Intrathecal Ziconotide Long-Term Efficacy and Safety for Severe Chronic Pain

In patients with severe chronic pain refractory to conventional therapy, intrathecal ziconotide provided long-term pain relief, particularly when used as first-line intrathecal therapy. These results from the interim analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM) were published in Pain Practice.¹

Intrathecal ziconotide is currently approved for the management of severe chronic pain in patients “for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.”²

Several randomized controlled trials (RCTs) showed that intrathecal ziconotide, a nonopioid selective and reversible N-type calcium channel blocker, provided effective analgesia in patients with severe chronic pain who have not responded to conventional therapy.^3-5 However, the follow-up periods in these RCTs were short, ranging from 10 days to 3 weeks, and only limited data exist on the efficacy of intrathecal ziconotide in clinical practice.

The PRIZM study tracks the long-term safety and efficacy of intrathecal ziconotide in patients with refractory chronic severe pain in the clinical practice setting. In an interim analysis, researchers compared the efficacy of ziconotide as first-line intrathecal therapy vs not first agent in pump (FIP-).

The primary efficacy end point was patient-reported “average pain for the past 24 hours,” as measured by the 0 to 10 Numeric Pain Rating Scale (NPRS).

Of 93 patients enrolled, 61.3% were women and 95.7% had chronic pain due to non-cancer causes. The percentage of patients treated with ziconotide as first agent in pump (FIP+) and with ziconotide FIP- were 54.8% and 45.2% of the study population, respectively.

FIP+ and FIP- patients had similar NPRS scores at baseline (7.4 vs 7.9). At 6 months, patients in the FIP+ group experienced a nearly 30% reduction in NPRS score, while patients in the FIP- group had a 6.4% increase in NPRS score. At 12 months, the NPRS score had decreased from baseline by 34.4% and 3.4% in patients receiving ziconotide FIP+ vs FIP-, respectively.

Treatment response, defined as a decrease in NPRS score by ≥30% from baseline, was achieved by 50% of FIP+ patients compared with only 11.1% of FIP- patients at 12 months.

In addition, more patients in the FIP+ group reported overall improvement from baseline, as measured by the Patient Global Impression of Change score, than patients in the FIP- group at 6 months (69.2% vs 35.7%) and at 12 months (85.7% vs 71.4%).

Adverse events were more frequent with ziconotide first in pump (80.4%) than with ziconotide not first in pump (59.5%). The most common adverse events for FIP+ and FIP- were nausea (19.6% vs 7.1%), confusional state (9.8% vs 11.9%), and dizziness (13.7% vs 7.1%). FIP+ patients were more likely than FIP- patients to discontinue study treatment due to adverse events (23.5% vs 7.1%). Rates of serious adverse events, such as depression and suicidal ideation, were 19.6% and 23.8% in the FIP+ and FIP- groups, respectively.

Summary and Applicability

Intrathecal ziconotide has been shown to be effective for treating refractory severe chronic pain, but evidence is lacking on the long-term efficacy and safety of this treatment in clinical practice. Ziconotide, when administered as FIP+ reduced pain scores to a greater extent and resulted in clinical improvement in more patients than when other agents were used as FIP+.

Adverse events were more common in the FIP+ group than in the FIP- group. “The adverse event profile was consistent with ziconotide prescribing information,” the researchers wrote.

The researchers plan to follow all patients in PRIZM for up to 18 months or until ziconotide discontinuation. “The final analysis of the PRIZM study will provide additional information on the long-term effectiveness and safety of [intrathecal] ziconotide in the management of chronic pain in clinical practice,” they wrote.

Limitations and Disclosures

The efficacy analyses were performed on available patient data and do not reflect the effects of discontinuing treatment due to adverse events or lack of efficacy.

This study was funded by Jazz Pharmaceuticals.

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References

1. Deer T, Rauck RL, Kim P, et al. Effectiveness and safety of intrathecal ziconotide: interim analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM) [published online July 14, 2017] Pain Pract. doi:10.1111/papr.12599

2. Prialt^® (ziconotide) solution, intrathecal infusion [package insert]. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2013.

3. Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291(1):63-70. doi:10.1001/jama.291.1.63

4. Rauck RL, Wallace MS, Leong MS, et al; Ziconotide 301 Study Group. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage. 2006;31(5):393-406. doi:10.1016/j.jpainsymman.2005.10.003

5. Wallace MS, Charapata SG, Fisher R, et al; Ziconotide Nonmalignant Pain Study 96-002 Group. Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial. Neuromodulation. 2006;9(2):75-86. doi:10.1111/j.1525-1403.2006.00055.x