Spondyloarthritis (SpA) is a complex inflammatory disease involving multiple cytokine pathways, including tumor necrosis factor-α (TNF-α) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling. Despite advances in biologic and targeted synthetic therapies, up to 40% of patients with SpA remain refractory to monotherapy. This case series from a tertiary care center in India evaluated the efficacy and safety of dual-targeted therapy (DTT) combining tofacitinib, a JAK inhibitor, with TNF inhibitors in four patients with refractory SpA and psoriatic arthritis (PsA). All four patients had longstanding disease (mean duration 11.5 years) and had failed at least one prior biologic. Case 1 (PsA): Long-standing disease (24 years) failed optimized adalimumab; following DTT, disease activity in psoriatic arthritis (DAPSA) score improved from high disease activity (36) to low disease activity (8). Case 2 (SpA): Refractory to two TNF inhibitors; after adding tofacitinib, the Ankylosing Spondylitis Disease Activity Score incorporating C-reactive protein (ASDAS-CRP) score improved from very high activity (3.7) to low disease activity (1.7). Case 3 (SpA): Presented with very high ASDAS-CRP (3.8); rapid clinical response and laboratory remission (ASDAS-CRP, 1.6) were achieved within months of starting DTT. Case 4 (SpA): Failed adalimumab monotherapy; the addition of tofacitinib led to an improvement in ASDAS-CRP from 3.5 to 1.7. No serious adverse events or significant laboratory abnormalities were observed over 5-18 months. DTT combines extracellular TNF-α blockade with intracellular JAK-STAT inhibition. This addresses the pathway redundancy and compensatory mechanisms in refractory SpA. Our findings add to the emerging real-world evidence supporting DTT therapy as a promising option for patients with refractory SpA. Our real-world findings demonstrate improved disease control and safety when monotherapy fails. Future prospective studies are essential to optimize the selection, dosing, and long-term safety of DTT. Combining two different anti-inflammatory drugs helps patients with hard-to-treat inflammatory spine and joint disease. Spondyloarthritis is a chronic condition causing inflammation in the spine and joints, leading to pain, stiffness, and reduced movement. Some patients also develop psoriatic arthritis, which affects both the skin and joints. While modern treatments have improved outcomes, approximately one-third of patients continue to have active disease despite trying multiple medications. Current treatments typically target one inflammatory pathway at a time. TNF inhibitors block a specific protein (tumor necrosis factor) that drives inflammation, while JAK inhibitors (like tofacitinib) prevent inflammatory signals from working inside immune cells. When one treatment fails, doctors usually switch to a different single medication rather than combining two. This study from an Indian hospital examined four patients whose arthritis remained severe despite trying conventional medications and at least one biologic drug. Instead of switching to another single therapy, doctors prescribed a combination of tofacitinib with a TNF inhibitor (adalimumab or etanercept). The idea was that blocking inflammation at two different points might work better than targeting just one pathway. All four patients improved significantly. Their disease activity scores dropped from high to low levels, blood tests showed reduced inflammation, and two patients achieved complete disease remission. The combination was well-tolerated, with no serious side effects observed during follow-ups lasting 5 to 18 months. These results suggest that using two targeted therapies together—one blocking inflammation outside cells and another blocking signals inside cells—may benefit patients who haven’t responded to standard treatments. This “dual therapy” approach addresses the complex nature of inflammatory arthritis, where multiple inflammatory pathways work together to cause disease. While this small study shows promise, larger research trials are needed to confirm these findings, identify which patients would benefit.
Central sensitization (CS) contributes to persistent pain in psoriatic arthritis (PsA), yet its prevalence, independent predictors, and association with therapeutic refractoriness remain incompletely characterized across disease phenotypes. To evaluate CS prevalence and clinical correlates in unselected PsA patients excluding fibromyalgia, with emphasis on predictors, multidimensional pain phenotypes, and the association between CS and therapeutic refractoriness. Cross-sectional observational study. A total of 228 consecutive PsA patients were recruited from April to November 2025 at a single tertiary center. Patients with fibromyalgia (2016 modified ACR criteria, systematically screened) were excluded. CS was assessed using the Central Sensitization Inventory (CSI ⩾40). Disease activity, functionality, pain phenotypes (PAIN DETECT questionnaire (PDQ)), sleep quality (Pittsburgh Sleep Quality Index), depression and anxiety (Hospital Anxiety and Depression Scale), and physical activity (International Physical Activity Questionnaire) and therapeutic refractoriness were systematically measured. Binary and linear regression analyses identified independent predictors of CS. CS was present in 35.1% of patients. CS was associated with higher disease activity indices (Clinical Disease Activity Index for Psoriatic Arthritis: 14 vs 9.8, p = 0.001; Ankylosing Spondylitis Disease Activity Score with C-reactive protein: 4.8 vs 1.8, p = 0.007), greater functional disability (Health Assessment Questionnaire-Disability Index: 0.8 vs 0.2, p = 0.001), increased neuropathic pain (55.6% vs 8.2%, p = 0.001), and notably higher prevalence of therapeutic refractoriness (61.5% vs 6.8%, p = 0.003). Independent predictors of CS presence were depression severity (HADS-D: odds ratio (OR) = 1.32, p = 0.01), poor sleep quality (Pittsburgh Sleep Quality Index: OR = 1.21, p = 0.001), and PDQ (OR = 1.07, p = 0.03). Depression, sleep quality, and fatigue explained 47% of CS variance in linear regression. Approximately one-third of unselected PsA patients experience CS, which independently contributes to therapeutic refractoriness despite inflammatory control. Psychosocial factors-particularly sleep dysfunction and depression-emerge as robust predictors of CS. These findings support systematic CS screening in PsA patients with inadequate symptomatic response and highlight the need for integrated biopsychosocial interventions addressing both inflammatory and non-inflammatory pain mechanisms. Central sensitization (pain hypersensitivity) is common in psoriatic arthritis and linked to poor treatment response, sleep problems, and depression Why was this study done? Psoriatic arthritis (PsA) is a condition that causes joint pain, stiffness, and swelling. Many patients continue to feel significant pain even when medication has successfully treated the swelling and inflammation. This type of pain may be caused by “central sensitization,” a condition where the nervous system becomes overly sensitive and amplifies pain signals. We wanted to find out how common this is in PsA patients, what factors (like sleep or mood) might be related to it, and if it makes treatments seem less effective. What did the researchers do? We studied 228 patients with PsA in a hospital setting. We specifically excluded patients who already had a diagnosis of fibromyalgia to ensure we were looking at pain related to PsA. We used questionnaires to measure central sensitization, pain levels, depression, anxiety, sleep quality, fatigue, and physical activity. We also checked their medical records to see if their treatments were working. What did the researchers find? We found that about one in three patients (35.1%) had central sensitization. These patients had higher pain scores and more difficulty with daily activities, even though their blood tests showed similar levels of inflammation to those without this condition. Importantly, patients with central sensitization were much more likely to be classified as having “difficult-to-treat” disease (refractory), often failing multiple biological medications. We also found that poor sleep, depression, and fatigue were strong predictors of having this type of pain. What do the findings mean? This study suggests that for many patients with PsA, persistent pain is caused by the nervous system rather than active inflammation. Doctors should check for central sensitization before switching strong medications, as these patients might benefit more from treatments that address sleep, mood, and pain sensitivity rather than just more anti-inflammatory drugs.
Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease affecting peripheral and axial joints, entheses, skin, and nails, requiring coordinated multidisciplinary management. Since the 2018 edition of ESPOGUÍA, significant advances-including the availability of IL-17A/F, IL-23, and JAK inhibitors, as well as emerging evidence regarding axial PsA-have prompted the need for an updated guideline. The 2024 ESPOGUÍA provides evidence-based recommendations for the diagnosis and management of PsA, integrating multidisciplinary collaboration, active nursing participation, lifestyle counseling, and specific considerations for axial disease. A panel comprising rheumatologists, dermatologists, gastroenterologists, ophthalmologists, nurses, methodologists, and patient representatives formulated clinical questions using the Population, Intervention, Comparator, and Outcomes (PICO) framework. Systematic literature reviews were performed, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to critically assess the quality of evidence and guide the formulation of recommendations. The guideline emphasizes early intervention and the appropriate use of conventional synthetic DMARDs, biologic therapies, and JAK inhibitors across different disease domains, including the management of extra-musculoskeletal manifestations. Lifestyle measures, such as smoking cessation and weight management, are highlighted due to their demonstrated impact on disease activity and long-term outcomes. The essential role of specialized rheumatology nurses in patient education, treatment adherence, and counseling on modifiable risk factors is also underscored. ESPOGUÍA 2024 provides a comprehensive, multidisciplinary, and patient-centered framework for PsA management, including axial involvement, and identifies persistent gaps in early diagnosis, biomarker development, and long-term outcomes, thereby outlining priorities for future research. Diagnosing and Treating Psoriatic Arthritis: Highlights from the 2024 Spanish Clinical Guidelines Psoriatic arthritis (PsA) is a long-term inflammatory disease that can affect the joints, spine, skin, nails, and enthesis. Symptoms and disease severity vary widely, so many people with PsA need care from several healthcare professionals working together. Since the last Spanish clinical guideline was published in 2018, major advances have been made in PsA treatment. New targeted medicines are now available, and there is better understanding of PsA that affects the spine (axial PsA). These changes led to an update of the guideline. The 2024 ESPOGUÍA guideline provides clear, evidence-based recommendations for diagnosing and managing PsA. It emphasizes multidisciplinary care, including the important role of nurses, and highlights the value of healthy lifestyle habits such as stopping smoking and maintaining a healthy weight. The guideline also includes specific advice for people with spinal involvement. A multidisciplinary group of doctors, nurses, researchers, and patient representatives developed the guideline using internationally accepted methods. They reviewed the best available scientific evidence and assessed its quality before making recommendations. The updated recommendations focus on early diagnosis and timely treatment to reduce symptoms and prevent long-term damage. They cover the use of conventional treatments, biological therapies, and newer targeted drugs, depending on individual disease features. Conditions affecting organs beyond the joints are also addressed. Specialized rheumatology nurses are recognized as key members of the care team, supporting patient education, treatment adherence, and lifestyle counselling. Overall, ESPOGUÍA 2024 offers a comprehensive, patient-centred approach to psoriatic arthritis care and identifies priorities for future research, including earlier diagnosis and better long-term outcomes.
Hand osteoarthritis (HOA) is a prevalent degenerative joint disorder that causes pain, functional disability, and considerable socioeconomic burden. China's rapid population aging and widespread engagement in repetitive manual labor may have accelerated to the rise of HOA. However, long-term trends and future projections of its disease burden remain insufficiently characterized. To describe trends in HOA incidence, prevalence, and DALYs from 1990 to 2021, examine differences across age and sex, and project future disease burden. A population-based descriptive study using GBD 2021 data to examine trends and project the burden of hand osteoarthritis in Chinese adults aged 30 years and older across national and subnational regions. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life year rate (ASDR) were analyzed by sex and age group. Temporal trends were quantified using Joinpoint regression to calculate annual and average annual percent changes (APC, AAPC), and future trends were projected to 2036 using an autoregressive integrated moving average (ARIMA) model. Between 1990 and 2021, the burden of HOA increased substantially worldwide, with China showing a faster rise than the global average. In China, ASIR rose from 59.12 to 92.70 per 100,000, ASPR from 988.51 to 1603.85, and ASDR from 31.57 to 51.26, corresponding to AAPCs of 1.46%-1.58%. Females experienced consistently higher rates than males and faster growth. The disease burden rose sharply after age 50 and peaked between 65 and 79 years. Joinpoint analysis revealed multiple inflection points, with the steepest acceleration occurring from 2015 to 2019 (APC >5%). ARIMA projections indicate that male rates will plateau or slightly decline by 2035, whereas female rates will continue rising, potentially exceeding 150 per 100,000 for incidence and 3000 per 100,000 for prevalence. The burden of HOA in China is increasing rapidly and is likely associated with population aging, sex-specific biological vulnerability, and occupational exposure. Women and elderly adults are disproportionately affected, with widening sex and age disparities. Targeted interventions-including ergonomic protection, menopausal health management, and early rehabilitation-are essential to mitigate the projected rise in disease burden and to improve musculoskeletal health in an aging population. Temporal trends and future projections of hand osteoarthritis burden in China from 1990 to 2021 Hand osteoarthritis is a common condition where the joints in the fingers and thumbs break down, causing pain and stiffness that can make daily tasks difficult. As China’s population gets older and people use their hands intensively for both manual jobs and digital devices like smartphones, this problem is getting much worse. A new study looked at data from 1990 to 2021 to understand how widespread and severe hand osteoarthritis has become in China. The findings show a fast and significant increase. The number of new cases, the total number of people living with the condition, and its overall impact on people’s lives and health have all nearly doubled over those 30 years. This rise in China has been faster than the global average. The burden of this disease is not shared equally. Women are affected more often and more severely than men, and the gap is widening. For everyone, the risk increases sharply after age 50, with the highest rates seen in adults aged 65 to 79. The fastest period of increase happened very recently, between 2015 and 2019. Using this data, researchers forecast trends to 2036. They predict that while the rate for men may level off, the number of women developing and living with hand osteoarthritis will continue to climb significantly. The main drivers behind this rising trend are the aging population, hormonal changes after menopause in women, repetitive hand use in certain jobs, and the widespread use of digital technology. To address this growing public health challenge, the study suggests that targeted steps are needed. These include promoting hand-friendly work tools and habits, providing better health support for women around menopause, and offering early rehabilitation programs. Taking action is crucial to reduce future pain and disability and improve the quality of life for China’s aging population.
Knee osteoarthritis (KOA) remains the most prevalent form of osteoarthritis and a major cause of global disability. The Kellgren-Lawrence (KL) grading system, though widely used, suffers from inter- and intra-observer variability, especially in early disease stages. Artificial intelligence (AI) offers a transformative approach to automate KL grading on plain radiographs, providing consistent, reproducible, and scalable diagnostic solutions. This narrative review synthesizes recent advances in AI-based KL grading models, focusing on methodological frameworks, performance, clinical applicability, and limitations. Narrative review of peer-reviewed studies applying AI-based methods for KL grading of KOA on radiographic images. Literature search was conducted across PubMed, Embase, Web of Science, and Google Scholar to identify studies published between 2016 and 2025. Eligible studies satisfied predefined selection criteria, applied AI-based methods to radiographic grading of KOA. The review focused on model architectures, dataset characteristics, validation strategies, performance metrics, and comparisons with expert radiographic assessment. Eighteen eligible studies were included. Convolutional neural networks (CNN) remain the core of automated KL grading, evolving from standard classification models to ensemble and ordinal regression frameworks. Model performance was evaluated against expert-assigned KL grades as reference standard, with reported accuracies ranging from 75% to 98% and area under the curve values up to 0.98. Agreement with expert annotations, Cohen's kappa (κ), ranged from 0.67 to 0.86. Deep Siamese networks, Faster R-CNNs, and ensemble frameworks have enhanced localization of KOA radiographic features, thereby interpretability relative to human radiologic assessment. Ordinal regression and attention-based visualization (saliency and class activation mappings) reduced misclassification between adjacent KL grades. Persistent challenges included subjective ground-truth labeling, dataset imbalance particularly under-representation of early (KL 0-1) and severe (KL 4) disease, and limited external validation. Models trained primarily on Osteoarthritis Initiative and Multicenter Osteoarthritis Study datasets showed reduced generalizability on external hospital datasets. AI-driven KL grading demonstrates near-human accuracy and strong promise for clinical integration. However, addressing labeling subjectivity, dataset diversity, and explainability remains essential for trustworthy deployment. While KL grading is inherently radiograph-based, integration of clinical metadata and longitudinal radiographic data may support more robust disease characterization. Federated learning frameworks offer a pathway to improve generalizability while preserving data privacy. How artificial intelligence can improve the Kellgren–Lawrence grading of knee osteoarthritis diagnosis on X-rays What is this research about? Knee osteoarthritis (KOA) is a common joint disease, causing pain and reduced mobility. Its severity is typically assessed using the Kellgren–Lawrence (KL) grading system based on knee X-rays, but results can vary between observers, especially in early disease. This review examined how artificial intelligence (AI) can improve the consistency, speed, and objectivity of KL grading. Why is this study important? KOA is a major global cause of disability. Early and accurate diagnosis is critical to slow disease progression and delay surgical intervention. Because traditional KL grading depends on expert interpretation and is prone to variability, AI-assisted grading offers the potential to standardize assessments and support clinical decision-making. How is the research conducted? The review analyzed studies published between 2016 and 2025 that applied AI to grade KOA severity from knee X-rays. It evaluated AI model types, datasets, and performance compared with expert readers. Most studies used deep learning models capable of learning imaging patterns automatically. What does the research find? Across 18 studies, AI models achieved accuracies between 75% and 98%, often matching expert performance. Convolutional neural networks (CNNs) were most effective, identifying features such as joint space narrowing and osteophytes. Ordinal regression and attention-based visualization improved grading of adjacent disease stages and interpretability. Key limitations included inconsistent labeling, limited dataset diversity, and scarce external validation. What do these findings mean? AI-based KL grading can provide fast, reproducible, and objective assessments, supporting clinicians, especially where radiology expertise is limited. While not a replacement for clinicians, AI shows strong potential as a decision-support tool. Future work should prioritize diverse datasets, explainable models, and real-world validation to enable safe clinical adoption.
Psoriatic arthritis (PsA) is a complex inflammatory disease with significant musculoskeletal, dermatological, and comorbidity burden. Despite therapeutic advances, many patients remain difficult to treat (D2T). Conventional definitions often overlook distinctions between inflammatory and non-inflammatory drivers, risking inappropriate treatment escalation. Two consensus frameworks-the European Alliance of Associations for Rheumatology (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-have recently been proposed to better capture this complexity based on disease drivers. To evaluate the applicability, overlap, and clinical utility of EULAR and GRAPPA definitions for difficult/complex-to-manage (D2M/C2M) and treatment-refractory PsA (TR-PsA) in a real-world cohort. We conducted a retrospective analysis within the prospective Ottawa Rheumatology CompreHEnSive TReatment and Assessment (ORCHESTRA) cohort, including consecutive PsA patients initiating or switching advanced therapy between April 2022 and September 2025. Patients were classified according to EULAR and GRAPPA frameworks into the broader D2M-PsA (EULAR) and C2M-PsA (GRAPPA) groups, and narrower inflammation-restricted TR-PsA subsets. Prevalence, overlap, and agreement were assessed using descriptive statistics and kappa analysis. Baseline clinical, comorbidity, and ultrasound characteristics were compared across groups. Seventy-six PsA patients were included. GRAPPA identified more patients as C2M-PsA (35/76; 46%) than EULAR's D2M-PsA (16/76; 21%). All EULAR D2M-PsA patients were included in C2M-PsA, whereas 19 additional patients were uniquely identified by GRAPPA due to less stringent treatment failure thresholds. Agreement between EULAR D2M-PsA and GRAPPA C2M-PsA was moderate (κ = 0.48). TR-PsA classification showed perfect agreement (κ = 1.000), with identical patients identified by both frameworks. D2M/C2M patients had longer disease duration and greater prior therapy exposure than non-D2T patients, while objective inflammatory measures were largely comparable. EULAR and GRAPPA D2T PsA frameworks share conceptual intent but differ in real-world clinical capture. EULAR preferentially enriches for multidomain involvement and inflammatory refractoriness after multiple therapy failures, whereas GRAPPA identifies a broader population reflecting earlier disease complexity. While both frameworks identified the same patients using inflammation-restricted criteria, differences in operationalization limit assumptions of interchangeability. Understanding how different frameworks define “difficult-to-treat” psoriatic arthritis in real-world patients Psoriatic arthritis (PsA) is a chronic inflammatory condition that can affect joints, skin, and many other aspects of health. Although several effective treatments are available, some patients remain difficult to manage. In these patients, ongoing symptoms may be caused by active inflammation, but also by other factors such as pain sensitization, comorbid conditions, or treatment intolerance. Distinguishing between these causes is important to avoid unnecessary escalation of immune-suppressing therapy. Recently, two expert groups—GRAPPA and EULAR—proposed new frameworks to better define “difficult-to-treat” PsA by considering disease drivers rather than treatment failure alone. However, how these frameworks perform in real-world clinical practice has not been well studied. In this study, we applied both frameworks to a real-world cohort of PsA patients from the ORCHESTRA registry in Canada who were starting or changing advanced therapies. We compared how often each framework identified patients as difficult-to-manage, how much they overlapped, and whether they identified similar clinical profiles. We found that the GRAPPA framework identified more patients as having complex or difficult-to-manage PsA, capturing patients earlier in their disease course with fewer treatment failures. In contrast, the EULAR framework identified a smaller group with more advanced disease and greater treatment exposure. When focusing only on patients with true inflammatory treatment refractoriness, both frameworks identified exactly the same patients. Overall, our findings suggest that while GRAPPA and EULAR share similar goals, they identify different patient populations in practice. GRAPPA may be more useful for recognizing early disease complexity, while EULAR may better identify patients with established inflammatory refractoriness. These differences should be considered when using these frameworks in clinical care and research.
Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive dysfunction. Alexithymia-difficulty identifying and describing emotions-has been reported in up to 48% of FM patients and is associated with increased psychological distress and pain intensity, yet its specific contribution to FM remains unclear. This study aimed to assess the interplay among alexithymia, self-compassion, pain catastrophizing, and hope to inform future integrated and emotion-focused treatment strategies for FM. We conducted a cross-sectional investigation, consecutively recruiting 112 Caucasian women meeting the 2016 American College of Rheumatology criteria for FM between October 2023 and June 2024. Socio-demographic, clinical, and psychometric data were collected at baseline. Disease burden was evaluated using the Widespread Pain Index, Symptom Severity Scale (SSS), Polysymptomatic Distress Scale, modified Fibromyalgia Assessment Scale, and revised Fibromyalgia Impact Questionnaire (FIQ-R). Psychological constructs were assessed using the Toronto Alexithymia Scale (TAS-20), Adult Hope Scale, Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), and Self-Compassion Scale (SCS). Participants were stratified into non-alexithymic, borderline, and alexithymic groups according to TAS-20 thresholds. Group differences were analyzed through χ2 or Kruskal-Wallis tests, and associations were examined using univariable and multivariable linear regression models (α = 0.05). Alexithymic traits were identified in 51.8% of patients. Individuals with alexithymia exhibited significantly higher anxiety, depression, and total HADS scores (all p < 0.01), greater pain catastrophizing (p = 0.003), and lower levels of hope (p < 0.05). Two self-compassion components, self-judgment and overidentification, were also significantly impaired (p = 0.012). Univariable analyses showed that alexithymia was positively associated with FM severity indices (SSS, FIQ-R) and psychological distress and negatively associated with hope and several self-compassion domains (all p < 0.001). In multivariable models, SSS (p < 0.001), PCS-Helplessness (p = 0.005), and SCS-Overidentification (p = 0.020) emerged as significant independent associated variables. Alexithymia represents a prominent marker of emotional vulnerability in FM, closely linked to symptom severity, maladaptive pain coping, and reduced hope and self-compassion. Integrating these constructs into FM assessment and management may support more comprehensive, emotion-focused therapeutic approaches. Understanding how emotional difficulties, negative thinking about pain, and low self-compassion shape the experience of fibromyalgia in women, to support better clinical assessment and more integrated treatment strategies Fibromyalgia (FM) is a long-lasting condition that causes widespread pain, fatigue, sleep problems, and other symptoms that strongly affect daily life. Many people with FM also struggle to recognize, understand, or express their emotions. This difficulty, known as alexithymia, may make it harder to cope with pain and stress, but its specific impact in FM is still not fully understood. In this study, we evaluated 112 Caucasian women diagnosed with FM to explore how alexithymia relates to disease burden and key psychological factors: hope, self-compassion, and pain catastrophizing (a pattern of negative thoughts about pain). All participants completed questionnaires measuring symptom severity and emotional well-being. Over half of the women in the study showed signs of alexithymia. Compared to those without alexithymia, these patients reported higher levels of anxiety and depression, more catastrophic thinking about pain, and lower levels of hope and self-compassion. They also tended to experience more severe fibromyalgia symptoms, particularly fatigue, sleep problems, and overall distress. When we analysed the data in detail, three factors were strongly linked to higher levels of alexithymia: 1. Greater symptom severity, 2. A stronger sense of helplessness toward pain, and 3. A tendency to become overwhelmed by negative experiences, reflected by low scores in the self-compassion domain of overidentification. These findings suggest that emotional difficulties are deeply intertwined with the experience of fibromyalgia. Addressing alexithymia and related psychological factors may help clinicians better understand patient needs and deliver more personalized care. Treatments that support emotional awareness, coping strategies, and self-compassion—such as mindfulness-based approaches—may be particularly helpful for individuals who struggle with these aspects. Overall, our results highlight that managing FM effectively requires attention not only to physical symptoms.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the axial skeleton, with tumor necrosis factor inhibitors (TNFi) as the standard first-line biologic disease-modifying antirheumatic drugs since the early 2000s. Interleukin-17 inhibitors (IL-17i) have emerged as effective alternatives, but the optimal sequencing after first-line TNFi discontinuation remains uncertain. To compare real-world treatment persistence of IL-17i and TNFi as second-line therapies following initial TNFi discontinuation in patients with axSpA. A nationwide retrospective cohort study using the Korean National Health Insurance Service-National Health Information Database (2010-2023). We included patients with axSpA who initiated TNFi as first-line targeted therapy and received IL-17i or TNFi as second-line therapy. The primary outcome was discontinuation of the second-line drug within 1 year. Drug retention was analyzed using Kaplan-Meier curves, and discontinuation risk was estimated using Cox proportional hazards models with multivariable adjustment, inverse probability of treatment weighting (IPTW), and IPTW with covariate adjustment. Subgroup analyses were conducted by type of prior treatment failure (primary or secondary). Among 1,660 patients (IL-17i: 375; TNFi: 1285), overall treatment persistence and discontinuation risk were similar between groups. However, patients with primary treatment failure had significantly higher discontinuation risk with TNFi versus IL-17i, with adjusted hazard ratios ranging from 1.54 (95% CI, 1.14-2.07) to 2.11 (95% CI, 1.13-3.94). Results remained consistent across all analytic approaches. While overall persistence was comparable, IL-17i showed greater retention than TNFi among patients with primary treatment failure to initial TNFi therapy. Treatment continuation with interleukin-17 inhibitors versus TNF inhibitors after switching from initial TNF inhibitor therapy in axial spondyloarthritis: findings from a nationwide Korean health insurance database study. Axial spondyloarthritis (axSpA), including ankylosing spondylitis, is a chronic inflammatory disease that affects the spine and sacroiliac joints. Biologic therapies such as tumor necrosis factor inhibitors (TNFi) are commonly used, but some patients discontinue these treatments because of insufficient response or side effects. After stopping the first TNFi, patients may switch either to another TNFi or to an interleukin-17 inhibitor (IL-17i). This study analyzed nationwide Korean health insurance data from 2010 to 2023 to compare how long patients continued their second biologic treatment after discontinuing the first TNFi. We evaluated treatment persistence (drug retention) and the risk of discontinuation within one year. The analysis included 1,660 patients with axSpA who received either IL-17i (375 patients) or TNFi (1,285 patients) as second-line therapy. Overall, treatment persistence was similar between IL-17i and TNFi users. However, in patients whose first TNFi failed to show sufficient effect (referred to as primary failure), those who switched to an IL-17i were significantly more likely to continue treatment than those who switched to another TNFi. These findings were consistent across several statistical analyses. In conclusion, both IL-17i and TNFi are effective options as second-line biologic therapies for patients with axSpA. However, IL-17i may provide better treatment continuity for those who did not respond adequately to their initial TNFi. These results may assist clinicians and patients in selecting optimal second-line biologic treatments for axial spondyloarthritis.
The recent availability of infliximab subcutaneous biosimilar in Europe represents a significant advancement in therapeutic delivery. Real-world data regarding the new formulation are still limited. To describe subcutaneous infliximab (scIFX) use in immune-mediated inflammatory diseases (IMIDs), evaluating clinical effectiveness, treatment persistence, and factors influencing drug retention rates (DRRs). Adult patients with IMIDs treated with scIFX either de novo or after switching from intravenous infliximab (ivIFX) were included. Disease activity was assessed using standard indices, and persistence was evaluated through 18-month DRRs. In total, 201 patients were included (66.7% women): 68 with psoriatic arthritis (33.8%), 66 axial spondyloarthritis (32.8%), 18 rheumatoid arthritis (9.0%), 18 Behçet's disease (9.0%), 16 juvenile idiopathic arthritis (8.0%), 10 Takayasu arteritis (5.0%), and 5 other IMIDs (2.5%). Median treatment duration was 14 months (interquartile range 13.0). Ninety-five patients (47.3%) switched from ivIFX, while 106 initiated scIFX de novo, of whom 74 (78.3%) received induction. Median disease activity grades improved from baseline through 24 months (p < 0.001). Fifty-five subjects (27.4%) discontinued scIFX. DRRs were 88.5%, 76.9%, and 68.3% at 6, 12, and 18 months, respectively. DRRs were higher in switchers versus de novo initiators (p = 0.038), also controlling for baseline activity and loading protocol (hazard ratio = 0.25 [95% confidence interval: 0.075-0.848], p = 0.026). De novo patients without induction had lower DRRs (p = 0.033) than those receiving induction, whereas line of biologic therapy (p = 0.066) and body mass index (BMI; p = 0.445) had no effect on scIFX DRRs. Adverse events occurred in 21 patients (10.4%). ScIFX appears effective across IMIDs, with sustained retention over time. Prior ivIFX exposure and use of induction protocols are associated with improved persistence, while treatment line and BMI appear not to influence outcomes. Studying the effectiveness of infliximab subcutaneous injections in inflammatory diseases This study looked at how well a medicine called subcutaneous infliximab (scIFX) works for people with several inflammatory diseases, such as arthritis, Behçet’s disease, and Takayasu arteritis. These diseases cause the immune system to attack the body and lead to pain and inflammation. Infliximab is usually given through a drip (an IV infusion), but the newer form can be injected under the skin, which is quicker and easier. Doctors collected information from 201 adults who received scIFX. About half had already been treated with infliximab through IV infusion and then switched to the injection. The other half started directly with scIFX. Some people starting treatment received extra early doses (induction) to help the medicine work faster. After more than a year of treatment, most people’s symptoms improved and stayed better over time. About 7 out of 10 people were still using scIFX after 18 months. People who had previously used the IV version or received the extra starting doses were more likely to continue treatment. Side effects happened in about 1 in 10 people, but no unexpected safety problems were found. Overall, scIFX seems to be an effective and well-tolerated treatment that many patients can continue long-term. Having used IV infliximab before, or starting with extra doses, may help people stay on the treatment longer.
Interleukin 8 (IL-8) is a chemokine involved in the pathogenesis of rheumatoid arthritis (RA). However, the clinical significance of its circulating levels remains poorly defined, partly due to technical challenges in measuring IL-8 in serum. Consequently, data on the relationship between serum IL-8 concentrations and specific disease manifestations in RA are limited. In this study, we aimed to investigate the associations between serum IL-8 levels and clinical, serological, and cardiovascular features in patients with RA. Cross-sectional study. A total of 216 RA patients were recruited. They underwent comprehensive evaluations, including disease-related characteristics and disease activity indices. Moreover, complete lipid profile, insulin resistance indices, metabolic syndrome criteria, and carotid ultrasound for carotid stiffness, intima-media thickness and carotid plaque detection were assessed. The SCORE2 -Systemic Cardiovascular Risk Estimation- was also calculated. IL-8 serum levels were measured using Simoa (Single Molecule Array) technique. A multivariable linear regression analysis was performed to examine the associations between disease characteristics and IL-8. C-reactive protein and IL-6 were significantly associated with higher IL-8 levels after multivariable adjustment. Likewise, disease activity scores were independently and positively correlated with higher serum IL-8 concentrations after adjustment for covariates. In contrast, rheumatoid factor and anti-citrullinated protein antibodies positivity showed no association with IL-8 levels. With respect to cardiovascular features, higher SCORE2 and carotid intima media thickness values were positively related to increased IL-8 concentrations. Serum IL-8 levels are independently and positively associated with disease activity scores in patients with RA. These findings suggest that IL-8 may have potential as a biomarker in this population but requires prospective validation and comparison with standard markers. The observed relationship between IL-8 levels and the SCORE2 risk calculator suggests a potential association between IL-8 and cardiovascular disease. The amount of interleukin-8 in the blood reflects how active rheumatoid arthritis is This study looked at the role of interleukin-8 (IL-8), a molecule involved in inflammation, in people with rheumatoid arthritis (RA). Although IL-8 is known to play a part in RA, its importance in everyday clinical practice has been unclear, partly because it is difficult to measure accurately in the blood. To address this, we measured IL-8 levels in 216 patients with RA and examined how these levels related to various aspects of the disease, including how active it was, blood test results, and risk factors for heart disease. We found that people with more active disease and higher levels of inflammation also had higher amounts of IL-8 in their blood. Additionally, those with a greater estimated risk of cardiovascular disease, as measured by the SCORE2 tool, tended to have higher IL-8 levels as well. However, the presence of certain antibodies commonly seen in RA was not linked to IL-8 concentrations. Overall, these findings suggest that IL-8 could be a useful marker for monitoring disease activity and possibly cardiovascular risk in people living with RA.
Body composition is increasingly recognized as an important modulator of chronic inflammation. However, the association between body composition parameters and disease activity in axial spondyloarthritis (axSpA) remains to be clearly established. We aimed to investigate the association between muscle, subcutaneous fat composition assessed via computed tomography (CT) imaging, and disease activity in patients with axSpA. This is a retrospective data registry observational study. This study analyzed 215 patients with axSpA. Body composition parameters were measured from pelvic CT scans. Parameters included the total adipose tissue volume to total skeletal muscle volume ratio (TATV/TSMV), a single-slice subcutaneous adipose tissue to skeletal muscle area ratio (SAT/SM), and skeletal muscle (SM) radiodensity. Disease activity was evaluated using the Ankylosing Spondylitis Disease Activity Score (ASDAS). Associations were analyzed using multivariate linear regression and restricted cubic splines (RCS). The probability of achieving major improvement (MI, ΔASDAS 2.0) was compared using Kaplan-Meier analysis. After adjusting for age, sex, and disease duration, a higher TATV/TSMV ratio, rather than the single-slice SAT/SM ratio, was independently associated with increased ASDAS-C-reactive protein (β = 0.722, 95% confidence interval (CI): 0.215-1.231, p = 0.004). SM radiodensity showed an inverse, nonsignificant association (p = 0.48). RCS analysis identified a threshold effect of the TATV/TSMV ratio on disease activity at 0.65 (nonlinear p = 0.045). Above this threshold, a higher ratio was significantly associated with elevated ASDAS-CRP (hazard ratio (HR) = 3.64, 95% CI: 1.13-11.71, p = 0.029). Patients with a ratio <0.65 had a significantly higher probability of achieving MI (HR = 1.64, 95% CI: 1.04-2.59, log-rank p = 0.04). The pelvic TATV/TSMV ratio is an independent imaging biomarker associated with higher disease activity and lower odds of clinical improvement in patients with axSpA. A cut-off value of 0.65 may be a promising tool for risk stratification in clinical practice. Can the ratio of fat to muscle in the pelvic area predict the severity of axial spondyloarthritis? A new study finds that patients with a higher fat ratio have greater disease activity and a lower chance of clinical improvement Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the spine. The balance of fat and muscle in the body (body composition) may influence chronic inflammation, but its specific link to disease severity in axSpA was unclear. This study investigated whether body composition measured from routine pelvic computed tomography (CT) scans relates to disease activity in axSpA. We analyzed data from 215 patients, calculating pelvic fatto-muscle ratios and muscle density from CT images. Disease activity was assessed using the standard Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP). After adjusting for age, sex, and disease duration, a higher ratio of total fat volume to total muscle volume was independently linked to worse disease activity, while other measures were not significant. We identified a key threshold: a ratio of 0.65. Patients with a ratio above 0.65 had significantly higher disease activity and a lower probability of major clinical improvement. Conversely, those below this threshold had a better chance of improvement. In summary, the pelvic fat-to-muscle volume ratio is a practical imaging biomarker. A ratio above 0.65 predicts higher disease activity and a poorer outlook in axSpA. This finding could help doctors identify high-risk patients earlier for more personalized management.
Axial spondyloarthritis (axSpA) is an inflammatory disease in which, despite expanding therapeutic options, a substantial proportion of patients do not achieve the desired treatment target, highlighting the emerging concept of difficult-to-manage (D2M) axSpA. To identify characteristics and predictive factors of D2M axSpA and to develop machine learning models for early identification. Longitudinal observational cohort study with external validation. Patients with axSpA from the SpA-Paz cohort initiating a first biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) between 2004 and 2019 were included. D2M was defined as failure of ⩾2 b/tsDMARDs, and very good responders (GR) as retention of the first b/tsDMARD ⩾3 years or discontinuation due to improvement. Baseline clinical data and baseline/6-month disease activity measures were collected. Factors associated with D2M were assessed using descriptive, comparative, and logistic regression analyses. Classification and Regression Tree (CART) models were developed and externally validated with the REGISPONSERBIO registry. Of 311 patients initiating b/tsDMARDs, 101 were included (42 D2M, 59 GR), with a D2M prevalence of 13.5%. D2M patients were more often smokers, Human Leukocyte Antigen B27 (HLA-B27) negative, and had higher rates of enthesitis and comorbidities. Baseline Axial Spondyloarthritis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) did not differ between groups, but after 6 months D2M patients showed higher disease activity (ASDAS 2.8 vs 1.6, BASDAI 5.4 vs 3.3; both p < 0.001). Multivariable models identified ASDAS, or BASDAI plus C-reactive protein (all at 6 months), as predictors of D2M. CART models achieved areas under the receiver operating characteristic curve of 0.70 (95% confidence interval (CI) 0.46-0.93; ASDAS model) and 0.76 (95% CI 0.55-0.97; BASDAI model), with external validation confirming discrimination. D2M axSpA affects approximately 1 in 8 patients initiating advanced therapy and is associated with smoking, HLA-B27 negativity, enthesitis, comorbidities, and poor 6-month response to first-line b/tsDMARDs. CART models using routine clinical data may support early identification. Identifying difficult-to-manage axial spondyloarthritis patients early in routine care: using clinical information and early treatment response to flag people more likely to need several advanced treatments Why was this study done? Axial spondyloarthritis is a long-term inflammatory condition that mainly affects the spine, but it can also involve other joints and cause symptoms involving the gut, eyes, and skin. Although several advanced treatments are available, some people do not improve enough and may need to change treatments more than once (“difficult-to-manage” disease). Early clues could help plan closer monitoring and earlier care decisions. What did the researchers do? Patients with axial spondyloarthritis from a hospital in Madrid, Spain, who started a first advanced treatment between 2004 and 2019 were studied. Two groups were compared: those who stopped at least two advanced treatments for any reason (difficult-to-manage) and those who did very well on the first treatment for ⩾3 years or stopped due to major improvement (very good responders). Clinical information was collected at the start and at 6 months. The researchers also developed clinical classification tools and tested them in an external Spanish registry. What did they find? Of 311 patients starting advanced treatment, 101 met the study definitions (42 difficult-to-manage and 59 very good responders). Difficult-to-manage disease affected about 1 in 8 patients. These patients were more often smokers, less often carriers of a genetic marker linked to the disease, and more likely to have inflammation of entheses and other health conditions. The clearest early warning sign was poor improvement after 6 months on the first advanced treatment; a standard disease activity score at 6 months was the strongest predictor. In the external registry, the classification tools showed acceptable performance in classifying patients as difficult-to-manage. What do these findings mean? Everyday clinic measures (especially the 6-month response to the first advanced treatment) may help identify patients at higher risk earlier, so care teams can monitor them more closely and adjust treatment sooner when needed.
Tocilizumab (TCZ), an interleukin-6 receptor inhibitor, is effective for moderate to severe rheumatoid arthritis (RA). However, maintaining remission after TCZ withdrawal remains challenging, and the treatment duration required before discontinuation to minimize relapse risk is unclear. To identify a TCZ treatment-duration threshold before withdrawal that is associated with a lower risk of relapse in patients with RA. This was a retrospective study including 97 patients with RA who discontinued intravenous TCZ after stable disease control. We retrospectively analyzed 97 RA patients who achieved remission or low disease activity prior to TCZ withdrawal. The primary outcome was relapse within 12 months post-discontinuation. Cox proportional hazards regression identified independent predictors, while restricted cubic spline (RCS) modeling assessed non-linear associations between treatment duration and relapse risk. A simplified risk stratification tool was developed and internally validated using bootstrap resampling. Among 97 patients with RA who discontinued TCZ after stable disease control, most were biologic-naïve (98.9%), the mean disease duration was 72.9 ± 52.7 months, and concomitant methotrexate and hydroxychloroquine were used in 73.2% and 47.4% of patients, respectively. During the 12-month follow-up, 54 patients (55.7%) relapsed. TCZ treatment duration was an independent protective factor (adjusted HR = 0.892 per month, p = 0.002), whereas anti-citrullinated protein antibody (ACPA) positivity was associated with increased relapse risk (adjusted HR = 2.122, p = 0.031). RCS analysis demonstrated an L-shaped non-linear relationship, identifying an empirically derived duration threshold at approximately 200 days associated with lower relapse risk. A simplified score assigning 1 point each for ACPA positivity and TCZ duration < 200 days stratified patients into low- (0 points), intermediate- (1 point), and high-risk (2 points) groups, with relapse rates of 27.3%, 53.8%, and 91.7%, respectively; the model showed acceptable discrimination (AUC = 0.76). Longer TCZ treatment duration and ACPA negativity were associated with a lower risk of relapse after TCZ withdrawal. An approximately 200-day treatment duration may serve as a clinically informative threshold for risk-stratified withdrawal decisions in routine practice, although disease control after withdrawal should be interpreted in the context of ongoing background therapy rather than confirmed drug-free remission. How long should tocilizumab be used before stopping in rheumatoid arthritis? Rheumatoid arthritis is a long-term condition in which the immune system attacks the joints, causing pain, swelling, and damage. Tocilizumab is a medicine that can control the disease well, but doctors and patients often face an important question: when can it be safely stopped? In this study, we reviewed 97 patients with rheumatoid arthritis whose disease was well controlled before they stopped tocilizumab. We then followed them for 12 months to see who remained stable and who had a return of symptoms. We found that a little more than half of the patients had a relapse within 1 year after stopping treatment. Two factors were especially important. First, patients who stayed on tocilizumab for a longer time were less likely to relapse. Second, patients who had a positive anti-citrullinated protein antibody blood test were more likely to relapse. Our analysis suggested that about 200 days of treatment may be an important time point. Patients who stopped treatment before this were much more likely to have their disease come back. We also developed a simple tool based on treatment duration and antibody status that could separate patients into low-, medium-, and high-risk groups. These results suggest that stopping tocilizumab too early may increase the chance of relapse, especially in patients with a positive antibody test. This may help doctors and patients make more informed decisions about treatment withdrawal. However, because this was a single-center retrospective study, larger studies are needed to confirm these findings.
Myofascial pain syndrome (MPS) is one of the most common causes of chronic pain. It is characterized by trigger points (TrPs) that are located within palpable taut bands (TBs) in muscles and their fascial structures. Traditionally, this clinical condition has been regarded as a dysfunction of the musculoskeletal system, commonly associated with mechanical overload, such as acute strain, repetitive movements, and/or abnormal posture holding. However, the intrinsic mechanisms underlying its development remain a subject of debate. This review proposes a paradigm shift: to consider MPS as a physiological protective response rather than a pathological disorder. From this perspective, the TrP-TB complex may represent a dual contributor to structural and functional protection. On the one hand, it might limit potentially harmful movements through local and segmental sensitization mechanisms. On the other hand, it could enhance joint stability by increasing the tension of the muscle fibers that form the TB and its intramuscular connective tissue, potentially augmenting proprioceptive input. This new perspective offers a revised conceptual framework in which phenomena traditionally interpreted as purposeless manifestations of painful dysfunction may instead be understood as defensive and/or compensatory responses. Such a perspective both broadens understanding of MPS and may encourage the development of treatment protocols that go beyond classical techniques, which focus mainly on inactivating TrPs and managing pain. This new perspective suggests incorporating strategies to modulate load, perform functional training, and address both peripheral and central sensitization within a comprehensive, multilevel framework. Ultimately, this perspective may help achieve more durable and sustainable therapeutic outcomes, possibly contributing to a reduction in the prevalence of pain-related disability associated with MPS. Is myofascial pain a disease—Or the body’s way of protecting its own musculoskeletal system? Myofascial pain syndrome (MPS) is a common cause of long-lasting muscle pain. It involves sensitive areas called trigger points, found in taut bands of muscle and surrounding fascial tissue. These are associated with many chronic musculoskeletal conditions, including low back pain, neck pain, sciatica, shoulder pain, and others. Traditionally, MPS has been viewed as a form of damage or pathological injury within muscle fibres, caused by strain, poor posture, or repetitive movements. This review presents a new perspective. It suggests that MPS may not be a disorder, but rather the body’s way of protecting itself from further harm. Just as fever was once considered harmful but it is now widely recognised as a helpful physiological response to infection, MPS may also serve a protective function. Taut bands and trigger points may form in muscles to limit potentially harmful movements and improve joint stability by increasing muscle tension and body awareness—particularly in response to actual or potential damage to muscles and joints. The review offers a clear and well-supported possible explanation of the pathophysiological mechanisms behind this protective response, based on current medical evidence. It also recommends treatment approaches that go beyond simply relieving pain. These include exercises to improve movement, reduce mechanical strain, and enhance posture, along with interventions that help regulate how the nervous system processes and responds to pain. This broader strategy may lead to longer-lasting relief and help reduce disability caused by chronic muscle pain—both in individual patients and across the general population.
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory noninfectious disease of the bone that predominantly affects children and adolescents. Bisphosphonates (BPs) are used to treat of CNO with most clinical experience involving pamidronate. Neridronate (NER) is an amino BP with a chemical structure and potency close to pamidronate. This study aims to evaluate the effectiveness and safety of NER in patients with CNO. Monocentric retrospective cohort study. This is a retrospective cohort study conducted on patients included in the monocentric CAMELOT (Chronic non-bActerial osteoMyELitis: A mOnocentric regisTry) registry. Response to treatment was evaluated semiquantitatively based on clinical, laboratory, and radiological domains. The cohort consisted of 27 subjects. Thirteen (48%) received NER alone. At baseline, patients receiving NER alone tended to have a higher rate of vertebral fractures than those treated with combination therapy (46% vs 29%; p = 0.4). The median number of peripheral lesions at magnetic resonance imaging was clearly lower in patients treated with NER alone (0 (interquartile range (IQR) 0-2) vs 2 (IQR 1-5); p = 0.01). An overall response (complete or partial) to NER was documented in all but one patient (96%). Six patients (22%) achieved a complete response in all the three domains, 83% of whom (n = 5) received NER without any other concomitant treatments. Interestingly, using a Receiver Operating Characteristic-derived cutoff of 2 years from CNO diagnosis, all patients who achieved a complete response (100%) had received NER within the first 2 years from diagnosis, compared with 57% (n = 12) of those who did not (p = 0.07). No long-term NER complications were observed. Neridronate appears to be a safe and effective option for CNO, particularly in patients with recent-onset disease, spinal involvement, and fewer peripheral lesions. Early initiation may be associated with higher rates of complete response, though further studies are needed to confirm these findings. Neridronate treatment for chronic nonbacterial osteomyelitis: Real-world evidence on effectiveness, safety, and the importance of early treatment Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease that can cause bone pain, swelling, and fractures, particularly affecting children and young adults. Because the disease is uncommon, there is limited information on the best treatment options and on their long-term safety. Neridronate is a medication that reduces bone inflammation and is increasingly used in CNO, but real-life data on its effectiveness are still scarce. In this study, we analyzed patients with CNO included in the CAMELOT registry, a single-center database that collects clinical information from routine care. We evaluated how well patients responded to neridronate by looking at symptoms, blood tests for inflammation, and imaging findings. We also assessed possible side effects. A total of 27 patients were included. Almost half received neridronate alone, while others received it together with additional treatments. Overall, neridronate was effective in nearly all patients, with improvement seen in symptoms, laboratory markers, or imaging findings. About one in five patients achieved a complete response, meaning improvement in all evaluated areas. Most of these patients were treated with neridronate alone. Importantly, all patients who achieved a complete response had started neridronate within two years of being diagnosed with CNO. This suggests that earlier treatment may lead to better outcomes. Neridronate was well tolerated, and no long-term safety concerns were observed during follow-up. In summary, neridronate appears to be a safe and effective treatment for chronic nonbacterial osteomyelitis, especially when started early in the disease course and in patients with spinal involvement or fewer affected bones. Further studies are needed to confirm these findings in larger groups of patients.
Knee osteoarthritis (KOA) is a leading cause of chronic pain and disability worldwide. Although exercise therapy is the recommended first-line treatment, many patients continue to experience pain and functional limitations. Dry needling (DN) has emerged as a potential adjunct therapy targeting myofascial and neuropathic pain mechanisms. To evaluate the effectiveness of DN combined with exercise therapy compared with exercise therapy alone for pain reduction and functional improvement in patients with KOA. Systematic review and meta-analysis of randomized controlled trials. A systematic search of PubMed, ClinicalTrials.gov, and the Cochrane Library was conducted from inception to October 23, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Studies involving adults with KOA comparing DN plus exercise with exercise alone or sham DN plus exercise were included. The primary outcome was pain intensity (Visual Analog Scale/Numeric Pain Rating Scale), while secondary outcomes included WOMAC scores, neuropathic pain, functional performance, and psychosocial measures. Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with the I 2 statistic, and risk of bias was evaluated using the Cochrane RoB-2 tool. Six randomized controlled trials involving 453 participants were included. Compared with exercise alone, DN plus exercise significantly reduced pain at 3 months (MD -1.91; 95% CI -2.60 to -1.21; I 2 = 66%). Significant improvements were also observed in WOMAC pain, stiffness, and physical function at short- and mid-term follow-up. Long-term outcomes (6-12 months) showed favorable trends, although CIs were wider. DN combined with exercise therapy may offer short- to mid-term improvements in pain and function in patients with KOA compared with exercise alone. However, the evidence is limited by a small number of studies, moderate certainty, and substantial heterogeneity, warranting cautious interpretation. The long-term benefits remain uncertain. Trial registration: PROSPERO (Registration ID: (CRD420261285294)). Does adding dry needling to exercise help reduce pain and improve movement in people with knee arthritis? Knee osteoarthritis is a common condition that causes long-term knee pain, stiffness, and difficulty walking or doing daily activities. Exercise is one of the most recommended treatments because it helps strengthen the muscles around the knee and improve movement. However, many people still have ongoing pain even after following an exercise program. Dry needling is a treatment where a trained healthcare professional inserts thin needles into tight or painful muscle areas. It is different from acupuncture and is used to reduce muscle tension and pain. Some therapists use dry needling together with exercise, but it is not clear whether this combination works better than exercise alone. In this study, we reviewed and combined results from six high-quality clinical trials including 453 people with knee osteoarthritis. We compared people who received dry needling plus exercise with those who received exercise alone. Our findings showed that people who received dry needling together with exercise had greater pain relief and better physical function in the short and medium term (around 3 months after treatment). Improvements in stiffness and daily activities were also seen. The long-term benefits were less certain, as fewer studies followed patients for longer periods. Overall, adding dry needling to an exercise program may provide extra short-term benefits for people with knee osteoarthritis. More research is needed to understand how long these benefits last.
The relationship between biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and the incidence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) remains unclear. To investigate the influence of b/tsDMARDs on the development of ILD in patients with RA, particularly in Asian patients. Retrospective cohort study. We examined data from patients with seropositive RA who had no prior ILD between January 1, 2010, and October 31, 2022, utilizing the Nationwide Korean Health Insurance Review and Assessment database. Cohort A consisted of individuals initiating b/tsDMARDs, while Cohort B included those starting conventional DMARDs, including individuals who subsequently began b/tsDMARDs. Patients were observed from the medication index date until the onset of ILD, death, or the conclusion of the study. In Cohort A, multivariate Cox proportional hazards analysis was conducted, followed by propensity score matching (PSM) analysis. In Cohort B, a time-dependent Cox proportional hazards analysis was performed, accounting for methotrexate (MTX) pretreatment period. In Cohort A (13,908 patients), the crude incidence rate (IR) of ILD was 3.05 per 1000 person-years. After multivariable adjustment and PSM, no statistically significant differences in ILD development were observed among the biologics classes, with hazard ratios (HRs) ranging from 0.81 to 1.19 when compared to tumor necrosis factor (TNF) inhibitors as a reference. In Cohort B (75,013 patients), the overall IR was 2.8 per 1000 person-years. Time-dependent multivariable Cox analysis, adjusting for baseline characteristics and MTX pretreatment duration, showed no statistically significant differences between biologic users and MTX maintainers (adjusted HR range: 0.74-1.29, all p > 0.05). No specific b/tsDMARDs consistently showed significant differences in ILD incidence compared to other b/tsDMARDs. Biologics showed no significant increase in the risk of ILD compared to MTX maintainers. TNF inhibitors performed similarly to non-TNF biologics and Janus kinase inhibitors in terms of ILD incidence. The incidence of interstitial lung disease found unchanged by the kinds of biologics or targeted synthetic disease modifying antirheumatic drugs Although biologic or targeted synthetic antirheumatic drug (b/tsDMARD) have improved the prognosis of RA, it is unclear which one class is specifically more helpful or harmful. Utilizing the extensive Nationwide Korean Health Insurance Review and Assessment (HIRA) database, which covers nearly the entire Korean population, this retrospective observational cohort study included two distinct cohorts: Cohort A, comprising patients initiating b/tsDMARD therapy after at least one year on cDMARDs, and Cohort B, consisting of patients starting cDMARDs with or without subsequent transition to b/tsDMARDs. Over a mean follow-up duration of approximately four years in both cohorts, multivariate Cox proportional analysis followed by propensity score matching analysis in Cohort A, and a time-dependent multivariate Cox analysis accounting for the methotrexate pretreatment period in Cohort B, did not show any specific class is better or worse in terms of the incidence of ILD.
Older age is a risk factor for serious infection (SI) associated with biologic or targeted synthetic DMARDs (b/tsDMARDs) use in rheumatoid arthritis (RA). Among older adults with RA, one-third are diagnosed at ⩾60 years (late-onset RA, LORA), while others are diagnosed earlier (young-onset RA, YORA). LORA is characterized by a more acute onset and heightened inflammatory burden due to age-related immune dysregulation. Whether RA onset age independently affects infection risk with b/tsDMARDs remains unclear. Evaluate SI risk in older adults with RA initiating b/tsDMARDs, stratified by RA onset age: LORA versus YORA. Retrospective cohort study using prospectively collected registry data. From FORWARD, the National Databank for Rheumatic Diseases (2001-2019), we identified RA patients aged ⩾60 years who initiated (1) anti-TNF then (2) subsequent non-TNF b/tsDMARDs. Patients were categorized as LORA versus YORA and matched using kernel-based propensity scores. SI was defined as an infection requiring hospitalization, intravenous antibiotics, or death. Multivariable Cox models estimated the risk of SI in LORA versus YORA. Among 1379 LORA and 2727 weighted YORA patients initiating anti-TNF therapy, the crude incidence of SI was 28.2 and 20.5 per 1000 person-years. In adjusted models, LORA was not associated with increased anti-TNF-related SI risk compared to YORA (HR 0.82, 95% CI 0.63-1.02). Among 198 LORA and 675 weighted YORA patients subsequently initiating non-TNF b/tsDMARDs, the crude incidence of SI was 17.3 versus 19.5 per 1000 person-years. In adjusted models, LORA was not associated with increased non-TNF related SI risk (aHR 0.81, 95% CI 0.31-2.12). Across cohorts, older age was independently associated with increased SI risk. For anti-TNF, prior SI and recent long-term glucocorticoid use, and for non-TNF, HAQ disability were also associated with SI. Age at RA onset was not independently associated with SI risk following b/tsDMARD initiation. Risk stratification should prioritize functional status and treatment history. Does the age at which rheumatoid arthritis begins affect the risk of serious infection in older adults treated with biologic medications? Older adults with rheumatoid arthritis (RA) are known to have a higher risk of serious infections when treated with biologic or targeted synthetic medications. However, it is unclear whether this risk is influenced by the age at which RA first develops. Some people develop RA later in life, while others are diagnosed earlier but continue treatment into older age. In this study, we examined adults aged 60 years and older with RA who started biologic or targeted therapies. We compared people whose RA began at age 60 or later (late-onset RA) with those who were diagnosed earlier in life (young-onset RA). We evaluated the risk of serious infections, defined as infections requiring hospitalization, intravenous antibiotics, or resulting in death. We found that the risk of serious infection did not differ meaningfully based on whether RA began earlier or later in life, both among patients starting anti-TNF therapies and among those starting other biologic or targeted treatments after prior anti-TNF use. Instead, infection risk was more strongly related to other factors, including older age, a prior history of serious infection, worse physical function, and recent long-term use of glucocorticoids (steroids). These findings suggest that, in older adults with RA, infection risk is influenced less by the age at which RA began and more by functional status and treatment-related factors. Efforts to reduce long-term steroid use, optimize disease-modifying therapy, and support physical function may be important strategies to lower infection risk in this population.
Public involvement is standard practice to enhance the quality, equity and impact of musculoskeletal pain research. In this review, we aimed to reflect on our own learning journey across multiple musculoskeletal projects and identify lessons learned from meaningful involvement. We then consider the changes needed at the researcher, funder and institutional levels to support involvement as a driver of relevance and impact. This is a narrative position paper drawing on experiential learning from three musculoskeletal pain studies and ongoing community engagement. We reflected on what we have learned from public contributors in our research, focusing on how involvement reshaped study priorities and tools. Lessons were synthesised to highlight recurring themes, supported by reference to reviews, guidance and empirical studies. Across all projects, several key themes emerged: (1) emphasis on purpose rather than process; (2) co-production and partnership rather than review; (3) flexibility and adaptation rather than predetermined steps; (4) relevant public contributors and partners; (5) focus on 'learning' rather than 'doing'; and (6) approaches to diversity and inclusion. Public partnerships should be a collaborative, transformative, relational and learning-based process that reshapes all aspects of research. Realising this potential might require flexible funding for early engagement, training in facilitation and reflexivity, sustained support beyond the research project to promote impact, and taking steps beyond building more infrastructure towards strengthening the systems that enable involvement to work effectively. Working together to improve muscle, joint, and bone pain research through shared learning This paper looks at how public partners (patients, service users, carers and members of the public with relevant lived experience) are involved in research on conditions affecting pain, muscles, bones, and joints. Involving the public in research is now widely expected. Not only does this approach ensures that research genuinely reflects the priorities of the public, but it also shapes the research question and methods to ensure relevance, thereby increasing the likelihood that the findings are meaningful and usable in the real-world. It ensures that research is conducted for the benefit of the public with public input. Involvement is not always meaningful. From our experience, we found that when involvement was genuine and followed the principles of good practice, it not only reshaped the research and tool design but also provided clearer pathways to end-user benefit, underpinned by continuous two-way learning. As we reflect on working with public partners as equals in co-creating our research, it has not only shaped the research to ensure it aligns with our public partners’ priorities, but it has also shaped us as researchers. As researchers, we also face challenges: we must learn to negotiate with public partners as equals and need appropriate support, such as flexible funding, to respond effectively to their knowledge and expertise.
Mononeuritis multiplex (MM) is a severe and clinically heterogeneous form of peripheral neuropathy, most commonly arising in the context of systemic vasculitis in rheumatology practice. Despite its potential to cause substantial functional impairment, data on its clinical spectrum, management, and outcomes remain limited. This study aimed to comprehensively evaluate the clinical characteristics, underlying etiologies, treatment approaches, and outcomes of MM in a nationwide multicenter rheumatology cohort. Retrospective, multicenter observational study. Adult patients diagnosed with MM by rheumatologists across 27 tertiary referral centers were included. Data were collected using a standardized case report form, encompassing demographic features, clinical presentation, electrophysiological findings, laboratory parameters, treatment modalities, and outcomes. Neurological status was assessed at the final follow-up visit. A total of 72 patients were analyzed (mean age 53.5 ± 14.9 years; 61.1% male). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was the most common underlying etiology (68%), with eosinophilic granulomatosis with polyangiitis being the predominant subtype. The typical clinical presentation consisted of acute-onset, asymmetric, distal involvement of the lower extremities, with foot drop as the most frequent manifestation (69.4%). Electrophysiological findings were consistent with a classical MM pattern in the majority of patients. Most patients received high-dose glucocorticoids combined with immunosuppressive therapy. Over a median follow-up of 29 months, 81.9% of patients achieved complete or partial neurological improvement. Outcomes were similar between ANCA-associated and non-ANCA-related diseases. MM represents a clinically diverse but potentially manageable neurological complication of rheumatic diseases. Early recognition supported by electrophysiological assessment, together with timely immunosuppressive treatment, may improve clinical outcomes. A multidisciplinary approach is essential to optimize long-term recovery and functional status. Nerve damage causing weakness in the arms or legs in people with rheumatic diseases: findings from a nationwide study Some people with rheumatic diseases can develop sudden damage to the nerves, which may cause weakness, numbness, or pain in the arms or legs. This condition can lead to problems such as difficulty walking or lifting the foot, commonly known as foot drop. If not recognized early, nerve damage may become permanent and seriously affect daily life. In this study, we looked at people who developed this type of nerve damage while having a rheumatic disease. Information was collected from many hospitals across the country to better understand how these patients present, how they are treated, and how well they recover over time. Most patients developed symptoms suddenly, often affecting one or more nerves in the legs. Many first noticed weakness rather than pain, and foot drop was a common early sign. The nerve problem was often linked to inflammatory rheumatic diseases that affect blood vessels. Treatment usually involved strong anti-inflammatory medicines and drugs that suppress the immune system. Encouragingly, most patients showed partial or complete improvement after treatment, especially when therapy was started early. However, some patients continued to experience long-term nerve symptoms, such as weakness or chronic pain. These findings show that nerve damage in rheumatic diseases, although serious, is often treatable. Recognizing warning signs like sudden weakness or foot drop and starting treatment promptly may greatly improve recovery. Close cooperation between different medical specialists is important to ensure early diagnosis and the best possible outcome for patients.