Biologics are complex protein-based medications derived from living organisms, used primarily to treat immune-related diseases. Unlike small-molecule drugs synthesized from chemicals, biologics are produced using advanced biotechnology, making their replication difficult. Biosimilars are nearly identical alternatives to biologics, and they offer a cost-effective option that produces equivalent safety or efficacy outcomes as their reference biologics. Biosimilars are not classified as generic drugs and have a unique regulatory pathway. While biosimilars must demonstrate structural, functional, and clinical similarity to reference biologics, regulatory requirements vary across the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO). The FDA used to mandate clinical studies for interchangeability status, while the EMA and WHO had more flexible approval pathways that enable broader biosimilar adoption. However, the FDA’s approach is evolving, and they may grant interchangeability with scientific justification without separate switching studies. Regulatory inconsistencies extend beyond biosimilars, as batch-to-batch variability in brand-name biologics does not face the same scrutiny as biosimilar approvals. Addressing these regulatory disparities and greater alignment among the FDA, EMA, and WHO may enhance biosimilar adoption. Acceptance of biosimilars may expand treatment accessibility, reduce healthcare costs, and maintain standards of safety and efficacy in managing musculoskeletal diseases.
Biologics are complex protein-based medications derived from living organisms, used primarily to treat immune-related diseases. Unlike small-molecule drugs synthesized from chemicals, biologics are produced using advanced biotechnology, making their replication difficult. Biosimilars are nearly identical alternatives to biologics, and they offer a cost-effective option that produces equivalent safety or efficacy outcomes as their reference biologics. Biosimilars are not classified as generic drugs and have a unique regulatory pathway. While biosimilars must demonstrate structural, functional, and clinical similarity to reference biologics, regulatory requirements vary across the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO). The FDA used to mandate clinical studies for interchangeability status, while the EMA and WHO had more flexible approval pathways that enable broader biosimilar adoption. However, the FDA’s approach is evolving, and they may grant interchangeability with scientific justification without separate switching studies. Regulatory inconsistencies extend beyond biosimilars, as batch-to-batch variability in brand-name biologics does not face the same scrutiny as biosimilar approvals. Addressing these regulatory disparities and greater alignment among the FDA, EMA, and WHO may enhance biosimilar adoption. Acceptance of biosimilars may expand treatment accessibility, reduce healthcare costs, and maintain standards of safety and efficacy in managing musculoskeletal diseases.
DOI: https://doi.org/10.37349/emd.2025.100798
This article belongs to the special issue Biosimilars: State of the Art in the Treatment of Rheumatic Diseases
Systemic inflammatory rheumatic disorders are associated with an increased risk of malignancy. The mechanism linking malignancy and rheumatic diseases is complex and multidirectional, and is only partially understood. This review focused on the incidence of neoplastic diseases in patients with the most common systemic rheumatic disorders. Rheumatoid arthritis is associated with a risk of malignancy that is about 10% higher than in the general population, and this is more related to the disease itself than to medication. Systemic lupus erythematosus is associated with an increased risk of neoplasms, particularly haematological malignancies such as non-Hodgkin lymphoma. The risk increases with long-lasting active disease. Systemic sclerosis is associated with an increased risk of lung and liver cancer, as well as malignancies of the haematological system. Men and patients with RNA polymerase III antibodies are at a higher risk. Dermatomyositis and polymyositis are subgroups of idiopathic inflammatory myopathy associated with a high risk of malignancy. Male gender and old age are additional risk factors. Other rheumatic diseases are also thought to be associated with an increased risk of cancer. Currently, the data are insufficient for a clear distinction to be made between subgroups at risk. Most patients with systemic autoimmune disorders are at enhanced risk of malignancy to some degree. The management of these patients should include procedures for the early detection of age- and population-specific malignancies, as well as those which are more prevalent in the patient population suffering from the individual rheumatic disease. It is important to note that an atypical disease course or increased treatment resistance for a rheumatic disorder may indicate that the observed changes are an expression of a paraneoplastic syndrome or that a new neoplasm is modifying the clinical course of an already diagnosed rheumatic disease.
Systemic inflammatory rheumatic disorders are associated with an increased risk of malignancy. The mechanism linking malignancy and rheumatic diseases is complex and multidirectional, and is only partially understood. This review focused on the incidence of neoplastic diseases in patients with the most common systemic rheumatic disorders. Rheumatoid arthritis is associated with a risk of malignancy that is about 10% higher than in the general population, and this is more related to the disease itself than to medication. Systemic lupus erythematosus is associated with an increased risk of neoplasms, particularly haematological malignancies such as non-Hodgkin lymphoma. The risk increases with long-lasting active disease. Systemic sclerosis is associated with an increased risk of lung and liver cancer, as well as malignancies of the haematological system. Men and patients with RNA polymerase III antibodies are at a higher risk. Dermatomyositis and polymyositis are subgroups of idiopathic inflammatory myopathy associated with a high risk of malignancy. Male gender and old age are additional risk factors. Other rheumatic diseases are also thought to be associated with an increased risk of cancer. Currently, the data are insufficient for a clear distinction to be made between subgroups at risk. Most patients with systemic autoimmune disorders are at enhanced risk of malignancy to some degree. The management of these patients should include procedures for the early detection of age- and population-specific malignancies, as well as those which are more prevalent in the patient population suffering from the individual rheumatic disease. It is important to note that an atypical disease course or increased treatment resistance for a rheumatic disorder may indicate that the observed changes are an expression of a paraneoplastic syndrome or that a new neoplasm is modifying the clinical course of an already diagnosed rheumatic disease.
DOI: https://doi.org/10.37349/emd.2025.100797
DOI: https://doi.org/10.37349/emd.2025.100796
Commercialized non-autologous biologics are produced from a variety of human tissues and are intended to treat a wide range of musculoskeletal pathologies. This survey focuses on non-autologous biologic products that are delivered via the topical or percutaneous (i.e., injected) routes. The regulatory framework established in the USA will be reviewed, including an assessment of specific categories of non-autologous biologics with their intended uses, since regulatory compliance of a specific composition or physical form of a non-autologous biologic is tightly linked to its advertised use. Guidance is provided on how to manage emerging products whose regulatory status might be unclear. Clinical safety and efficacy for non-autologous biologics for wound and burn care, including minimally processed placental products in sheet form as well as bio-engineered viable cell composite products, are well established, although efficacy tends to be wound type-specific. Micronized placental tissue products have been investigated in treating osteoarthritis of the knee and hip, and for plantar fasciitis, but require large-scale clinical studies and remain to be approved by the United States Food and Drug Administration (USFDA). Several emerging types (secretomes, exosomes) of non-autologous biologics are well documented in pre-clinical studies, but human studies are lacking. There are no Phase 3 studies reported on a secretome-based product, while there is just one Phase 3 clinical trial on-going for a bone marrow progenitor cell derived exosome product that is being used to treat acute respiratory distress syndrome. There has been substantial progress in the commercialization of exosome-based products, with studies in treating musculoskeletal pathologies a priority. Progress has been made in assessing the treatment of osteoarthritic knees and discogenic low back pain with cultured progenitor cells. However, utility and safety of these investigational products remains to be determined.
Commercialized non-autologous biologics are produced from a variety of human tissues and are intended to treat a wide range of musculoskeletal pathologies. This survey focuses on non-autologous biologic products that are delivered via the topical or percutaneous (i.e., injected) routes. The regulatory framework established in the USA will be reviewed, including an assessment of specific categories of non-autologous biologics with their intended uses, since regulatory compliance of a specific composition or physical form of a non-autologous biologic is tightly linked to its advertised use. Guidance is provided on how to manage emerging products whose regulatory status might be unclear. Clinical safety and efficacy for non-autologous biologics for wound and burn care, including minimally processed placental products in sheet form as well as bio-engineered viable cell composite products, are well established, although efficacy tends to be wound type-specific. Micronized placental tissue products have been investigated in treating osteoarthritis of the knee and hip, and for plantar fasciitis, but require large-scale clinical studies and remain to be approved by the United States Food and Drug Administration (USFDA). Several emerging types (secretomes, exosomes) of non-autologous biologics are well documented in pre-clinical studies, but human studies are lacking. There are no Phase 3 studies reported on a secretome-based product, while there is just one Phase 3 clinical trial on-going for a bone marrow progenitor cell derived exosome product that is being used to treat acute respiratory distress syndrome. There has been substantial progress in the commercialization of exosome-based products, with studies in treating musculoskeletal pathologies a priority. Progress has been made in assessing the treatment of osteoarthritic knees and discogenic low back pain with cultured progenitor cells. However, utility and safety of these investigational products remains to be determined.
DOI: https://doi.org/10.37349/emd.2025.100795
This article belongs to the special issue Innovation in Orthopedics
Background:
The ongoing digital transformation of healthcare has enabled innovative technologies that improve diagnosis, treatment planning, and outcomes. Among these, three-dimensional (3D) printing has gained prominence in surgical disciplines for converting digital imaging data into patient-specific physical models. In orthopedics and traumatology, 3D printing is used to produce anatomical models, surgical guides, and custom implants, thereby enhancing preoperative planning, surgical precision, and interdisciplinary communication. Despite its growing adoption, integrating 3D printing into clinical workflows remains complex and requires stringent quality assurance. Each phase of the production process—from image acquisition and segmentation to material selection and post-processing—affects the safety and performance of the final product. Standardized quality approaches and regulatory frameworks are therefore essential to ensure reproducibility, biocompatibility, and patient safety. This systematic review consolidates current knowledge on quality standards and implementation strategies for 3D printing in orthopedic and traumatological care. It identifies practical pathways for clinical integration while highlighting challenges, opportunities, and areas for future research.
Methods:
A systematic literature search was conducted in PubMed, the Cochrane Library, and the Web of Science, following the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) 2015 checklist and supplemented by manual searches. Reference management was performed using Rayyan QCRI (Qatar Computing Research Institute). Abstracts and full texts were analyzed with Voyant Tools to identify thematic focuses based on collocate analysis.
Results:
Nineteen publications met the inclusion criteria. The review highlights a focused but limited body of literature. Key factors influencing product quality include material choice, manufacturing accuracy, and adherence to validated quality control protocols.
Discussion:
With increasing digitalization and the integration of artificial intelligence, future quality initiatives will likely emphasize standardized preoperative planning, ethical oversight, and regulatory compliance to support personalized care models in orthopedics and traumatology.
Background:
The ongoing digital transformation of healthcare has enabled innovative technologies that improve diagnosis, treatment planning, and outcomes. Among these, three-dimensional (3D) printing has gained prominence in surgical disciplines for converting digital imaging data into patient-specific physical models. In orthopedics and traumatology, 3D printing is used to produce anatomical models, surgical guides, and custom implants, thereby enhancing preoperative planning, surgical precision, and interdisciplinary communication. Despite its growing adoption, integrating 3D printing into clinical workflows remains complex and requires stringent quality assurance. Each phase of the production process—from image acquisition and segmentation to material selection and post-processing—affects the safety and performance of the final product. Standardized quality approaches and regulatory frameworks are therefore essential to ensure reproducibility, biocompatibility, and patient safety. This systematic review consolidates current knowledge on quality standards and implementation strategies for 3D printing in orthopedic and traumatological care. It identifies practical pathways for clinical integration while highlighting challenges, opportunities, and areas for future research.
Methods:
A systematic literature search was conducted in PubMed, the Cochrane Library, and the Web of Science, following the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) 2015 checklist and supplemented by manual searches. Reference management was performed using Rayyan QCRI (Qatar Computing Research Institute). Abstracts and full texts were analyzed with Voyant Tools to identify thematic focuses based on collocate analysis.
Results:
Nineteen publications met the inclusion criteria. The review highlights a focused but limited body of literature. Key factors influencing product quality include material choice, manufacturing accuracy, and adherence to validated quality control protocols.
Discussion:
With increasing digitalization and the integration of artificial intelligence, future quality initiatives will likely emphasize standardized preoperative planning, ethical oversight, and regulatory compliance to support personalized care models in orthopedics and traumatology.
DOI: https://doi.org/10.37349/emd.2025.100794
This article belongs to the special issue Innovation in Orthopedics
Aim:
To evaluate the efficacy and tolerability of febuxostat (FBX) and benzbromarone (BNZ) combination therapy in patients with difficult-to-treat (D2T) gout.
Methods:
This observational study was performed at two centers and included patients fulfilling the 2015 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) gout classification criteria, with clinical tophi and suboptimal response to standard urate-lowering therapy. A two-step treatment regimen was implemented: a 6-month dose escalation of the FBX dose followed by add-on BNZ. Demographic, clinical, and laboratory data—including cardiovascular risk factors (CVRFs), history of nephrolithiasis, liver enzymes, and estimated glomerular filtration rate (eGFR)—were recorded. Changes in serum urate (SUA) and eGFR were analyzed using paired t-tests.
Results:
The study population comprised 15 patients (87% male, median age 59 years) with longstanding gout [median 15 years, range 3–31; interquartile range (IQR) 8–25]. Baseline SUA was 10.3 ± 1.7 mg/dL; mean eGFR was 63.7 ± 23.6 mL/min. CVRFs were common (hypertension, 93%; dyslipidemia, 73%: major adverse cardiovascular events, 13%; diabetes, 7%). At 12 months, SUA had decreased significantly to 2.9 ± 1.1 mg/dL (Δ = 7.4 mg/dL; p < 0.01), with FBX alone contributing to a Δ of 5.4 mg/dL and BNZ an additional Δ of 2.1 mg/dL (both p < 0.01). Tophi resolved in 60% of patients. No serious adverse events or significant changes in liver or renal function were observed. One unrelated death was recorded.
Conclusions:
FBX + BNZ was effective and well-tolerated in patients with severe D2T gout, achieving a substantial reduction in SUA and clinically significant dissolution of tophi.
Aim:
To evaluate the efficacy and tolerability of febuxostat (FBX) and benzbromarone (BNZ) combination therapy in patients with difficult-to-treat (D2T) gout.
Methods:
This observational study was performed at two centers and included patients fulfilling the 2015 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) gout classification criteria, with clinical tophi and suboptimal response to standard urate-lowering therapy. A two-step treatment regimen was implemented: a 6-month dose escalation of the FBX dose followed by add-on BNZ. Demographic, clinical, and laboratory data—including cardiovascular risk factors (CVRFs), history of nephrolithiasis, liver enzymes, and estimated glomerular filtration rate (eGFR)—were recorded. Changes in serum urate (SUA) and eGFR were analyzed using paired t-tests.
Results:
The study population comprised 15 patients (87% male, median age 59 years) with longstanding gout [median 15 years, range 3–31; interquartile range (IQR) 8–25]. Baseline SUA was 10.3 ± 1.7 mg/dL; mean eGFR was 63.7 ± 23.6 mL/min. CVRFs were common (hypertension, 93%; dyslipidemia, 73%: major adverse cardiovascular events, 13%; diabetes, 7%). At 12 months, SUA had decreased significantly to 2.9 ± 1.1 mg/dL (Δ = 7.4 mg/dL; p < 0.01), with FBX alone contributing to a Δ of 5.4 mg/dL and BNZ an additional Δ of 2.1 mg/dL (both p < 0.01). Tophi resolved in 60% of patients. No serious adverse events or significant changes in liver or renal function were observed. One unrelated death was recorded.
Conclusions:
FBX + BNZ was effective and well-tolerated in patients with severe D2T gout, achieving a substantial reduction in SUA and clinically significant dissolution of tophi.
DOI: https://doi.org/10.37349/emd.2025.100793
This article belongs to the special issue Pharmacological and Non-Pharmacological Management of Gout
Bone marrow mesenchymal stem cells (BMSCs) are multipotent progenitor cells with the capacity to differentiate into various mesenchymal lineages, including osteogenic, chondrogenic, and adipogenic tissues, rendering them promising candidates for regenerative medicine. This review delves into current foundational and preclinical research concerning BMSCs, with a particular emphasis on the use of genetically modified rat-derived BMSCs expressing green fluorescent protein (GFP) to facilitate in vivo cell tracking during tissue repair. It also examines various administration strategies, including intra-articular injections and magnetically guided cell targeting, to evaluate their therapeutic efficacy. Emerging evidence highlights the pivotal role of BMSCs in regenerating musculoskeletal tissues, including muscle, meniscus, and cartilage. Notably, the application of external magnetic fields (EMF) to direct magnetically labeled BMSCs to injury sites has demonstrated encouraging outcomes in cartilage repair. Furthermore, advances in BMSC culture techniques, single-cell genetic analysis, and tissue engineering methodologies may further augment their therapeutic potential. Preclinical and early-phase clinical studies underscore the promise of BMSCs as a minimally invasive therapeutic modality in orthopedic and regenerative medicine. Further research is essential to refine their applications and optimize delivery strategies, such as the use of internal magnetic fields generated by magnetized material implanted in damaged knee cartilage, to ensure long-term efficacy and safety.
Bone marrow mesenchymal stem cells (BMSCs) are multipotent progenitor cells with the capacity to differentiate into various mesenchymal lineages, including osteogenic, chondrogenic, and adipogenic tissues, rendering them promising candidates for regenerative medicine. This review delves into current foundational and preclinical research concerning BMSCs, with a particular emphasis on the use of genetically modified rat-derived BMSCs expressing green fluorescent protein (GFP) to facilitate in vivo cell tracking during tissue repair. It also examines various administration strategies, including intra-articular injections and magnetically guided cell targeting, to evaluate their therapeutic efficacy. Emerging evidence highlights the pivotal role of BMSCs in regenerating musculoskeletal tissues, including muscle, meniscus, and cartilage. Notably, the application of external magnetic fields (EMF) to direct magnetically labeled BMSCs to injury sites has demonstrated encouraging outcomes in cartilage repair. Furthermore, advances in BMSC culture techniques, single-cell genetic analysis, and tissue engineering methodologies may further augment their therapeutic potential. Preclinical and early-phase clinical studies underscore the promise of BMSCs as a minimally invasive therapeutic modality in orthopedic and regenerative medicine. Further research is essential to refine their applications and optimize delivery strategies, such as the use of internal magnetic fields generated by magnetized material implanted in damaged knee cartilage, to ensure long-term efficacy and safety.
DOI: https://doi.org/10.37349/emd.2025.100792
This article belongs to the special issue Cell Therapy and Tissue Engineering for Musculoskeletal Conditions: From Pre-clinical Studies to Clinical Trials
Gout is the most common inflammatory arthritis, and its prevalence is increasing in part due to the rise in chronic kidney disease (CKD). Guidelines for managing gout from the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) provide limited guidance for patients with advanced renal disease, partly due to the exclusion of this group of from clinical trials. This, along with concerns about adverse drug reactions contributes to the undertreatment of gout in advanced CKD. Gout management involves different phases: treatment of acute gout flares, implementing prophylaxis to prevent attacks and urate-lowering therapy (ULT). In this review, we examine the management of gout, with particular attention to recommended adjustments for patients with advanced CKD, those undergoing dialysis, or individuals who have received renal transplants. We review the medications used in the management of gout and suggest adjustments for their selection and dose in patients with advanced CKD. The article discusses colchicine, glucocorticoids, and IL1-β inhibitors for acute gout treatment and provides recommendations for flare prophylaxis. We review the use of xanthine oxidase inhibitors (allopurinol, febuxostat) and pegloticase as urate-lowering therapies for patients with advanced CKD, on dialysis, or with renal transplants. The possible side effects of gout treatments in patients with CKD and the suggested monitoring protocols are discussed. The potential impact of allopurinol, colchicine, and IL1-β inhibitors on cardiovascular disease outcomes are reviewed. Finally, new targets and drugs being explored for treating gout in patients with advanced CKD are discussed.
Gout is the most common inflammatory arthritis, and its prevalence is increasing in part due to the rise in chronic kidney disease (CKD). Guidelines for managing gout from the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) provide limited guidance for patients with advanced renal disease, partly due to the exclusion of this group of from clinical trials. This, along with concerns about adverse drug reactions contributes to the undertreatment of gout in advanced CKD. Gout management involves different phases: treatment of acute gout flares, implementing prophylaxis to prevent attacks and urate-lowering therapy (ULT). In this review, we examine the management of gout, with particular attention to recommended adjustments for patients with advanced CKD, those undergoing dialysis, or individuals who have received renal transplants. We review the medications used in the management of gout and suggest adjustments for their selection and dose in patients with advanced CKD. The article discusses colchicine, glucocorticoids, and IL1-β inhibitors for acute gout treatment and provides recommendations for flare prophylaxis. We review the use of xanthine oxidase inhibitors (allopurinol, febuxostat) and pegloticase as urate-lowering therapies for patients with advanced CKD, on dialysis, or with renal transplants. The possible side effects of gout treatments in patients with CKD and the suggested monitoring protocols are discussed. The potential impact of allopurinol, colchicine, and IL1-β inhibitors on cardiovascular disease outcomes are reviewed. Finally, new targets and drugs being explored for treating gout in patients with advanced CKD are discussed.
DOI: https://doi.org/10.37349/emd.2025.100791
This article belongs to the special issue Evaluation and Outcomes in the Management of Gout
Fracture non-union remains a significant clinical challenge despite considerable advances in diagnostic imaging and treatment modalities. Unpredictable healing, repeated interventions, and prolonged disability contribute to high patient morbidity and increased healthcare costs. Early and reliable prediction of non-union is therefore essential for timely intervention. This review discusses traditional radiographic assessment using the Radiologic Union Scale for the Tibia (RUST), its inherent limitations, and the emerging role of artificial intelligence (AI) and deep learning in fracture analysis. In addition, we review recent studies—including Bayesian classifiers and simulation models—that integrate AI for early prediction of non-union, and we provide an updated summary table of key studies.
Fracture non-union remains a significant clinical challenge despite considerable advances in diagnostic imaging and treatment modalities. Unpredictable healing, repeated interventions, and prolonged disability contribute to high patient morbidity and increased healthcare costs. Early and reliable prediction of non-union is therefore essential for timely intervention. This review discusses traditional radiographic assessment using the Radiologic Union Scale for the Tibia (RUST), its inherent limitations, and the emerging role of artificial intelligence (AI) and deep learning in fracture analysis. In addition, we review recent studies—including Bayesian classifiers and simulation models—that integrate AI for early prediction of non-union, and we provide an updated summary table of key studies.
DOI: https://doi.org/10.37349/emd.2025.100790
This article belongs to the special issue Innovation in Orthopedics
Primary care physicians (PCPs) play a critical role in the management of gout worldwide. However, significant gaps in gout care persist, underscoring the need for improved approaches to its management. While some guidelines, such as those from the American College of Physicians (ACP) published in 2016, support a more reactive treat-to-symptoms approach, others from the American College of Rheumatology (ACR) and the European Alliance Of Associations For Rheumatology advocate for a proactive treat-to-target (TTT) strategy—focused on achieving optimal serum urate levels through urate lowering therapy (ULT). This divergence reflects differing clinical priorities and differential interpretation of the evidence and it may contribute to variability in care delivery. Improving gout management requires greater engagement from both patients and healthcare providers, with particular emphasis on increasing adherence to ULT. Patients need enhanced support to better understand the importance of sustained urate lowering treatment, while healthcare providers may benefit from clearer guidance aligned with evidence-based strategies to foster greater patient trust and confidence. This article provides an overview of the current state of guidelines, highlights areas of agreement and discordance between them, and identifies key areas for improving care delivery. It additionally offers insight into alternative care delivery strategies, such as those involving non-physician health professionals, which have shown promise in enhancing patient outcomes. Future research should focus on continued development of innovative, multi-modal interventions to improve ULT adherence, including health system-based initiatives and collaborative care models.
Primary care physicians (PCPs) play a critical role in the management of gout worldwide. However, significant gaps in gout care persist, underscoring the need for improved approaches to its management. While some guidelines, such as those from the American College of Physicians (ACP) published in 2016, support a more reactive treat-to-symptoms approach, others from the American College of Rheumatology (ACR) and the European Alliance Of Associations For Rheumatology advocate for a proactive treat-to-target (TTT) strategy—focused on achieving optimal serum urate levels through urate lowering therapy (ULT). This divergence reflects differing clinical priorities and differential interpretation of the evidence and it may contribute to variability in care delivery. Improving gout management requires greater engagement from both patients and healthcare providers, with particular emphasis on increasing adherence to ULT. Patients need enhanced support to better understand the importance of sustained urate lowering treatment, while healthcare providers may benefit from clearer guidance aligned with evidence-based strategies to foster greater patient trust and confidence. This article provides an overview of the current state of guidelines, highlights areas of agreement and discordance between them, and identifies key areas for improving care delivery. It additionally offers insight into alternative care delivery strategies, such as those involving non-physician health professionals, which have shown promise in enhancing patient outcomes. Future research should focus on continued development of innovative, multi-modal interventions to improve ULT adherence, including health system-based initiatives and collaborative care models.
DOI: https://doi.org/10.37349/emd.2025.100788
This article belongs to the special issue Pharmacological and Non-Pharmacological Management of Gout
Aim:
This study aimed to explore the prevalence and risk factors of gout among fishermen in the Niger Delta.
Methods:
A total of 300 fishermen, aged 25–65 years, were recruited through stratified sampling. Data on demographic characteristics, seafood and alcohol consumption, physical activity, obesity, and family history of gout were collected using structured questionnaires and clinical assessments. Logistic regression analysis was applied to identify significant predictors of gout.
Results:
The study found that the prevalence of gout was 27%, with the highest occurrence among participants aged 46–55 years. Significant risk factors included high seafood intake (OR = 3.2, P < 0.01), alcohol consumption (OR = 2.8, P < 0.01), obesity (OR = 1.9, P = 0.03), physical inactivity (OR = 1.7, P = 0.04), and family history of gout (OR: 1.5, P = 0.05). Seafood consumption was identified as the most significant predictor of gout.
Conclusions:
This study revealed a significant prevalence of gout among fishermen in the Niger Delta, with high seafood consumption, alcohol intake, obesity, family history and physical inactivity identified as major contributors. Targeted public health interventions, such as dietary education programs, campaigns to reduce alcohol consumption, initiatives to promote physical activity, and regular health screenings, are essential to mitigate the prevalence and impact of gout among fishermen.
Aim:
This study aimed to explore the prevalence and risk factors of gout among fishermen in the Niger Delta.
Methods:
A total of 300 fishermen, aged 25–65 years, were recruited through stratified sampling. Data on demographic characteristics, seafood and alcohol consumption, physical activity, obesity, and family history of gout were collected using structured questionnaires and clinical assessments. Logistic regression analysis was applied to identify significant predictors of gout.
Results:
The study found that the prevalence of gout was 27%, with the highest occurrence among participants aged 46–55 years. Significant risk factors included high seafood intake (OR = 3.2, P < 0.01), alcohol consumption (OR = 2.8, P < 0.01), obesity (OR = 1.9, P = 0.03), physical inactivity (OR = 1.7, P = 0.04), and family history of gout (OR: 1.5, P = 0.05). Seafood consumption was identified as the most significant predictor of gout.
Conclusions:
This study revealed a significant prevalence of gout among fishermen in the Niger Delta, with high seafood consumption, alcohol intake, obesity, family history and physical inactivity identified as major contributors. Targeted public health interventions, such as dietary education programs, campaigns to reduce alcohol consumption, initiatives to promote physical activity, and regular health screenings, are essential to mitigate the prevalence and impact of gout among fishermen.
DOI: https://doi.org/10.37349/emd.2025.100789
Biosimilars are biologic products that provide equal mechanisms and efficacy to that of their original biologic references. This paper aims to provide a comprehensive overview of the numerous ways biosimilars are improving care for individuals living with rheumatoid arthritis (RA), from the effective application of biosimilars in treatment-naive RA patients, switching from an original biologic to a biosimilar, to the ability to tailor biologic therapy in respect to mechanisms provided by different biologic classes. Biosimilars provide a significant reduction in cost and provide patients with treatment options that do not exhibit adverse drug reactions (ADRs) as exhibited with methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Understanding mechanisms to discern patient response to biologic therapies will gain increasing importance as biosimilars with different targeted mechanisms enter the market. Patients who do not respond to one class of biologic medicine now have alternative biosimilars available to support their care. Study results support that patients initiated on biosimilars stay on biosimilars, so it is prudent to remain aware of the biosimilars available and candidates in development.
Biosimilars are biologic products that provide equal mechanisms and efficacy to that of their original biologic references. This paper aims to provide a comprehensive overview of the numerous ways biosimilars are improving care for individuals living with rheumatoid arthritis (RA), from the effective application of biosimilars in treatment-naive RA patients, switching from an original biologic to a biosimilar, to the ability to tailor biologic therapy in respect to mechanisms provided by different biologic classes. Biosimilars provide a significant reduction in cost and provide patients with treatment options that do not exhibit adverse drug reactions (ADRs) as exhibited with methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Understanding mechanisms to discern patient response to biologic therapies will gain increasing importance as biosimilars with different targeted mechanisms enter the market. Patients who do not respond to one class of biologic medicine now have alternative biosimilars available to support their care. Study results support that patients initiated on biosimilars stay on biosimilars, so it is prudent to remain aware of the biosimilars available and candidates in development.
DOI: https://doi.org/10.37349/emd.2025.100787
This article belongs to the special issue Biosimilars: State of the Art in the Treatment of Rheumatic Diseases
Calcium pyrophosphate deposition (CPPD) disease is the most prevalent crystal related arthropathy in the older-aged population. The clinical spectrum of CPPD arthropathy can include asymptomatic, acute, and chronic inflammatory disease that primarily results in irreversible structural joint damage. The manifestations and impact of structural damage that result from other inflammatory non-degenerative features of chronic CPP crystal inflammatory arthritis are often underrecognized and may lead to an inaccurate perception of disease severity. This pictorial essay sought to display the disease burden and various presentations of chronic inflammatory CPP crystal arthritis. Sonographic imaging of cases with chronic CPP arthritis was presented for diagnostic considerations and to demonstrate the extent of irreversible articular and peri-articular damage occurring at a structural level. Evolving understanding of the imaging characteristics of CPPD disease will provide a better appreciation of disease morbidity caused by this condition and stress the need to expand efforts to find effective treatments to dissolve crystal deposition and targeted therapies that will contain the inflammatory response to crystals. Recognizing the anatomic consequences of tissue damage that arise from CPPD disease should also help reflect on potential surgical alternatives to mitigate the progression of structural complications until effective disease modifying agents for this condition emerge.
Calcium pyrophosphate deposition (CPPD) disease is the most prevalent crystal related arthropathy in the older-aged population. The clinical spectrum of CPPD arthropathy can include asymptomatic, acute, and chronic inflammatory disease that primarily results in irreversible structural joint damage. The manifestations and impact of structural damage that result from other inflammatory non-degenerative features of chronic CPP crystal inflammatory arthritis are often underrecognized and may lead to an inaccurate perception of disease severity. This pictorial essay sought to display the disease burden and various presentations of chronic inflammatory CPP crystal arthritis. Sonographic imaging of cases with chronic CPP arthritis was presented for diagnostic considerations and to demonstrate the extent of irreversible articular and peri-articular damage occurring at a structural level. Evolving understanding of the imaging characteristics of CPPD disease will provide a better appreciation of disease morbidity caused by this condition and stress the need to expand efforts to find effective treatments to dissolve crystal deposition and targeted therapies that will contain the inflammatory response to crystals. Recognizing the anatomic consequences of tissue damage that arise from CPPD disease should also help reflect on potential surgical alternatives to mitigate the progression of structural complications until effective disease modifying agents for this condition emerge.
DOI: https://doi.org/10.37349/emd.2025.100786
This article belongs to the special issue Multifaceted Imaging in Rheumatic and Musculoskeletal Diseases
The temporomandibular joint (TMJ) involvement is an underestimated feature of juvenile idiopathic arthritis (JIA) since it is usually asymptomatic at presentation for an undeterminable time. Late diagnosis of TMJ arthritis in JIA patients leads to delayed treatment, long-term orofacial disturbances, and impaired health-related quality of life (HRQOL). Therefore, the detection of TMJ involvement is fundamental and represents a challenge. This perspective presents state-of-the-art current initiatives and available tools for early diagnosis of TMJ arthritis in children with JIA. Standardized protocols and multidisciplinary efforts for improving clinical skills in the assessment of TMJ in JIA are presented and commented on. An overview of imaging efforts for early detection of TMJ involvement in JIA is also provided, with a critical review of the advantages and limitations of different techniques, imaging protocols, and scoring systems. The perspective offers insights into the correct use and improvement of available and potential tools for early identification of TMJ arthritis in JIA subjects who deserve timely multidisciplinary treatment, avoiding both underestimation and over-diagnosis of TMJ arthritis in routine clinical practice.
The temporomandibular joint (TMJ) involvement is an underestimated feature of juvenile idiopathic arthritis (JIA) since it is usually asymptomatic at presentation for an undeterminable time. Late diagnosis of TMJ arthritis in JIA patients leads to delayed treatment, long-term orofacial disturbances, and impaired health-related quality of life (HRQOL). Therefore, the detection of TMJ involvement is fundamental and represents a challenge. This perspective presents state-of-the-art current initiatives and available tools for early diagnosis of TMJ arthritis in children with JIA. Standardized protocols and multidisciplinary efforts for improving clinical skills in the assessment of TMJ in JIA are presented and commented on. An overview of imaging efforts for early detection of TMJ involvement in JIA is also provided, with a critical review of the advantages and limitations of different techniques, imaging protocols, and scoring systems. The perspective offers insights into the correct use and improvement of available and potential tools for early identification of TMJ arthritis in JIA subjects who deserve timely multidisciplinary treatment, avoiding both underestimation and over-diagnosis of TMJ arthritis in routine clinical practice.
DOI: https://doi.org/10.37349/emd.2025.100785
This article belongs to the special issue Multifaceted Imaging in Rheumatic and Musculoskeletal Diseases
This sub-analysis of the PROPER study aimed to evaluate outcomes following the transition from reference adalimumab (ADL) to SB5 (Imraldi™) in routine clinical practice in Spanish patients with rheumatoid arthritis (RA). Adult Spanish patients (n = 73) with RA who initiated SB5 as part of routine clinical practice following treatment with reference ADL were recruited. Outcome measures included persistence on SB5, clinical characteristics, and disease activity scores at the time of transition to SB5 treatment, clinical management over time, and safety. At Week 48, the Kaplan-Meier [95% confidence interval (CI)] estimate of the probability of persistence on SB5 after switching from reference ADL was 0.84 (0.73–0.90) and 83.6% (46/55) of patients were in remission or had low disease activity. The majority of patients [83.6% (61/73)] experienced no disease flare during the study period and reported that the injection was “simple or very simple” to administer (baseline: 66.7%; Week 48: 69.0%) and were generally “satisfied or very satisfied” with the duration of the injection. In total, 21 patients (21/73, 28.8%) reported at least one drug-related adverse event, which were mild in most cases (17/21, 80.9%). In a Spanish cohort of patients with RA transitioning from reference ADL to SB5, the probability of SB5 persistence was high and treatment effectiveness was maintained for up to 48 weeks. There were no new safety signals and SB5 was well tolerated. These findings suggest that there is no evidence to mitigate against transition from reference ADL to SB5 in patients with RA (Clinicaltrials.gov listing: NCT04089514).
This sub-analysis of the PROPER study aimed to evaluate outcomes following the transition from reference adalimumab (ADL) to SB5 (Imraldi™) in routine clinical practice in Spanish patients with rheumatoid arthritis (RA). Adult Spanish patients (n = 73) with RA who initiated SB5 as part of routine clinical practice following treatment with reference ADL were recruited. Outcome measures included persistence on SB5, clinical characteristics, and disease activity scores at the time of transition to SB5 treatment, clinical management over time, and safety. At Week 48, the Kaplan-Meier [95% confidence interval (CI)] estimate of the probability of persistence on SB5 after switching from reference ADL was 0.84 (0.73–0.90) and 83.6% (46/55) of patients were in remission or had low disease activity. The majority of patients [83.6% (61/73)] experienced no disease flare during the study period and reported that the injection was “simple or very simple” to administer (baseline: 66.7%; Week 48: 69.0%) and were generally “satisfied or very satisfied” with the duration of the injection. In total, 21 patients (21/73, 28.8%) reported at least one drug-related adverse event, which were mild in most cases (17/21, 80.9%). In a Spanish cohort of patients with RA transitioning from reference ADL to SB5, the probability of SB5 persistence was high and treatment effectiveness was maintained for up to 48 weeks. There were no new safety signals and SB5 was well tolerated. These findings suggest that there is no evidence to mitigate against transition from reference ADL to SB5 in patients with RA (Clinicaltrials.gov listing: NCT04089514).
DOI: https://doi.org/10.37349/emd.2025.100784
This article belongs to the special issue Biosimilars: State of the Art in the Treatment of Rheumatic Diseases
Aim:
The use of anti-TNF drugs is well-established for treating axial spondyloarthritis (axSpA). The introduction of biosimilars offers a more accessible alternative, but data on the switching of adalimumab biosimilars in the axSpA population remain somewhat controversial and are limited to SB5 and ABP 501 and to the European population. This study aims to evaluate the clinical efficacy of switching from originator adalimumab to the biosimilar adalimumab-AACF in Latin American axSpA patients over a 12-month period in a real-life analysis.
Methods:
This observational study included patients with axSpA who had been treated with originator adalimumab for at least three months and switched to the biosimilar. Disease activity parameters and C-reactive protein (CRP) levels were assessed at baseline (T0) and compared at 6 (T6) and 12 months (T12) following the switch.
Results:
Twenty-eight patients were included, with a mean duration of originator adalimumab use of 87.6 months. Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP remained stable when comparing T0 to T6 [1.56 (± 0.88) vs. 1.50 (± 0.82), P = 0.73] and T12 [1.56 (± 0.88) vs. 1.26 (± 0.86), P = 0.13]. A similar pattern was observed for ASDAS-erythrocyte sedimentation rate (ESR; P > 0.05) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; P > 0.05). The rate of remission/low disease activity was consistent, recorded at 71.4% at baseline, 78.6% at T6 (P = 0.62) and 78.6% at T12 (P = 0.68). CRP levels did not show significant variation (P > 0.05) across time points. Notably, the one-year drug retention rate was 94.6%.
Conclusions:
This real-world study highlights for the first time the feasibility and efficacy of transitioning from originator adalimumab to biosimilar AACF in axSpA, providing support for its use in long-term management and offering enhanced accessibility without compromising therapeutic outcomes. These results add valuable Latin American data to the body of evidence on biosimilar integration into clinical practice.
Aim:
The use of anti-TNF drugs is well-established for treating axial spondyloarthritis (axSpA). The introduction of biosimilars offers a more accessible alternative, but data on the switching of adalimumab biosimilars in the axSpA population remain somewhat controversial and are limited to SB5 and ABP 501 and to the European population. This study aims to evaluate the clinical efficacy of switching from originator adalimumab to the biosimilar adalimumab-AACF in Latin American axSpA patients over a 12-month period in a real-life analysis.
Methods:
This observational study included patients with axSpA who had been treated with originator adalimumab for at least three months and switched to the biosimilar. Disease activity parameters and C-reactive protein (CRP) levels were assessed at baseline (T0) and compared at 6 (T6) and 12 months (T12) following the switch.
Results:
Twenty-eight patients were included, with a mean duration of originator adalimumab use of 87.6 months. Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP remained stable when comparing T0 to T6 [1.56 (± 0.88) vs. 1.50 (± 0.82), P = 0.73] and T12 [1.56 (± 0.88) vs. 1.26 (± 0.86), P = 0.13]. A similar pattern was observed for ASDAS-erythrocyte sedimentation rate (ESR; P > 0.05) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; P > 0.05). The rate of remission/low disease activity was consistent, recorded at 71.4% at baseline, 78.6% at T6 (P = 0.62) and 78.6% at T12 (P = 0.68). CRP levels did not show significant variation (P > 0.05) across time points. Notably, the one-year drug retention rate was 94.6%.
Conclusions:
This real-world study highlights for the first time the feasibility and efficacy of transitioning from originator adalimumab to biosimilar AACF in axSpA, providing support for its use in long-term management and offering enhanced accessibility without compromising therapeutic outcomes. These results add valuable Latin American data to the body of evidence on biosimilar integration into clinical practice.
DOI: https://doi.org/10.37349/emd.2025.100783
This article belongs to the special issue Biosimilars: State of the Art in the Treatment of Rheumatic Diseases
Routine regulatory requirements for large comparative efficacy trials (CETs) to support marketing approval of monoclonal antibody (mAb) biosimilars have been the focus of extensive debate in the last few years. This review examines the mounting evidence, accumulated over the past decade, focusing on relevant literature and data published in the European Product Assessment Reports (EPARs) for the fifteen anti-TNFα biosimilars approved to date. The potential for residual uncertainties that may require resolution through CETs following comparative physico-chemical, in-vitro potency, and single dose studies in healthy subjects is examined. It is noted that structural and physicochemical differences between biosimilars and reference products are detectable using modern analytical methods at levels well below those that could impact clinical outcomes, and that in vitro potency testing is fully capable of revealing clinically relevant differences. Additionally, comparative pharmacokinetic studies in healthy participants provide a sensitive assessment of potential differences in drug exposure and immunogenicity. The added value of CETs is further questioned in the light of the fact that anti-TNFα’s display a flat dose-response relationship, meaning that unlike cell-based assays, CETs have limited sensitivity to detect potency differences. Initial concerns about extrapolating data from rheumatoid arthritis studies to support marketing approval of other indications such as inflammatory bowel disease for which not all anti-TNFα’s are effective have been alleviated by post-approval studies. Additionally, as of the end of 2024, no cases where clinical efficacy data were necessary to resolve residual quality concerns have arisen following regulatory assessment of 56 mAb biosimilars and fusion proteins. CETs add significant cost and delay to the development of biosimilars and the time is now ripe to re-examine the need for these CET’s and for further evolution in regulatory thinking.
Routine regulatory requirements for large comparative efficacy trials (CETs) to support marketing approval of monoclonal antibody (mAb) biosimilars have been the focus of extensive debate in the last few years. This review examines the mounting evidence, accumulated over the past decade, focusing on relevant literature and data published in the European Product Assessment Reports (EPARs) for the fifteen anti-TNFα biosimilars approved to date. The potential for residual uncertainties that may require resolution through CETs following comparative physico-chemical, in-vitro potency, and single dose studies in healthy subjects is examined. It is noted that structural and physicochemical differences between biosimilars and reference products are detectable using modern analytical methods at levels well below those that could impact clinical outcomes, and that in vitro potency testing is fully capable of revealing clinically relevant differences. Additionally, comparative pharmacokinetic studies in healthy participants provide a sensitive assessment of potential differences in drug exposure and immunogenicity. The added value of CETs is further questioned in the light of the fact that anti-TNFα’s display a flat dose-response relationship, meaning that unlike cell-based assays, CETs have limited sensitivity to detect potency differences. Initial concerns about extrapolating data from rheumatoid arthritis studies to support marketing approval of other indications such as inflammatory bowel disease for which not all anti-TNFα’s are effective have been alleviated by post-approval studies. Additionally, as of the end of 2024, no cases where clinical efficacy data were necessary to resolve residual quality concerns have arisen following regulatory assessment of 56 mAb biosimilars and fusion proteins. CETs add significant cost and delay to the development of biosimilars and the time is now ripe to re-examine the need for these CET’s and for further evolution in regulatory thinking.
DOI: https://doi.org/10.37349/emd.2025.100782
This article belongs to the special issue Biosimilars: State of the Art in the Treatment of Rheumatic Diseases
Pyogenic arthritis (PA) related mortality trends have not been studied well across various demographics in the United States (US). This cross-sectional study aimed to evaluate these trends among the US population aged ≥ 25 years from 1999–2020 using data from the CDC WONDER database. We identified all the deaths where PA was listed as the underlying or contributing cause of death, using the ICD-10 code M00. Age-adjusted mortality rates (AAMRs) were calculated per 1 million US population and the Joinpoint regression model was used to assess the annual mortality trends by calculating the annual percent change (APC) in AAMRs. Between 1999 and 2020, 13,965 total deaths occurred among US adults aged ≥ 25 years with an AAMR of 2.94. The overall AAMR of PA increased significantly from 1999 to 2020 with an APC of 2.01 (p < 0.01). Males and older adults had consistently higher AAMRs than their respective counterparts. Non-Hispanic (NH) American Indians/Alaska Natives and NH Blacks/African Americans had higher mortality rates compared with other racial groups. The Midwest had the highest overall AAMR, followed by the West, Northeast, and South regions. In conclusion, PA mortality has been on the rise and targeted interventions are warranted to reduce disproportionate mortality rates among vulnerable populations.
Pyogenic arthritis (PA) related mortality trends have not been studied well across various demographics in the United States (US). This cross-sectional study aimed to evaluate these trends among the US population aged ≥ 25 years from 1999–2020 using data from the CDC WONDER database. We identified all the deaths where PA was listed as the underlying or contributing cause of death, using the ICD-10 code M00. Age-adjusted mortality rates (AAMRs) were calculated per 1 million US population and the Joinpoint regression model was used to assess the annual mortality trends by calculating the annual percent change (APC) in AAMRs. Between 1999 and 2020, 13,965 total deaths occurred among US adults aged ≥ 25 years with an AAMR of 2.94. The overall AAMR of PA increased significantly from 1999 to 2020 with an APC of 2.01 (p < 0.01). Males and older adults had consistently higher AAMRs than their respective counterparts. Non-Hispanic (NH) American Indians/Alaska Natives and NH Blacks/African Americans had higher mortality rates compared with other racial groups. The Midwest had the highest overall AAMR, followed by the West, Northeast, and South regions. In conclusion, PA mortality has been on the rise and targeted interventions are warranted to reduce disproportionate mortality rates among vulnerable populations.
DOI: https://doi.org/10.37349/emd.2025.100781
Chronic pain is a common problem in rheumatology. A distinction is made between nociceptive pain and nociplastic pain. Nociceptive pain is, for example, mechanistically explained by persistent inflammation. Neuropathic pain is caused by nerve damage of various possible causes. In contrast, nociplastic pain is not due to tissue damage or a lesion in the somatosensory nervous system—at least not with the currently available techniques. Nociplastic pain is based on an altered perception of pain through modulation of stimulus processing. The concept of central sensitization, together with other neurobiological and psychosocial mechanisms, is considered to be the best explanation for such pain conditions. The syndrome of fibromyalgia (FM), considered to be due to central sensitization, plays a major role in rheumatology—both in terms of differential diagnosis and because the management of inflammatory rheumatic diseases can be made more difficult by the simultaneous presence of FM. During the coronavirus pandemic, persistent pain syndromes with similarities to FM were described following a COVID-19 infection. There is a growing scientific controversy as to whether the so-called long COVID syndrome (LCS) is a separate entity or just a variant of FM.
Chronic pain is a common problem in rheumatology. A distinction is made between nociceptive pain and nociplastic pain. Nociceptive pain is, for example, mechanistically explained by persistent inflammation. Neuropathic pain is caused by nerve damage of various possible causes. In contrast, nociplastic pain is not due to tissue damage or a lesion in the somatosensory nervous system—at least not with the currently available techniques. Nociplastic pain is based on an altered perception of pain through modulation of stimulus processing. The concept of central sensitization, together with other neurobiological and psychosocial mechanisms, is considered to be the best explanation for such pain conditions. The syndrome of fibromyalgia (FM), considered to be due to central sensitization, plays a major role in rheumatology—both in terms of differential diagnosis and because the management of inflammatory rheumatic diseases can be made more difficult by the simultaneous presence of FM. During the coronavirus pandemic, persistent pain syndromes with similarities to FM were described following a COVID-19 infection. There is a growing scientific controversy as to whether the so-called long COVID syndrome (LCS) is a separate entity or just a variant of FM.
DOI: https://doi.org/10.37349/emd.2025.100780
Musculoskeletal ultrasound has become a valuable imaging tool in the diagnosis and management of rheumatologic disorders. Expertise in recognizing sonographic findings of pathology is the basis for its successful application in clinical use. This article will provide descriptions and a pictorial essay of ultrasound findings in common musculoskeletal manifestations of rheumatologic disorders.
Musculoskeletal ultrasound has become a valuable imaging tool in the diagnosis and management of rheumatologic disorders. Expertise in recognizing sonographic findings of pathology is the basis for its successful application in clinical use. This article will provide descriptions and a pictorial essay of ultrasound findings in common musculoskeletal manifestations of rheumatologic disorders.
DOI: https://doi.org/10.37349/emd.2025.100779
This article belongs to the special issue Multifaceted Imaging in Rheumatic and Musculoskeletal Diseases
