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Search Results (291)

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Keywords = antirheumatic drug

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31 pages, 2032 KiB  
Review
Leflunomide Applicability in Rheumatoid Arthritis: Drug Delivery Challenges and Emerging Formulation Strategies
by Ashish Dhiman and Kalpna Garkhal
Drugs Drug Candidates 2025, 4(3), 36; https://doi.org/10.3390/ddc4030036 - 1 Aug 2025
Viewed by 207
Abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) [...] Read more.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article
(This article belongs to the Section Marketed Drugs)
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60 pages, 3898 KiB  
Review
The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis
by Kalina A. Nikolova-Ganeva, Nikolina M. Mihaylova, Lidiya A. Kechidzhieva, Kristina I. Ivanova, Alexander S. Zarkov, Daniel L. Parzhanov, Momchil M. Ivanov and Andrey S. Marchev
Int. J. Mol. Sci. 2025, 26(14), 6813; https://doi.org/10.3390/ijms26146813 - 16 Jul 2025
Viewed by 503
Abstract
Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis [...] Read more.
Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5–1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules. Full article
(This article belongs to the Special Issue Natural Products as Multitarget Agents in Human Diseases)
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14 pages, 258 KiB  
Article
Prevalence and Risk Factors of Latent Tuberculosis Infection Detected by IGRA in Patients with Immune-Mediated Inflammatory Diseases Before and During Biologic DMARD Therapy (TITAN Study)
by José Antonio Mata-Marín, Marisol Apaez-Iglesias, Ana Luz Cano-Díaz, Juan Pablo Sánchez-Navarro, Diana Edith Fernández-Madinaveitia, Gustavo Barriga-Angulo, Salma Triana-González, Alberto Chaparro-Sánchez, Ericka Nelly Pompa-Mera and Jesús Enrique Gaytán-Martínez
J. Clin. Med. 2025, 14(14), 4990; https://doi.org/10.3390/jcm14144990 - 15 Jul 2025
Viewed by 424
Abstract
Background/Objectives: Patients with immune-mediated inflammatory diseases (IMIDs) treated with disease-modifying antirheumatic drugs (DMARDs) are at increased risk of latent tuberculosis infection (LTBI) reactivation, influenced by DMARD type. This study aimed to determine LTBI prevalence using interferon-gamma release assays (IGRAs) and identify associated [...] Read more.
Background/Objectives: Patients with immune-mediated inflammatory diseases (IMIDs) treated with disease-modifying antirheumatic drugs (DMARDs) are at increased risk of latent tuberculosis infection (LTBI) reactivation, influenced by DMARD type. This study aimed to determine LTBI prevalence using interferon-gamma release assays (IGRAs) and identify associated risk factors in IMID patients in a middle-high TB burden setting in Mexico. Methods: A cross-sectional study was conducted from July 2024 to April 2025 at an IMID clinic. Patients aged ≥18 years, either receiving DMARDs or prior to initiating treatment, were included. LTBI was diagnosed using the QuantiFERON-TB Gold Plus assay. Bivariate analysis was performed using the chi-square test, and multivariate analysis was conducted. Results: LTBI prevalence was 34.2% (95% CI 29.1–39.7%) according to QFT-Plus and 35.6% (95% CI 29.7–42.0%) according to TSTs (n = 230). Prior TB exposure was the strongest risk factor (aOR 4.20, 95% CI 1.74–10.12, p = 0.001), while rheumatoid arthritis was associated with a lower LTBI likelihood (aOR 0.31, 95% CI 0.16–0.59, p < 0.001). Conclusions: A high prevalence of LTBI was observed in patients with IMIDs treated with DMARDs. Prior tuberculosis exposure was strongly associated with LTBI. These findings highlight the importance of LTBI screening in this population to prevent reactivation. Full article
(This article belongs to the Section Infectious Diseases)
14 pages, 1017 KiB  
Article
Evaluation of Nurse-Implemented Self-Management Interventions for Patients with Chronic Inflammatory Arthritis in Bulgaria
by Stefka Stoilova, Mariela Geneva-Popova and Stanislava Popova-Belova
J. Clin. Med. 2025, 14(14), 4854; https://doi.org/10.3390/jcm14144854 - 9 Jul 2025
Viewed by 339
Abstract
Objective: To evaluate the role of nurses in self-management interventions for chronic inflammatory arthritis (CIA). Key areas of interest included the following: (1) providing education on self-injection techniques for biologic disease-modifying antirheumatic drugs (bDMARDs), (2) promoting healthy lifestyles, and (3) supporting mental health. [...] Read more.
Objective: To evaluate the role of nurses in self-management interventions for chronic inflammatory arthritis (CIA). Key areas of interest included the following: (1) providing education on self-injection techniques for biologic disease-modifying antirheumatic drugs (bDMARDs), (2) promoting healthy lifestyles, and (3) supporting mental health. Patients’ satisfaction with the care received was also examined. Methods: A cross-sectional study involving CIA patients, rheumatologists, and nurses was conducted. Participants assessed nurses’ competence in areas such as training for bDMARD self-injection, lifestyle guidance, and emotional support. Satisfaction scores and preferences in managing side effects were also analyzed. Results: The participants expressed high confidence in the nurses’ ability to support CIA self-management. The patients rated the nurses significantly higher than doctors in training for self-injection (p = 0.002) and offering guidance on nutrition and healthy habits (p = 0.002). Although it was not a statistically significant difference, the patients also showed stronger trust in the nurses’ ability to provide psychological and emotional support. Most patients (93.0%) would contact a rheumatologist in case of side effects; 35.5% would seek a nurse. The patients attended by both a doctor and nurse reported significantly higher satisfaction compared to those seen only by a rheumatologist (p < 0.001). Both the doctors and nurses acknowledged the importance of the nurse–patient relationship for effective care (p = 0.527). Conclusions: The findings highlight the critical role of nurses in patient education—particularly in training for self-injection and promoting a healthy lifestyle and mental well-being. Their involvement is strongly associated with higher patient satisfaction and contributes significantly to the overall effectiveness of care in CIA management. Full article
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15 pages, 266 KiB  
Article
Adverse Drug Reactions in an Intensive Care Unit of a Secondary Care Lithuanian Hospital: A Prospective Observational Study
by Greta Masiliūnienė, Gintautas Gumbrevičius, Edgaras Stankevičius and Edmundas Kaduševičius
Healthcare 2025, 13(13), 1592; https://doi.org/10.3390/healthcare13131592 - 3 Jul 2025
Viewed by 330
Abstract
Background and Objectives: Previous studies have shown that a major part of adverse drug reactions (ADRs) are preventable, and they contribute to increased morbidity, mortality, and costs. To our knowledge, no study investigating preventable ADRs has been carried out in Lithuania. Therefore, [...] Read more.
Background and Objectives: Previous studies have shown that a major part of adverse drug reactions (ADRs) are preventable, and they contribute to increased morbidity, mortality, and costs. To our knowledge, no study investigating preventable ADRs has been carried out in Lithuania. Therefore, the aim of this study was to characterize ADRs in the intensive care unit (ICU) of a secondary care Lithuanian hospital as well as to identify drug classes and organ systems most commonly implicated in preventable and nonpreventable ADRs. Materials and Methods: This observational prospective study was conducted in an 18-bed ICU of Kaunas Hospital of the Lithuanian University of Health Sciences from 1 September 2021 to 31 August 2023. All ADRs were assessed for causality, severity, and preventability. The Anatomical Therapeutic and Chemical (ATC) system was used to classify drug classes implicated in ADRs. The organ systems affected were analyzed using the Medical Dictionary for Regulatory Activities (MedDRA). Results: A total of 154 patients with a median age of 78.8 years (range, 18–97) were enrolled into this study. There were 255 ADRs identified; preventable ADRs accounted for 87.5%. Among the preventable ADRs, the top three therapeutic subgroups were antithrombotic agents (26.5%), anti-inflammatory and antirheumatic products (22.0%), and blood substitutes and perfusion solutions (20.2%). Meanwhile, among nonpreventable ADRs, antibacterials for systemic use (62.5%) and antithrombotic agents (46.9%) were the two most common therapeutic subgroups. The gastrointestinal as well as the skin and subcutaneous tissues organ systems were more likely to be affected by nonpreventable ADRs (56.3% vs. 17.5%, p ˂ 0.05 and 12.5% vs. 0.4%, p ˂ 0.05, respectively), while the renal and urinary organ systems were more likely to be affected by preventable ADRs (38.1% vs. 6.3%, p ˂ 0.05). Conclusions: Our study showed a very high incidence of preventable ADRs (87.5%). Drugs affecting blood and blood-forming organs were most frequently implicated in these ADRs. This area deserves special attention and strategies need to be implemented to reduce the incidence of preventable ADRs and their impact on the healthcare system. Moreover, it emphasizes the need for future studies at a national level as, to our knowledge, this is the first study addressing the issues of avoidable harm at the ICU of one Lithuanian hospital. Full article
(This article belongs to the Section Critical Care)
21 pages, 885 KiB  
Article
Survival Outcomes and Prognostic Factors in Rheumatoid Arthritis Patients Receiving Biologic or Targeted Synthetic Therapy: Real-World Data
by Zhaklin Apostolova, Tanya Shivacheva and Tsvetoslav Georgiev
Antibodies 2025, 14(3), 54; https://doi.org/10.3390/antib14030054 - 30 Jun 2025
Viewed by 653
Abstract
Objectives: The present study aimed to evaluate the long-term survival of patients with rheumatoid arthritis (RA) receiving biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in a real-world setting, and to identify key prognostic factors influencing mortality within this cohort. Methods: This retrospective, [...] Read more.
Objectives: The present study aimed to evaluate the long-term survival of patients with rheumatoid arthritis (RA) receiving biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in a real-world setting, and to identify key prognostic factors influencing mortality within this cohort. Methods: This retrospective, observational cohort study analyzed 165 patients with confirmed RA who were on b/tsDMARD treatment for at least six months as of June 2017. Patient data, including demographics, disease duration, prior therapeutic regimens, and global functional status were extracted from medical records to collect data covering a seven-year follow-up period, extending from June 2017 to December 2024. Corticosteroid use was defined as continuous systemic intake during the RA activity analysis period. Survival outcomes were analyzed using Kaplan-Meier methods and multivariate Cox proportional hazards models to identify independent predictors of mortality. Results: Over a mean follow-up of 9.4 years, the mortality rate was 13.5 deaths per 1000 treatment-years, with an overall survival rate of 87.3%. Advanced functional disability and prolonged corticosteroid use were independently associated with higher mortality risk. In subgroup analyses, chronic kidney disease significantly increased mortality among patients on TNF inhibitors. In contrast, patients who remained on their initial anti-IL6 therapy had lower mortality, though this may reflect survivor bias. Conclusions: This study highlights the importance of long-term b/tsDMARD intervention in RA patients, with observed low mortality and high survival rates. Subgroup findings suggest the importance of comorbidity management in TNFi users and therapeutic stability in anti-IL6 users. Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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29 pages, 510 KiB  
Systematic Review
Impact of Biologic Drugs on Comorbidity Outcomes in Rheumatoid Arthritis: A Systematic Review
by Soumaya Boussaid, Rim Dhahri, Safa Rahmouni, Halil İbrahim Ceylan, Marwa Hassayoun, Maissa Abbes, Khaoula Zouaoui, Ismail Dergaa, Sonia Rekik, Nadia Boussaid, Imen Gharsallah, Raul Ioan Muntean and Hela Sahli
J. Clin. Med. 2025, 14(13), 4547; https://doi.org/10.3390/jcm14134547 - 26 Jun 2025
Viewed by 615
Abstract
Background: The management of rheumatoid arthritis (RA) has advanced significantly with the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). Despite these therapeutic strides, RA prognosis remains profoundly affected by comorbid conditions, particularly cardiovascular and metabolic complications, which increase both morbidity and mortality. The [...] Read more.
Background: The management of rheumatoid arthritis (RA) has advanced significantly with the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). Despite these therapeutic strides, RA prognosis remains profoundly affected by comorbid conditions, particularly cardiovascular and metabolic complications, which increase both morbidity and mortality. The role of bDMARDs in modulating comorbidities remains underexplored, with limited evidence on their effects across various non-RA conditions, such as respiratory, diabetic, and hematologic disorders. This systematic review aimed to evaluate the impact of bDMARDs on the progression and outcomes of comorbidities in RA patients, providing insights to guide personalized treatment approaches. Methods: This systematic review was registered in PROSPERO (CRD42022345903) and followed the PRISMA guidelines. Original research articles from PubMed and Scopus, published up to 18 July 2024, were included. Studies assessing the impact of bDMARDs on comorbidities in RA patients met the eligibility criteria. Results: A total of thirteen studies met the inclusion criteria. They were published from inception until July 2024. The studied comorbidities included pulmonary conditions (asthma, chronic obstructive pulmonary disease, and interstitial lung disease) (n = 2); diabetes (n = 3); anemia (n = 3); and malignancies (n = 3). The bDMARDs studied were tumor necrosis factor inhibitors (TNFis) (n = 9); Rituximab (n = 5); Tocilizumab (n = 5); Abatacept (n = 5); and Anakinra (n = 2). The most reported effects of bDMARDs on comorbidities were the following: (i) an exacerbation of pulmonary comorbidities for Abatacept and TNFis; (ii) patients switched to or initiated on Abatacept as their first targeted disease-modifying antirheumatic drug (tDMARD) showed directionally lower rates and costs of T2DM-related complications compared with patients switching to or initiating other tDMARDs; (iii) there was no difference between Abatacept and TNFis or Rituximab/Tocilizumab regarding diabetes treatment switching or intensification; (iv) Anakinra significantly reduced the HbA1c%; (v) decreased serum hepcidin levels and improvement in anemia were observed in patients treated with TNFis or Tocilizumab; and (vi) no decrease in overall survival time or the significant incident malignancy rate was noted in RA patients. Conclusions: Overall, bDMARDs appear safe for use in RA patients with comorbidities and may even provide specific benefits for conditions such as anemia and diabetes. These findings suggest that clinicians could consider tailoring biologic therapy based on each patient’s comorbidity profile, potentially enhancing both RA management and comorbidity outcomes. For instance, selecting biologics such as Anakinra or Tocilizumab might be advantageous for RA patients with concurrent diabetes or anemia, given their observed metabolic and hematologic benefits. This personalized approach could improve the quality of life and reduce healthcare costs by addressing RA and associated comorbidities more effectively. Full article
(This article belongs to the Section Immunology)
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15 pages, 946 KiB  
Article
Insulin Predicts Methotrexate Response by Affecting the Transcription of Methotrexate Target Genes in the Treatment-Naive Rheumatoid Arthritis
by Victoria M. E. Lundgren, Malin C. Erlandsson, Venkataragavan Chandrasekaran, Sofia Töyrä Silfverswärd, Rille Pullerits and Maria I. Bokarewa
Cells 2025, 14(13), 964; https://doi.org/10.3390/cells14130964 - 24 Jun 2025
Viewed by 474
Abstract
Methotrexate (MTX), the most common first-line treatment in rheumatoid arthritis, is often insufficient, with no model capable of predicting response. The RA classification criteria, including autoantibodies and inflammation, were applied to 257 patients with newly diagnosed inflammatory arthritis in the cohort study, estimating [...] Read more.
Methotrexate (MTX), the most common first-line treatment in rheumatoid arthritis, is often insufficient, with no model capable of predicting response. The RA classification criteria, including autoantibodies and inflammation, were applied to 257 patients with newly diagnosed inflammatory arthritis in the cohort study, estimating MTX response. A total of 172 patients received MTX as the first anti-rheumatic drug and response was recorded at 1 year follow-up. A multivariable logistic regression used variables distinct between MTX-responders and non-responders to build the predictive model of response. Overall, 53.5% of MTX treated patients responded. Non-responders were frequently autoantibody positive, and responders were older, had lower RA classification scores, frequent corticosteroid use, and high insulin levels at baseline. Inflammation parameters were comparable between the groups. In the multiple regression analysis, the RA classification score and age at the first visit were strong predictors of MTX response (AUC 0.697, p < 0.0001). Including blood levels of insulin and IFNg improved AUC to 0.782 (p < 0.0001), offering early discrimination between responders and non-responders with high accuracy. Cellular experiments showed that insulin could be used to estimate MTX response by demonstrating that insulin changed the transcription of MTX target genes in the folate metabolism after exposing CD4+ cells ex vivo, which could facilitate MTX response in immune cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Targets of Autoimmune Diseases)
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14 pages, 651 KiB  
Article
Safety and Efficacy of Simultaneous Vaccination with Polysaccharide Conjugate Vaccines Against Pneumococcal (13-Valent Vaccine) and Haemophilus Type B Infections in Children with Systemic Juvenile Idiopathic Arthritis: Prospective Cohort Study
by Ekaterina Alexeeva, Tatyana Dvoryakovskaya, Dmitry Kudlay, Anna Fetisova, Ivan Kriulin, Elizaveta Krekhova, Anna Kabanova, Vladimir Labinov, Elizaveta Labinova and Mikhail Kostik
Vaccines 2025, 13(6), 644; https://doi.org/10.3390/vaccines13060644 - 15 Jun 2025
Viewed by 639
Abstract
Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening [...] Read more.
Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article
(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)
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10 pages, 2778 KiB  
Case Report
Protracted Tonsillitis as an Atypical Initial Manifestation of Methotrexate-Induced EBV-Positive Lymphoproliferative Disorder in Rheumatoid Arthritis: A Case Report and Literature Review
by Ting-Shen Lin, Tang-Yi Tsao, Shih-Wei Chen, Min-Cheng Ko and Stella Chin-Shaw Tsai
Diagnostics 2025, 15(12), 1517; https://doi.org/10.3390/diagnostics15121517 - 14 Jun 2025
Cited by 1 | Viewed by 527
Abstract
Background and Clinical Significance: Methotrexate is widely used as a disease-modifying antirheumatic drug for rheumatoid arthritis (RA), yet prolonged immunosuppression may lead to rare complications, including Epstein–Barr virus (EBV)-positive lymphoproliferative disorders (LPDs). Case Presentation: We present the case of a 70-year-old woman with [...] Read more.
Background and Clinical Significance: Methotrexate is widely used as a disease-modifying antirheumatic drug for rheumatoid arthritis (RA), yet prolonged immunosuppression may lead to rare complications, including Epstein–Barr virus (EBV)-positive lymphoproliferative disorders (LPDs). Case Presentation: We present the case of a 70-year-old woman with RA on chronic immunosuppressive therapy who developed symptoms resembling recurrent tonsillitis. CT imaging revealed bilateral necrotic palatine tonsils and extensive necrotic lymphadenopathy involving the cervical, mediastinal, and axillary regions. Bilateral tonsillectomy was performed due to concerns about malignancy or infection, and histopathology confirmed a polymorphic EBV-positive LPD with Hodgkin-like features, consistent with iatrogenic immunodeficiency-associated LPD. Methotrexate was subsequently discontinued, and the patient was managed conservatively without systemic chemotherapy. Clinical recovery was observed during follow-up. Conclusions: This case highlights the importance of considering methotrexate-associated LPDs in the differential diagnosis of atypical tonsillar infections in immunosuppressed patients, particularly when necrotic features or systemic lymphadenopathy are present. The pathogenesis may involve EBV reactivation under impaired immune surveillance due to methotrexate, leading to abnormal B-cell proliferation and clonal expansion. This case is contextualized through a comparative analysis of published reports, highlighting clinical features and treatment responses of methotrexate-associated EBV-positive LPDs in the form of a focused literature review. Full article
(This article belongs to the Special Issue Diagnosis and Management in Otolaryngology 2025)
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21 pages, 306 KiB  
Review
Individualized Management of Osteoarthritis: The Role of Pharmacogenomics to Optimize Pain Therapy
by Isabella M. Sturgeon and Youssef M. Roman
Future Pharmacol. 2025, 5(2), 30; https://doi.org/10.3390/futurepharmacol5020030 - 13 Jun 2025
Viewed by 1174
Abstract
Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying [...] Read more.
Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying Antirheumatic Drugs (DMARDs) for OA, current treatment strategies largely focus on symptom relief rather than disease modification. These symptomatic treatments often fail to account for the substantial inter-individual variability in drug response. Pharmacogenomics (PGx), the study of how genetic variation influences drug response, offers a promising approach to personalize OA therapy. This review explores the clinical and pharmacogenomic considerations of commonly used OA medications—acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol—focusing on gene–drug interactions that influence efficacy, safety, and metabolism. Evidence-based recommendations from the Clinical Pharmacogenetics Implementation Consortium guidelines are discussed, where applicable, to highlight actionable genetic variants in very important pharmacogenes such as CYP2D6, CYP2C9, and other important drug-metabolizing encoding genes such as CYP2E1 and UGT1A6. While PGx data are not currently embedded in OA clinical treatment guidelines, their integration into clinical practice may enhance therapeutic outcomes and minimize adverse drug events. This review underscores the potential of PGx as a clinical tool in OA pain management, paving the way toward truly personalized medicine. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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15 pages, 617 KiB  
Article
Italian Multicenter Real-World Study on the Twelve-Month Effectiveness, Safety, and Retention Rate of Guselkumab in Psoriatic Arthritis Patients
by Fabiola Atzeni, Cinzia Rotondo, Cesare Siragusano, Addolorata Corrado, Alberto Cauli, Roberto Caporali, Maria Sole Chimenti, Fabrizio Conti, Valentina Picerno, Elisa Gremese, Federica Camarda, Serena Guiducci, Roberta Ramonda, Luca Idolazzi, Angelo Semeraro, Marco Sebastiani, Giovanni Lapadula, Gianfranco Ferraccioli and Florenzo Iannone
J. Clin. Med. 2025, 14(12), 4111; https://doi.org/10.3390/jcm14124111 - 10 Jun 2025
Viewed by 728
Abstract
Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with [...] Read more.
Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article
(This article belongs to the Special Issue Targeted Treatment in Chronic Inflammatory Arthritis)
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14 pages, 790 KiB  
Article
Role of High Serum Tenascin C Levels as Potential Biomarker of Persistent Inflammation in Patients with Ankylosing Spondylitis Despite Treatment with cs-DMARDS or Anti-TNF Agents
by Alejandro Martelli-Garcia, Yussef Esparza-Guerrero, Heriberto Jacobo-Cuevas, Ana Miriam Saldaña-Cruz, Norma Guadalupe Gonzalez-Montoya, Cesar Arturo Nava-Valdivia, Eli Efrain Gomez-Ramirez, Maria Luisa Vazquez-Villegas, Juan Manuel Ponce-Guarneros, Melissa Ramirez-Villafaña, Norma Alejandra Rodriguez-Jimenez, Alberto Daniel Rocha-Muñoz, Ernesto German Cardona-Muñoz, Jaime Morales-Romero, Laura Gonzalez-Lopez and Jorge Ivan Gamez-Nava
Diagnostics 2025, 15(12), 1457; https://doi.org/10.3390/diagnostics15121457 - 7 Jun 2025
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Abstract
Background/Objectives: Ankylosing spondylitis (AS) is a severe chronic inflammatory rheumatic disease involving the spine, sacroiliacs, and peripheral joints. A lack of therapeutic response leads to severe sequelae. Currently, new markers are being tested to identify patients with poor outcomes. Tenascin C (TNC) is [...] Read more.
Background/Objectives: Ankylosing spondylitis (AS) is a severe chronic inflammatory rheumatic disease involving the spine, sacroiliacs, and peripheral joints. A lack of therapeutic response leads to severe sequelae. Currently, new markers are being tested to identify patients with poor outcomes. Tenascin C (TNC) is involved in triggering some relevant mechanisms of inflammation. Today, it remains unclear whether TNC levels might be useful as a biomarker of persistent activity. The aim of this study was to evaluate in AS whether serum levels of tenascin C are associated with persistent disease activity despite treatment. Methods: We included AS patients who had been treated with conventional synthetic disease-modifying antirheumatic drugs (cs-DMARDS) or anti-TNF agents for at least three months in a cross-sectional study. Response was assessed with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); scores ≥ 4 indicate persistent disease activity, while scores < 4 indicate inactive disease. Serum TNC levels, C-reactive protein (CRP) levels, and Erythrocyte Sedimentation Rate (ESR) were determined through the ELISA technique, nephelometry, and the Westergren method, respectively. Results: We evaluated 58 patients with AS (62.1% men); of them, 33 (56.9%) had persistent active disease (BASDAI ≥ 4) despite treatment and 25 (43.1%) had inactive disease (BASDAI < 4). The median TNC level was 18.6 ng/mL. BASDAI correlated with TNC levels (rho: 0.528, p < 0.001), CRP (0.352, p = 0.007), and ESR (0.342, p = 0.009). Patients with persistently active AS had higher serum TNC levels than those with inactive AS (35.2 vs. 6 ng/mL, p < 0.001). No differences in TNC level were found in patients treated with cs-DMARDS vs. anti-TNF agents. The ROC curve for serum tenascin C in active AS patients had an area under the curve = 0.78 (CI 95%: 0.65–0.91) with optimal serum tenascin C cutoff (>13.85 ng/mL). Sensitivity for detecting active AS was higher with TNC compared to ESR and CRP. Conclusions: We suggest that an elevated TNC level may be a useful biomarker of persistent disease activity despite treatment in AS; further studies should investigate the role of TNC levels in predicting the progression of the disease. Full article
(This article belongs to the Special Issue Recent Advances in Clinical Biochemical Testing)
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21 pages, 3372 KiB  
Article
Ultrasound Evaluation of Therapeutic Response to Tofacitinib and Upadacitinib in Patients with Rheumatoid Arthritis—Real-Life Clinical Data
by Vladimira Boyadzhieva, Konstantin Tachkov, Soner Emin, Zhaklin Apostolova, Rumen Stoilov, Guenka Petrova and Nikolay Stoilov
Biomedicines 2025, 13(6), 1339; https://doi.org/10.3390/biomedicines13061339 - 30 May 2025
Viewed by 693
Abstract
Background: In recent years, musculoskeletal ultrasonography (MSUS) has established itself as a reliable method for evaluating disease activity in combination with clinical examination and laboratory tests. Objectives: In this pilot study, we aimed to evaluate the ultrasound response to treatment with [...] Read more.
Background: In recent years, musculoskeletal ultrasonography (MSUS) has established itself as a reliable method for evaluating disease activity in combination with clinical examination and laboratory tests. Objectives: In this pilot study, we aimed to evaluate the ultrasound response to treatment with tofacitinib and upadacitinib on tendons and joints in comparison to clinical and laboratory results in patients with RA who have shown inadequate response to conventional synthetic and/or biologic disease-modifying antirheumatic drugs (cs/b DMARDs). Methods: This study presents the MSUS assessment of therapeutic response in RA patients treated with tofacitinib or upadacitinib over a 24-week period. In a prospective, single-center study, patients were treated with upadacitinib 15 mg/daily or tofacitinib 2 × 5 mg/daily or 11 mg/daily, in combination with or without methotrexate or another conventional DMARDs. Disease activity was assessed by DAS28-CRP, CDAI, and SDAI, as well as MSUS. Patients were evaluated at baseline for ultrasound measures and at weeks 2, 4, 8, 12, and 24 for the rest of the indicators. For each patient, we used two ultrasound (US) scores (gray-scale, GS, and power Doppler, PD scores) and the system of European Alliance of Associations for Rheumatology outcome measures in rheumatology (EULAR-OMERACT) US scoring (combined GS and PD). We also calculated the tenosynovitis score (GS and PD) according to OMERACT recommendations. Results: A total of 53 patients were recruited. A total of 25 patients with a mean age of 56 ± 11.6 SD were followed in the upadacitinib group, and 22 patients with a mean age of 56.9 ± 11.3 were followed in the tofacitinib group. At baseline, DAS28-CRP for the upadacitinib group was 5.57 ± 1.24, and for tofacitinib, it was 4.77 ± 1.47. The baseline visit (GS, PD, and combined—US) and tendon US scores (GS and PD) were, respectively, 23 ± 2.96, 15 ± 2.56, 24.08 ± 3.36, 11.04 ± 2.21, and 8.44 ± 1.65 for the upadacitinib group. USGS-J—23 ± 3.55, USPD-J—13.36 ± 2.44, OMERACT composite—23.4 ± 3.84, USGS-T—12.18 ± 2.23, and USPD-T—9.5 ± 1.92 were found in the patients treated with tofacitinib. In both groups of patients, a significant reduction was found in both DAS28-CRP and the described MSUS scores at weeks 8, 12, and 24 (p < 0.05). Conclusions: Upadacitinib managed to produce lower echography scores much faster than tofacitinib; however, the differences in effectiveness evened out at weeks 12 and 24, with all patients being adequately controlled. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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9 pages, 1437 KiB  
Case Report
Diagnosis and Management of Chronic Nonbacterial Osteomyelitis in a Dog
by Young-Sun Jeong, Yun-Joo Geum and Hyun-Jung Han
Animals 2025, 15(11), 1593; https://doi.org/10.3390/ani15111593 - 29 May 2025
Viewed by 475
Abstract
This case presents the first documented successful medical management of chronic nonbacterial osteomyelitis (CNO) in a small dog—a condition rarely described in veterinary medicine. A 4-year-old castrated male Pomeranian dog weighing 4.6 kg was presented with a 3-week history of right hindlimb lameness. [...] Read more.
This case presents the first documented successful medical management of chronic nonbacterial osteomyelitis (CNO) in a small dog—a condition rarely described in veterinary medicine. A 4-year-old castrated male Pomeranian dog weighing 4.6 kg was presented with a 3-week history of right hindlimb lameness. Radiographic examination revealed osteolytic lesions, periosteal reactions, and decreased muscle mass in the affected limb. Microbial and blood culture tests showed negative results, whereas cytological and histopathological analyses of the right distal femur confirmed neutrophilic inflammation and osteomyelitis, leading to a diagnosis of CNO. Clinical and radiographic improvements were observed following administration of bisphosphonates, disease-modifying anti-rheumatic drugs, and glucocorticoids. This case underscores the possibility of non-infectious osteomyelitis in dogs and suggests that adapting human treatment strategies may be beneficial. Further research is needed to clarify the diagnostic criteria and pathophysiology of CNO in veterinary medicine. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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