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

Oo, Win Min

doi:10.1177/1759720x221090297

Cited by 35 publications

(18 citation statements)

References 186 publications

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“…Current treatment approaches are focused on relieving symptoms, as no treatment has been identified for disease modification (eg, improvements in both symptoms and joint structure, such as cartilage health) . First-line symptomatic management comprises nonpharmacological approaches including (1) exercise therapy; (2) weight loss (if overweight or obese); (3) prescription of walking aids or braces (if indicated, eg, during pain flares); and (4) education and self-management, alongside possible institution of pharmacological options such as nonsteroidal anti-inflammatory drugs (NSAIDs; topical or oral) and, only if required (ie, inadequate response to all other therapies), intra-articular therapies such as steroids.…”

Section: Osteoarthritismentioning

confidence: 99%

Evaluation and Treatment of Knee Pain

Duong,

Oo,

Ding

et al. 2023

JAMA

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ImportanceApproximately 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.ObservationsKnee 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). Patellofemoral pain typically affects people younger than 40 years who are physically active and has a lifetime prevalence of approximately 25%. The presence of anterior knee pain during a squat is approximately 91% sensitive and 50% specific for patellofemoral pain. Meniscal tears affect an estimated 12% of the adult population and can occur following acute trauma (eg, twisting injury) in people younger than 40 years. Alternatively, a meniscal tear may be a degenerative condition present in patients with knee OA who are aged 40 years or older. The McMurray test, consisting of concurrent knee rotation (internal or external to test lateral or medial meniscus, respectively) and extension (61% sensitivity; 84% specificity), and joint line tenderness (83% sensitivity; 83% specificity) assist diagnosis of meniscal tears. Radiographic imaging of all patients with possible knee OA is not recommended. First-line management of OA comprises exercise therapy, weight loss (if overweight), education, and self-management programs to empower patients to better manage their condition. Surgical referral for knee joint replacement can be considered for patients with end-stage OA (ie, no or minimal joint space with inability to cope with pain) after using all appropriate conservative options. For patellofemoral pain, hip and knee strengthening exercises in combination with foot orthoses or patellar taping are recommended, with no indication for surgery. Conservative management (exercise therapy for 4-6 weeks) is also appropriate for most meniscal tears. For severe traumatic (eg, bucket-handle) tears, consisting of displaced meniscal tissue, surgery is likely required. For degenerative meniscal tears, exercise therapy is first-line treatment; surgery is not indicated even in the presence of mechanical symptoms (eg, locking, catching).Conclusions and RelevanceKnee OA, patellofemoral pain, and meniscal tears are common causes of knee pain, can be diagnosed clinically, and can be associated with significant disability. First-line treatment for each condition consists of conservative management, with a focus on exercise, education, and self-management.

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Section: Osteoarthritismentioning

confidence: 99%

Evaluation and Treatment of Knee Pain

Duong,

Oo,

Ding

et al. 2023

JAMA

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“…MTX is an anti-metabolite agent approved since many years as a conventional DMARD for RA for which it still represents an anchor drug, being recommended as a first line of therapy by all the most prominent scientific societies. 40,[47][48][49] MTX suppresses the proliferation of immune and inflammatory cells in RA synovium and consequently inhibits the release of pro-inflammatory cytokines. For its mechanism of action, it was hypothesized that MTX can have a beneficial role in HOA patients with synovitis phenotype.…”

Section: Mtxmentioning

confidence: 99%

“…For its mechanism of action, it was hypothesized that MTX can have a beneficial role in HOA patients with synovitis phenotype. 40 Our literature search found only one published study, a randomized, double-blind, placebo-controlled trial, analyzing the efficacy of MTX in symptomatic EHOA patients. The drug was administered orally to 32 patients, at the dosage of 10 mg weekly, while other 32 patients received an oral placebo for 12 months.…”

Section: Mtxmentioning

confidence: 99%

An update on the use of conventional and biological disease-modifying anti-rheumatic drugs in hand osteoarthritis

Tenti

Bruyère

Cheleschi

et al. 2023

Therapeutic Advances in Musculoskeletal

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Osteoarthritis (OA) is a highly prevalent condition worldwide associated with pain, progressive disability, reduced participation in social activities, and impaired quality of life. Despite its growing burden, the therapeutic options are still limited and almost exclusively addressed to symptoms’ management, while no disease-modifying OA drugs able to prevent or retard disease progression are actually available. For these reasons, in the last decades, relevant efforts to find new potential therapeutic targets in OA have been made and a number of existing conventional and biological disease-modifying anti-rheumatic drugs (DMARDs), including hydroxychloroquine (HCQ), methotrexate (MTX), tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 inhibitors, commonly used to treat inflammatory rheumatic diseases, have been repurposed for the treatment of OA and explored also in hand osteoarthritis (HOA). The current narrative review was aimed to provide a comprehensive and updated understanding of the possibilities and the criticisms related to the treatment of HOA with conventional and biological DMARDs. Unfortunately, therapy with conventional and biologic drugs in HOA has not achieved the expected success, despite a rationale for their use exists. Thus, our findings outline the urgent need to enhance the exploration of HOA basic molecular mechanisms to find new potential therapeutic targets, personalized for each patient, and appropriate for the different subsets of HOA and for the different phases of disease.

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“…Osteoarthritis (OA) is the most prevalent chronic degenerative disease worldwide. It was estimated that globally 22.9% (corresponding to 654.1 million) of people over 40 years of age suffered from this disease in 2020 [ 1 , 2 ]. It is a disease that progressively affects the cartilage, synovial membrane, bone and periarticular tissues [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Etanercept (ETA) is a soluble fusion protein consisting of two 75 kD human TNFR IIs, each linked to an Fc portion of human IgG1 [ 13 ]. It was the first TNF inhibitor approved to treat rheumatoid arthritis in the United States in 1998 and in Europe in 2000 [ 1 ]. In more recent years, it was used to treat inflammatory OA.…”

Section: Introductionmentioning

confidence: 99%

Thermosensitive Injectable Hydrogels for Intra-Articular Delivery of Etanercept for the Treatment of Osteoarthritis

García-Couce

Schomann

Chung

et al. 2022

Gels

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The intra-articular administration of drugs has attracted great interest in recent decades for the treatment of osteoarthritis. The use of modified drugs has also attracted interest in recent years because their intra-articular administration has demonstrated encouraging results. The objective of this work was to prepare injectable-thermosensitive hydrogels for the intra-articular administration of Etanercept (ETA), an inhibitor of tumor necrosis factor-α. Hydrogels were prepared from the physical mixture of chitosan and Pluronic F127 with β-glycerolphosphate (BGP). Adding β-glycerolphosphate to the system reduced the gelation time and also modified the morphology of the resulting material. In vitro studies were carried out to determine the cytocompatibility of the prepared hydrogels for the human chondrocyte line C28/I2. The in vitro release study showed that the incorporation of BGP into the system markedly modified the release of ETA. In the in vivo studies, it was verified that the hydrogels remained inside the implantation site in the joint until the end of the study. Furthermore, ETA was highly concentrated in the blood of the study mice 48 h after the loaded material was injected. Histological investigation of osteoarthritic knees showed that the material promotes cartilage recovery in osteoarthritic mice. The results demonstrate the potential of ETA-loaded injectable hydrogels for the localized treatment of joints.

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

Cited by 35 publications

References 186 publications

Evaluation and Treatment of Knee Pain

Evaluation and Treatment of Knee Pain

An update on the use of conventional and biological disease-modifying anti-rheumatic drugs in hand osteoarthritis

Thermosensitive Injectable Hydrogels for Intra-Articular Delivery of Etanercept for the Treatment of Osteoarthritis

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