Use of Intrathecal Ziconotide for Frequent Severe and Intractable Sickle Cell Disease-Related Pain
Authors: McDowell Gladstone C , Mitchell Jerry , Moore Timothy D. 
Published: October 2019

Abstract
Abstract 1062
Many patients with sickle cell disease (SCD) have recurrent, severe vaso-occlusive pain crises, with profound consequences for their quality of life. These pain crises are sometimes responsive to medical management of the underlying disease or to palliative opioid or nonopioid therapies, but in other cases, the pain is intractable. In addition, patients with SCD are prone to chronic, debilitating pain from related conditions.
We decided to test intrathecal (IT) ziconotide therapy using an implantable pump with the addition of a Personal Therapy Manager (PTM) patient control accessory in patients with SCD and severe, intractable pain. Ziconotide is a direct and selective inhibitor of N-type calcium channels, believed to reduce signaling in spinal pain pathways. In randomized, controlled trials, ziconotide has been shown to reduce severe chronic pain of various etiologies. We identified 2 patients with SCD and a history of prolonged, intractable pain as suitable candidates. After successful IT ziconotide bolus dose trials demonstrated the utility of ziconotide, these patients were implanted with programmable IT infusion pumps with PTM. Ziconotide was titrated to effect over several weeks.
Patient 1 was a 29-year-old female with a history of SCD and hemoglobin of 7, MCV of 83, and platelet count of 297. She had been treated at major academic centers and by private practice hematologists with maximal medical therapy including hydroxyurea and folic acid. She was hospitalized about once a month in the previous 12 months for administration of IV opioids with patient-controlled analgesia (PCA). Currently she has evidence of aseptic necrosis of both hips, not improved by intra-articular steroid injections; she is not a candidate for joint replacements in view of her youth. She underwent a 1-mcg fluoroscopically directed IT bolus trial of ziconotide, with a reduction in her average visual analog scale (VAS) pain score of 9/10 to 0/10 for 48 hours, which was an unusual occurrence for her. She was able to sleep without difficulty and had improvement in her bilateral lower extremity, hip, rib, and back pain. A pump was then implanted for continuous IT infusion of ziconotide. She has not required emergency room visits or hospitalization for sickle cell crises since pump implantation. She is currently at 3.75 mcg/d of ziconotide with a PTM dose of 0.350 mcg every 3 hours and is interested in returning to work. She has not experienced any significant adverse events during the ziconotide titration phase.
Patient 2 was a 31-year-old female with a history of hemoglobin S and thalassemia trait. She had bilateral avascular necrosis of the shoulders and hips and had been treated with chronic opioid therapy (fentanyl 50 mcg) but was still being hospitalized monthly for pain management. She had been treated at 2 major academic institutions as well as multiple community hospitals. The patient admitted to previous use of marijuana and cocaine in an effort to control her pain, as well as to obtaining pain medications from multiple physicians. She responded to a 7-mcg IT ziconotide trial with pain reduction from 8/10 to 0/10 for several days and then underwent implantation of a programmable pump with PTM. Following pump implantation she had satisfactory analgesia and did not require any emergency room visits for pain at a stable ziconotide dose of 1.5 mcg/d with a PTM dose of 0.150 mcg every 3 hours. This patient was receiving home refills and developed a pump pocket infection, requiring explantation of her IT infusion pump. Currently, she is poorly controlled on long-acting opioids and has requested reimplantation of her pump with ziconotide monotherapy.
Here we describe 2 cases of successful pain management in SCD with IT ziconotide. While receiving continuous IT infusion of ziconotide, both patients were able to be titrated off of high-dose, long-acting opioids. In addition, the PTM proved useful for dosage finding during the titration phase as well as for aborting pain flares. We are in the process of studying a larger number of patients to better define the improvements achieved in functional status, analgesia, and healthcare savings with improved pain management using ziconotide in patients with SCD.

Disclosures:
McDowell: Azur Pharma: Speakers Bureau.