Systemic lupus erythematosus in Aboriginal and Torres Strait Islander peoples in Australia: addressing disparities and barriers to optimising patient care.

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.

A Systematic Overview of Contraindications and Special Warnings for Biologic and Targeted Synthetic Disease Modifying Antirheumatic Drugs: Establishing a Framework to Create a "Safety Checklist".

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.

Immune Checkpoint Inhibitor-induced Polymyalgia Rheumatica.

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.

The Need for Classification Criteria of Immune Checkpoint Inhibitor-induced inflammatory Arthritis: A Scoping Review.

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.

Characterising polymyalgia rheumatica on whole-body 18F-FDG PET/CT: an atlas.

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.

Impact of the COVID-19 Pandemic on Health Care Access and Diagnosis of Pulmonary Arterial Hypertension Among Patients With Systemic Sclerosis.

OBJECTIVE: Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH. METHODS: South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc. Frequency of annual rheumatology assessments, pulmonary function tests (PFT), and transthoracic echocardiography (TTE) to screen for PAH were compared with rates from before the pandemic. RESULTS: A total of 312 of 810 patients with SSc responded (38.5% response); 273 were female (87.5%), the median age was 64.7 years, 77.2% had limited disease, the median illness duration was 15.6 years, 15.7% were immunosuppressed, 32.1% had interstitial lung disease, and 6.4% had PAH. A total of 65.7% of consultations were by telehealth, of which 81.2% were by telephone. Compared with respondents in South Australia (n = 109), Victorian respondents (n = 203) experiencing prolonged lockdown, reported reduced access to their rheumatologist (49.3% vs 27.9%; P = 0.004), greater use of consultation by video (17.3% vs 2.1%; P = 0.008), greater health care disruption (49.0% vs 23.2%; P < 0.001), and worse mental health (P = 0.002). Respondents reported reduced access to PFT and TTE (31.7% and 22.5%, respectively). Annual visits, PFT, TTE, and new diagnoses of PAH were reduced in 2020 to 2022 compared with 2011 to 2019. CONCLUSION: The COVID-19 pandemic-related disruption to health care for patients with SSc was associated with worse mental health and reduced screening and diagnosis of PAH, which may impact long-term outcomes.

Medicines stewardship.

Medicines stewardship refers to coordinated strategies and interventions to optimise medicines use, usually within a specific therapeutic area. Medicines stewardship programs can reduce variations in practice and improve patient outcomes. Therapeutic domains for medicines stewardship are chosen to address frequently used drug classes associated with a high risk of adverse outcomes. Some examples include antimicrobial, opioid analgesic, anticoagulation and psychotropic stewardship. Common elements of successful stewardship programs include multidisciplinary leadership, stakeholder engagement, tailored communication strategies, behavioural changes, implementation science methodologies, and ongoing program monitoring, evaluation and reporting. Medicines stewardship is a continual quality improvement process that requires ongoing support and resources, as well as clinician and consumer engagement, to remain sustainable. It is critical for hospital-based medicines stewardship programs to consider impacts on care in the community when making and communicating changes to patient therapy. This ensures that stewardship efforts are sustained across transitions of care.

JAK inhibitors and black box warnings: what is the future for JAK inhibitors?

INTRODUCTION: Janus kinase inhibitors (JAKi) have dramatically improved the treatment of various autoimmune and myeloproliferative disorders. Recently, concern has arisen regarding their safety in patients with rheumatoid arthritis. AREAS COVERED: Here, we provide a comprehensive summary of the major current and emerging JAKi and their indications, address recent studies on comparative safety, and provide insight into their future and use. We emphasize that the application of the research findings on a case-by-case basis should consider a patient's age, comorbidities, disease for which JAKi is being considered, disease activity, the JAKi target(s), alternate treatment options available for the patient, and the planned duration of JAKi. EXPERT OPINION: Rheumatologists are used to prescribing therapies in which a risk-to-benefit assessment is required as well as to screening and monitoring the safety of medications. Thus, rheumatologists are already practiced in applying specific criteria to effectively screen and monitor patients who are candidates for JAKi therapy. Ongoing research will help to clarify any mechanisms underlying differential safety signals between JAK and other therapies, what the balance between risk and efficacy is, who the susceptible subpopulations are, and whether safety signals are shared between different JAKis and across indications.

Managing Cardiovascular and Cancer Risk Associated with JAK Inhibitors.

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.

Imaging of giant cell arteritis - recent advances.

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.

Diagnosis of septic arthritis in the acute care setting: the value of routine intra-operative sample culture.

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.

Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution.

OBJECTIVE: To identify reports of colchicine-induced neuropathy and myopathy and ascertain risk factors associated with this toxicity at commonly used doses. METHODS: A systematic review of case reports was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA methodology). PubMed and EMBASE were searched through October 2021 for case reports of neuropathy and/or myopathy associated with the use of colchicine at therapeutic doses. RESULTS: A total of 143 cases of neuromyopathy from 99 articles were identified as having a "definite" or "probable" association with colchicine usage, as assessed by the Naranjo algorithm. Most of these cases presented with features of both neuropathy and myopathy (n=72, 51%) but symptoms of myopathy were predominant. The mean total daily dose was 1.25±0.60 mg and 48% had been taking colchicine for more than 12 months before presenting with neuromyopathy. A total of 117 (82%) of all reports had either a significant co-morbidity or possible colchicine drug-drug interaction, while 57 (40%) had both risk factors. A total of 26 cases (18%) had no significant risk factor but only 15 of these reports contained complete descriptions of the patient's co-morbidities and co-medications. Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days. There were 3 deaths reported which were due to multi-organ failure despite cessation of colchicine and medical management. Colchicine was restarted at reduced doses in 15 cases and 73% had no symptom recurrence. CONCLUSION: Neuromyopathy is an uncommon but reported adverse effect of colchicine. Cases generally present with proximal myopathy symptoms. Cases of colchicine neuromyopathy are largely reported in patients on commonly used doses. Renal and hepatic dysfunction and medications that inhibit cytochrome P450 3A4 isozyme (CYP3A4) and P-glycoprotein (P-gp) appear to be the most significant risk factors. Fortunately, cessation of colchicine generally leads to complete resolution of symptoms. Recommencement of colchicine at reduced doses appeared to be usually safe.

Developing a deep learning natural language processing algorithm for automated reporting of adverse drug reactions.

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.

COVID-19 vaccine hesitancy in inflammatory arthritis patients: serial surveys from a large longitudinal national Australian cohort.

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.

Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group.

INTRODUCTION: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains. METHODS: As the initial step of the core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter. RESULTS: We identified 69 publications, over a third of which utilized non-specific diagnoses of "arthritis," "arthralgia," and/or "PMR". Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 subsequent response, as well as 32 tumor response. CONCLUSION: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. There were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use.