IL-6 induces chondrocyte catabolism mainly via Stat3 signalling, a pathway activated in cartilage from joint subjected to DMM. Systemic blockade of IL-6 or STAT-3 can alleviate DMM-induced OA in mice.

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Purpose There has been much debate regarding the use of intra-articular injections of platelet-rich plasma (PRP) as symptomatic treatment for knee osteoarthritis. The objective of this consensus was to develop guidelines for PRP injections in knee osteoarthritis according to the French National Authority for Health recommendations. Methods Fifteen physicians from different French-speaking countries (10 rheumatologists, 4 specialists in rehabilitation and sports medicine and 1 radiologist) were selected for their expertise in the areas of PRP and osteoarthritis. A comprehensive literature review was conducted on Medline including all published therapeutic trials, open studies, meta-analysis and systematic reviews focusing on the effects of PRP in knee OA, as well as fundamental studies concerning the characteristics of the various types of PRP and their mechanisms, indexed before April 2019. Using the method recommended by the French National Authority for Health inspired by the Delphi consensus process, 25 recommendations were finally retained and evaluated. The recommendations were classified as appropriate or not appropriate, with strong or relative agreement, or uncertain if a consensus was not achieved. Results Among the 25 recommendations selected, the main ones are the following: (1) Intra-articular injections of PRP are an effective symptomatic treatment for early to moderate knee osteoarthritis. This recommendation was considered appropriate with a relative agreement (Median = 8; rank = 6–9). Level of evidence 1A. (2) A PRP treatment sequence in knee osteoarthritis may include 1–3 injections. This recommendation was considered appropriate with a strong agreement (Median = 9; rank = 7–9). Level of evidence 1A. (3) Leucocytes-poor PRP should be preferred in knee osteoarthritis. This recommendation was considered appropriate with a relative agreement (Median = 8; rank = 5–9). Level of evidence 5. (4) Intra-articular PRP knee injections should be performed under ultrasound or fluoroscopic guidance. This recommendation was considered uncertain with no consensus (Median = 8; rank = 3–9). Level of evidence 5. (5) PRP should not be mixed with an anesthetic or intra-articular corticosteroid. This recommendation was considered appropriate with a relative agreement (Median = 9; rank = 6–9). Level of evidence 5 Conclusion Those 25 recommendations should standardize and facilitate the use of IA PRP injections, which are considered by experts as an effective treatment especially in early or moderate knee OA. Although a strong or relative agreement from the experts was obtained for most of the recommendations, many of them had a very low level of evidence (Level 5) and were principally based on the clinical experience of the experts.

Figure 1 Timeline showing the relationship between serum eosinophil count and treatment with immune checkpoint inhibitors (double arrow: nivolumab 1 mg/kg and ipilimumab 3 mg/kg infusions; single arrow: nivolumab 3 mg/kg infusion).

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Background:There has been much debate regarding the use of intra-articular injections of platelet-rich plasma (PRP) as symptomatic treatment for knee osteoarthritis. The heterogeneity of the preparation and injection protocols limits the extrapolation of data from randomized controlled trials and meta-analyses.Objectives:The objective of this expert consensus was to develop the first clinical practice recommendations for PRP injections in knee osteoarthritis.Methods:Fifteen physicians (10 rheumatologists, 4 specialists in rehabilitation and sport medicine and 1 interventional radiologist) from different countries were selected given to their expertise in the fields of PRP and osteoarthritis. Twenty-five recommendations were finally retained after several meetings using the modified Delphi method to establish clinical consensus. All experts voted their agreement or not for each recommendation using a score between 1 (totally inappropriate) and 9 (totally appropriate). Depending on the median value and extreme scores, recommendations were judged as appropriated or unappropriated with a strong or relative agreement but could also be judged as uncertain due to indecision or absence of consensus.Results:The main recommendations are listed below:- Intra-articular injections of PRP constitute an efficient treatment of early or moderate symptomatic knee osteoarthritis. Median = 8 [6-9] – Appropriate. Relative agreement.- Intra-articular injections of PRP may be useful in severe knee osteoarthritis (Kellgren-Lawrence grade IV). Median = 7 [6-7] – Appropriate. Relative agreement.- Intra-articular injections of PRP in knee osteoarthritis should be proposed as second-line therapy, after failure of non-pharmacological and pharmacological (oral and topic) symptomatic treatment. Median = 9 [5-9] – Appropriate. Relative agreement.- Intra-articular injections of PRP should not be performed in osteoarthritis flare-up with significant effusion. Median = 7 [5-9] – Appropriate. Relative agreement.- Intra-articular PRP treatment may include 1 to 3 consecutive injections. Median = 9 [7-9] – Appropriate. Strong agreement.- Leukocyte-poor PRP should be preferred for knee OA treatment. Median = 8 [5-9] – Appropriate. Relative agreement.- PRP injections should be performed under ultrasound or fluoroscopic guidance. Median = 8 [3-9] – Uncertain. No consensus.- PRP should not be mixed with injectable anesthetic or corticosteroid. Median = 9 [6-9] – Appropriate. Relative agreement.Conclusion:Twenty-five recommendations were discussed by an international multidisciplinary task force group in order to provide a basis for standardization of clinical practices and future research protocols.Disclosure of Interests:Florent Eymard Consultant of: Regenlab, Paul Ornetti: None declared, Jérémy Maillet Consultant of: Regenlab, Eric Noel Consultant of: Regenlab, Philippe Adam Consultant of: Regenlab, Virginie Legré Boyer Consultant of: Regenlab, Thierry Boyer Consultant of: Regenlab, Fadoua Allali: None declared, Vincent Grémeaux Bader: None declared, Jean-François Kaux: None declared, Karine Louati: None declared, Martin Lamontagne Consultant of: Pendopharm, Fabrice Michel: None declared, Pascal Richette: None declared, Hervé Bard Consultant of: Regenlab