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STUDY DESIGN: Multicenter prospective cohort study. OBJECTIVE: The study aims to validate the recently developed OF score for treatment decisions in patients with osteoporotic vertebral compression fractures (OVCF). METHODS: This is a prospective multicenter cohort study (EOFTT) in 17 spine centers. All consecutive patients with OVCF were included. The decision for conservative or surgical therapy was made by the treating physician independent of the OF score recommendation. Final decisions were compared to the recommendations given by the OF score. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5 L, and Barthel Index. RESULTS: In total, 518 patients (75.3% female, age 75 ± 10) years were included. 344 (66%) patients received surgical treatment. 71% of patients were treated following the score recommendations. For an OF score cut-off value of 6.5, the sensitivity and specificity to predict actual treatment were 60% and 68% (AUC .684, P < .001). During hospitalization overall 76 (14.7%) complications occurred. The mean follow-up rate and time were 92% and 5 ± 3.5 months, respectively. While all patients in the study cohort improved in clinical outcome parameters, the effect size was significantly less in the patients not treated in line with the OF score's recommendation. Eight (3%) patients needed revision surgery. CONCLUSIONS: Patients treated according to the OF score's recommendations showed favorable short-term clinical results. Noncompliance with the score resulted in more pain and impaired functional outcome and quality of life. The OF score is a reliable and save tool to aid treatment decision in OVCF.
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BACKGROUND: Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. OBJECTIVE: This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. METHODS: Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). RESULTS: ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. CONCLUSIONS: ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.