The correlation between patient reported outcomes and biomarkers for knee osteoarthritis

Bumsup Lee, Martin Wang, Soo-Hyun Lew, Jung Jong Cho, Tae Won Kim, Nipun Sodhi, Hiba K. Anis, Michael A. Mont


Background: Novel non-operative treatment modalities, including injections of genetically engineered chondrocytes (GEC), have been developed to target the inflammatory pathways implicated in knee osteoarthritis (OA). Patient reported outcome measures (PROMs) have been the cornerstone of knee OA diagnostics and are frequently used to quantify treatment efficacy but their subjective nature limits their utility. However, inflammatory biomarkers of knee OA provide quantitative data but are less commonly used to assess the severity and progression of OA. Therefore, the purpose of this study was to correlate PROMs with biomarkers in knee OA. Specifically, we compared International Knee Documentation (IKDC) scores with serum C-terminal telopeptide of type I collagen (sCTX-I), urine C-terminal telopeptide of type II collagen (uCTX-II), and joint space width (JSW) in patients receiving GEC injections or placebo injections for knee OA.
Methods: A multi-center, double-blinded, randomized, placebo-controlled study was conducted between November 2013 and August 2015. A total of 163 patients were enrolled and randomized to receive GEC injections or placebo injections in a 1:1 ratio of treatment to control. The PROMs assessed were IKDC scores which evaluated three domains: symptoms, sports and daily activity, and difference in knee function. The biomarkers assessed were sCTX-I, uCTX-II, and JSW. Outcomes were measured at baseline as well as at 6, 9, and 12 months after the injections. Scatter plots were created to graphically represent the correlations. Pearson’s correlation coefficients were utilized to determine associations between IKDC scores and each of the three biomarkers.
Results: Significant correlations were identified between PROMs and inflammatory biomarkers of knee OA at 6, 9, and 12 months post-treatment with GEC injections. In the GEC cohort, as IKDC scores improved, improvements in sCTX-I levels were also observed. Correlations between IKDC scores and sCTX-I levels were statistically significant at 9 months (r=−0.42, P<0.001) and 12 months (r=−0.23, P=0.049) following treatment. Additionally, there were significant correlations between IKDC scores and uCTX-II levels in the GEC cohort at 6 months (r=−0.294, P=0.011), 9 months (r=−0.383, P<0.001), and 12 months (r=−0.420, P<0.001) post-treatment. In both GEC and placebo cohorts, JSW was observed to improve as IKDC scores improved. In the GEC cohort, a statistically significant correlation was observed at 12 months post-treatment (r=0.400, P<0.001).
Conclusions: Newer treatment options for knee OA target the inflammatory pathways that mediate the destruction of bone and cartilage. Inflammatory biomarkers are an objective alternative to assess the severity and progression of OA. This study found significant correlations between an established PROM (IKDC scores) and inflammatory biomarkers in knee OA (sCTX-I, uCTX-II, and JSW). For newer non-operative treatment modalities, such as GEC injections, inflammatory biomarkers of knee OA should be utilized to evaluate the severity and progression of knee OA.