Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial.

INTRODUCTION: Incubation of blood with CrSO(4)-coated glass beads stimulates the synthesis of anti-inflammatory cytokines, such as interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, and IL-13. As IL-1beta is thought to play a key role in the development of osteoarthritis (OA), this product, also known as Orthokin, might be a viable treatment for symptomatic knee OA. The aim of the current study was to evaluate the efficacy of Orthokin for treatment of symptomatic knee OA in a randomized, multicentre, double-blind, placebo-controlled trial. PATIENTS AND METHODS: One hundred and sixty-seven patients received six intra-articular injections either with Orthokin or physiological saline. The primary efficacy objective consisted of 30% superiority on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3, 6, 9, and 12 months post-treatment. Additionally, the patients completed the visual analogue scale for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Clinical Rating System. RESULTS: Orthokin and placebo treatment resulted in similar improvements on the WOMAC (16.8% vs 16.5%, respectively; n.s.). Orthokin resulted in significantly more improvement for KOOS symptom (P = 0.002) and KOOS sport (P = 0.042) parameters as compared to placebo treatment. For most other outcome parameters, Orthokin-treated patients consistently showed higher improvement compared to placebo-treated patients, although none of these differences were statistically significant. Two serious adverse events were observed in the Orthokin group: one patient with repeated severe inflammatory reactions of the knee joint within hours after the injection and one patient with septic arthritis which was attributed to the injection procedure rather than the product. CONCLUSION: The statistically significant improvement of KOOS symptom and sport parameters together with the consistently higher, though non-statistically significant, improvement of most other parameters demonstrates that Orthokin clearly induces a biological response different from placebo treatment and warrant future investigations into the possible chondroprotective effect of Orthokin. However, in the current study the primary efficacy objective was not met and, therefore, the use of Orthokin currently cannot yet be recommended for the treatment of OA.

The correlation and reproducibility of histological scoring systems in cartilage repair.

In recent years, the field of cartilage tissue engineering has seen a sharp increase in publications using many tissue engineering techniques and various analysis methods. Comparison between studies remains difficult, due to a lack of uniformity in methods used. A broad range of histological scoring systems is used to examine cartilage quality. Unfortunately, so far little is known on the reliability and correlation of these scoring systems. The objective of this study was to compare two frequently used cartilage repair grading scales, namely, the comprehensive O'Driscoll and the simple Pineda scale. We determined the intra- and interobserver variability of each score as well as the correlation between them. Thirty-eight joint section samples with variable cartilage quality were examined. Three observers documented their findings with both systems at two points in time. Statistical analysis showed very good intra- and interobserver reliability as well as a good correlation between the two scores. For the intraobserver variability of the O'Driscoll scale, we found an average difference of 0.05 with a SD of 0.93 in a 24-point score and a kappavalue of 0.87. For the interobserver reliability, the average difference was 0.001, SD 2.25, and a kappavalue of 0.92. The Pineda scale showed an average difference of 0.86 with a SD of 1.38 in a 14-point score and a kappavalue of 0.86 for the intraobserver reliability, whereas values for the interobserver reliability were average difference 0.82, SD 0.96, and a kappavalue of 0.89. The comparison between the two scales showed a high, inversely related correlation with a correlation coefficient of 0.71. From these results, we concluded that both the O'Driscoll and the Pineda scales are reliable semiquantitative cartilage scoring systems and that acceptance for general use of these two scores will benefit the reliability of literature on tissue engineering for cartilage repair. Thus, the added strength of comparison between published study results allows better understanding of cartilage repair publications and increases the impact of their results.