The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids

Middelkoop, Marienke van; Arden, N K; Atchia, I.; Birrell, Fraser; Chao, Jeannie; Rezende, Márcia Uchôa de; Lambert, Robert G.; Ravaud, Philippe; Bijlsma, J. W. J.; Doherty, Michael; Dziedzic, Krysia; Lohmander, L. Stefan; McAlindon, Timothy E.; Zhang, Weiya; Bierma-Zeinstra, Sita M A

doi:10.1016/j.joca.2016.01.983

Cited by 91 publications

(59 citation statements)

References 38 publications

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“…The therapies for OA patients were mainly to relieve the pain and inflammation [21]. Researches had shown that the important pathological feature of OA contained articular cartilage degeneration, which was largely attributed to apoptosis of chondrocytes [22].…”

Section: Discussionmentioning

confidence: 99%

miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

Wei

Zhang

2020

Preprint

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Background: Osteoarthritis (OA) is a common subtype of arthritis with prevalence increase with age, and is characterized by the degeneration of articular cartilage. Chondrocytes play curial role in the formation of the articular cartilage. This work aimed to figure out the effect of miR-200a/b in chondrocytes of OA, as well as the underlying molecular mechanism. Methods: Cell viability, apoptosis, pro-inflammatory factors secretion, and matrix degradation were detected with cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting, separately. Expression of miR-200a/b and fucosyltransferase 4 (FUT4) was measured by RT-qPCR (RNA level) and western blot (protein level). The relationship between miR-200a/b and FUT4 was verified by dual-luciferase assay and RNA immunoprecipitation (RIP) assay. Results: Interleukin 1β (IL-1β) induced OA cell model in primary chondrocytes ex-vivo, as evidenced by cell viability inhibition, apoptosis rate promotion, and IL-6 and tumor necrosis factor α (TNF-α) resection enhancement, as well as Collegen 2a1 (Col2a1) and Aggrecan expression inhibition. Expression of miR-200a/b was downregulated in knee articular cartilage of OA patients and IL-1β-induced primary chondrocytes. miR-200a/b overexpression decreased IL-1β-induced cell injuries, which was further blocked by FUT4 upregulation. Mechanically, FUT4 was negatively regulated by miR-200a/b via target binding. Conclusion: miR-200a/b could alleviate IL-1β-induced chondrocyte injuries via targeting its downstream gene FUT4, suggesting that miR-200a/b-FUT4 axis might be a potential candidate to the treatment of OA.

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Section: Discussionmentioning

confidence: 99%

miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

Wei

Zhang

2020

Preprint

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“…An explorative, pre-defined, subgroup analysis will be performed assessing the interaction effects between injections regarding the severity of knee pain at baseline (NRS pain score of > = 7 versus < 7) on the primary outcome [47]. Generalized estimating equations will be used to analyze differences between groups concerning adverse events, medical consumption and medication usage.…”

Section: Subgroup Analysismentioning

confidence: 99%

Effectiveness of intramuscular gluteal glucocorticoid injection versus intra-articular glucocorticoid injection in knee osteoarthritis: design of a multicenter randomized, 24 weeks comparative parallel-group trial

Mol

Runhaar

Bos

et al. 2020

BMC Musculoskelet Disord

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Background: The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An intra-articular glucocorticoid injection is recommended in (inter) national guidelines for patients with knee osteoarthritis as an option for a flare of knee pain and/or for those who are not responding well to pain medication. An innovative approach that could replace the intra-articular injection is an intramuscular gluteal glucocorticoid injection. An intramuscular injection is easier to perform than an intra-articular injection with lesser risk of severe local adverse reactions. We hypothesize that intramuscular gluteal glucocorticoid injection is non-inferior in reducing knee pain compared to intra-articular glucocorticoid injection, with potentially a longer lasting effect than intra-articular injection. Methods/design: The study will be a pragmatic randomized controlled non-inferiority trial with two parallel groups. A total of 140 patients aged 45 years and older with knee osteoarthritis who contacted their general practitioner and have persistent knee pain (score ≥ 3 on 0-10 numerical rating scale; 0 = no knee pain) will be included. Patients will be randomly allocated (1:1) to an injection of 40 mg triamcinolone acetonide intra-articular in the knee joint or intramuscular in the ipsilateral ventrogluteal area. The effect of treatment will be evaluated by questionnaires at 2, 4, 8, 12, and 24 weeks after injection. The primary outcome is patients' reported severity of knee pain measured with the pain subscale of the Knee injury and Osteoarthritis Outcome Score 4 weeks after injection. Statistical analysis will be based on both the per-protocol and the intention-to-treat principle.(Continued on next page)

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“…Systematic reviews indicate low quality evidence that intra-articular corticosteroid injections may provide short term pain relief and a small improvement in physical function for up to six weeks in knee osteoarthritis compared with placebo 46. Patients with more severe disease are likely to experience greater improvement 7.…”

Section: What Is the Evidence Of Uncertainty?mentioning

confidence: 99%

Is there a place for intra-articular corticosteroid injections in the treatment of knee osteoarthritis?

Orchard

2020

BMJ

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The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids

Abstract: This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline.

Cited by 91 publications

References 38 publications

miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

Effectiveness of intramuscular gluteal glucocorticoid injection versus intra-articular glucocorticoid injection in knee osteoarthritis: design of a multicenter randomized, 24 weeks comparative parallel-group trial

Is there a place for intra-articular corticosteroid injections in the treatment of knee osteoarthritis?

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