Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial

Kloppenburg, Margreet; Ramonda, Roberta; Bobacz, Klaus; Kwok, Wing‐Yee; Elewaut, Dirk; Huizinga, Tom W J; Kroon, Féline P B; Punzi, Leonardo; Smolen, Josef S.; Cruyssen, Bert Vander; Wolterbeek, Ron; Verbruggen, Gust; Wittoek, Ruth

doi:10.1136/annrheumdis-2018-213202

Cited by 128 publications

(104 citation statements)

References 31 publications

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“…TNF blockade is efficacious in many inflammatory rheumatic diseases. Etanercept 50 mg/weekly (25 mg/weekly after 24weeks subcutaneously) was investigated in a 1-year multicentre randomized, double-blind placebo-controlled trial in 90 patients with erosive inflammatory hand OA 28 . The primary outcome, being change in VAS pain after 24 weeks, was not met.…”

Section: Novel Treatmentsmentioning

confidence: 99%

Osteoarthritis year in review 2019: epidemiology and therapy

Kloppenburg

Bérenbaum

2020

Osteoarthritis and Cartilage

417

298

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s u m m a r yOver the past year many studies and clinical trials have been published in the osteoarthritis (OA) field. This review is based on systematic literature review covering the period May 1 st , 2018 to April 19 th , 2019; the final selection of articles was subjective. Specifically those articles considered to be presenting novel insights and of potential importance for clinical practice, are discussed.Further evidence has emerged that OA is a serious disease with increasing impact worldwide. Our understanding of development of pain in OA has increased. Detailed studies investigating widely used pharmacological treatments have shown the benefits to be limited, whereas the risks seem higher than expected, suggesting further studies and reconsideration of currently used guidelines. Promising new pharmacological treatments have been developed and published, however subsequent studies are warranted. While waiting for new treatment modalities to appear joint replacement is an effective alternative; new data have become available on how long they might last.

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Section: Novel Treatmentsmentioning

confidence: 99%

Osteoarthritis year in review 2019: epidemiology and therapy

Kloppenburg

Bérenbaum

2020

Osteoarthritis and Cartilage

417

298

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“…Even if OA has been considered to a large extent a "wearand-tear disease", it involves "low-level" inflammation and the increase in the number of (12). This discovery focused the efforts of researchers to develop the biological therapy useful for the treatment of chronic forms of OA and having as targets the pro-inflammatory cytokines and other factors from the articular cartilage, synovial cells and subchondral bone (13). Nowadays, international fora elaborated arthrosis therapy guidelines.…”

Section: Resultsmentioning

confidence: 99%

New Molecular Targets in the Therapy of Arthrosis Patients

Pelin

Simona

Mihaela

et al. 2019

ARS Medica Tomitana

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Introduction: Arthrosis represents the progressive degeneration of the joint cartilage, accompanied by the narrowing of the articular space and inflammation, which affects 70% of the population after the age of 60. Research purpose: This paper reviews the opportunity of using proinflammatory cytokine inhibitors as a means of stopping the progress of arthrosis. Material and method: As a result to a research into various clinical trial registers (Arthritis Clinical Trials, Clinical Research and Drug Information) and on specialized e-platforms, 5 randomized, multicentric double-blind clinical studies have been identified, which monitored the efficiency of various biological molecules in the treatment of arthrosis (etanercept, adalimumab, litikizumab, fasinumab and tanezumab). Results: The current pharmacological interventions consist mainly in the prescription of analgesics (acetaminophen, opioid analgesics), non-steroidal and chondroprotective anti-inflammatories. The proinflammatory cytokine inhibitors are already widely used in the inflammatory joint diseases, such as the rheumatoid polyarthritis. Their introduction into the treatment of arthrosis blocks the disease’s etiopathogenic mechanisms. Discussions: Arthrosis physiopathology involves a series of systemic, biological, biochemical factors, molecular and enzymatic processes that generate minimum inflammation. IL-1b and TNF-α are two major cytokines produced by the synovial cells and chondrocytes, which are involved in the destruction of the cartilage matrix by stimulating the production of proteolytic enzymes (MMP and aggrecanase). Conclusions: The utilisation of proinflammatory cytokine inhibitors in arthrosis represents a therapeutic option that requires studies in order to establish whether the introduction of proinflammatory cytokine inhibitors in arthrosis therapy might slow down the disease’s etiopathogenic mechanisms.

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“…An absence of efficacy was also evident in four randomised controlled trials in hand osteoarthritis that targeted either tumour necrosis factor or interleukin (IL)-1 44 , 45 , 46 , 47 and two trials in knee osteoarthritis targeting IL-1, 48 , 49 one of which used an intra-articular approach. Despite promise from various small open-label studies, none of the randomised controlled trials met their primary study endpoints, suggesting that classical cytokine-driven inflammation is at the root of neither pain nor structural damage in osteoarthritis.…”

Section: Targeting Inflammation In Osteoarthritismentioning

confidence: 99%

Of mice and men: converging on a common molecular understanding of osteoarthritis

Vincent

2020

The Lancet Rheumatology

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Despite an increasing burden of osteoarthritis in developed societies, target discovery has been slow and there are currently no approved disease-modifying osteoarthritis drugs. This lack of progress is due in part to a series of misconceptions over the years: that osteoarthritis is an inevitable consequence of ageing, that damaged articular cartilage cannot heal itself, and that osteoarthritis is driven by synovial inflammation similar to that seen in rheumatoid arthritis. Molecular interrogation of disease through ex-vivo tissue analysis, in-vitro studies, and preclinical models have radically reshaped the knowledge landscape. Inflammation in osteoarthritis appears to be distinct from that seen in rheumatoid arthritis. Recent randomised controlled trials, using treatments repurposed from rheumatoid arthritis, have largely been unsuccessful. Genome-wide studies point to defects in repair pathways, which accords well with recent promise using growth factor therapies or Wnt pathway antagonism. Nerve growth factor has emerged as a robust target in osteoarthritis pain in phase 2–3 trials. These studies, both positive and negative, align well with those in preclinical surgical models of osteoarthritis, indicating that pathogenic mechanisms identified in mice can lead researchers to valid human targets. Several novel candidate pathways are emerging from preclinical studies that offer hope of future translational impact. Enhancing trust between industry, basic, and clinical scientists will optimise our collective chance of success.

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Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial

Cited by 128 publications

References 31 publications

Osteoarthritis year in review 2019: epidemiology and therapy

Osteoarthritis year in review 2019: epidemiology and therapy

New Molecular Targets in the Therapy of Arthrosis Patients

Of mice and men: converging on a common molecular understanding of osteoarthritis

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