Background/Purpose: Using data from a 4-year follow-up of knee OA patients who formerly received treatment with chondroitin sulfate (CS) within a 6-month clinical trial, we wanted to find predictors of the incidence of total knee replacement (TKR).

Methods: Knee OA patients participating in a randomized, double-blind controlled trial evaluating the impact of CS (Bioibérica S.A., Barcelona, Spain) (400 mg BID) vs. placebo who had serial MRI acquisitions (qMRI) and clinical evaluations of the symptomatic knee^[1] were contacted to evaluate retrospectively the incidence of TKR of the study knee. A sub-group of patients (n=57) who received the study medication and had all the MRI evaluations (intent to treat (ITT)) were selected for this post hoc retrospective analysis. The TKR incidence was assessed blindly to the treatment allocation with a standardized phone interview.

Results: The patients’ mean age was 63.2 years, 63% were female and the average body mass index (BMI) was 30.7 kg¨Mm². A total of 13 TKRs (22.8%) were performed on this sub-population in the time frame of 4 years after completion of the original study. Interestingly, there were more TKRs performed within the placebo group (n=9) than the CS group (n=4) (69% vs. 31%, p=0.15, logistic regression). We further investigated the predictors of long-term TKRs for the target knee by comparing, within the ITT cohort, the patients who had TKR (n=13) for the target knee to those who did not (n=44), using data at baseline or the change at 1 year. Baseline values of WOMAC pain (p=0.01, logistic regression) and function (p=0.04), bone marrow lesions (BMLs) in the medial tibial plateau (p=0.0008) and global knee (0.02), and C-reactive protein (CRP) level (p=0.05) were strong predictors of TKR. Changes at 1 year in the medial cartilage volume higher than 7% (p=0.03) and the change in WOMAC pain (p=0.02) and function (p=0.02) also predicted the occurrence of TKR. Multivariate analyses controlling for age, sex, and BMI revealed that baseline presence of BML (p=0.003) and WOMAC pain (p=0.006) were independent strong predictors of TKR. Time to occurrence of the TKR from the study inception also favored the CS group vs. placebo (Log-Rank, p=0.14). Cox regressions that included age, sex, and BMI in the model indicated that baseline values of WOMAC pain (p=0.0006), presence of BML in the medial compartment (p=0.0007) and CRP (p=0.02) were the strongest independent predictors of TKR over time.

Conclusion: Treatment with CS appeared to reduce the need for TKR. There are very few OA RCTs that use qMRI to probe knee structural outcomes. According to this study, predictors of long-term occurrence of a TKR were greater levels of knee pain, lower level of function and presence of BML at baseline, and greater loss of cartilage over time. This study links MRI findings to long-term clinical outcomes.

Reference: [1] Wildi LM, et al. Ann Rheum Dis 2011;70(6):982-9

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/total-knee-replacement-as-an-osteoarthritis-study-outcome-predictors-derived-from-long-term-observation-following-a-randomized-clinical-trial/