Title : Effectiveness and safety of intrathecal ziconotide: Interim analysis results from a single center of the patient registry of intrathecal ziconotide management
Abstract:
Introduction: The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluates effectiveness and safety of intrathecal (IT) ziconotide.
Methods: PRIZM is an open-label, long-term, multicenter (23 sites), observational study of adult patients with severe chronic pain who meet ziconotide prescribing information criteria. Study assessments are scheduled at baseline, weeks 1, 2, 3, 4, 8, and 12, and every 3 months thereafter through month 18. This interim analysis (data as of July 10, 2015) reports change from baseline to month 12 in “average pain for the past 24 hours” on the 11-point Numeric Pain Rating Scale (NPRS; primary efficacy measure) from the PRIZM site with the highest enrollment (site 9; n=13).
Results: Enrollment closed at 93 patients; data collection has completed. Site 9 enrolled 13 patients, 12 of whom received ziconotide as the first agent in pump (FIP+) and 1 as the second-or-later intrathecal agent in pump (FIP-). Mean (SD) baseline NPRS score was 7.8 (1.5) in FIP+ patients; baseline NPRS score was 4.0 for the FIP- patient. At the time of this analysis, 10/12 FIP+ patients (83.3%) were enrolled ≥12 months prior; 80.0% (8/10) of patients were still active in the study at month 12, of whom 37.5% (3/8) remained on ziconotide monotherapy. The FIP- patient was not enrolled in the study at month 12. The number of patient visits corresponded with the study schedule through week 8, after which patients were seen approximately 2 to 5 times more frequently than with per-protocol visits. In addition to continuous infusion dosing, all patients except for 1 in the FIP+ group had patient-administered bolus dosing enabled (via the Medtronic® Personal Therapy Manager). The onset and duration of patient-administered dosing varied. Mean (SD) ziconotide dose in FIP+ patients was 1.03 (0.08) mcg/d at baseline, 4.46 (5.76) mcg/d at week 12, 3.44 (2.92) mcg/d at month 6, and 1.52 (1.08) mcg/d at month 12. Dosing for FIPpatient was 1.20 mcg/d at baseline, 2.50 mcg/d at week 12 and 1.00 mcg/d at month 6. Mean (SEM) percentage change in NPRS score in FIP+ patients was -34.6% (9.0%) at week 12, -37.3% (9.3%) at month 6, and -46.1% (12.6%) at month 12. In the FIP- patient, percentage change in NPRS score was 100.0% at week 12 and month 6. In FIP+ patients, treatment response rates were 50.0% at week 12, 55.6% at month 6, and 50.0% at month 12 for response defined as ≥30% decrease in NPRS score. The FIP- patient did not respond to treatment. The most common adverse events (≥3 patients overall) were amnesia (38.5%), peripheral edema (30.8%), memory impairment (23.1%), nausea (23.1%), and vertigo (23.1%).
Conclusion: Pain reduction through month 12 was observed at the highest-enrolling PRIZM site and may be related to ziconotide use as the first IT agent in pump and/or investigator-specific practices (high frequency of patient contact, opportunity for dose adjustment, high use of patient-administered IT bolus dosing). The analysis was limited by the small patient population. The adverse events reported are consistent with ziconotide prescribing information.
