Nerve Growth Factor Antagonists: Is the Future of Monoclonal Antibodies Becoming Clearer?

Chronic pain is a pervasive problem that affects the patient, their significant others, and society in many ways. The past decade has seen advances in our understanding of the mechanisms underlying pain and in the availability of technically advanced diagnostic procedures; however, the most notable therapeutic changes have not been the development of novel evidenced-based methods, but rather changing trends in applications and practices within the available clinical armamentarium. We provide a general overview of empirical evidence for the most commonly used interventions in the management of chronic non-cancer pain, including pharmacological, interventional, physical, psychological, rehabilitative, and alternative modalities. Overall, currently available treatments provide modest improvements in pain and minimum improvements in physical and emotional functioning. The quality of evidence is mediocre and has not improved substantially during the past decade. There is a crucial need for assessment of combination treatments, identification of indicators of treatment response, and assessment of the benefit of matching of treatments to patient characteristics. Copyright © 2011 Elsevier Ltd. All rights reserved.

A 2007 American College of Physicians guideline addressed pharmacologic options for low back pain. New evidence and medications have now become available.

Increased nerve growth factor levels are associated with chronic pain conditions, including chronic low back pain (LBP). This study examined safety and analgesic efficacy of tanezumab, a humanized anti-nerve growth factor antibody, in adults with chronic LBP. Patients received intravenous tanezumab 200 μg/kg plus oral placebo (n=88), intravenous placebo plus oral naproxen 500 mg twice a day (n=88), or intravenous placebo plus oral placebo (n=41). Primary outcome was average LBP intensity (aLBPI) at Week 6. Secondary outcomes were proportion of patients with ≥30% or ≥50% reduction in aLBPI, Roland-Morris Disability Questionnaire and Brief Pain Inventory-short form scores, Patients' Global Assessment of LBP, Patients' Global Evaluation of study medication, and rescue medication use. Mean aLBPI change from baseline to Week 6 was greater with tanezumab vs naproxen (P=0.004) and placebo (P<0.001). Greater proportions of patients reported ≥30% and ≥50% reduction in aLBPI with tanezumab vs naproxen (P≤0.013) and placebo (P<0.001), and greater improvements in Roland-Morris Disability Questionnaire (P<0.001) and other secondary outcomes except rescue medication use. Tanezumab was associated with adverse events (AEs) of abnormal peripheral sensation that were generally mild and resolved before study completion; however, there were no serious AEs. Nine patients (4 of whom were tanezumab-treated) discontinued due to AEs. In conclusion, tanezumab resulted in analgesic efficacy that was clinically and statistically superior to placebo and naproxen in patients with chronic LBP. Tanezumab clinical development is on regulatory hold due to AEs in osteoarthritis patients. Copyright © 2011. Published by Elsevier B.V.