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Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts.

ABSTRACT:

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.

SUBMITTER: Eymard F

PROVIDER: S-EPMC8458198 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIntra-articular (IA) corticosteroid (CS) injections are the mainstay of treatment for symptomatic management in knee osteoarthritis (OA), particularly in the UK. IA platelet-rich plasma (PRP) injections are a promising alternative, but no systematic reviews to date have compared them to the current standard of care, IA CS injections. We aim to investigate the effect of IA PRP injections versus IA corticosteroid injections for the symptomatic management of knee OA.MethodsAll published trials comparing IA PRP and CS injections for knee OA were included. MEDLINE, EMBASE, Scopus and Web of Science were searched through June 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random effects model was used to calculate standardized mean difference with 95% confidence interval in WOMAC/VAS score (or subscores), comparing IA PRP to CS injections across studies.ResultsIncluded were eight studies and 648 patients, 443 (68%) were female, mean age 59 years, with a mean BMI of 28.4. Overall, the studies were considered at low risk of bias. Compared with CS injections, PRP was significantly better in reducing OA symptoms (pain, stiffness, functionality) at 3, 6 and 9 months post-intervention (P < 0.01). The greatest effect was observed at 6 and 9 months (- 0.78 (- 1.34 to - 0.23) standard mean deviations (SMD) and - 1.63 (- 2.14 to - 1.12) SMD respectively). At 6 months, this equates to an additional reduction of 9.51 in WOMAC or 0.97 on the VAS pain scales. At 6 months PRP allowed greater return to sporting activities than CS, measured by the KOOS subscale for sporting activity, of magnitude 9.7 (- 0.45 to 19.85) (P = 0.06). Triple injections of PRP, generally separated by a week, were superior to single injections over 12 months follow-up (P < 0.01).ConclusionsIA-PRP injections produce superior outcomes when compared with CS injections for symptomatic management of knee OA, including improved pain management, less joint stiffness and better participation in exercise/sporting activity at 12 months follow-up. Giving three IA-PRP, with injections separated by a week, appears more effective than 1 IA-PRP injection.Prospero trial registration numberCRD42020181928 .

Project description:Purpose ?The aim of the study was to evaluate the clinical effects of HYADD® 4, an hydrogel based on a hyaluronic acid derivative, in patients with symptomatic knee osteoarthritis, on symptoms, and joint function. Methods ?This retrospective study of patients with Kellgren-Lawrence grade II to IV knee osteoarthritis (American College of Rheumatology criteria) enrolled patients who had received two infiltrations of HYADD® 4, (24 mg/3 mL) 1?week apart, and evaluated: pain at rest, pain with movement, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score; change in nonsteroidal anti-inflammatory drugs (NSAIDs)/acetaminophen use; satisfaction with therapy; tolerability. Study duration was 6 months for all predefined endpoints, with a 6-month extension for pain symptoms only. Results ?After 6 months, all predefined endpoints were evaluable in 698 of 937 enrolled patients (74.5%). Mean WOMAC scores were reduced by 56.3% from baseline ( p ?<?0.05). NSAIDs/acetaminophen use ?2 times/week (48.8% of patients at baseline) was substantially reduced after 1?month and was 19.6% after 6 months. After 6 months, 85.6% of patients were satisfied about efficacy. There were no significant adverse effects. The effect on resting pain was rapid, strong, and lasting: reduction from baseline was 45.1% at 1?month ( p ?<?0.05), 56.8% at 6 months ( p ?<?0.05), and 53.6% at 12 months ( p ?<?0.05). Pain on moving was reduced by 47.4% after 6 months ( p ?<?0.05) and 46.0% after 12 months ( p ?<?0.05), results at 6 and 12 months were similar. Conclusion ?HYADD® 4 is a new-generation hyaluronic acid with distinctive viscoelastic and rheological properties. In patients with mild-to-severe knee OA (Kellgren-Lawrence grades II-IV), two consecutive infiltrations 1?week apart reduced WOMAC scores and NSAIDs/acetaminophen consumption for at least 6 months. In a subpopulation ( n ?=?106), efficacy on pain lasted approximately 12 months. Adverse events were reported in 11.2% of patients; the most frequent were arthralgias. No cases of allergic reactions or systemic effects were recorded. Level of Evidence ?Level IV, retrospective case series.

Project description:INTRODUCTION:The presence of leukocytes in platelet concentrates is deemed to cause deleterious effects when injected intra articularly. The aim of this study is to analyse both local and systemic effects induced by leukocyte-rich Platelet-rich Plasma (PRP) injections through a proteomic characterization of serial synovial fluid and blood samples obtained from subjects treated for knee OA. Secondary aim was to compare the effects on knee homeostasis and systemic response with those obtained with visco-supplementation. METHODS:Thirty-six OA patients treated either by autologous L-PRP or HA intra-articular knee injections, administered in series of three at one-week intervals, were analyzed. Just before the injection, 1 ml of synovial fluid was collected through the same needle way. In the same time, a peripheral blood sample was obtained and plasma separated. A further peripheral blood sample was collected at 2, 6, and 12 months. L-PRP, plasma and synovial fluid were tested by multiplex bead-based sandwich immunoassay by means of the Bio-Plex suspension array system (Bio-Rad Laboratories) for the presence of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and IL-4, IL-10, IL-13) and growth factors (FGF-b, HGF, PDGF-AB/BB). RESULTS:In general, pro-inflammatory cytokine levels were similar at basal condition and after treatment whereas anti-inflammatory ones were nearly undetectable. L-PRP administration did not modulate significant changes of cytokine concentrations either in synovial fluid or plasma, whatever the time points analyzed. No different trend was observed between L-PRP and HA administration in terms of pro- and anti-inflammatory cytokines, as well as growth factors. CONCLUSIONS:In contrast with the evidence reported by "in vitro" studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes, these results suggest that the presence leukocyte-rich PRP doesn't induce a relevant in vivo up regulation of pro-inflammatory mediators.

Project description:BackgroundHyaluronic acid (HA) and leukocyte-poor platelet-rich plasma (LP-PRP) are 2 nonoperative treatment options that have been studied in patients with hip osteoarthritis (OA).PurposeTo compare the efficacy of intra-articular injections of low-molecular weight (LMW) HA and LP-PRP in patients with hip OA.Study designRandomized controlled trial; Level of evidence, 1.MethodsA total of 34 patients (36 hips) presenting with signs of hip OA were randomized to receive 3 blinded, weekly intra-articular injections of either LP-PRP or LMW-HA. Patients were prospectively evaluated before injections and at 6 weeks and then at 3, 6, 12, and 24 months. The primary outcome, conversion to total hip arthroplasty (THA) or a hip resurfacing procedure, was analyzed along with secondary outcomes including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and hip range of motion.ResultsThe final analysis included 33 hips (mean Kellgren-Lawrence grade, 2.73) (LMW-HA: n = 14; LP-PRP: n = 19) in 31 patients (18 male; mean age, 53.8 years). Significantly more patients converted to THA or a hip resurfacing procedure in the LMW-HA group (7/14; 50.0%) (mean, 1.3 years after first injection) than the LP-PRP group (3/19; 15.8%) (mean, 0.73 years after first injection) (P = .035). There was no significant improvement or decline in any outcome scores within the LMW-HA group from before injections to 6 weeks or 3, 6, and 12 months. For the LP-PRP group, WOMAC overall (P = .032), joint (P = .030), and function scores (P = .025) significantly improved from before injections to 6 weeks, and WOMAC joint scores significantly improved from before injections to 6 months (P = .036). When comparing the difference between groups in internal rotation at 90° of hip flexion from before injections to 6 months, the LP-PRP group demonstrated a mean 5.0° improvement, while the LMW-HA group showed a mean 1.5° decrease (P = .028).ConclusionIntra-articular hip injections of LP-PRP in patients with hip OA resulted in an improvement in WOMAC scores and hip internal rotation at 6 months and delayed the need for THA or a hip resurfacing procedure compared with treatment with LMW-HA. A longer follow-up is necessary to further compare the effects of LP-PRP and LMW-HA injections in patients with hip OA.RegistrationNCT01920152 (ClinicalTrials.gov identifier).

Project description:The aim of the present study was to compare the clinical and economic benefits of intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) in Chinese patients with knee osteoarthritis (OA). A total of 86 patients (42 treated with PRP and 44 with HA) were treated with three weekly intra-articular injections. The inclusion criteria included patients between 18 and 75 years of age, with chronic knee pain or swelling lasting >3 months and X-ray findings of degenerative joint alterations according to the Kellgren-Lawrence score grade I-III. Clinical examinations were performed before treatment, at 1- and 6-month post-injection intervals. International Knee Documentation Committee subjective, Western Ontario and McMaster Universities and visual analogue scale scores were determined at each examination. Adverse reactions, average cost, treatment time and patient satisfaction were also recorded. Compared with patients injected with HA, PRP was found to be associated with increased and more severe post-injection pain and swelling, where the duration of adverse reactions was greater in the PRP group (P=0.02). During the follow-up evaluations, both groups showed statistically significant improvements in all clinical scores from pre-injection to 1- and 6-month assessments (P<0.05). However, no significant inter-group (PRP vs. HA) differences were observed in the clinical scores between the two follow-up time points. There were also no significant differences in clinical score between the groups with regards to the Kellgren-Lawrence grade I, II or III. The average cost of PRP injections was 22.8X that of HA administration and the average treatment time was 5X that of HA, but there was no significant difference in patient satisfaction. These preliminary results indicate that although PRP injections can significantly improve clinical outcome in patients with knee OA, PRP is not any more effective compared with HA. Furthermore, PRP injections are associated with higher costs and treatment times. Therefore, additional clinical studies are required before PRP injections can be considered as a first-line treatment option for knee OA.