Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
The Reduction in Serum Level of MMP-3 Seen in a Phase III Study in Knee Osteoarthritis Patients Is Predictive of the Protective Effect On Cartilage Volume Loss of a DMOAD Treatment
Pelletier1, Jean-Pierre, Raynauld1, Jean-Pierre, Abram2, François, Caron1, Judith, Mineau1, François, Haraoui3, B., Choquette4, Denis
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, Montreal, QC,
ArthroVision Inc., Montreal, QC,
Institut de Rhumatolgie de Montreal, Montreal, QC,
University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, Montreal, QC
Licofelone, a dual inhibitor of 5-lipoxygenase and cyclooxygenase, compared to naproxen was found to be a disease modifying drug (DMOAD) in a phase III study in knee osteoarthritis (OA) patients using quantitative MRI1. Very little information is available on the value of predictive and/or prognostic biomarkers in OA trials in which disease progression and cartilage volume loss were assessed using quantitative MRI. The present study explored the relationship between the protective effect of licofelone on cartilage volume loss and symptom relief, using the most relevant OA biomarkers.
A subset of 155 patients selected from a clinical trial evaluating the impact of licofelone (n=81; 200 mg bid) versus naproxen (n=74; 500 mg bid) on OA knee tissue structure, were studied. The patient population had a mean age of 60.5 years, 68% were female, and the average BMI was 32.3 kg/m2. Patients with KL grade IV were excluded. Only patients who had taken all the study medication according-to-protocol (ATP) throughout the two year period were considered for this sub-analysis. MRI acquisitions of the knee were done at baseline and two years of follow-up and the cartilage volume and bone marrow lesions quantitated. Patients underwent clinical evaluation using the WOMAC questionnaire (pain, stiffness and function). Seven biomarkers, relevant to OA structural progression, were measured at baseline and at two years: CRP, MMP-1, MMP-3, IL-6 and COMP in serum, and CTX-I and CTX-II in urine.
The increase in MMP-3 and MMP-1 levels in the patients was significantly less over time in the licofelone group vs. naproxen (p<0.0001 and p=0.05, respectively). Moreover, a positive correlation was found between the baseline values of MMP-3 (p=0.01) and COMP (p=0.03) and the cartilage volume loss at two years. The extent of increase in the levels of MMP-3 (p=0.02) and MMP-1 (p=0.06) over time was found to be associated with the severity of cartilage loss. CTX-I levels at baseline also correlated (p=0.02) with the increase in bone marrow lesion size in the medial compartment. The CRP levels at baseline were positively correlated with the worsening of symptoms: WOMAC total index (p=0.0009), pain (p=0.002) and function (p=0.001).
This study demonstrated that some serum biomarkers (MMP-3, MMP-1 and COMP) can predict the loss of cartilage in knee OA patients. However, levels of MMP-3 and to a lesser extent MMP-1 are the most useful predictive biomarkers in the monitoring of the DMOAD effect. CRP was found to be the most reliable marker for predicting the evolution of disease symptoms over time.
To cite this abstract, please use the following information:
Pelletier, Jean-Pierre, Raynauld, Jean-Pierre, Abram, François, Caron, Judith, Mineau, François, Haraoui, B., et al; The Reduction in Serum Level of MMP-3 Seen in a Phase III Study in Knee Osteoarthritis Patients Is Predictive of the Protective Effect On Cartilage Volume Loss of a DMOAD Treatment [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1944