Prospects of Disease-Modifying Osteoarthritis Drugs.

Osteoarthritis (OA) causes a massive disease burden with a global prevalence of nearly 23% in 2020 and an unmet need for adequate treatment, given a lack of disease-modifying drugs (DMOADs). The author reviews the prospects of active DMOAD candidates in the phase 2/3 clinical trials of drug development pipeline based on key OA pathogenetic mechanisms directed to inflammation-driven, bone-driven, and cartilage-driven endotypes. The challenges and possible research opportunities are stated in terms of the formulation of a research question known as the PICO approach: (1) population, (2) interventions, (3) comparison or placebo, and (4) outcomes.

Comparison of ultrasound guidance with landmark guidance for symptomatic benefits in knee, hip and hand osteoarthritis: Systematic review and meta-analysis of randomised controlled trials.

Introduction: More than half of the patients with moderate and severe osteoarthritis (OA) report unsatisfactory pain relief, requiring consideration of intra-articular (IA) injections as the second-line management. Ultrasound-guided IA injection has proven evidence of higher accuracy in administering IA injectates into the joints than landmark-guided or blind IA injections. However, questions remain about translating higher accuracy rates of ultrasound-guided injection into better clinical improvements.

Efficacy and safety of pentosan polysulfate sodium in people with symptomatic knee osteoarthritis and dyslipidaemia: protocol of the MaRVeL trial.

Introduction: Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia.

New therapeutic strategies in osteoarthritis.

Osteoarthritis (OA) is the most prevalent arthritis-type and is a major contributor to chronic joint pain, impaired physical function, and limited mobility. By the end of 2020, a total of 595 million, equal to 7·6% of the global population, had OA; this figure is expected to rise exponentially by 2050. Even while the disorder's intricate pathophysiology is starting to appear intelligible, we are yet to have a cure for the disorder.

Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics.

Objective: Women have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics.

Evaluation and Treatment of Knee Pain: A Review.

Importance: Approximately 5% of all primary care visits in adults are related to knee pain. Osteoarthritis (OA), patellofemoral pain, and meniscal tears are among the most common causes of knee pain.

Observations: Knee OA, affecting an estimated 654 million people worldwide, is the most likely diagnosis of knee pain in patients aged 45 years or older who present with activity-related knee joint pain with no or less than 30 minutes of morning stiffness (95% sensitivity; 69% specificity).

Inflammatory ultrasound features as prognostic factors of pain and functional outcomes following intra-articular platelet-rich plasma in knee osteoarthritis.

Aim: To explore inflammatory ultrasound predictors of improvements in pain and function over 2, 6, and 12 months following administration of intra-articular platelet-rich plasma (PRP) in knee osteoarthritis (OA).

Method: Patients with painful mild-moderate radiographic knee OA from a subset of the RESTORE RCT underwent ultrasound assessment according to the standardized OMERACT scanning protocol to detect inflammatory features such as synovitis, synovial hypertrophy, and effusion with power Doppler. The study knee was treated with 3 once-weekly PRP injections obtained after centrifugation at 1500 g for 5 min.

Sexual activity satisfaction in symptomatic hip osteoarthritis patients: A cross-sectional, national web-based study.

Aim: Despite high-interest rates in sex in people with hip osteoarthritis (OA), clinicians tend not to address sexual issues, especially in older adults. The objective of this study is to evaluate sexual activity and factors associated with sexual activity satisfaction in people with symptomatic hip OA.

Methods: A cross-sectional study was conducted among 252 participants with symptomatic hip OA in Australia.

The effect of pentosan polysulfate sodium for improving dyslipidaemia and knee pain in people with knee osteoarthritis: A pilot study.

Objective: To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS, Elmiron®) for dyslipidaemia and knee osteoarthritis (OA) related symptoms.

Method: This was a single-arm, open-label, prospective, non-randomised pilot study. People with painful knee OA and a history of primary hypercholesterolemia were included.

Efficacy, Safety, and Accuracy of Intra-articular Therapies for Hand Osteoarthritis: Current Evidence.

The lifetime risk of symptomatic hand osteoarthritis (OA) is 39.8%, with one in two women and one in four men developing the disease by age 85 years and no disease-modifying drug (DMOAD) available so far. Intra-articular (IA) therapy is one of the options commonly used for symptomatic alleviation of OA disease as it can circumvent systemic exposure and potential side effects of oral medications.

A narrative review of anti-obesity medications for obese patients with osteoarthritis.

Introduction: The prevalence of both obesity and osteoarthritis (OA) is increasing worldwide (twindemic), and the association between the two chronic diseases is also well established.

Areas Covered: In this narrative review, we will briefly describe the double burdens of both diseases, the impact of weight loss or gain on OA incidence and structural progression and discuss the biomechanical and anti-inflammatory mechanisms mediating these effects. FDA-approved anti-obesity drugs are summarized in terms of their clinical efficacy and safety profile, and the completed or ongoing phase 2/3 clinical trials of such drugs in OA patients with obesity are examined.

Associations of + 138 Ins/del A and + 5665 G/T polymorphisms of endothelin-1 gene with hypertension in Burmese people in Magway, Myanmar.

Background: Hypertension is one of the major public health problems worldwide, and is one of the recognized causes of premature deaths every year in the world. The purpose of this study was to investigate the associations between the + 138 insertion/deletion of adenine (Ins/del A) and + 5665 guanine-to-thymine (G/T) polymorphisms of the endothelin-1 gene and hypertension in the residents of Magway Township, Myanmar.

Methods: This study was a cross-sectional comparative study including 60 hypertensive patients and 60 control subjects in Magway Township, Myanmar.

Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs).

In spite of a major public health burden with increasing prevalence, current osteoarthritis (OA) management is largely palliative with an unmet need for effective treatment. Both industry and academic researchers have invested a vast amount of time and financial expense to discover the first diseasing-modifying osteoarthritis drugs (DMOADs), with no regulatory success so far. In this narrative review, we discuss repurposed drugs as well as investigational agents which have progressed into phase II and III clinical trials based on three principal endotypes: bone-driven, synovitis-driven and cartilage-driven.

Prospects of Disease-Modifying Osteoarthritis Drugs.

Osteoarthritis (OA) causes a massive disease burden with a global prevalence of nearly 23% in 2020 and an unmet need for adequate treatment, given a lack of disease-modifying drugs (DMOADs). The author reviews the prospects of active DMOAD candidates in the phase 2/3 clinical trials of drug development pipeline based on key OA pathogenetic mechanisms directed to inflammation-driven, bone-driven, and cartilage-driven endotypes. The challenges and possible research opportunities are stated in terms of the formulation of a research question known as the PICO approach: (1) population, (2) interventions, (3) comparison or placebo, and (4) outcomes.

Pain, function, and radiographic disease in trapeziometacarpal osteoarthritis.

Introduction: Trapeziometacarpal joint osteoarthritis (OA) produces significant functional impairment due to pain and loss of strength in both power and precision grips, but few studies have related radiographic scores to functional and pain-based measures.

Purpose: To investigate the association between markers of radiographic disease and outcomes for symptomatic and functional disease.

Study Design: This study in an exploratory analysis of baseline data from the first 100 participants in a clinical trial evaluating the efficacy of combined conservative therapies for base of thumb OA (COMBO).

Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial).

Introduction: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months.

Associations between radiographic features, clinical features and ultrasound of thumb-base osteoarthritis: A secondary analysis of the COMBO study.

Aim: To investigate the associations of ultrasound and radiographic features of thumb-base osteoarthritis (OA) with thumb-base pain and hand function at baseline and 12 weeks.

Method: Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb-base OA were analyzed. Participants who finished follow up were included in this secondary analysis.

Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.

Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.

Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.

Nerve Growth Factor (NGF) Inhibitors and Related Agents for Chronic Musculoskeletal Pain: A Comprehensive Review.

Musculoskeletal pain such as osteoarthritis (OA) and low back pain (LBP) are very common and contribute to enormous burden and societal costs, despite dramatic therapeutic advances over recent decades. Novel approaches and targeted therapies are required to satisfy the urgent unmet medical need of musculoskeletal pain relief in both conditions. Nerve growth factor (NGF) inhibitors have utilized novel mechanisms different from conventional drugs, which have a variety of gastrointestinal, cardiac, or renal adverse effects.

Reliability and Convergent Construct Validity of Quantitative Ultrasound for Synovitis, Meniscal Extrusion, and Osteophyte in Knee Osteoarthritis With MRI.

Aims: To determine: 1) inter-rater reliability of quantitative measurements of ultrasound-detected synovitis, meniscal extrusion, and osteophytes; and 2) construct (convergent) validity via correlations and absolute agreements between ultrasound- and gold-standard magnetic resonance imaging (MRI)-outcomes in knee osteoarthritis.

Methods: Dynamic ultrasound images for supra-patellar synovitis, meniscal extrusion, and osteophytes were acquired and quantified by a physician operator, musculoskeletal ultrasonographer, and medical student independently. On the same day, 3T MRI images were acquired.

Improving domain definition and outcome instrument selection: Lessons learned for OMERACT from imaging.

Objectives: Imaging is one of the most rapidly evolving fields in medicine. Unfortunately, many imaging technologies have been applied as measurement instruments without rigorous evaluation of the evidence supporting their truth, discriminatory capability and feasibility for that context of use. The Outcome Measures in Rheumatology (OMERACT) Filter 2.

The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date.

Osteoarthritis (OA) is a complex heterogeneous articular disease with multiple joint tissue involvement of varying severity and no regulatory-agency-approved disease-modifying drugs (DMOADs). In this review, we discuss the reasons necessitating the development of DMOADs for OA management, the classifications of clinical phenotypes or molecular/mechanistic endotypes from the viewpoint of targeted drug discovery, and then summarize the efficacy and safety profile of a range of targeted drugs in Phase 2 and 3 clinical trials directed to cartilage-driven, bone-driven, and inflammation-driven endotypes. Finally, we briefly put forward the reasons for failures in OA clinical trials and possible steps to overcome these barriers.