Signals for mineralization and inflammation are observed following treatment with fasinumab, a specific nerve growth factor inhibitor.

OBJECTIVE

Fasinumab is an investigational, fully-human, monoclonal antibody against nerve growth factor. Studies have shown that patients treated with fasinumab have statistically and clinically significant improvements in pain and physical function, but more frequently experience joint‑related adverse events compared with placebo-treated patients. This post hoc analysis explored biological changes associated with fasinumab therapy.

DESIGN

Changes in bone and mineralization markers (total alkaline phosphatase, bone-specific alkaline phosphatase [BSAP], procollagen type 1 N-terminal propeptide [P1NP], osteocalcin, and type I collagen cross-linked C-telopeptide) and inflammation (C-reactive protein [CRP]) were analyzed alongside magnetic resonance imaging in patients from Phase 2 and 3 clinical studies evaluating fasinumab in patients with osteoarthritis of the knee or hip.

RESULTS

In total, 5772 patients were included in this analysis. Dose-related increases in markers of bone formation/mineralization (alkaline phosphatase, BSAP, osteocalcin, and P1NP) were observed following treatment with fasinumab. Patients with arthropathies showed larger increases in alkaline phosphatase when compared with patients without (6 mg every 8 weeks difference 10.36 U/L, 95% CI: 0.06-20.66 U/L at Week 16). Increases in CRP were also noted following fasinumab treatment, and again, larger increases were seen in patients with arthropathies versus those without (6 mg every 8 weeks difference 3.09 mg/L, 95% CI: 0.07-6.12 mg/L at Week 16). Increases in CRP returned to near baseline levels following the last fasinumab treatment.

CONCLUSIONS

In this post hoc analysis, signals for bone turnover/mineralization, and inflammation increased following treatment with fasinumab. Increases were generally dose-dependent, reversible, and more pronounced in patients with arthropathy than those without.