Background/Purpose: Erosive hand osteoarthritis (OA) is a hand OA subset with high disease burden, although effective therapies are still lacking and clinical trials are scarce. Moreover, the low sensitivity-to-change of radiographs hampers outcome measurement of structural damage in short-term trials. Therefore, we explored the effect of etanercept on several biomarkers of bone, cartilage and inflammation.

Methods: Analyses were performed in a double blind trial comparing etanercept (50mg/week for 24 weeks, followed by 25mg/week up to 1 year) to placebo (NTR 1192). Ninety patients with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in ≥1 interphalangeal joint were included. The following biomarkers were measured with ELISA at baseline, 24 and 52 weeks: C-terminal collagen crosslinks I (CTX-I) in urine, and high sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), matrix metalloproteinase 3 (MMP3) and hyaluronic acid (HA) in serum. In some patients additional measurements at 4, 12, and 36 weeks were available. The effect of treatment on each biomarker at 24 and 52 weeks was estimated with generalised estimating equations in the intention to treat (ITT) and per protocol (PP) population, adjusting for baseline and study center. Patients fulfilling all inclusion criteria who completed the trial were included in the PP population.

Results: Biomarkers were measured in 78 patients (n=39 per group, 80.8% women, mean age 58.6 (SD 6.8), mean BMI 25.9 (SD 3.8)). Biomarker levels were comparable between groups at baseline, with large interquartile ranges (IQRs; table). Levels of hsCRP decreased slightly in both groups, but there were no between-group differences (at 24 weeks median 1.1 (IQR 0.7 to 4.2) and 1.7 (IQR 0.9 to 4.1) mg/L in placebo and etanercept group respectively). However, MMP3 levels decreased more in the etanercept group compared to placebo after 24 weeks (mean difference -1.44 ng/mL, 95% CI -2.82 to -0.05 (n=63)), although this difference was not sustained after etanercept dose reduction. No differences in the other biomarker levels were noted. PP analyses showed similar results.

Conclusion: Anti-TNF therapy reduced serum MMP3 levels, but not CTX-I, hsCRP, MPO and HA, in patients with erosive OA. The secretion of MMP3 is known to be stimulated by TNFα, and viewed as a marker of cartilage destruction. It remains unclear whether the observed decrease is merely a marker for decreased TNFα biological activity after anti-TNF, or that it is a sign of reduced cartilage damage in the etanercept group.