1. 2024;27;401-413Treatment Gaps and Emerging Therapies in Lumbar Disc Herniation
   Narrative Review
   Douglas P. Beall, MD, Kee D. Kim, MD, Kevin Macadaeg, MD, Kianoush Donboli, MD, Kinsuk Chauhan, MD, Mohan Sowlay, ., Amy Guo, PhD, and Alexander Vaccaro, MD, PhD.

BACKGROUND: Lumbar disc herniation (LDH) occurs when the central disc material, primarily the nucleus pulposus, is displaced beyond the outer annulus, compressing the spinal nerve roots. LDH symptoms, including radicular leg pain, radiculopathy, and low back pain, are associated with considerable disease burden and the significant utilization of health care resources.

OBJECTIVES: Provide overview of the current treatment landscape for LDH, identify unmet needs, and describe emerging treatments.

STUDY DESIGN: Narrative literature review.

METHODS: A review of literature concerning available LDH treatments and associated outcomes was conducted in PubMed to identify areas of unmet need. Some key words included “lumbar disc herniation,” “radicular leg pain,” “sciatica,” “treatment,” “therapy,” and “burden.”

RESULTS: For patients who do not respond to conservative therapy, epidural steroid injections (ESIs) are widely used for persistent LDH symptoms. While ESIs provide short-term improvements in radicular pain, evidence that ESIs bestow sustained benefits is limited. ESIs are not approved by the US Food and Drug Administration (FDA) and, in rare cases, carry risks of infection and neurological injury, as well as the potential for long-term systemic effects of glucocorticoids. In cases when nonsurgical treatment fails to relieve symptoms, lumbar discectomy can provide rapid pain relief; however, in addition to the risk of intraoperative complications, the long-term consequences of lumbar discectomy may include recurrent pain or herniation, revision discectomy, loss of disc height, and Modic changes. Treatments for LDH in late-stage clinical development include sustained-release ESI formulations and a novel agent for chemonucleolysis, a nonsurgical method of minimizing the volume of the displaced nucleus pulposus. Emerging minimally invasive therapies that address the underlying pathophysiology of the disease have the potential to bridge the gap between symptomatic treatments and surgery.

LIMITATIONS: Because this paper was a narrative review, literature search and selection processes were not systematic in nature. The evidence regarding the long-term efficacy of some treatments, such as discectomy, was limited by the high rates of crossover between the treatment groups.

CONCLUSIONS: The lack of sustained benefits associated with ESIs and the risks associated with surgery underscore the unmet need for novel, minimally invasive interventional therapies able to address the underlying nerve root compression in LDH.

KEY WORDS: Lumbar disc herniation, radicular leg pain, lumbar radiculopathy, epidural steroid injection, surgery, microdiscectomy, chemonucleolysis, condoliase, intradiscal therapy, minimally invasive treatment