Automatic substitution of biological medicines refers to a dispensing practice in community pharmacies in which a pharmacist substitutes a prescribed biological medicine with an interchangeable biologic product without contacting the prescriber. Automatic substitution of biological medicines in community pharmacies offers one possibility to reduce increased healthcare expenditures through price competition among biological medicines. The implementation of automatic substitution requires active engagement, information and coordination to maintain medication safety. Research on healthcare professionals' perceptions towards automatic substitution remains limited. This study provides insight into automatic substitution from the perspective of rheumatology nurses, whose role in rheumatology patient care is essential. The Aim of the study was to explore rheumatology nurses' perceptions of automatic substitution of biological medicines and its safe implementation. Data were collected through individual semi-structured interviews in 2025. The participants were rheumatology nurses (n = 10) with clinical experience in patient care, including injection and device guidance for patients. The data were analysed with inductive content analysis. To ensure comprehensive and transparent reporting, the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was utilised. Four categories were identified: (1) Perceptions of automatic substitution, (2) Factors supporting the implementation of automatic substitution, (3) Concerns related to automatic substitution, and (4) Safe implementation of automatic substitution. All interviewees acknowledged the critical roles of community pharmacies and healthcare personnel in ensuring safe implementation. Perceptions of automatic substitution were positive, although concerns were raised about medication-related issues and work-related challenges such as increased workload in patient counselling. Factors supporting the implementation of automatic substitution were mainly related to the suitability of biological medicines for substitution, and patients' experience of biological medicines and generic substitution. Rheumatology nurses' perceptions of automatic substitution were generally positive, and they considered biological medicines suitable for substitution. However, their concerns regarding work-related challenges and medication-related issues highlight the importance of ensuring sufficient resources to sustain patient safety. Successful and safe implementation of automatic substitution will require comprehensive patient counselling.
Up to one-third of people living with psoriasis develop psoriatic arthritis (PsA), and the majority have active psoriasis prior to the development of arthritis. Clinical risk factors, such as nail involvement, in conjunction with novel blood biomarkers, could improve PsA risk monitoring and early diagnosis. The aim of the HIPPOCRATES Prospective Observational Study (HPOS-www.hpos.study) is to follow a cohort living with psoriasis and identify risk factors for the development of PsA. HPOS is a patient-driven online prospective European observational cohort. Adult participants with psoriasis but with no prior diagnosis of PsA are eligible. Participants are invited to provide consent and join the study online. They complete a semi-structured questionnaire to collect data on demographics, psoriasis, comorbidities, risk factors for PsA, and the Psoriasis Epidemiology Screening Tool screening questionnaire. Follow-up is conducted through a questionnaire every 6 months. The primary outcome is the new onset of PsA confirmed by a diagnosis from their doctor. The study will also collect peripheral blood samples from a subset of participants for biomarker identification. This study follows the principles of the Declaration of Helsinki. To date, ethical approval has been granted by independent ethical committees in 10 countries. Studying a cohort of individuals with psoriasis will allow us to identify risk factors for arthritis development and to develop a risk calculator. This can support focused efforts on screening, patient education, and even studies looking to delay or prevent the onset of arthritis. This study, run via remote online data collection, provides an efficient way to recruit a large cohort (25,000) across multiple countries. However, challenges have had to be addressed with some key changes in study design, ethical review, and recruitment strategies required for each individual country. HPOS, Clinicaltrials.gov ID: NCT05858528, IRAS number 325080; https://clinicaltrials.gov/study/NCT05858528?locStr=United%20Kingdom&country=United%20Kingdom&cond=Psoriasis&term=HPOS&aggFilters=status%3Anot%20rec&rank=1. The HIPPOCRATES prospective observational study (HPOS) The HPOS Study, part of the HIPPOCRATES project, aims to find out what signs or factors can show which people with psoriasis might later develop Psoriatic Arthritis (PsA). PsA is a type of inflammatory arthritis that is related to the skin condition psoriasis. It occurs in about 1–2% of the general population but can develop in up to 30% of people who already have skin or nail psoriasis. Diagnosing PsA early can be difficult because symptoms can be vague or inconsistent, which means treatment often starts only after joint damage has already happened. By learning more about how psoriasis develops into PsA, researchers hope to find new ways to treat the disease earlier—or even prevent or delay it. The HPOS Study is an observational study that uses online questionnaires. Adults (aged 18 or older) who have psoriasis but not PsA can take part. Participants fill out a questionnaire every six months for three years. These questionnaires collect information about age, psoriasis details, lifestyle and health factors, early joint symptoms (using the PEST questionnaire), daily function, treatment satisfaction, disease impact, fatigue, and mental health. If early signs of PsA appear, participants are advised to contact a doctor for assessment. The study plans to recruit 25,000 people across 14 European countries (including the UK, Ireland, France, Germany, and others) and expects that around 675 participants will develop PsA each year. A smaller group of 3,000 participants will also provide a small finger-prick blood sample, which will help researchers look for blood markers that might predict PsA development. HPOS is the first large-scale European study to track how psoriasis progresses to PsA. The findings could lead to a “risk calculator” that helps doctors identify people at high risk of developing PsA earlier.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
To evaluate the relative strength of clinical and sociodemographic predictors of health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) under real-life conditions. This cross-sectional, observational study included adult patients fulfilling the 2010 American College of Rheumatology-European Alliance of Associations for Rheumatology classification criteria for RA, recruited from 11 public tertiary rheumatology centres in Brazil. To reflect real-life clinical practice, no restrictions were applied regarding disease stage or treatment status. HRQoL was assessed using the 12-item Short Form Health Survey (SF-12). Physical disability was measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Clinical and epidemiological variables were evaluated as candidate predictors. Associations were explored using bivariate analyses and multiple linear regression models. Standardised beta coefficients (zβ) were used to estimate the relative strength of independent predictors. 1079 patients were included; 89.4% were women and 56.0% were white, with a mean (SD) age of 57.0 (11.4) years and a median (IQR) disease duration of 152 (84.0-242.0) months.In multivariate analysis, the following remained independently associated with physical score: HAQ-DI score (β=-3.92, 95% CI (-4.56 to -3.28), zβ=-0.44, p<0.001), non-white race (β=-0.97, 95% CI (-1.80 to -0.14), zβ=-0.71, p=0.022) and absence of regular physical activities (β=0.56, 95% CI (0.04 to 1.09), zβ=-0.07, p=0.036).For mental score, remaining independent predictors were HAQ-DI (β=-5.00, 95% CI (-6.17 to -3.83), zβ=-0.31, p<0.001), fibromyalgia (β=-5.52, 95% CI (-7.76 to -3.26), zβ=-0.15, p<0.001), white race (β=3.32, 95% CI (1.79 to 4.84), zβ=0.13, p<0.001), current smoking (β=-4.95, 95% CI (7.42 to -2.48), zβ=-0.12, p<0.001), female biological sex (β=3.91, 95% CI (-6.36 to -1.46), zβ=-0.10, p=0.002) and Simplified Disease Activity Index (β=-0.91, 95% CI (-0.17 to -0.02), zβ=-0.09, p=0.018). Physical disability was the strongest determinant of impaired HRQoL in both physical and mental domains among participants with RA. Other relevant determinants of poorer physical HRQoL in descending order of relative strength were non-White race and absence of regular physical activity, while for poorer mental HRQoL, fibromyalgia, race, smoking status, female sex and disease activity. These findings reinforce functional preservation as a key therapeutic target in routine RA care.
Pain, fatigue, and impaired health-related quality of life are common manifestations of rheumatoid arthritis. The aim of this study was to compare the effects of active conventional treatment with three different biological disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes after 48 weeks, in patients with early rheumatoid arthritis using data from the NORD-STAR trial. NORD-STAR was an investigator-initiated open-label randomised controlled trial done at 29 rheumatology centres across Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients aged 18 years or older, with rheumatoid arthritis (according to the 2010 American College of Rheumatology-European Allience of Associations for Rheumatology classification criteria for rheumatoid arthritis), symptom duration less than 24 months and who were naïve to DMARDs were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab pegol, abatacept, or tocilizumab. The patient-reported outcomes assessed at baseline and weeks 4, 8, 12, 16, 24, 32, 40, and 48 included pain, patient's global assessment of disease activity, Health Assessment Questionnaire Disability Index, Fatigue, Short Form-36 (reflecting health-related quality of life, morning stiffness, and patient's acceptable symptom state). Linear mixed regression and logistic regression analyses were adjusted for sex, country, baseline patient-reported outcomes values, anti-citrullinated protein antibody status, and treatment group. Proportions of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) were assessed. There was lived experience involvement in the design and implementation of the study. This trial was registered with ClinicalTrials.gov, NCT01491815, and EudraCT, 2011-004720-35. Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; after exclusion of 17 patients not receiving tocilizumab due to administrative issues, the intention-to-treat population consisted of 795 patients (200 [25%] received active conventional treatment, 203 [26%] received certolizumab pegol plus methotrexate, 204 [26%] received abatacept plus methotrexate, and 188 [24%] received tocilizumab plus methotrexate). 547 (69%) of 795 patients were female, 248 (31%) were male, the mean age was 54 years (SD 15). Between baseline and week 48 large and clinically relevant improvements in patient-reported outcomes were observed in all treatment groups. At 48 weeks the biological DMARD groups had larger improvements in pain, fatigue, physical component score, and bodily pain of SF-36 compared with the active conventional treatment group. For pain, improvement exceeding MCID was reported by 155 (76%) of 203 patients with certolizumab pegol plus methotrexate and 162 (79%) of 204 patients with abatacept plus methotrexate compared with 136 (68%) of 200 patients in the active conventional treatment group. In the group of patients with tocilizumab and methotrexate 132 (70%) of 188 patients reported pain improvement exceeding MCID. The absolute differences between the biological DMARD groups and the active conventional treatment group were otherwise generally marginal. All treatment groups showed substantial improvements in patient-reported outcomes over time. Biological DMARDs produced somewhat greater gains in pain, fatigue, and physical quality of life measures than conventional treatments, though overall differences between groups were small. The results highlight that early treatment and effective disease control in rheumatoid arthritis lead to strong patient-reported benefits regardless of therapy type. Stockholm County Council, Swedish Medical Research Council, Swedish Rheumatism Association, Academy of Finland, Finska Läkaresällskapet, South-Eastern Health Region Norway, HUS Institutional grant, Icelandic Society for Rheumatology, Interregional grant from all health regions in Norway, NordForsk, Regionernes Medicinpulje, The Research Fund of University Hospital Reykjavik, UCB, Bristol Myers Squibb.
This study included patients diagnosed with Takayasu's arteritis (TAK) according to the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for TAK and compared the frequencies of items satisfied in the 2022 criteria between patients with young-onset TAK (YOTAK) and those with lateonset TAK (LOTAK). The medical records of 138 patients with TAK were retrospectively reviewed. YOTAK was arbitrarily defined as TAK diagnosed at 20-40 years of age, whereas LOTAK was defined as TAK classified at 41-60 years of age. The analyses were conducted by assessing and comparing the frequencies of items that fulfilled the 2022 criteria for TAK. The median age of the 138 patients diagnosed with TAK was 45.0 years, and 89.1% of the patients were female. Of the 138 patients, 47 and 91 were allocated to the YOTAK and LOTAK groups. Patients with LOTAK exhibited significantly higher frequencies of the items of vascular bruit (85.7% vs. 70.2%, OR 2.55 (95% CI 1.08-6.00), p=0.030), reduced pulse in upper extremities (73.6% vs. 42.6%, OR 3.77 (95% CI 1.79-7.92), p<0.001), and systolic blood pressure difference in arms (96.7% vs. 87.2%, OR 4.29 (95% CI 1.02-18.02), p=0.033) than those with YOTAK. Conversely, the involvement of the ascending aorta was significantly more frequently found in patients with YOTAK than those with LOTAK (19.1% vs. 7.7%, OR 0.35 (95% CI 0.12-0.99), p=0.046). Results of this study revealed that patients with LOTAK exhibited higher frequencies of vascular bruit, reduced brachial arterial pulse, and systolic blood pressure differences in arms, but a lower frequency of ascending aorta involvement than those with YOTAK.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease characterised by a highly heterogeneous presentation. Specific genetic variations predispose patients to the disease, and rare monogenic forms caused by single-gene variations have been identified in a small percentage of patients, often with early disease onset. In this study, we used exome sequencing in a large cohort of patient with juvenile-onset SLE to gain insight into the genetic basis of juvenile SLE (jSLE). Patients were selected if disease onset occurred before the age of 18. We performed exome sequencing on 263 individuals across 172 distinct families. The majority of cases were solo exomes (n = 118), while others included affected duos, trios, or multiplex families (n = 18 + 5 + 1), as well as classical trios with unaffected parents (n = 30). A molecular diagnosis consistent with the clinical presentation was established in 17 patients from unrelated families (10%). Among them, we identified pathogenic or likely pathogenic variants in genes previously associated with monogenic lupus, including a novel C1QA variant as well as other lupus-associated genes (COPA, ADAR, TLR7, IKZF3, RELA, PTPN11, SERPING1). Strikingly, exome sequencing also revealed variants in immunodeficiency-associated genes (IRAK4, USB1), autoinflammatory disorders (PSTPIP1) and unexpected candidates like ETV6, and MAN1B1 revealing previously unrecognised pathways in SLE development. Syndromic features and very early-onset (before the age of 5) were strongly associated with a higher diagnostic yield, reaching nearly 33% in these subgroups. This study expands our understanding of causes of lupus, highlighting its genetic heterogeneity. It also supports the systematic use of genetic testing in cases of juvenile lupus, especially those with very early onset or syndromic features, regardless of the clinical presentation. Given the range of unexpected molecular diagnoses identified in this study, pangenomic analysis such as exome or genome sequencing appears to be the most appropriate approach in these cases. This work was supported by: The Institut National de la Santé et de la Recherche Médicale (INSERM); Government grants managed by the Agence Nationale de la Recherche (ANR) as part of the "Investment for the Future" program: Institut Hospitalo-Universitaire Imagine (ANR-10-IAHU-01), Recherche Hospitalo-Universitaire (ANR-18-RHUS-0010); The Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH); The Fondation pour la Recherche Médicale (FRM: EQU202103012670, FDM202006011291); French and European grants managed by the ANR: ANR-14-CE14-0026 (Lumugène), ANR-21-CE17-0064 (SOCSIMMUNITY); The National Reference Center for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE).
Patient authors have been increasingly included on company-sponsored research publications, contributing a unique and needed expertise. Patients are routinely and rightfully remunerated for their contributions to advisory boards and non-authorship publication activities, such as peer review. However, the remuneration of patients for authorship activities has remained inconsistent and even contentious. Here, a working group of Good Publication Practice (GPP) steering committee members, patients and patient involvement and engagement experts, and industry partners present six commonly described barriers to and arguments against patient author remuneration. The working group provides practical solutions and counterarguments to enable industry sponsors to equitably, fairly, and transparently remunerate patient authors. The barriers include (1) general resistance to or unawareness of patient authorship; (2) conflict of interest and compliance risks; (3) operational and logistical challenges; (4) concerns about equity, fairness, and scalability; (5) external perceptions within scholarly publishing; and (6) lack of clarity regarding alternative methods of recognition. Solutions to these barriers are supported by a case study from industry to share real-world implementation recommendations. These recommendations provide an action plan for the development and utilization of a framework to enable patient author remuneration, based on one company's experience. In short, the principles and guidance that underpin fair remuneration in other patient engagement activities can and should be extended to authorship, ensuring appropriate recognition of the value that patient authors bring, rather than risking the absence of patient authors altogether. Many research articles of pharmaceutical company research include patients as authors. Patients are often involved in other stages of research such as helping design or review a research study and are usually paid for their time in those activities. However, only some pharmaceutical companies pay patient authors for their time working on research articles. In this article, the authors – including patient authors and other experts – describe six main reasons why pharmaceutical companies may not pay patient authors. These were identified through professional experience across the author group, from existing guidance on the topic, and during discussions with other colleagues and experts. The reasons include not valuing patient input, being unaware that patients can provide input, wanting to be transparent about payments, being unsure how to use payment systems, wanting to treat all authors equally, being worried about what others may think, and being unsure of other ways to recognize patient input besides payment. The authors explain why these reasons should not stop pharmaceutical companies from paying patient authors and give suggestions for how companies can start paying patients for their time working on research articles. They also share a case study of how one pharmaceutical company has overcome these challenges and now fairly and transparently pays patient authors for their time working on research articles. In short, there are many reasons why patient authors should be paid for their time, and it is better to understand these reasons and act accordingly, rather than to risk not including patient authors.
Inflammatory rheumatic diseases (IRDs) present substantial risks of infection-related comorbidities during pregnancy. This study evaluates the knowledge, experience, and perceptions of healthcare professionals concerning the prevention of these risks. An international, cross-sectional survey was administered using the SurveyMonkey platform. The survey was disseminated to healthcare professionals specializing in rheumatology, obstetrics, infectious diseases, internal medicine, general practice, and related disciplines through social media channels. Developed in accordance with European Alliance of Associations for Rheumatology (EULAR) recommendations, this survey comprised 30 questions, including multiple-choice, Likert-type, and open-ended formats. A total of 201 healthcare professionals from thirty-six countries participated in the study, with rheumatologists comprising the majority (n = 145, 72.1%). Systemic lupus erythematosus (n = 183), systemic vasculitis (n = 141), and rheumatoid arthritis (n = 86) were identified as the diseases associated with the highest risk of infection-related comorbidities. The most frequently recommended infectious conditions for screening included Hepatitis B (n = 142), urinary tract infections (n = 141), and Hepatitis C (n = 129). The primary risk factors were uncontrolled disease activity (n = 176), high-dose corticosteroid use (n = 164), and high disease severity (n = 162). The most significant systemic barriers were insufficient number of specialists (n = 156), and absence of multidisciplinary teams (n = 155). This study identifies structural and educational deficiencies in the management of infection-related comorbidities among pregnant patients with IRD. The results underscore the need for targeted clinical guidelines, enhanced multidisciplinary care models, and expanded pre-pregnancy counseling.
The heterogeneity of autoimmune diabetes may be associated with variable metabolic alterations. Our aim was to investigate differences in the metabolomic and lipidomic profile of autoimmune diseases and to identify pathways linked to beta cell damage. To this end, we compared latent autoimmune diabetes in adults (LADA) and type 1 diabetes, also comparing them with rheumatoid arthritis (RA), a related autoimmune condition, and healthy control participants. Metabolomic and lipidomic analyses were performed for 136 individuals (49 with LADA, 44 with type 1 diabetes, 29 with RA and 14 control participants). Omics of pancreatic islets from healthy donors were also evaluated after in vitro treatment with proinflammatory cytokines. LADA and type 1 diabetes differed from RA in terms of lipidomics and metabolomics. Phosphatidylethanolamines, ceramides, lysophosphatidylcholine and several metabolites at the entry sites of the tricarboxylic acid cycle were higher in type 1 diabetes compared with LADA. In pancreatic islets treated with proinflammatory cytokines, tryptophan concentration was reduced by 80%, indicating the activation of tryptophan metabolism in response to the inflammatory stimulus. In people with autoimmune disorders, kynurenine/tryptophan ratio (Kyn/Trp), a marker of tryptophan pathway activation, was higher than in the control group (Kyn/Trp ratio in control group, median [25th-75th percentile]: 0.014 [0.012-0.019]), with a progressive decline from RA (0.027 [0.022-0.032]) to LADA (0.021 [0.018-0.024]) and then to type 1 diabetes (0.018 [0.014-0.022]), ANCOVA p<0.0001. In LADA, Kyn/Trp was directly associated with fasting C-peptide levels in the multivariate regression model accounting for confounders (p=0.038). Metabolomic and lipidomic profiles differ between LADA and type 1 diabetes and vs RA, providing new insights into the heterogeneity of autoimmune diabetes. Our results confirm the involvement of tryptophan metabolism in autoimmune disorders, suggesting that the impaired activation of this pathway of immune tolerance in LADA is less pronounced than in type 1 diabetes, consistent with its milder degree of beta cell loss.
Osteogenesis imperfecta causes multiple fractures throughout life, causing substantial morbidity. To determine whether the parathyroid hormone analogue teriparatide followed by zoledronic acid reduces the risk of fractures in adults with osteogenesis imperfecta. Multicenter open-label, parallel-group, randomized clinical trial, conducted between May 17, 2017, and March 21, 2025, in adults attending one of 27 referral centers with a clinical diagnosis of osteogenesis imperfecta. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone turnover by serum procollagen type 1 N-terminal propeptide and C-terminal telopeptide of type 1 collagen. Fractures were confirmed by skeletal imaging. Several measures of health-related quality of life were assessed. Those in the active group received 20 μg of teriparatide daily by subcutaneous injection for 2 years followed by an infusion of 5 mg of zoledronic acid. In the standard care group, bisphosphonates and other bone-targeted medicines could be used but teriparatide and other bone anabolic drugs were prohibited. The primary end point was the number of participants with imaging-proven incident fractures adjudicated by reviewers blinded to treatment allocation. Secondary end points included the total number of fractures, changes in BMD, biochemical markers of bone turnover, and health-related quality of life. Of the 350 individuals randomized, 176 were allocated to receive teriparatide plus zoledronic acid, 174 to standard care, and 1 withdrew, leaving 349 evaluable participants. The mean age was 43.7 years (188 females [53.9%]). Most had type I osteogenesis imperfecta caused by pathogenic variants in the type 1 collagen genes. In the teriparatide plus zoledronic acid group 65 of 176 (36.9%) had incident fractures compared with 63 of 173 (36.4%) in the standard care group (absolute risk reduction, -1.57%; 95% CI, -9.90% to 5.89%; hazard ratio, 0.97; 95% CI, 0.68 to 1.38). Lumbar spine and total hip BMD increased significantly more with teriparatide plus zoledronic acid than standard care. Several quality-of-life measures favored teriparatide plus zoledronic acid. Adverse events were similar in both groups. This randomized clinical trial among adults with osteogenesis imperfecta found that teriparatide plus zoledronic acid did not reduce fracture risk compared with standard care despite significantly increasing BMD, suggesting the importance of reduced bone quality rather than low bone density in the pathogenesis of fracture. isrctn.org Identifier: ISRCTN15313991.
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis with multi-organ involvement and eosinophilia. We present a 61-year-old male with a history of eosinophilic asthma who developed progressive weakness and muscle aches six weeks after his second COVID-19 booster. Four to six weeks post vaccination, he developed myal gias and weakness, especially in proximal muscles, leading to a severe decline in function. Lab results showed leukocytosis (29.54 cells/mm³); 54% eosinophils; and elevated erythrocyte sedimentation rate (ESR), C-reactive protein, and creatine kinase levels at 13 736 u/L. Anti-myeloperoxidase antibodies were positive, while PR-3, C-ANCA, and P-ANCA were negative. Magnetic resonance imaging of the lower extremities showed intramuscular edema. Muscle biopsies confirmed EGPA. Diagnosed per American College of Rheumatology (ACR)/ European Alliance of Associations for Rheumatology (EULAR) criteria, he received pulse dose IV methylprednisolone with significant improvement. He was discharged on 60 mg prednisone and started on mepolizumab (300 mg subcutaneous once every 4 weeks). Eosinophilic granulomatosis with polyangiitis progresses through stages: asthma, eosinophilia with organ involvement, and vasculitis. This case highlights a unique presentation of rapid myositis without significant involvement of any other organs and vasculitis post-mRNA vaccination. While environmental factors may trigger EGPA, the role of COVID-19 vaccines remains hypothesis-generating. This case underscores the importance of post-market surveillance for rare events, contributing to the understanding of vaccine-related rheumatic disease triggers Cite this article as: Memdani A, Busa V, Avula S, Ford A, Nesheiwat J. Unmasking Eosinophilic granulomatosis with polyangiitis: a case of rapid-onset myositis following COVID-19 booster in an eosinophilic asthma patient. Eur J Rheumatol. 2025, 13(1), 0016, doi:10.5152/eurjrheum.2026.25016.
There is conflicting evidence regarding the merits of patellar resurfacing during total knee replacement (TKR), as previous randomised controlled trials (RCTs) have been under-powered and with follow-up of ten years or less. A pragmatic, multicentre, open-label RCT was initiated in 1999 in the UK. Within a partial-factorial design, participants were randomly allocated to receive or not receive patellar resurfacing during primary TKR and were followed up for 20 years. Adult (aged ≥18 years) patients due to have a primary TKR under the care of a collaborating surgeon were eligible. Participants were allocated (1:1) using an automated telephone service stratified by surgeon, with minimisation according to the patients' age (<60 years, 60-79 years, ≥80 years), sex, and location of d isease. The primary outcome measure was the Oxford Knee Score (OKS), analysed using repeated measures mixed-effects linear regression analysis with marginal differences reported. Secondary measures included the 12-Item Short Form Health Survey (SF-12), the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L), costs, cost-effectiveness, and subsequent knee surgery. This trial is registered with ISRCTN Registry, ISRCTN45837371. Between April 8, 1999, and Jan 13, 2003, 1715 participants (955 female and 760 male; mean age 70 years [SD 8], mean BMI 29·7 kg/m2) were randomly assigned: 861 to patellar resurfacing and 854 to no resurfacing. At the 20-year follow-up, 132 participants in the patellar resurfacing group and 110 participants in the non-resurfacing group provided outcome data, although marginal differences included earlier data for participants who died or had missing 20-year data. The marginal difference in OKS over the whole 20-year follow-up was 0·76 (95% CI -0·08 to 1·59; p=0·076) in favour of patellar resurfacing. During the 20-year follow-up period, although not significant, differences in OKS, SF-12, and EQ-5D-3L, readmissions, minor or intermediate operations, patella-related operations, major operations, and complications all favoured patellar resurfacing. At 20 years, the resurfaced group accrued significantly more quality-adjusted life-years (QALYs) than the non-resurfaced group (7·295 vs 6·884; difference 0·380, 95% CI 0·061 to 0·700; p=0·020). However, QALY differences were smaller in a sensitivity analysis assuming no difference in mortality (7·209 vs 6·964; difference 0·183, 95% CI -0·034 to 0·400; p=0·10). The cost of readmissions was non-significantly lower in the resurfaced group and offset the higher cost of primary TKR; therefore, overall 20-year health-care costs per participant were similar (£10 825 vs £10 889; difference -£6, 95% CI -£721 to £708; p=0·99). There was no significant difference in primary outcome (OKS) or other clinical endpoints. However, as clinical differences tend to support patellar resurfacing, the resurfacing group had significantly higher QALYs. There was no difference in costs over the 20-year period, and patellar resurfacing had a 99% probability of being cost-effective at any threshold above £10 000 per QALY gained. The evidence is therefore weighted towards resurfacing being the approach of first choice. UK National Institute for Health and Care Research Health Technology Assessment Programme.
This systematic literature review (SLR) aims to update the evidence regarding therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), building on the previous SLR informing the European Alliance of Associations for Rheumatology (EULAR) points to consider for the management of D2T RA. Three research questions addressed efficacy or safety of treatments in patients with RA with (1) active disease and limited treatment options; (2) active disease with ≥2 prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and (3) poor health-related quality of life and low objective disease activity (non-pharmacological interventions). MEDLINE, Embase and Cochrane Library were searched until July 2025. Meta-analysis and meta-regression were conducted. We screened 8589 records and included 131 studies. For research question (RQ)1, evidence on DMARD efficacy and safety was synthesised across a wide spectrum of comorbidities including obesity, cardiovascular disease, history of malignancy and respiratory comorbidities. For RQ2, all b/tsDMARDs except otilimab demonstrated better efficacy than placebo (mostly high risk of bias). Meta-regression showed efficacy was maintained for Janus kinase inhibitors (JAKi) despite increasing number of prior bDMARD failures (1 to ≥3). Safety results confirmed the increased occurrence of infection and malignancy with JAKi. For RQ3, limited evidence suggested orthopaedic surgical intervention as a potential non-pharmacological option in patients with D2T RA. This SLR summarised evidence supporting DMARD efficacy/safety across multiple comorbidities. In patients with active RA with ≥2 prior bDMARDs, JAKi offer substantial clinical benefits but require careful risk stratification given cardiovascular and malignancy risks. Furthermore, standardised reporting and dedicated studies on non-pharmacological interventions are urgently needed. CRD42024593584.
Systemic-onset juvenile idiopathic arthritis (sJIA) follows a variable and unpredictable course, with long-term outcomes remaining inconsistent worldwide despite therapeutic advancements. This study aimed to evaluate the disease course and clinical outcomes of the sJIA cohort after 5-year follow-up. The study retrospectively analyzed 100 sJIA patients with at least 5 years of follow-up. Ten patients were excluded due to insufficient data. Data on demographics, clinical features, treatments, outcomes, and complications were collected. The mean age at disease onset was 6.75 ± 3.64 years, with a median follow-up of 7 years. Common clinical manifestations included fever (100%), arthritis (96%), rash (55%), and hepatosplenomegaly (32%). Polyarticular arthritis was observed in 70.83% of cases. Treatment modalities included Non-steroidal anti-inflammatory drugs (100%), steroids (89%), methotrexate (86%), thalidomide (31%), lenalidomide (21%), and tocilizumab (13%). While 11% of patients responded to NSAIDs alone,46% achieved remission with glucocorticoids and methotrexate. A total of 46% of the patients exhibited a monocyclic disease course, and 27% of the patients had polycyclic and persistent courses. On multivariate analysis, diagnostic delay (odds ration (OR) = 1.02, 95% CI: 1.01-1.03) and symmetric arthritis (OR = 2.36, 95% CI: 1.65-3.32) were identified as key predictors of persistent disease. Common complications included infections (20%), joint damage (14%), and macrophage activation syndrome (11%). At 5 years, 62% achieved drug-free remission, 16% remained in remission on medication, and 21% had active disease. Mortality was noted in 1 patient due to a suspected cerebrovascular accident or meningitis. Delayed diagnosis and symmetric arthritis at onset increased the risk of persistent disease, highlighting the need for early and aggressive treatment for better outcomes. Cite this article as: Rao AP, B A, Kumar A, et al. Five-year outcomes of systemic-onset juvenile idiopathic arthritis in India: insights into disease course and predictive factors. Eur J Rheumatol. 2026, 13(1), 0068, doi: 10.5152/eurjrheum.2026.25068.
OBJECTIVE: This study aimed to 1) develop and test the reliability of a semiquantitative ultrasound score to assess muscle quality in patients with rheumatoid arthritis (RA), and 2) evaluate how incorrect adjustments of ultrasound settings affect muscle quality assessment. METHODS: The Spanish Ultrasound Muscle Assessment in RA (SpUMAR) Score consisted of a semiquantitative 0–3 score based on the degree of loss of the normal muscle ultrasound pattern that was agreed upon by 15 rheumatologists expert in musculoskeletal ultrasound. A total of 164 static ultrasound images of the four bellies of the quadriceps muscle from 57 patients with RA were scored by the experts in two rounds. Additionally, the experts scored 20 ultrasound images that were acquired with incorrectly adjusted settings, which were interposed among the other images. Gwet’s AC2, Fleiss' kappa (κ), Cohen’s κ, applying linear weighting, were used for agreement analysis. RESULTS: The interobserver reliability of SpUMAR was moderate in both rounds (Gwet’s AC2 [95% CI] 0.57 [0.54–0.60] and 0.54 [0.51–0.57], percent agreement 81.76% and 80.28%, respectively). Intraobserver reliability between the two rounds was good (Gwet’s AC2 [95% CI] 0.66 [0.64–0.68]). The agreement between the scores given to the images with incorrect settings and the original scores for those images was poor in both rounds (κ [95% CI]: 0.27 [0.21–0.33] and 0.30 [0.24–0.36], respectively). CONCLUSION: Multiobserver assessment of muscle quality using the SpUMAR score demonstrated acceptable reliability in patients with RA. Incorrect adjustment of ultrasound settings greatly affects muscle quality scoring; therefore, their standardised optimisation is necessary for multicentre studies.
To evaluate the short-term effects of professional scaling and polishing on nine oral health and dental aesthetic outcomes in current smokers and never smokers. A total of 371 participants from the SMILE Study Cohort (305 smokers and 66 never smokers) were assessed at baseline (V0) and 14 days after scaling and polishing (V1). Outcomes included Modified Gingival Index (MGI), quantitative light-induced fluorescence parameters (ΔR30, reflecting the percentage of tooth surface covered by mature plaque, and ΔR120, reflecting the percentage covered by thicker deposits including calculus), MacPherson-modified Lobene Stain Index (MLSI) for buccal and lingual surfaces, Whitening Index for Dentistry (WID), Simple Oral Hygiene score (SOH), oral health-related quality of life (OHQoL), and general health perception (EQ-VAS). Linear mixed model analysis was used for between-group comparisons of V0-V1 changes. At baseline, smokers exhibited significantly worse values across all objective indices. Following intervention, significant improvements were observed in MGI, ΔR30, ΔR120, MLSI, and SOH in both groups (p<0.0001). MGI improved by a median of -0.5 units in smokers (IQR: -0.8/-0.2) and -0.08 units in never smokers (IQR: -0.3/-0.02); the magnitude of improvement was significantly greater in smokers (p<0.0001). Similarly, greater reductions in ΔR120 (p=0.010), buccal MLSI (p<0.0001), and lingual MLSI (p<0.0001) were observed in smokers compared to never smokers. WID showed no significant changes in either group. OHQoL improved slightly without between-group differences; EQ-VAS did not change significantly. Professional scaling and polishing produced consistent short-term improvements in objective oral health indicators in both smokers and never smokers, with greater gains among smokers reflecting their higher baseline burden. Regular professional mechanical plaque removal is clinically beneficial for smokers, producing measurable short-term improvements in gingival and aesthetic parameters even in the presence of ongoing tobacco exposure, although smoking cessation remains essential for long-term oral health.
Systemic Lupus Erythematosus (SLE) presents a significant diagnostic challenge for clinicians due to its diverse clinical manifestations and overlap with other autoimmune conditions. Large Language Models (LLMs) are currently regarded as having the potential to assist clinicians in expediting decision-making. This study aimed to evaluate the performance of four LLMs in differentiating SLE from clinically mimicking conditions. A retrospective diagnostic accuracy study was conducted involving 100 patients at a rheumatology center: 50 patients with confirmed SLE and 50 non-SLE patients with conditions including rheumatoid arthritis, systemic sclerosis, axial spondyloarthritis, psoriatic arthritis, myositis, ANCA-associated vasculitis, mixed connective tissue disease, undifferentiated connective tissue disease, and fibromyalgia. Four LLMs were evaluated: Deepseek, ChatGPT 4.0, Claude Sonnet 4, and Gemini. The 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria were applied. Diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), and Area Under the Receiver Operating Characteristic Curve (AUC) were calculated. IBM SPSS Statistics version 25 was used for all analyses. Gemini achieved the highest performance score, with an accuracy of 96% (95% CI: 91.2-100.0%), sensitivity of 94% (95% CI: 89.3-98.7%), specificity of 98% (95% CI: 93.1-100.0%), and an AUC of 0.960. ChatGPT 4.0 and Claude Sonnet 4 exhibited comparable accuracy. Deepseek recorded the lowest performance score. Gemini demonstrated significant potential to assist clinicians in differentiating SLE from mimicking conditions. Nevertheless, prospective validation in real-world clinical settings is required before these tools can be reliably integrated into clinical practice.
To determine the prevalence of cerebral atrophy in a multi-ethnic systemic lupus erythematosus (SLE) cohort and to identify its associated clinical factors. In this cross-sectional study (2024-2025), adults fulfilling the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE at University Malaya Medical Centre were recruited. Demographic, clinical, serological, vascular and treatment data were collected. Disease activity and cumulative damage were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Non-contrast CT brain scans were performed with cerebral atrophy graded using the validated Global Cortical Atrophy (GCA) score. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Fisher's exact test and χ2 test were used to test the association between two categorical variables where appropriate, while group differences were tested using the Mann-Whitney U test. Univariable and multivariable logistic regression analyses were considered to identify variables that were significantly associated with cerebral atrophy. Seventy patients (92.9% female; median age 40 (IQR 31.75-50.25) years; median disease duration 12 (IQR 4-19) years were included. Cerebral atrophy was present in 52.9%, predominantly mild (75.7%). From univariate comparisons, patients with cerebral atrophy were significantly older in age, had longer disease duration, lower education, higher SDI and poorer MoCA scores. Multivariable analysis showed that older age (OR 1.10 per year, 95% CI 1.04 to 1.18) and neuropsychiatric SLE (NPSLE) (OR 4.58, 95% CI 1.05 to 24.07) contributed to increased odds of cerebral atrophy, while higher educational attainment was linked with reduced odds of cerebral atrophy (OR 0.22, 95% CI 0.06 to 1.03). Cerebral atrophy is common in SLE and independently associated with age, education, NPSLE and cognitive impairment, reflecting neuroinflammatory and neurodegenerative mechanisms. These findings underscore the importance of cognitive screening and targeted monitoring of high-risk patients.