Disease-modifying Drugs Research Articles

Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis

Osteoarthritis is a leading cause of disability, and disease-modifying osteoarthritis drugs (DMOADs) could represent a pivotal advancement in treatment. Identifying the potential of antidiabetic medications as DMOADs could impact patient care significantly. We designed a comprehensive analysis pipeline involving two-sample Mendelian Randomization (MR) (genetic proxies for antidiabetic drug targets), summary-based MR (SMR) (for mRNA), and colocalisation (for drug-target genes) to assess their causal relationship with 12 osteoarthritis phenotypes. Summary statistics from the largest genome-wide association meta-analysis (GWAS) of osteoarthritis and gene expression data from the eQTLGen consortium were utilised. Seven out of eight major types of clinical antidiabetic medications were identified, resulting in fourteen potential drug targets. Sulfonylurea targets ABCC8/KCNJ11 were associated with increased osteoarthritis risk at any site (odds ratio (OR): 2.07, 95% confidence interval (CI): 1.50-2.84, P<3×10-4), while PPARG, influenced by thiazolidinediones (TZDs), was associated with decreased risk of hand (OR: 0.61, 95% CI: 0.48-0.76, P<3×10-4), finger (OR: 0.50, 95% CI: 0.35-0.73, P<3×10-4), and thumb (OR: 0.49, 95% CI: 0.34-0.71, P<3×10-4) osteoarthritis. Metformin and GLP1-RA, targeting GPD1 and GLP1R respectively, were associated with reduced risk of knee and finger osteoarthritis. In the SMR analyses, gene expression of KCNJ11, GANAB, ABCA1, and GSTP1, targeted by antidiabetic drugs, was significantly linked to at least one osteoarthritis phenotype and was replicated across at least two gene expression datasets. Additionally, increased KCNJ11 expression was related to decreased osteoarthritis risk and co-localised with at least one osteoarthritis phenotype. Our findings suggest a potential therapeutic role for antidiabetic drugs in treating osteoarthritis. The results indicate that certain antidiabetic drug targets may modify disease progression, with implications for developing targeted DMOADs. This study was funded by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (2022), the Shanghai Municipal Health Commission Health Industry Clinical Research Project (Grant No. 20224Y0139), Beijing Natural Science Foundation (Grant No. 7244458), and the Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation (Grant No. GZC20230130).

Subclinical psoriatic arthritis and disease interception-where are we in 2024?

Psoriatic arthritis (PsA) is a chronic rheumatic disease that usually appears in patients with skin psoriasis, making it a model for detection of joint disease in the pre-clinical phases in a setting where therapy for cutaneous disease may ameliorate or prevent arthritis development. Such PsA prevention appears credible due to the increasingly recognized closely shared immunopathology between the skin and joints, especially the entheses. Recently, several initiatives have explored the concept of pre-clinical PsA, and nomenclatures have been developed with the recent EULAR nomenclature proposing a simplified three stages from psoriasis to clinical PsA development, namely at risk of PsA, subclinical PsA and early PsA. A better comprehension of early PsA and the identification of individuals predisposed to its development could enable interventions to 'prevent' the appearance of PsA. Several recent retrospective observational studies have demonstrated disease interception feasibility, i.e. treatment of people with psoriasis may prevent the appearance of PsA, in particular using biologic disease-modifying drugs. However, further data is urgently required due to unexpected findings in some studies where TNF inhibition for psoriasis does not reduce the rate of PsA development. In this review we address the current challenges in early PsA, including comparisons of pre-PsA nomenclature sets, its risk factors, and the potential for disease interception.

A simplified model to understand the targeted disease-modifying anti-inflammatory drugs

This review presents a simplified model to understand better how disease-modifying anti-inflammatory drugs (DMAIDs) work in immune-mediated inflammatory diseases (IMIDs) with a focus on rheumatology, dermatology, and gastroenterology. In this model, IMIDs are listed on a spectrum from autoinflammatory to autoimmune characterised by the involvement of either mostly the innate or the adaptive immune system. DMAIDs specifically target these immune components and have shown efficacy in distinct IMIDs. DMAID classes include TNF blockers, IL-1 blockers, IL-6 receptor blockers, IL-17 blockers, IL-23 blockers, and janus kinase inhibitors.

A Pilot Phase 2 Randomized Trial to Evaluate the Safety and Potential Efficacy of Etravirine in Friedreich Ataxia Patients.

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a disease-modifying drug for Friedreich ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted a pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into three severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Safety endpoints were the number and type of adverse events and number of dropouts. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T - 4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T + 4). Etravirine was reasonably tolerated, and adverse events were generally mild. Four months of etravirine treatment did not significantly increase the peak oxygen uptake but was associated with a change in the progression of the SARA score (p value < 0.001), compared to the 4 months pre- and post-treatment. It also significantly increased peak workload (p value = 0.021). No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine treatment was safe, reasonably well tolerated and appreciably improved neurological function and exercise performance. Even though a placebo effect cannot be ruled out, these results suggest that etravirine may represent a potential therapeutic agent in FRDA deserving testing in a randomized placebo-controlled clinical trial.

Time to start disease modifying drugs for adults with seropositive rheumatoid arthritis: results of the first year of the national New Zealand Rheumatology Association (NZRA) audit.

This audit describes variation in the time from referral to starting disease modifying drug (DMARD) for people with newly diagnosed seropositive rheumatoid arthritis (RA), how frequently this was within the recommended 6 weeks and whether regional, service-level or patient-level factors were associated with this variation. Rheumatologists submitted data on new patients with a new diagnosis of rheumatoid factor and/or cyclic-citrullinated peptide antibody positive RA. The association between visit funding, ethnicity, socio-economic deprivation, rurality, local specialist staffing levels and the time to DMARD treatment was assessed using Cox proportional-hazard models. Data were collected on 355 patients over 12 months. Overall, 64.8% of patients commenced DMARD treatment within 6 weeks of referral and this was associated with rheumatologist FTE per 100,000 population (adjusted HR 2.47, 95%CI 1.27-4.81; p=0.008) and the rurality (Geographic Classification of Health [GCH]) of the patient (for R2 compared to U1 adjusted HR 0.20, 95%CI 0.09-0.43; p<0.001). There was no association between time to DMARD and ethnicity or socio-economic deprivation. There was significant variation in time to DMARD treatment, mainly related to variation in rheumatologist staffing levels and patient rurality. Rheumatologist staffing levels of 1.0 FTE/100,000 population was associated with 80% of patients meeting the recommended 6-week time to DMARD treatment.

Role of the C-reactive Protein-to-Albumin Ratio in Assessing Disease Activity in Elderly Patients With Rheumatoid Arthritis.

Nowadays, one measure that is more helpful in assessing the level of inflammation than either C-reactive protein (CRP) or albumin alone is the C-reactive protein-to-albumin ratio (CAR). Our study set out to assess the CAR in elderly individuals with rheumatoid arthritis (RA) and its correlation with other parameters. Included in the research were patients who were being followed up on for RA between January 2021 and January 2024 and categorized according to their age at the time of enrolment and assigned to one of two groups: younger patients, defined as <60 years of age, and those aged ≥60 years, who were recorded as elderly patients. The clinical evaluation of the patients and laboratory data measured for each patient included age, gender, disease duration, medications, CRP, erythrocyte sedimentation rate (ESR), albumin, neutrophil-to-lymphocyte ratio (NLR), and CAR. Disease activity was assessed with the disease activity score 28 (DAS 28)-ESR. The health assessment questionnaire was used to measure the functional status. Ninety-four patients (<60 years: 58 and ≥60 years: 36) were included. The mean age of the elderly patients was 65.80 ± 5.33 years. Female predominance was similar in both the RA groups (<60 years: 50 patients (86.2%) vs. ≥60 years: 31 (86.1%)). The distribution of biological and disease-modifying drugs did not significantly differ between the groups. With the exception of albumin, there was no statistically significant difference between the groups for ESR, CRP, CAR, NLR, or DAS28-ESR. Elderly patients with a DAS28-ESR of 2.6 and above had a statistically significant higher CAR than the remission group (3.44±3.73 vs. 2.71±5.73, respectively). There was no statistically significant difference in the NLR value of elderly patients with a DAS28-ESR of 2.6 and above compared to the remission group (3.06 ± 2.95 vs. 2.65 ± 1.38, respectively). In addition, CAR was positively correlated with ESR, CRP, and DAS28-ESR (r = 0.726, p < 0.001; r = 0.954, p < 0.001; r = 0.339, p = 0.043, respectively). However, there was no discernible correlation between CAR and HAQ, NLR, or disease duration. In elderly RA patients, our study demonstrated the correlation between CAR and inflammatory biomarkers and the DAS28-ESR. According to this, CAR may prove to be a useful biomarker for assessing inflammation and disease activity in clinical settings.

A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease

In Alzheimer’s disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs Brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, as well as synaptic transmission and plasticity. Using cerebrospinal fluid and post-mortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aβ in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential of a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

Rehabilitation Strategies for Patients With Spinal Muscular Atrophy in the Era of Disease-Modifying Therapy.

The impact of disease-modifying therapy ranges from cure to no impact with a wide range of intermediates. In cases where the intermediate group reaches a plateau after the acquisition of some muscle strength, it is necessary to set a functional level appropriate for increased motor power and establish a long-term exercise plan to maintain it. As the disease status stabilizes and the life span increases, early nonsurgical interventions are required, such as using a standing frame to prevent joint contracture, applying a spinal brace at the early stage of scoliosis, and maintaining sitting postures that exaggerate lumbar lordosis. In cases where scoliosis and hip displacement occur and progress even after conservative managements are implemented, early referral to surgery should be considered. Oromotor activity and swallowing function are influenced not only by the effects of disease-modifying drugs, but also by post-birth experience and training. Therefore, although the feeding tube cannot be removed, it is necessary to make efforts to simulate the infant feeding development while maintaining partial oral feeding. Since the application period of non-invasive ventilators has increased, it has become more important to prevent long-term complications such as facial abrasion, skin allergy, orthodontic deformities, and maxillary flattening caused by the interface. Dual ventilator mode or interface can also be utilized.

Quantitative Cartilage T2 and T1rho Mapping: Is There a Clinical Role? From the AJR Special Series on Quantitative Imaging.

Despite more than 20 years of development, the MRI-based cartilage compositional biomarkers T2 and T1rho have not been routinely applied in clinical practice. This review examines these measures' historical development and frames the challenges in the application of these quantitative imaging tools to the care of patients with cartilage injury and osteoarthritis using the hierarchical model of efficacy proposed by Fryback and Thornbury. T2 and T1rho have been validated for the evaluation of early compositional and structural changes in cartilage extracellular matrix. Yet, these biomarkers lack direct correlation with pain or function loss, lack standardization of methods for acquisition and analysis, and have a limited role in guiding therapeutic management given the absence of effective disease-modifying osteoarthritis drugs. These issues present significant challenges in the path to the biomarkers' future implementation in clinical care. Nonetheless, these MRI-based cartilage compositional biomarkers provide an essential tool for musculoskeletal research and can provide important information on the biophysical properties of cartilage that will continue to contribute to our understanding of cartilage injury and osteoarthritis pathogenesis.

COVID-19 in patients with rheumatic diseases: frequency and course

Objectives. The aim of the study was to assess frequency and severity of COVID-19 in patients with rheumatic diseases (RD).Patients and methods. The study included information on the presence or absence of COVID-19 in the medical history of 9185 patients with immunoinflammatory RD (IIRD) and 491 patients with osteoarthritis (OA) who were observed at the V. A. Nasonova Research Institute of Rheumatology from September 21, 2021 to December 28, 2023.Results. The incidence of COVID-19 in the analyzed IIRD was significantly higher compared to OA (p&lt;0.02). All IIRD included in the analysis are characterized by an increased risk of COVID-19 incidence when compared with OA by 1.7–3.5 times. Patients with rheumatoid arthritis, ankylosing spondylitis, Sjögren's disease, systemic sclerosis, psoriatic arthritis, systemic lupus erythematosus, microcrystalline arthritis, ANCA- associated vasculitis and poly/dermatomyositis were significantly more likely (p&lt;0.009) to receive COVID-19 therapy compared with the control group. Patients with these diseases are characterized by an increased risk of treatment for COVID-19 by 1.7–6.5 times compared with OA. Also, patients with inflammatory joint diseases (IJD), connective tissue diseases (CTDs) and systemic vasculitis (SV) were hospitalized with COVID-19 more often than patients with OA (p=0.013, p=0.003 and p&lt;0.001, respectively). Patients with IJD, CTDs and SV are characterized by an increased risk of hospitalization with COVID-19 by 3.5–6.8 times compared with OA. In addition, elderly patients with IIRD are characterized by an increasing risk of treatment, hospitalization and use of biologics or targeted synthetic disease-modifying drugs for COVID-19.Conclusion. According to the data obtained, the problem of COVID-19 remains very significant for patients with RD. This dictates the need to continue studying risk factors for adverse outcomes of the disease and vaccine prevention of this infectious pathology.

Cladribine effects on patient-reported outcomes and their clinical and biometric correlates in highly active relapsing multiple sclerosis at first switch: the observational, multicenter, prospective, phase IV CLADFIT-MS study.

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients' lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient's experience and self-assessed impact of treatment on daily life.

Effects of nusinersen on motor function in children with spinal muscular atrophy: a retrospective study.

Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease. Nusinersen is the first disease modifying drug approved to treat patients with SMA. Our study aimed to evaluate the efficacy of nusinersen treatment on motor function in children with SMA. A retrospective analysis was conducted on the data of 52 genetically confirmed SMA patients from November 2020 to September 2023. Motor function was assessed based on standardized scales from baseline to 14 months of follow-up. Of patients in this study, the majority had SMA type 2 (40/52, 76.9%), 5 (9.6%) and 7 (13.5%) patients had SMA types 1 and 3, respectively. The median disease duration was 11 months (range 0-52), and the median age at initiation of treatment was 44.5 months (range 5-192). Motor function of all the patients with SMA improved from baseline to 14 months of follow-up. Mean increases of 4.6-point (p = 0.173), 4.7-point (p = 0.021) and 2.7-point (p = 0.013) were observed from baseline to 14 months of follow-up for the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores, the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), respectively. Increased disease duration and age of treatment initiation were negatively correlated with the changes in HFMSE scores (r = -0.567, p = 0.043; r = -0.771 and p = 0.002, respectively). Similar results were observed for the RULM scores (r = -0.714, p = 0.014; r = -0.638 and p = 0.035, respectively). Our study suggested that 14 months of treatment with nusinersen was effective and improved the motor function of children with SMA types 1, 2, or 3. In addition, disease duration and age at treatment initiation were negatively correlated with treatment outcome in the patients.

The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection – a novel disease-modifying osteoarthritis drug

BackgroundDespite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats.MethodsWe evaluated KBP-336’s effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology.ResultsAfter 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues.ConclusionOverall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.

Treatment Outcomes of Patients with Orbital Inflammatory Diseases: Should Steroids Still Be the First Choice?

Objective: To clarify the therapy response in orbital inflammatory diseases (OID), we analyzed the treatment effects of steroid therapy, the use of disease-modifying antirheumatic drugs (DMARDS), and biologicals in our tertiary referral center cohort. Methods: We collected the clinical and demographic data of all patients treated for non-specific orbital inflammation (NSOI) (n = 111) and IgG4-ROD (n = 13), respectively at our center from 2008 to 2020 and analyzed them with descriptive statistics. NSOI were sub-grouped according to the location into either idiopathic dacryoadenitis (DAs) (n = 78) or typical idiopathic orbital myositis (n = 32). Results: Mean age at first clinical manifestation was significantly different between subgroups (IOI: 49.5 ± 18, IgG4-ROD: 63.2 ± 14, p = 0.0171). Among all examined OID, 63 patients (50%) achieved full remission (FR) with corticosteroids (NSOI 53%/IgG4-ROD 31%). In contrast, classic myositis showed a significantly higher response (76%). Disease-modifying drugs (DMARDS) for myositis accomplished only 33% FR (NSOI 57%) and 66% did not respond sufficiently (NSOI 43%). The biologic agent (Rituximab) was significantly more efficient: 19 of 23 patients (82%) achieved full remission and only 4 (17%) did not respond fully and needed orbital irradiation or orbital decompressive surgery.

Therapeutic Applications and Challenges of a Widely Used Antifolate Drug

Introduction and purpose: Methotrexate (MTX) is an antifolate metabolite that interferes with the synthesis and repair of DNA and with cell replication. It has anti-inflammatory and immunomodulatory properties and was first used in 1951 for the treatment of RA and psoriasis. Methotrexate (4-amino-10-methylfolic acid, MTX) is a popular disease-modifying drug for the treatment of rheumatoid arthritis, psoriasis and leukaemia. MTX is an antagonist of folic acid, primarily through inhibition of the proliferative effect. MTX and its metabolites are associated with many serious adverse effects, including gastrointestinal and hepatic toxicity, myelosuppression, stomatitis, etc. Taking methotrexate may contribute to a reduction in the quality of life for patients. Additionally, long-term use of methotrexate requires regular monitoring, which can be burdensome and stressful for patients. In this context, different approaches have been used to improve the therapeutic properties of MTX and to reduce its adverse effects. The long history of the drug has made it possible to assess its efficacy and to collect data on adverse events, including potentially life-threatening adverse events. This article aims to provide a literature-based overview of current knowledge about methotrexate in clinical practice. Materials and Methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed. Conclusion: The result is a picture of methotrexate as a drug that is used for many conditions, but is associated with many side effects that can be a significant problem for patients and healthcare professionals.

Real-world evidence from Germany and the United States: Treatment initiation on low-efficacy versus high-efficacy therapies in patients with multiple sclerosis

BackgroundThe hit-hard-and-early (HHAE) strategy where treatment is initiated with high-efficacy therapies opposed to low-efficacy therapies presents a potential paradigm shift in multiple sclerosis (MS) management. This study aimed to assess the adoption of the HHAE strategy in Germany and the United States (US) from 2020 to 2022 based on real-world data. MethodsThe analysis was based on longitudinal, patient-level data from Germany and the US. For Germany, data was extracted from the Permea platform covering approximately 44 % of all German community pharmacy dispensing. For the US, data from the Komodo Healthcare Map™ was utilized, covering medical benefit data from around 88 % of the US patient population. Patients ≥18 years old and who had at least 2 prescriptions for MS-related disease-modifying drugs (DMDs) between January 2020 and December 2022 were included. To approximate therapy beginners, a washout period of one year before treatment start was applied, excluding all patients who had an MS-related DMD prescription or claim in 2019. Cohort entry date was the day of the first MS-related DMD dispense or claim. DMDs were classified as high-efficacy and low-efficacy based on the Multiple Sclerosis Therapy Consensus Group (MSTCG). Group differences were assessed with two-sided χ2-square and t-tests. Results29,604 MS therapy beginners were identified in the German and 49,791 MS therapy beginners were identified in the US dataset. 29.6 % of MS therapy beginners in Germany and 61.6 % in the US followed the HHAE strategy. Between 2020 and 2022, a significant 14 % increase in the HHAE strategy was observed in both countries (p < 0.0001). High-efficacy therapy beginners switched from their initially prescribed therapy less frequently than low-efficacy therapy beginners: 6.9 % of high-efficacy vs. 19.5 % of low-efficacy therapy beginners in Germany (p < 0.0001) and 5.5 % of high-efficacy vs. 25.0 % low-efficacy therapy beginners in the US (p < 0.0001) switched from their first prescribed DMD. ConclusionBetween 2020 and 2022, the adoption of the HHAE strategy increased in both countries, with the US exhibiting nearly double the adoption rates. High-efficacy therapy beginners were less likely to switch from their initially prescribed medication than low-efficacy therapy beginners. Real world evidence can provide valuable insights into rapidly changing treatment patterns in patients with MS.

Is yearly interferon gamma release assay latent tuberculosis infection screening warranted among patients with rheumatological diseases on disease-modifying drugs in non-endemic settings?

Patients living with rheumatologic diseases on disease-modifying antirheumatic drugs (DMARD) are at an increased risk of developing tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection (LTBI) before initiating DMARD. However, data is lacking on the value of yearly screening for LTBI. A retrospective chart review was conducted on adult patients (≥ 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed. Among 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin. In a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.

Inflammation as a therapeutic target for osteoarthritis: A literature review of clinical trials.

The burden of osteoarthritis (OA) is rapidly increasing with population aging, but there are still no approved disease-modifying drugs available. Accumulating evidence has shown that OA is a heterogeneous disease with multiple phenotypes, and it is unlikely to respond to one-size-fits-all treatments. Inflammation is recognized as an important phenotype of OA and is associated with worse pain and joint deterioration. Therefore, it is believed that anti-inflammatory treatments may be more effective for OA with an inflammatory phenotype. In this review, we summarized clinical trials that evaluated anti-inflammatory treatments for OA and discussed whether these treatments are more effective in inflammatory OA phenotypes compared to general OA patients.

Osteoporosis knowledge and awareness among rheumatoid arthritis patients: A cross-sectional controlled study.

The aim of this study was to investigate the levels of knowledge and awareness of osteoporosis (OP) in patients with rheumatoid arthritis (RA). The cross-sectional study included 100 RA patients (26 males, 74 females; mean age: 51±11 years; range, 28 to 67 years) who had not been diagnosed with OP and a control group of 50 healthy subjects (16 males, 34 females; mean age: 53±11 years; range, 29 to 70 years) between February 2022 and June 2022. The demographic data of age, sex, and education level of all the participants were recorded. Disease duration and the drugs used were recorded for the RA patients. The revised Osteoporosis Knowledge Test and the Osteoporosis Health Belief Scale questionnaires were completed by the participants. There was no significant difference determined between the RA patients and the control group in OP knowledge levels. A positive correlation was determined between education level and OP knowledge level and between disease duration and OP awareness level. RA patients with a family history of OP, those in the postmenopausal period, and those using biological disease-modifying drugs thought they were at risk of OP at a higher rate. While the levels of knowledge and awareness of OP were determined to be similar in the RA patients and the control group, the vast majority of RA patients did not know that they were at risk of developing OP. In addition, when the data obtained in this study are taken into consideration, there appears to be a need for health strategies such as educational programs and informing RA patients about OP.

A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.

Osteoarthritis (OA) is a chronic disorder caused by degenerative changes in articular cartilage, which are mainly manifests as degeneration of cartilage, subchondral bone remodeling, as well as synovial inflammation. Over the next few decades, OA and its burden will continue to increase worldwide, posing a major public health challenge for the foreseeable future. Treatment for OA includes non-pharmacological, pharmacological, and surgical treatments. Existing conservative treatments and joint surgery can only alleviate the symptoms and cannot be cured, so new therapies for OA are urgently needed. Since advances in the understanding of OA pathophysiology, researchers have identified some potential therapeutic targets against degeneration of cartilage, subchondral bone remodeling and synovial inflammation, enabling development of the disease-modifying OA drugs (DMOADs). Additionally, a number of new technologies are also being investigated for treating OA, such as RNA interference (RNAi), CRISPR/Cas9 and PROTAC. The goal of this review is to describe the current development status of DMOADs and to discuss the potential of emerging therapeutic approaches for treating OA, thus providing a reference for OA treatments.