Immunogenicity of osteogenic protein 1: results from a prospective, randomized, controlled, multicenter pivotal study of uninstrumented lumbar posterolateral fusion

Abstract

The aim in this study was to detect and quantify antibody responses against recombinant human osteogenic protein 1 (OP-1) and to compare these responses to patient clinical outcomes and safety information. A controlled, open-label, randomized, prospective, multicenter pivotal study was performed in which patients with single-level Grade I or II degenerative lumbar spondylolisthesis (Meyerding classification) and spinal stenosis underwent decompression and uninstrumented posterolateral spinal arthrodesis. Three hundred thirty-six patients were randomized in a 2:1 fashion to receive either OP-1 Putty or autogenous iliac crest bone graft. Patients were evaluated at regular postoperative intervals for radiographic results, clinical outcomes, and safety parameters for more than 36 months. Serum samples were collected over this period and evaluated for the presence of anti–OP-1 antibodies and neutralizing activity by using a battery of in vitro binding assays (including enzyme-linked immunosorbent assay [ELISA]) and cell-based bioassays, respectively. Antibodies were predominantly seen in the OP-1–treated patients, although some responses were recorded preoperatively and in patients receiving autograft alone. Antibody production peaked in the 6-week to 3-month postoperative time frame and diminished thereafter. Neutralizing antibodies (Nabs) were detected at 1 time point at least in 25.6% of the patients treated with OP-1 Putty, but were not found in any patient following the 24-month postoperative time period. A single autograft patient (1.2%) also presented with OP-1 Nabs. An anti–OP-1 antibody status did not correlate with any measure of patient outcomes or adverse events. Recombinant human OP-1 (bone morphogenetic protein 7), like many recombinant human proteins, induces an immune response following its use as a bone graft alternative. This response was transient and diminished over time, and there was no statistical evidence to suggest an association between Nab status and any of the efficacy or safety criteria that were examined.