Intra-articular injection with Autologous Conditioned Plasma does not lead to a clinically relevant improvement of knee osteoarthritis: a prospective case series of 140 patients with 1-year follow-up.

Background and purpose - Platelet-rich plasma (PRP) is broadly used in the treatment of knee osteoarthritis, but clinical outcomes are highly variable. We evaluated the effectiveness of intra-articular injections with Autologous Conditioned Plasma (ACP), a commercially available form of platelet-rich plasma, in a tertiary referral center. Second, we aimed to identify which patient factors are associated with clinical outcome. Patients and methods - 140 patients (158 knees) with knee osteoarthritis (Kellgren and Lawrence grade 0-4) were treated with 3 intra-articular injections of ACP. The Knee Injury and Osteoarthritis Outcome Score (KOOS), pain (Numeric Rating Scale; NRS), and general health (EuroQol 5 Dimensions; EQ5D) were assessed at baseline and 3, 6, and 12 months' follow-up. The effect of sex, age, BMI, Kellgren and Lawrence grade, history of knee trauma, and baseline KOOS on clinical outcome at 6 and 12 months was determined using linear regression. Results - Mean KOOS increased from 37 at baseline to 44 at 3 months, 45 at 6 months, and 43 at 12 months' follow-up. Mean NRS-pain decreased from 6.2 at baseline to 5.3 at 3 months, 5.2 at 6 months, and 5.3 at 12 months. EQ5D did not change significantly. There were no predictors of clinical outcome. Interpretation - ACP does not lead to a clinically relevant improvement (exceeding the minimal clinically important difference) in patients suffering from knee osteoarthritis. None of the investigated factors predicts clinical outcome.

Effect of Autologous Conditioned Plasma Injections in Patients With Knee Osteoarthritis.

Background: Autologous conditioned plasma (ACP) is a commercially available platelet concentrate with promising results from clinical trials. Purpose: To evaluate the clinical outcome after 3 consecutive injections of ACP in patients with knee osteoarthritis (OA) and study the influence of ACP composition and different patient factors as predictors of treatment effect. Study Design: Case series; Level of evidence, 4. Methods: This prospective case series included 260 patients (307 knees) who received ACP treatment for knee OA. The mean patient age was 51 ± 10 years. Improvement up to 12 months' follow-up was measured using the Knee injury and Osteoarthritis Outcome Score (KOOS). ACP composition was analyzed in 100 patients. The predictive value of age, sex, history of knee trauma, Kellgren-Lawrence OA grade, body mass index, and ACP composition was evaluated using generalized estimating equations. Results: The mean overall KOOS improved from 38 ± 14 at baseline to 45 ± 18 at 3 months, 45 ± 18 at 6 months, and 43 ± 18 at 12 months (all P < .05); 40% of patients achieved an improvement above the minimal clinically important difference (MCID) of 8 after 6 months and 33% after 12 months. The variation in ACP composition did not correlate with KOOS (P > .05). Older age led to a greater clinical benefit (ß = 0.27; P = .05), whereas bilateral treatment predicted worse outcomes (ß = -5.6; P < .05). Conclusion: The improvement in KOOS after treatment with ACP did not reach the MCID in most study patients. Older age was a predictor for better outcomes. The composition of ACP varied between patients but did not predict outcomes within the evaluated range. The study findings show the limited benefit of ACP treatment for knee OA and call for caution with routine use in clinical practice.

Five-Year Outcome of 1-Stage Cell-Based Cartilage Repair Using Recycled Autologous Chondrons and Allogenic Mesenchymal Stromal Cells: A First-in-Human Clinical Trial.

BACKGROUND: Long-term clinical evaluation of patient outcomes can steer treatment choices and further research for cartilage repair. Using mesenchymal stromal cells (MSCs) as signaling cells instead of stem cells is a novel approach in the field. PURPOSE: To report the 5-year follow-up of safety, clinical efficacy, and durability after treatment of symptomatic cartilage defects in the knee with allogenic MSCs mixed with recycled autologous chondrons in first-in-human study of 1-stage cartilage repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study is an investigator-driven study aiming at the feasibility and safety of this innovative cartilage repair procedure. Between 2013 and 2014, a total of 35 patients (mean ± SD age, 36 ± 8 years) were treated with a 1-stage cartilage repair procedure called IMPACT (Instant MSC Product Accompanying Autologous Chondron Transplantation) for a symptomatic cartilage defect on the femoral condyle or trochlear groove. Subsequent follow-up after initial publication was performed annually using online patient-reported outcome measures with a mean follow-up of 61 months (range, 56-71 months). Patient-reported outcome measures included the KOOS (Knee injury and Osteoarthritis Outcome Score), visual analog scale for pain, and EuroQol-5 Dimensions. All clinical data and serious adverse events, including additional treatment received after IMPACT, were recorded. A failure of IMPACT was defined as a chondral defect of at least 20% of the index lesion with a need for a reintervention including a surgical procedure or an intra-articular injection. RESULTS: Using allogenic MSCs, no signs of a foreign body response or serious adverse reactions were recorded after 5 years. The majority of patients showed statistically significant and clinically relevant improvement in the KOOS and all its subscales from baseline to 60 months: overall, 57.9 ± 16.3 to 78.9 ± 17.7 (P < .001); Pain, 62.3 ± 18.9 to 79.9 ± 20.0 (P = .03); Function, 61.6 ± 16.5 to 79.4 ± 17.3 (P = .01); Activities of Daily Living, 69.0 ± 19.0 to 89.9 ± 14.9 (P < .001); Sports and Recreation, 32.3 ± 22.6 to 57.5 ± 30.0 (P = .02); and Quality of Life, 25.9 ± 12.9 to 55.8 ± 26.8 (P < .001). The visual analog scale score for pain improved significantly from baseline (45.3 ± 23.6) to 60 months (15.4 ± 13.4) (P < .001). Five cases required reintervention. CONCLUSION: This is the first study showing the midterm safety and efficacy of the proof of concept that allogenic MSCs augment 1-stage articular cartilage repair. The absence of serious adverse events and the clinical outcome support the longevity of this unique concept. These data support MSC-augmented chondron transplantation (IMPACT) as a safe 1-stage surgical solution that is considerably more cost-effective and a logistically advantageous alternative to conventional 2-stage cell-based therapy for articular chondral defects in the knee.

Reduction of pin tract infections during external fixation using cadexomer iodine.

PURPOSE: Knee joint distraction (KJD) is a joint-preserving treatment for younger osteoarthritis patients. KJD has shown positive results in regular care, but the external fixation frame often caused pin tract skin infections. Therefore, the use of cadexomer iodine was included in the wound care protocol. The goal of this cross-sectional study was to evaluate whether use of this ointment reduced the number of patients with infections during KJD treatment. METHODS: Patients treated with KJD in regular care were included if they gave consent for use of their data and completed treatment with the newest distraction device before 2020. All patients followed a wound care protocol, which since March 2019 included using cadexomer iodine ointment. The number of patients experiencing pin tract infections was compared between patients who did (March 2019-December 2019) and did not (November 2017-March 2019) use the ointment. RESULTS: Sixty-seven patients were included; 34 patients used cadexomer iodine and 33 patients did not. Patient who did not use cadexomer iodine experienced twice as many infections (64% vs 32%;p = 0.010). There was a significant difference in the number of patients with serious infections, requiring more antibiotics than the standard 7-day oral antibiotics (30% without vs 6% with cadexomer iodine; p = 0.009). CONCLUSIONS: The use of cadexomer iodine ointment during KJD results in a significant reduction of the number of patients experiencing pin tract infections during treatment. Use of this ointment should be considered standard protocol during KJD treatment and could be of value in general external fixator usage as well.

Knee joint distraction in regular care for treatment of knee osteoarthritis: A comparison with clinical trial data.

OBJECTIVES: Knee joint distraction (KJD) has been evaluated as a joint-preserving treatment to postpone total knee arthroplasty in knee osteoarthritis patients in three clinical trials. Since 2014 the treatment is used in regular care in some hospitals, which might lead to a deviation from the original indication and decreased treatment outcome. In this study, baseline characteristics, complications and clinical benefit are compared between patients treated in regular care and in clinical trials. METHODS: In our hospital, 84 patients were treated in regular care for 6 weeks with KJD. Surgical details, complications, and range of motion were assessed from patient hospital charts. Patient-reported outcome measures were evaluated in regular care before and one year after treatment. Trial patients (n = 62) were treated and followed as described in literature. RESULTS: Patient characteristics were not significantly different between groups, except for distraction duration (regular care 45.3±4.3; clinical trials 48.1±8.1 days; p = 0.019). Pin tract infections were the most occurring complication (70% regular care; 66% clinical trials), but there was no significant difference in treatment complications between groups (p>0.1). The range of motion was recovered within a year after treatment for both groups. WOMAC questionnaires showed statistically and clinically significant improvement for both groups (both p<0.001 and >15 points in all subscales) and no significant differences between groups (all differences p>0.05). After one year, 70% of patients were responders (regular care 61%, trial 75%; p = 0.120). Neither regular care compared to clinical trial, nor any other characteristic could predict clinical response. CONCLUSIONS: KJD as joint-preserving treatment in clinical practice, to postpone arthroplasty for end-stage knee osteoarthritis patient below the age of 65, results in an outcome similar to that thus far demonstrated in clinical trials. Longer follow-up in regular care is needed to test whether also long-term results remain beneficial and comparable to trial data.