Efficacy of a Targeted Drug Delivery on‐Demand Bolus Option for Chronic Pain

Bolash, Robert; Niazi, Tariq Khan; Kumari, Monika; Azer, Gerges; Mekhail, Nagy

doi:10.1111/papr.12602

Cited by 12 publications

(12 citation statements)

References 32 publications

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“…The 2012 PACC recommendations suggested that patient‐controlled dosages be 5–20% of the total daily dosage. In a retrospective review from the Cleveland Clinic, up to 30% of the 24‐hour dose could be administered safely during each patient‐activated dose, up to four times daily . This represents a significantly larger incremental increase of the 24‐hour dose, suggesting that more prospective or retrospective data are required.…”

Section: Recommended Starting Dosagesmentioning

confidence: 99%

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

Deer¹,

Pope²,

Hayek

et al. 2017

Neuromodulation: Technology at the Neural Interface

Self Cite

263

262

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Section: Recommended Starting Dosagesmentioning

confidence: 99%

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

Deer¹,

Pope²,

Hayek

et al. 2017

Neuromodulation: Technology at the Neural Interface

Self Cite

263

262

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“…For pain gene therapy, it is optimal to have the therapeutic analgesic molecule be delivered only to the pathological tissues and cells [72, 73] in order to reduce the side effects of treatment. DRG are a site in the peripheral somatosensory pathway that is critically involved in the development and maintenance of peripheral nerve injury-induced chronic pain [74–76].…”

Section: Discussionmentioning

confidence: 99%

AAV-encoded CaV2.2 peptide aptamer CBD3A6K for primary sensory neuron-targeted treatment of established neuropathic pain

Shin

Xiang

et al. 2019

Gene Ther

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Transmission of pain signals from primary sensory neurons to secondary neurons of the central nervous system is critically dependent on presynaptic voltage-gated calcium channels. Calcium channel-binding domain 3 (CBD3), derived from the collapsin response mediator protein 2 (CRMP2), is a peptide aptamer that is effective in blocking N-type voltage-gated calcium channel (CaV2.2) activity. We previously reported that recombinant adeno-associated virus (AAV)-mediated restricted expression of CBD3 affixed to enhanced green fluorescent protein (EGFP) in primary sensory neurons prevents the development of cutaneous mechanical hypersensitivity in a rat neuropathic pain model. In this study, we tested whether this strategy is effective in treating established pain. We constructed AAV6-EGFP-CBD3A6K (AAV6-CBD3A6K) expressing a fluorescent CBD3A6K (replacing A to K at position 6 of CBD3 peptide), which is an optimized variant of the parental CBD3 peptide that is a more potent blocker of CaV2.2. Delivery of AAV6-CBD3A6K into lumbar (L) 4 and 5 dorsal root ganglia (DRG) of rats 2 weeks following tibial nerve injury (TNI) induced transgene expression in neurons of these DRG and their axonal projections, accompanied by attenuation of pain behavior. We additionally observed that the increased CaV2.2α1b immunoreactivity in the ipsilateral spinal cord dorsal horn and DRG following TNI was significantly normalized by AAV6-CBD3A6K treatment. Finally, the increased neuronal activity in the ipsilateral dorsal horn that developed after TNI was reduced by AAV6-CBD3A6K treatment. Collectively, these results indicate that DRG-restricted AAV6 delivery of CBD3A6K is an effective analgesic molecular strategy for the treatment of established neuropathic pain.

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“…Although morphine or ziconotide monotherapy are the only medications approved by the Food and Drug Administration for use with this technology, there also is significant off-label use of other medications. Literature suggests that, by providing targeted drug delivery, intrathecal drug-delivery systems are more effective in controlling pain, with reduced side-effects, at a fraction of the dosing requirements of systemic opioids (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…It has previously been shown that an intrathecal drug-delivery system can eliminate or reduce the use of systemic opioids among patients with chronic noncancer pain (4)(5)(6)(7)(8)(9)(10)(11). Using commercial health insurance claims data from 2008 to 2011, we examined opioid discontinuation and all-cause healthcare utilization among patients newly implanted with an intrathecal drug-delivery system, finding that 51% of patients had eliminated use of systemic opioids at one year following intrathecal drug-delivery system implantation (9).…”

Section: Introductionmentioning

confidence: 99%

Systemic Opioid Reduction and Discontinuation Following Implantation of Intrathecal Drug-Delivery Systems for Chronic Pain: A Retrospective Cohort Analysis

Hatheway

Bansal

Ricker

2020

Neuromodulation: Technology at the Neural Interface

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Objective: The study evaluated systemic opioid utilization before and after initiation of intrathecal drug therapy in patients with chronic, noncancer pain, as well as the effect of opioid elimination on payer costs. Methods: This was a retrospective cohort analysis of administrative claims data (2011-2016), evaluating patients using systemic opioids for chronic, noncancer pain, newly implanted with an intrathecal drug-delivery system. Patients were excluded for spasticity, cancer, and device explant. The primary outcome was reduction or discontinuation of systemic morphine milligram equivalents during a 395-day follow-up period. The secondary outcome was total commercial insurer payments. Results: Of 9223 total patients, 631 met selection criteria. From baseline to 395-day follow-up, average daily morphine milligram equivalents decreased in 81.5% of patients, and 43.3% discontinued systemic opioid therapy entirely. Among patients who continued systemic opioids, average daily morphine milligram equivalents decreased in 74.9% of patients. Logistic regression found that morphine milligram equivalents of <50 mg/day prior to initiation of intrathecal drug delivery was associated with two times the odds of discontinuation vs. ≥90 mg/day (odds ratio = 2.08, 95% confidence interval 1.42-3.02, p = 0.001). Mean annual payer costs were reduced 29% for patients who discontinued vs. continued systemic opioids (−$11,115 per patient). Conclusions: A meaningful proportion of patients discontinue or decrease systemic opioid use following initiation of intrathecal drug delivery. Standard of care should include opioid dose tapering prior to intrathecal drug delivery to maximize the probability of systemic opioid discontinuation.

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Efficacy of a Targeted Drug Delivery on‐Demand Bolus Option for Chronic Pain

Abstract: Utilizing an intrathecal bolus to treat incident pain was a safe way to manage unpredictable breakthrough pain and may represent a cost-saving opportunity by eliminating the need for oral analgesic medications.

Cited by 12 publications

References 32 publications

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

AAV-encoded CaV2.2 peptide aptamer CBD3A6K for primary sensory neuron-targeted treatment of established neuropathic pain

Systemic Opioid Reduction and Discontinuation Following Implantation of Intrathecal Drug-Delivery Systems for Chronic Pain: A Retrospective Cohort Analysis

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