Cost Effectiveness Analysis of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. A Systematic Review Literature

The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA

The Economic Burden of Biological Therapy in Rheumatoid Arthritis in Clinical Practice: Cost-Effectiveness Analysis of Sub-Cutaneous Anti-TNFα Treatment in Italian Patients:

Rheumatoid arthritis (RA), with a prevalence of 0.46%, is found in about 272,004 patients in Italy. The socioeconomic cost of rheumatoid arthritis in Italy in 2002 has been estimated at €1,600 million. Cost-effectiveness evaluations have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. Many cost-effective studies have been based on the variation of Health Assessment Questionnaire (HAQ) in clinical trials. The objective of this study is to perform a cost-effective analysis of 86 patients with rheumatoid arthritis in therapy with adalimumab 40 mg every other week and etanercept 50 mg/week for two years in a population of patients observed in clinical practice. The group of patients in therapy with adalimumab had also taken methotrexate, mean dose 12.4±2.5 mg/week (22 patients) or leflunomide 20 mg/day (16 patients). The group of patients in therapy with etanercept had also taken methotrexate, mean dose 11.7±2.6 mg/week (24 patients) or leflunomide 20 mg/day (24 patients). Incremental costs and QALYs (quality adjusted life years) gains are calculated compared with baseline, assuming that without biologic treatment patients would remain at the baseline level through the year. Conversion HAQ scores to utility were based on the Bansback algorithm. The results after two years showed: in the group methotrexate+adalimumab the QALY gained was 0.62±0.15 with a treatment cost of €26,517.62 and a QALY/cost of €42,521.13. In the group methotrexate+etanercept the QALY gained was 0.64±0.26 with a treatment cost of €25,020.96 and a QALY/cost of €39,171.76. The result of using etanercept in association with methotrexate is cost-effectiveness with a QALY gained under the acceptable threshold of €50,000. These are important data for discussion from an economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice

What Do We Know About Clodronate Now? A Medical and Veterinary Perspective.

There has recently been some controversy over the use of bisphosphonates in horses and some confusion regarding the different classes of bisphosphonates and the differences between the mechanism of actions and effects of each class. This review article explores the different bisphosphonate classes and their different effects and mechanisms of action based on research from both the human and equine veterinary fields. This collaborative review between veterinary surgeons and medical doctors describes the latest use of bisphosphonates in humans and horses, including safety aspects, and allows comparisons to be drawn between the two fields. Potential future uses of bisphosphonates are also discussed

Clodronate in the management of different musculoskeletal conditions

INTRODUCTION: Clodronic acid is a non-nitrogen-containing bisphosphonate largely used from some decades in the prevention and treatment of postmenopausal and secondary osteoporosis. in addition to antiresorptive activity, clodronate has shown anti-inflammatory and analgesic properties, and modulatory effects on bone and cartilage metabolism. EVIDENCE ACQUISITION: A literature review has been conducted to characterize the mechanism of action of clodronate and to retrieve available evidence about the use of clodronate in primary and secondary osteoporosis, and its potential role in other musculoskeletal conditions and orthopedic surgery. EVIDENCE SYNTHESIS: The efficacy and safety of the available clodronate formulations (oral, intravenous and intramuscular) in the prevention and treatment of postmenopausal and secondary osteoporosis, including corticosteroid-induced osteoporosis and bone mass loss secondary to endocrine, gastrointestinal and neoplastic diseases, have been demonstrated in a variety of clinical trials. The analgesic, anti-inflammatory, bone- and chondro-modulating properties of clodronate have allowed to expand its use in other musculoskeletal conditions to those currently approved. clodronate has proven to be beneficial in the treatment of osteoarthritis of the knee and of the hand, in the management of complex regional pain syndrome, and in the peri- and postoperative phase in subjects undergoing arthroplasty. CONCLUSIONS: The analysis of the available literature has shown that clodronate has relevant musculoskeletal effects beyond the antiresorptive activity. Further research is needed to better position clodronate therapy in the management of these conditions and to define the optimal formulation and dose regimen in any of the tested new indications

Physical activity prevents cartilage degradation: a metabolomics study pinpoints the involvement of vitamin B6

Osteoarthritis (OA) is predominantly characterized by the progressive degradation of articular cartilage, the connective tissue produced by chondrocytes, due to an imbalance between anabolic and catabolic processes. In addition, physical activity (PA) is recognized as an important tool for counteracting OA. To evaluate PA effects on the chondrocyte lineage, we analyzed the expression of SOX9, COL2A1, and COMP in circulating progenitor cells following a half marathon (HM) performance. Therefore, we studied in-depth the involvement of metabolites affecting chondrocyte lineage, and we compared the metabolomic profile associated with PA by analyzing runners' sera before and after HM performance. Interestingly, this study highlighted that metabolites involved in vitamin B6 salvage, such as pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate, were highly modulated. To evaluate the effects of vitamin B6 in cartilage cells, we treated differentiated mesenchymal stem cells and the SW1353 chondrosarcoma cell line with vitamin B6 in the presence of IL1\u3b2, the inflammatory cytokine involved in OA. Our study describes, for the first time, the modulation of the vitamin B6 salvage pathway following PA and suggests a protective role of PA in OA through modulation of this pathway

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Bone fracture risk: Density and microarchitecture qualification

Osteoporosis is a systemic skeletal disease where an increase in bone fragility is due to low bone mass and micro-architectural deterioration of bone tissue, which occur over a long period of time without clinical significance. Currently, Double Energy X-ray Absorption (DEXA) is the gold standard for bone mineral density assessment and the diagnosis of osteoporosis, but the majority of fractures occur in patients who would not be considered at fracture risk based on their Bone Mineral Density (BMD) values. It has long been known that fracture risk depends not only on mass loss, but also on bone architecture, whose alterations are an independent factor of increased fragility. The Bone Elastic Structure Test, BES TEST\uae, is a recently introduced analysis that assesses bone quality as expressed by the elastic properties of the trabecular micro-architecture from a virtual biopsy of the patient and could be a helpful add-on to densitometry for predicting fragility fractures and patient monitoring. The aim of this study is the comparison of DEXA and BES TEST\uae ability as 3-year risk estimators in a clinical application. In the CONTROL group, the BSI T-score is significantly different from the femoral DEXA T-score (p = 0.0005). In the FRACTURED group, the BSI T-score is significantly different from both the femoral DEXA T-score (p = 0.0266) and the lumbar DEXA T-score (p = 0.0051). Inter-group t-test statistical analysis (95% significance) shows that the femoral DEXA T-score (neck) of the CONTROL and the FRACTURED groups are not significantly different (p = 0.1478), while the BSI T-score of the CONTROL and the FRACTURED groups highlights a significant difference (p = 0.0001). Despite the small number of subjects, our data seem to confirm that the BSI could be a helpful add-on to densitometry for predicting fragility fractures and patient monitoring

Role of the osteochondral unit in the pathogenesis of osteoarthritis: focus on the potential use of clodronate

: Osteoarthritis (OA) is a chronic disease characterized by inflammation and progressive deterioration of the joint. The etiology of OA includes genetic, phlogistic, dismetabolic and mechanical factors. Historically, cartilage was considered the target of the disease and therapy was aimed at protecting and lubricating the articular cartilage. The osteochondral unit is composed of articular cartilage, calcified cartilage, and subchondral and trabecular bone, which work synergistically to support the functional loading of the joint. Numerous studies today show that OA involves the osteochondral unit, with the participation therefore of the bone in the starting and progression of the disease, which is associated with chondropathy. Cytokines involved in the process leading to cartilage damage are also mediators of subchondral bone edema. Therefore, OA therapy must be based on the use of painkillers and bisphosphonates for both the control of osteometabolic damage and its analgesic activity. Monitoring of the disease of the osteochondral unit must be extensive, since bone marrow edema can be considered as a marker of the evolution of OA. In the present review we discuss some of the pathogenetic mechanisms associated with osteoarthritis, with particular focus on the osteochondral unit and the use of clodronate