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The first inhabitants of Australia and the traditional owners of Australian lands are the Aboriginal and Torres Strait Islander peoples. Aboriginal and Torres Strait Islander peoples are two to four times more likely to have systemic lupus erythematosus (SLE) than the general Australian population. Phenotypically, SLE appears distinctive in Aboriginal and Torres Strait Islander peoples and its severity is substantially increased, with mortality rates up to six times higher than in the general Australian population with SLE. In particular, Aboriginal and Torres Strait Islander peoples with SLE have increased prevalence of lupus nephritis and increased rates of progression to end-stage kidney disease. The reasons for the increased prevalence and severity of SLE in this population are unclear, but socioeconomic, environmental, and biological factors are all likely to be implicated, although there are no published studies investigating these factors in Aboriginal and Torres Strait Islander peoples with SLE specifically, indicating an important knowledge gap. In this Review, we summarise the data on the incidence, prevalence, and clinical and biological findings relating to SLE in Aboriginal and Torres Strait Islander peoples and explore potential factors contributing to its increased prevalence and severity in this population. Importantly, we identify health disparities and deficiencies in health-care provision that limit optimal care and outcomes for many Aboriginal and Torres Strait Islander peoples with SLE and highlight potentially addressable goals to improve outcomes.
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BACKGROUND/AIM: The purpose of this review is to provide an overview of the contraindications, special warnings, and boxed warnings with the aim to establish a framework to create a prescription safety checklist for a class of drugs or disease indication. This study covers biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs). METHODS: We identified contraindications, boxed warnings, and special warnings provided by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The study included b/tsDMARDs approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), and juvenile idiopathic arthritis (JIA) within the drug-classes anti-CD20, tumor necrosis factor inhibitors (TNFi), interleukin-1 inhibitors (IL-1i), cytotoxic T-lymphocyte-associated protein (CTLA) 4, interleukin-12/23 inhibitors (IL-12/23i), interleukin 6 receptor inhibitors (IL-6Ri), Janus kinase inhibitors (JAKi), phosphodiesterase 4 inhibitors (PDE4i), interleukin-17 inhibitors (IL-17i), and interleukin-23 inhibitors (IL-23i). RESULTS: All drug classes, except PDE4i, had contraindications and/or warnings related to infections, including tuberculosis. A warning about herpes zoster was listed for anti-CD20, IL-1i, IL-6Ri, and JAKi, while a warning about hepatitis reactivation was listed for anti-CD20, TNFi, IL-1i, CTLA4-Ig, IL-6Ri, and JAKi. Malignancy risk was mentioned for all drug classes except PDE4i, IL-17i, and IL-23i. Other warnings included demyelinating disease (TNFi, CTLA4-Ig, and IL-6Ri), heart failure (anti-CD20 and TNFi), major adverse cardiac events (JAKi and IL-12/23) and venous thromboembolism (JAKi), hyperlipidemia (IL-6Ri and JAKi), liver impairment (TNFi, IL-1i, IL-6Ri, and JAKi), kidney impairment (IL-1i, JAKi, and PDE4i), inflammatory bowel disease (IL-17i), gastrointestinal perforation (IL-6Ri, JAKi), cytopenia (anti-CD20, TNFi, IL-1i, IL-6Ri, JAKi), and depression (PDE4i). Contraindications and warnings appeared to increase with the passage of time since the drug's approval. CONCLUSION: This review provides an overview to establish the framework to create an easily accessible and actionable prescription safety checklist from individual medical product prescription information provided by regulatory medical authorities.
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Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications.
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Inibidores de Checkpoint Imunológico , Polimialgia Reumática , Polimialgia Reumática/induzido quimicamente , Polimialgia Reumática/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversosRESUMO
Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) is an immune-related adverse event that can occur as a result of receiving ICIs for cancer treatment. Thus far, ICI-IA has been described variably in the literature, in part due to varying presentations that evolve over time, as well as a lack of standardized definitions and classification. This scoping review aggregates various descriptions of ICI-IA, highlighting the most prominent attributes of ICI-IA from categories such as symptoms, signs, imaging, and laboratory findings as well as discussing potential mimic conditions.
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Artrite , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Artrite/tratamento farmacológico , Artrite/induzido quimicamente , Neoplasias/tratamento farmacológico , Neoplasias/imunologiaRESUMO
The impact of modern imaging in uncovering the underlying pathology of PMR cannot be understated. Long dismissed as an inflammatory syndrome with links to the large vessel vasculitis giant cell arteritis (GCA), a pathognomonic pattern of musculotendinous inflammation is now attributed to PMR and may be used to confirm its diagnosis. Among the available modalities, 18F-fluorodeoxyglucose (18F-FDG) PET/CT is increasingly recognized for its high sensitivity and specificity, as well as added ability to detect concomitant large vessel GCA and exclude other relevant differentials like infection and malignancy. This atlas provides a contemporary depiction of PMR's pathology and outlines how this knowledge translates into a pattern of findings on whole body 18F-FDG PET/CT that can reliably confirm its diagnosis.
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Janus kinase inhibitors (JAKi) have enormous appeal as immune-modulating therapies across many chronic inflammatory diseases, but recently this promise has been overshadowed by questions regarding associated cardiovascular and cancer risk emerging from the ORAL Surveillance phase 3b/4 post-marketing requirement randomized controlled trial. In that study of patients with rheumatoid arthritis with existing cardiovascular risk, tofacitinib, the first JAKi registered for chronic inflammatory disease, failed to meet non-inferiority thresholds when compared with tumor necrosis factor inhibitors for both incident major adverse cardiovascular events and incident cancer. While this result was unexpected by many, subsequently published observational data have also supported this finding. Notably, however, such a risk has largely not yet been demonstrated in patients outside the specific clinical situation examined in the trial, even in the face of many studies examining this. Nevertheless, this signal has practically re-aligned approaches to both tofacitinib and other JAKi to varying extents, in other patient populations and contexts: within rheumatoid arthritis, but also in psoriatic arthritis, axial spondyloarthritis, inflammatory bowel disease, atopic dermatitis, and beyond. Application to individual patients can be more challenging but remains important to harness the substantive potential of JAKi to the maximum extent safely possible. This review not only explores the evolution of the regulatory response to the signal, its informing data, biological plausibility, and its impact on guidelines, but also the many factors that clinicians must consider in navigating cardiovascular and cancer risk for their patients considering JAKi as immune-modulating therapy.
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Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Doenças Inflamatórias Intestinais , Inibidores de Janus Quinases , Neoplasias , Humanos , Inibidores de Janus Quinases/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Antirreumáticos/efeitos adversos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
Imaging is increasingly being used to guide clinical decision-making in patients with giant cell arteritis (GCA). While ultrasound has been rapidly adopted in fast-track clinics worldwide as an alternative to temporal artery biopsy for the diagnosis of cranial disease, whole-body PET/CT is emerging as a potential gold standard test for establishing large vessel involvement. However, many unanswered questions remain about the optimal approach to imaging in GCA. For example, it is uncertain how best to monitor disease activity, given there is frequent discordance between imaging findings and conventional disease activity measures, and imaging changes typically fail to resolve completely with treatment. This chapter addresses the current body of evidence for the use of imaging modalities in GCA across the spectrum of diagnosis, monitoring disease activity, and long-term surveillance for structural changes of aortic dilatation and aneurysm formation and provides suggestions for future research directions.
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Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Diagnóstico por Imagem , Ultrassonografia , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologiaRESUMO
Objective: Diagnosing septic arthritis can be challenging and frequently involves clinical assessment, laboratory investigations and synovial fluid analysis. We sought to determine the utility of synovial aspiration and intra-operative synovial fluid and tissue culture for the accurate diagnosis of septic arthritis. Methods: We carried out a retrospective review of the records of patients referred to a tertiary orthopaedic unit with possible septic arthritis between 2015 and 2019 inclusive, including clinical and laboratory data for this cohort study. Performance characteristics were determined for synovial aspiration, intra-operative synovial fluid and tissue culture in diagnosing expert review-determined true septic arthritis. Concordance between discharge diagnosis, antibiotic prescribing and true septic arthritis was determined. Results: Of 268 patients identified with suspected septic arthritis, 143 underwent both synovial fluid aspiration and intra-operative synovial fluid and tissue biopsy culture. True septic arthritis was not differentiated significantly by laboratory parameters including serum white cell count (WCC), CRP or synovial WCC. Considering only patients with negative pre-operative synovial aspirate cultures, intra-operative samples led to diagnosis of true septic arthritis in 6 of 63 patients [number needed to treat (NNT) 10.5]. For all patients sampled in theatre, positive synovial tissue biopsy was the only evidence of true septic arthritis in six (NNT 23.9). Despite insufficient microbiological evidence, 27 of the 59 patients who did not have septic arthritis received a discharge diagnosis of septic arthritis, 26 of whom were discharged with antibiotics. Conclusion: Intra-operative sample collection, particularly tissue biopsy, increases the likelihood of a true septic arthritis diagnosis. Such measures might help to reduce diagnostic ambiguity in clinical practice and might therefore reduce overtreatment.
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OBJECTIVES: To determine COVID-19 vaccine hesitancy rates in inflammatory arthritis patients and identify factors associated with changing vaccine hesitancy over time. METHODS: This investigation was a prospective cohort study of inflammatory arthritis patients from community and public hospital outpatient rheumatology clinics enrolled in the Australian Rheumatology Association Database (ARAD). Two surveys were conducted, one immediately prior to (pre-pandemic) and another approximately 1 year after the start of the pandemic (follow-up). Coronavirus disease 2019 (COVID-19) vaccine hesitancy was measured at follow-up, and general vaccine hesitancy was inferred pre-pandemic; these were used to identify factors associated with fixed and changing vaccine beliefs, including sources of information and broader beliefs about medication. RESULTS: Of the 594 participants who completed both surveys, 74 (12%) were COVID-19 vaccine hesitant. This was associated with pre-pandemic beliefs about medications being harmful (P < 0.001) and overused (P = 0.002), with stronger beliefs resulting in vaccine hesitancy persistent over two time points (P = 0.008, P = 0.005). For those not vaccine hesitant pre-pandemic, the development of COVID-19 vaccine hesitancy was associated with a lower likelihood of seeking out vaccine information from health-care professionals (P < 0.001). COVID-19 vaccine hesitancy was not associated with new influenza vaccine hesitancy (P = 0.138). CONCLUSION: In this study of vaccine beliefs before and during the COVID-19 pandemic, factors associated with COVID-19 vaccine hesitancy in inflammatory arthritis patients varied, depending on vaccine attitudes immediately prior to the start of the pandemic. Fixed beliefs reflected broader views about medications, while fluid beliefs were highly influenced by whether they sought out information from health-care professionals, including rheumatologists.
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Artrite , COVID-19 , Humanos , Vacinas contra COVID-19/uso terapêutico , Pandemias , Estudos Prospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Austrália/epidemiologia , Artrite/tratamento farmacológico , VacinaçãoRESUMO
OBJECTIVE: The use of colchicine has been associated with varying degrees of myelosuppression. Despite expanded use in cardiovascular and inflammatory conditions, there remains clinician concern because of potential myelosuppressive side effects. A systematic review was conducted to explore the reported myelosuppressive events of colchicine. METHODS: A systematic review was conducted using the MeSH terms ("colchicine") AND ("myelosuppression," "bone*," "marrow," "suppression," "aplasia," "leukopenia/leucopenia," "lymphopenia," "neutropenia") on September 1, 2020, and was updated on November 30, 2021. The search was conducted in PubMed, ScienceDirect, Scopus, Embase, and Cochrane Library. The search included references published from 1978 to 2020 and was limited to English-language observational studies (ie, case reports, case series, case control studies, and cohort studies) or trial data. RESULTS: In total, 3233 articles were screened, with 30 studies of 47 patients with myelosuppression from colchicine identified. Most patients with myelosuppression had comorbidities, including renal impairment (21/47, 44.7%). Out of 47 patients, 15 (31.9%) and 13 (27.7%) were reported to be concurrently taking cytochrome P450 3A4 (CYP3A4) inhibitors and P-glycoprotein (P-gp) efflux transporter inhibitors, respectively. Patients with renal impairment accounted for the majority of overall patients taking these CYP3A4 and P-gp inhibitors (8/15, 53.3%, and 8/13, 61.5%, respectively). Out of 21 patients with renal impairment, 13 had worsening cytopenia during colchicine use. The presentations ranged from moderate anemia (grade 2) to severe thrombocytopenia, neutropenia, and leukopenia (grade 4). CONCLUSION: Colchicine has few reports of myelosuppression. The majority of patients with myelosuppression had preexisting renal impairment or concomitant CYP3A4 or P-gp inhibitor use. Caution should be taken in this subset of patients with increased monitoring.
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Doenças da Medula Óssea , Neutropenia , Humanos , Colchicina , Citocromo P-450 CYP3A , Comorbidade , Neutropenia/induzido quimicamenteRESUMO
The detection of adverse drug reactions (ADRs) is critical to our understanding of the safety and risk-benefit profile of medications. With an incidence that has not changed over the last 30 years, ADRs are a significant source of patient morbidity, responsible for 5%-10% of acute care hospital admissions worldwide. Spontaneous reporting of ADRs has long been the standard method of reporting, however this approach is known to have high rates of under-reporting, a problem that limits pharmacovigilance efforts. Automated ADR reporting presents an alternative pathway to increase reporting rates, although this may be limited by over-reporting of other drug-related adverse events. We developed a deep learning natural language processing algorithm to identify ADRs in discharge summaries at a single academic hospital centre. Our model was developed in two stages: first, a pre-trained model (DeBERTa) was further pre-trained on 1.1 million unlabelled clinical documents; secondly, this model was fine-tuned to detect ADR mentions in a corpus of 861 annotated discharge summaries. This model was compared to a version without the pre-training step, and a previously published RoBERTa model pretrained on MIMIC III, which has demonstrated strong performance on other pharmacovigilance tasks. To ensure that our algorithm could differentiate ADRs from other drug-related adverse events, the annotated corpus was enriched for both validated ADR reports and confounding drug-related adverse events using. The final model demonstrated good performance with a ROC-AUC of 0.955 (95% CI 0.933 - 0.978) for the task of identifying discharge summaries containing ADR mentions, significantly outperforming the two comparator models.
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Aprendizado Profundo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Processamento de Linguagem Natural , Sistemas de Notificação de Reações Adversas a Medicamentos , Algoritmos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , FarmacovigilânciaRESUMO
OBJECTIVES: There is scant research about laboratory monitoring in people taking conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for rheumatic disease. Our objective was to conduct a scoping study to assess the range of current attitudes and the variation in practice of laboratory monitoring of csDMARDs by rheumatologists and trainees. METHODS: Australian and overseas rheumatologists or trainees were invited through newsletter, Twitter and personal e-mail, to complete an anonymous online survey between 1 February and 22 March 2021. Questions focused on laboratory tests requested by csDMARD prescribed, frequency/pattern of monitoring, influence of additional factors and combination therapy, actions in response to abnormal tests, and attitudes to monitoring frequencies. Results were presented descriptively and analysed using linear and logistic regression. RESULTS: There were 221 valid responses. Most respondents were from Australia (n = 53, 35%) followed by the US (n = 39, 26%), with a slight preponderance of women (n = 84, 56%), ≥ 11 years in rheumatology practice (n = 83, 56%) and in mostly public practice (n = 79, 53%). Respondents had a wide variation in the frequency and scheduling of tests. In general, respondents reported increasing monitoring frequency if patients had numerous comorbidities or if both methotrexate and leflunomide were being taken concurrently. There was a wide variety of responses to abnormal monitoring results and 27 (40%) considered that in general, monitoring tests are performed too frequently. CONCLUSIONS: The results demonstrated a wide variation in the frequency of testing, factors that should influence this, and what responses to abnormal test results are appropriate, indicates a likely lack of evidence and the need to define the risks, benefits and costs of different csDMARD monitoring regimens.
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Deep learning has emerged as the leading method in machine learning, spawning a rapidly growing field of academic research and commercial applications across medicine. Deep learning could have particular relevance to rheumatology if correctly utilized. The greatest benefits of deep learning methods are seen with unstructured data frequently found in rheumatology, such as images and text, where traditional machine learning methods have struggled to unlock the trove of information held within these data formats. The basis for this success comes from the ability of deep learning to learn the structure of the underlying data. It is no surprise that the first areas of medicine that have started to experience impact from deep learning heavily rely on interpreting visual data, such as triaging radiology workflows and computer-assisted colonoscopy. Applications in rheumatology are beginning to emerge, with recent successes in areas as diverse as detecting joint erosions on plain radiography, predicting future rheumatoid arthritis disease activity, and identifying halo sign on temporal artery ultrasound. Given the important role deep learning methods are likely to play in the future of rheumatology, it is imperative that rheumatologists understand the methods and assumptions that underlie the deep learning algorithms in widespread use today, their limitations and the landscape of deep learning research that will inform algorithm development, and clinical decision support tools of the future. The best applications of deep learning in rheumatology must be informed by the clinical experience of rheumatologists, so that algorithms can be developed to tackle the most relevant clinical problems.