Real-world utilisation and switching between Janus kinase inhibitors in Australian patients with rheumatoid arthritis in the OPAL dataset.

OBJECTIVES: To describe use and treatment persistence for Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) by line of therapy, and the mechanism of action for the drug switched to after JAKi discontinuation. METHODS: This was a retrospective, observational analysis using the OPAL dataset, a large collection of deidentified electronic medical records from 112 rheumatologists around Australia. Adult patients with RA were included if they initiated tofacitinib (TOF), baricitinib (BARI) or upadacitinib (UPA) between 1 October 2015 and 30 September 2021. Data were summarised using descriptive statistics. Kaplan-Meier survival was used to analyse treatment persistence. RESULTS: 5,900 patients initiated JAKi within the study window (TOF n=3,662, BARI n=1,875, UPA n=1,814). Median persistence was similar across JAKi within each line of therapy where there was sufficient follow-up, and almost 3 years for first-line: 34.9 months (95% CI 30.8, 40.7; n=1,408) for TOF, 33.6 months (95% CI 25.7, not reached; n=545) for BARI. While JAKi to JAKi switching occurred across all lines of therapy, switches to a tumour necrosis factor inhibitor (TNFi) were more frequent after first- or second-line JAKi. JAKi monotherapy use at baseline increased with line of therapy, and was highest at follow-up after switching to another JAKi. 'Lack of efficacy' was the most common reason for discontinuing JAKi. CONCLUSIONS: In this large analysis of Australian real-world practice separated by line of therapy, treatment persistence for JAKi was high overall subject to differential follow-up, but declined in later lines. JAKi to JAKi switching was observed across all lines of therapy.

Comparative effectiveness of etanercept originator and biosimilar for treating rheumatoid arthritis: implications for cost-savings.

BACKGROUND AND AIMS: This study aimed to assess the comparative effectiveness of the etanercept (ETN) originator (Enbrel) and ETN biosimilar SB4 (Brenzys) as first-line treatment in patients with rheumatoid arthritis (RA), while also exploring the potential cost-savings associated with this approach in Australia. METHODS: Clinical data were obtained from the Optimising Patient outcomes in rheumatoLogy Australian real-world data set. Adult patients with RA who had initiated treatment with the ETN originator or biosimilar as their first-recorded biologic or targeted synthetic disease-modifying antirheumatic drug between 1 April 2017 and 31 December 2020 were included. Treatment persistence was analysed using survival analysis. Cost-savings were estimated based on data reported by the Australian National Prescribing Service MedicineWise. RESULTS: Propensity score matching followed by inverse probability of treatment weighting selected patients taking originator (n = 209) or biosimilar (n = 141) with similar baseline characteristics and eliminated small differences in baseline disease activity. The median time for 50% of the patients to stop treatment was 19.4 months (95% confidence interval [CI], 14.7-36.4 months) for the originator and 22.4 months (95% CI, 15.0-33.1 months) for the biosimilar (P = 0.95). As a result of pricing policies established by the Australian Government, introduction of the ETN biosimilar would have resulted in a cost-savings of over AU$9.5 million for 1 year of treatment for the patients reported in this study. CONCLUSION: Treatment persistence using either ETN originator or biosimilar was similar. The cost of all brands of ETN markedly reduced upon listing of the ETN biosimilar, resulting in significant savings for the Australian Government.

Using big data from real-world Australian rheumatology encounters to enhance clinical care and research.

OBJECTIVES: OPAL (Optimising Patient outcomes in Australian rheumatoLogy) Rheumatology is an independent not for profit Australian clinical research organisation which is the custodian of one of the largest datasets of patients with rheumatic diseases in the world, containing real-world clinical data from more than >175,000 unique patients collected over more than 900,000 clinical consultations. We describe the evolution and outcomes of the OPAL dataset, with particular reference to the use of big data derived from real-world clinical encounters to enhance clinical care and research. METHODS: De-identified data are regularly extracted and aggregated from the electronic medical records (EMR) of consenting patients treated by approximately 100 rheumatologists around Australia. The EMR shared by OPAL clinicians was specifically customised for rheumatology and collects comprehensive information on demographics, disease history, activity and severity, co-morbidities, pathology, and medication use. In addition, OPAL captures multifaceted outcomes data from the patient perspective through a novel electronic patient-reported outcome (ePRO) delivery system which allows for health-related quality of life measures to be matched with clinical indices. RESULTS: Since inception in 2009, OPAL has produced 35 publications and abstracts. OPAL also provides real-world data to determine drug utilisation, efficacy and safety, elucidate the natural history of disease, highlight areas of unmet need, guide medical affairs and commercial strategy, and to support regulatory and reimbursement submissions. CONCLUSIONS: The extensive, evolving and organic OPAL dataset reflects the complexities of clinical rheumatological practice. It provides unique opportunities to enhance clinical care and research.

Stress modulates key psychological processes and characteristic symptoms in females with fibromyalgia.

OBJECTIVES: To examine how stress interacts with psychological processes and key phenotypic symptom characteristics in females with fibromyalgia. METHODS: Ninety-eight women with fibromyalgia, diagnosed according to ACR 1990 criteria, and 35 female healthy controls without pain were studied. Applied questionnaires included the following: Perceived Stress scale [PSS], Fibromyalgia Impact Questionnaire [FIQ], Perceived Control of Internal States (PCOIS), Mastery scale and the Profile of Mood States scale (POMS). RESULTS: Perceived stress correlated significantly with the characteristic features of fibromyalgia including pain (p<0.05) and sleep change, fatigue and cognitive dysfunction (all p<0.001). Perceived stress correlated inversely with measures of control and positively with mood and neuroticism (all p<0.001). When controlling for stress, most of these variables were no longer significant, suggesting that stress impacts on the majority of variables associated with FM. CONCLUSIONS: Stress in females with fibromyalgia associates with both key symptoms and a range of relevant psychological variables. Stress appears to have a major role in modulating several key 'up-stream' processes in fibromyalgia.

Historical bioarcheological aspects of diffuse idiopathic skeletal hyperostosis in humans.

OBJECTIVE: To identify diffuse idiopathic skeletal hyperostosis (DISH) in the human bioarcheological record to seek out temporal, geographic and dietary information to enhance better understanding of this common condition. MATERIALS AND METHODS: A review of available literature was conducted. RESULTS: DISH has been identified in hominin populations over millions of years, including several different human species. The distribution of DISH in ancient populations is diverse, both temporally and geographically. Where available, dietary intake of subjects with DISH, in contrast to those without DISH, suggests that metabolic factors associate with DISH. CONCLUSION: DISH is a ubiquitous human disorder over the ages. Metabolic factors appear important in ancient populations of those with DISH.

The Relation of Physical Comorbidity and Multimorbidity to Fibromyalgia, Widespread Pain, and Fibromyalgia-related Variables.

OBJECTIVE: To investigate the relation of physical (non-psychological) comorbidity and multimorbidity to quantitative measures of fibromyalgia (FM) and musculoskeletal pain. METHODS: We studied 12,215 patients in a research databank with quantitative measures of FM-related variables (FMV) that included binary determinations of FM and widespread pain (WSP), and constituent variables of FM diagnosis that included the WSP index (WPI), the symptom severity score (SSS), and the polysymptomatic distress scale (PSD). We assessed self-reported comorbid conditions and covariates that included age, sex, body mass index, hypertension, smoking history, and total household income. We used nearest-neighbor matching and regression adjustment treatment effects models to measure the effect of comorbidities on FMV. RESULTS: We found a positive association between FMV and the probability of having each comorbid condition. Patients with ≥ 1 comorbidities had PSD, WPI, and SSS increases of 3.0 (95% CI 2.7-3.3), 1.8 (95% CI 1.6-2.0), and 1.2 (95% CI 1.1-1.3) units, respectively, and an increase in FM prevalence from 20.4% to 32.6%. As the number of comorbid conditions present increased from 1 to 4 or more, PSD, WPI, SSS, and FM percent increased stepwise. For patients with ≥ 4 conditions, the predicted prevalence of FM was 55.2%. CONCLUSION: FM and FMV are associated with an increase in the number of comorbidities, and the association can be measured quantitatively. However, the association of WSP and FM may be an effect of definitions of WSP and FM, because comorbidity increases are also present with subsyndromal levels of both conditions.

All-cause and cause-specific mortality in persons with fibromyalgia and widespread pain: An observational study in 35,248 persons with rheumatoid arthritis, non-inflammatory rheumatic disorders and clinical fibromyalgia.

PURPOSE: Studies of the relation of fibromyalgia (FM) and widespread pain (WSP) to mortality have differed as to the presence or absence of an association and the extent of cause-specific mortality. However, no studies have investigated which definitions of FM and WSP associate with mortality, nor of FM mortality in other diseases. We investigated these issues and the meaning of mortality in patients with FM. METHODS: We used Cox regression to study 35,248 rheumatic disease patients with up to 16 years of mortality follow-up in all patients and separately in those with diagnoses of rheumatoid arthritis (RA) (N = 26,458), non-inflammatory rheumatic disorders (NIRMD) (N = 5,167) and clinically diagnosed FM (N = 3,659). We applied 2016 FM criteria and other FM and WSP criteria to models adjusted for age and sex as well as to models that included a full range of covariates, including comorbid disease and functional status. We estimated the degree of explained of variance (R2) as a measure of predictive ability. RESULTS: We found positive associations between al`l definitions of FM and WSP and all-cause mortality, with relative risks (RR)s ranging from 1.19 (95%CI 1.15-1.24) for American College of Rheumatology (ACR) 1990 WSP to 1.38 (1.31-1.46) in age and sex adjusted revised 2016 criteria (FM 2016). However, in full covariate models the FM 2016 RR reduced further to 1.15 (1.09-1.22). The association with mortality was noted with RA (1.52 (1.43-1.61)), NIRMD (1.43 (1.24-1.66)) and clinical FM (1.41 (1.14-1.75) - where 37% of FM diagnosed patients did not satisfy FM 2016 criteria. In the all-patient analyses, the age and sex explained variation (R2) was 0.255, increasing to 0.264 (4.4%) when FM 2016 criteria were added, and to 0.378 in a full covariate model. Death causes related to FM 2016 status included accidents, 1.45 (1.11-1.91); diabetes 1.78 (1.16-2,71); suicide, 3.01 (1.55-5.84) and hypertensive related disorders, 3.01 (1.55-5.84). Cancer deaths were less common 0.77 (0.68-0.88). CONCLUSIONS: FM is weakly associated with mortality within all criteria definitions of FM and WSP examined (3.4% of explained variance), and across all diseases (RA, NIRMD, clinical FM) equally. Clinical and criteria-defined FM had different mortality outcomes. We found no evidence for a positive association of cancer and FM or WSP.

Fibromyalgia remains a significant burden in rheumatoid arthritis patients in Australia.

AIM: High rates of fibromyalgia (FM) are reported in rheumatoid arthritis (RA) patients. Advances in RA management have occurred, but information regarding current significance of FM in RA is limited. This investigation estimated the prevalence and health effects of concomitant FM in Australian RA patients. METHODS: Participants were recruited from Australian rheumatology clinics. Subjects were assessed using the 1990 and 2011 American College of Rheumatology (ACR) FM criteria and the polysymptomatic distress score (PDS) was calculated. A medical history and a clinical examination were recorded. RA Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS-28 ESR), and the Short Form-36 survey (SF-36) were completed. RESULTS: Of 117 RA patients, 33.3% (n = 39) met 1990 ACR FM criteria and 41.9% (n = 49) met 2011 ACR FM criteria. RA patients with comorbid FM had worse outcomes across all domains of health as defined by the SF-36 (P < 0.05). There was correlation between both physical and mental health outcomes and the PDS (P < 0.001). RA patients with FM on average took 1.18 extra ongoing prescribed medications (P < 0.05), despite comparable RA disease activity (DAS-28: 3.09 vs. 3.27, P = NS). Comorbid central sensitivity conditions were more common in patients with FM (P < 0.001). CONCLUSION: FM continues to demonstrate a high prevalence in a population of RA patients. RA patients with FM have more symptoms of other chronic sensitivity syndromes in addition to FM. They have a lower quality of life outcome and higher medication use. This has important clinical implications in terms of diagnosis, response to therapy, prescribing choices and clinical outcomes.

Measuring quality of life in rheumatic conditions.

Musculoskeletal disorders often have associated pain, functional impairment and work disability, and, not surprisingly, are the most common reasons for utilizing healthcare resources. Rheumatoid arthritis (RA) and fibromyalgia (FM) are causes of musculoskeletal pain and disability. Research indicates that there is a widespread impact of RA and FM on physical, psychological and social factors in affected individuals, and thus, outcome measures that encompass multiple aspects of quality of life are needed. Generic measures of quality of life identify associations between physical conditions and mental health and highlight the need to address psychological functioning to ultimately improve the individuals' quality of life.

Fibromyalgia has a high prevalence and impact in cardiac failure patients.

OBJECTIVE: Chronic cardiac failure (CCF) shares several clinical features with fibromyalgia (FM), a syndrome of increased central sensitivity and musculoskeletal pain. FM frequently coexists with other chronic illness. Musculoskeletal pain is reported in patients with CCF; however, the prevalence and impact of FM in patients with CCF is not known. This research aims to assess the prevalence and effects of concurrent FM in patients with CCF and to identify other coexisting central sensitivity syndromes. MATERIAL AND METHODS: In a cross-sectional study, demographic, clinical, and functional information was gathered from participants with CCF from public and private clinics. Cardiac failure severity was rated using the New York Heart Association (NYHA) scale. FM diagnosis was determined using 2011 American College of Rheumatology (ACR) criteria. The short-form 36 (SF-36) assessed overall health function. RESULTS: Of the 57 CCF participants (63.2% male, mean age 70.3 years), 22.8% (n=13) met FM diagnostic criteria. CCF patients with FM had poorer outcomes across multiple SF-36 domains (p<0.05), compared to those without, despite having comparable CCF severity. Those with FM were more likely to report other central sensitivity syndromes, especially temporomandibular joint dysfunction (mean Δ=23%, p<0.05), headache (mean Δ=28.8%, p<0.05), and irritable bladder (mean Δ=14%, p<0.05). CONCLUSION: High prevalence of FM was found in patients with CCF. This was associated with increased likelihood of other comorbid central sensitivity syndromes and with poorer clinical outcomes. The recognition of coexisting FM in patients with CCF provides an important opportunity to improve health outcomes by managing FM-related symptoms, in addition to symptoms that relate specifically to CCF.

Fibromyalgia syndrome: which antidepressant drug should we choose.

Fibromyalgia syndrome [FM] has core clinical features of widespread pain and widespread abnormal tenderness. The specific cause of the altered neurophysiology that underpins these clinical manifestations remains unclear. However, increased sensitisation of neural networks that relates to pain, as well as interacting mechanoreceptors, appear important targets for modulation by pharmacological agents. Further, many FM patients have emotional distress and some are depressed. Antidepressant agents have therapeutic benefits in FM. If depression is present antidepressant drugs will provide typical benefits to mood but not always to other key outcome measures, such as pain or tenderness. Selective serotonin receptor reuptake blockers are not as effective for overall FM improvement as drugs that block both serotonin and norepinephrine in a relatively balanced way. Thus tricyclic antidepressants will improve many important FM outcomes but are effective in only about 40 percent of individuals. Newer agents of this class, such as duloxetine and milnacipran, show improvement in key FM outcomes in about 60 percent of patients. Longer term studies will indicate the durability of these responses and the overall tolerance of the drugs. Any drug therapy will need to be integrated with appropriate education, exercise and attention to psychological modulatory factors to achieve best results.

Is there a role for opioids in the treatment of fibromyalgia?

The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia.

PTPN22 R620W minor allele is a genetic risk factor for giant cell arteritis.

Giant cell arteritis (GCA) is one of the commonest forms of vasculitis in the elderly, and may result in blindness and stroke. The pathogenesis of GCA is not understood, although environmental, infectious and genetic risk factors are implicated. One gene of interest is PTPN22, encoding lymphoid protein tyrosine phosphatase (Lyp), expressed exclusively in immune cells, which is proposed to be an 'archetypal non-HLA autoimmunity gene'. The minor allele of a functional PTPN22 single nucleotide polymorphism (rs2476601, R620W), which disrupts an interaction motif in the protein, was originally reported to be associated with biopsy-proven GCA in Spanish patients, with supporting data from three replicate Northern European studies. Recently, this observation was extended with additional patients and controls, and studies encompassing European, Scandinavian, UK and American patients. The aim of our study was to determine the association between PTPN22 rs2476601 (R620W) and biopsy-proven GCA in an Australian case cohort.

Models of adjustment to chronic illness: using the example of rheumatoid arthritis.

There are a number of theoretical frameworks that attempt to explain how individuals may adjust to threats to health and serious physical illness. The three major paradigms that attempt to organize key components of health and adaptation to illness include the following: the biomedical model which emphasizes disease; psychological models of adaptation to illness; and biopsychosocial models with the latter two emphasizing health, functioning, and well-being. Each of these three major paradigms, including biomedical, psychosocial, and biopsychosocial frameworks, is discussed and critiqued in turn, and contributions and theoretical issues in terms of adjustment to chronic illness, particularly rheumatoid arthritis (RA), are highlighted. Furthermore, a biopsychosocial framework for conceptualizing adjustment to physical illness is proposed that incorporates elements from key existing biomedical and psychosocial models of adaptation to chronic physical health issues.

Personality and fibromyalgia syndrome.

OBJECTIVES: We aimed to review how personality characteristics contribute to the onset, maintenance or modulation of fibromyalgia. METHOD: The databases Medline and PsychINFO were examined from 1967 to 2012 to identify studies that investigated associations between fibromyalgia and personality. Search terms included fibromyalgia and personality, trait psychology, characteristics and individual differences. RESULTS: Numerous studies indicate that patients with fibromyalgia experience psychological distress. Various instruments have been used to evaluate distress and related psychological domains, such as anxiety or depression, in fibromyalgia. In many cases, these same instruments have been used to study personality characteristics in fibromyalgia with a subsequent blurring of cause and effect between personality and psychological distress. In addition, the symptoms of fibromyalgia may change pre-illness personality characteristics themselves. These issues make it difficult to identify specific personality characteristics that might influence the fibromyalgia process. Despite this inherent problem with the methodologies used in the studies that make up this literature review, or perhaps because of it, we found no defined personality profile specific to fibromyalgia. However, many patients with fibromyalgia do show personality characteristics that facilitate psychological responses to stressful situations, such as catastrophising or poor coping techniques, and these in turn associate with mechanisms contributing to fibromyalgia. CONCLUSION: No specific fibromyalgia personality is defined but it is proposed that personality is an important filter that modulates a person's response to psychological stressors. Certain personalities may facilitate translation of these stressors to physiological responses driving the fibromyalgia mechanism.

Abatacept in the treatment of lupus.

INTRODUCTION: In contrast to other areas in rheumatology, the therapeutic armamentarium in systemic lupus erythematosus (SLE) has lagged behind due to a number of reasons. While SLE is the prototypical multi-system autoimmune disease, its low incidence and the heterogeneity in its clinical manifestations have made it difficult to study. Despite advances in the understanding and application of immunology, the emergence of new targets has not been successfully validated largely due to the difficult-to-use outcome measures. Among the many targets studied, co-stimulation blockade that prevents activation of T cells by antigen-presenting cells, poses an interesting concept that is plausible based on basic science, animal and early human studies. AREAS COVERED: The authors hereby review the development of abatacept in the treatment of SLE and possible future directions. EXPERT OPINION: Despite failure to achieve primary efficacy end points, the studies of abatacept in lupus provided tantalising evidence that co-stimulatory blockade is a feasible option worthy of further exploration.

Clinical characteristics of 150 consecutive fibromyalgia patients attending an Australian public hospital clinic.

AIM: To describe clinical characteristics of fibromyalgia in an Australian population. METHOD: Data was collected from 150 consecutive patients with clinical features of fibromyalgia seen in an Australian public hospital clinic. Demographic information and clinical characteristics were recorded. Significant correlations between clinical characteristics were identified, then used in multiple regression analyses to identify factors influencing outcome in physical function, pain, fatigue and sleep disturbance. Clinical features in groups who were or were not using different treatment strategies were compared. RESULTS: Most patients were female and Caucasian. The majority reported a recognizable trigger factor and many had associated conditions, most commonly headache and irritable bowel syndrome. Physical function was significantly accounted for by pain levels (P = 0.001); pain score was significantly predicted by tenderness (P = 0.002) and physical function level (P = 0.001); fatigue levels were significantly influenced by age (P = 0.007) and sleep disturbance (P < 0.001), and sleep disturbance was significantly predicted by fatigue (P < 0.001). Just over one-third (34%) of patients were using fibromyalgia medications (low-dose tricyclic antidepressant, pregabalin or duloxetine); however, they had less anxiety (P = 0.006) and better reported physical function (P = 0.04) than those who were not. Less than half (43.6%) of the patients were regularly exercising; however, they had reduced overall illness impact scores (P = 0.004), better physical function (P = 0.01) and less fatigue (P = 0.03), anxiety (P = 0.02) and depressive features (P = 0.008) than non-exercisers. CONCLUSION: Baseline clinical characteristics in this group were comparable to other study populations. The use of management modalities with proven benefit in fibromyalgia was limited; however, those patients who were engaged in regular exercise or using medication had better self-reported outcome measures than those who were not.

The use of opioids in fibromyalgia.

Fibromyalgia syndrome (FMS) is a chronic disorder of widespread pain with high personal and societal burdens. Although targeted pharmacotherapies have become available in recent years, it remains a challenging condition to treat. Despite no randomized controlled trials addressing the short- or long-term use of opioids in FMS, their use remains prevalent. In this article we discuss the role of opioids and other analgesics in the management of FMS, with particular focus on problems associated with their use. We review aspects of the pathophysiology of FMS and consider how specific factors may contribute to the lack of efficacy of opioids in this condition. Finally, we discuss drugs with combined opioid and anti-opioid action and their roles in FMS. There is insufficient evidence to recommend the routine use of opioids in FMS. As well as having a significant adverse effect profile, their inefficacy may be due to their inability to target the pathophysiologic processes involved in this central sensitization syndrome.