic techniques, which should include a further development of various imaging modalities, in order to provide accurate diagnosis and appropriate therapy.
PubMed: 37928511
DOI: 10.3892/etm.2023.12242 -
Reumatologia 2023
PubMed: 36998582
DOI: 10.5114/reum.2023.124336 -
Clinical and Experimental Rheumatology Apr 2023
Topics: Humans; Polymyalgia Rheumatica; Giant Cell Arteritis; Fluorodeoxyglucose F18
PubMed: 36995322
DOI: 10.55563/clinexprheumatol/3bozph -
Ugeskrift For Laeger Feb 2023
Topics: Humans; Polymyalgia Rheumatica; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Giant Cell Arteritis; Positron-Emission Tomography
PubMed: 36762378
DOI: No ID Found -
Human Vaccines & Immunotherapeutics Dec 2024We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile...
We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.
Topics: Adult; Humans; Middle Aged; Giant Cell Arteritis; Polymyalgia Rheumatica; COVID-19 Vaccines; Ad26COVS1; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; Vaccination
PubMed: 38563792
DOI: 10.1080/21645515.2024.2334084