Italian Registry on Long-Term Intrathecal Ziconotide Treatment

Abstract

Background: Ziconotide is commonly used for intrathecal (IT) therapy of chronic pain, and has been recently indicated as a first-line IT drug. It is also extremely useful for patients intolerant or refractory to the common IT drugs (such as morphine). The literature, excluding registration studies, mostly includes small samples, and gives only fragmentary evidence on the long-term risks and benefits of ziconotide. Objective: To collect data on safety and efficacy of long-term ziconotide IT infusion in Italian pain centers. Study Design: Retrospective cohort study on the use of ziconotide in Italy. The study was designed and coordinated by the Foundation ISAL (Algological Sciences Research and Training Institute). Patients treated with ziconotide from several pain therapy and neurosurgery units were included in the study, allowing the creation of the first Italian Registry of Ziconotide. Setting: Seventeen Italian public and private pain and neurosurgery centers. Methods: Patients suffering from cancer or non-cancer intractable chronic pain who had been treated with ziconotide IT infusion for at least one month. Efficacy was analyzed considering changes on the visual analog scale of pain intensity from baseline observation. Safety was assessed by monitoring the number and intensity of adverse events. Results: Currently, 104 patients are included in the Italian Registry of Ziconotide. Ziconotide was administered as the first IT drug choice to 55 patients. Seventy-two patients reported at least a 30% pain intensity reduction with a mean dose of 4.36 µg/d. The sustained analgesic effect (P < 0.001) of the ziconotide IT therapy was observed in a group of 45 patients who remained in the study over 6 months without treatment interruptions and with relatively stable doses. Sixty-six patients reported at least one side effect related to ziconotide. However, adverse events have not always been decisive for treatment interruptions. Limitations: Data were collected retrospectively from different pain centers that used different methods for ziconotide treatment and clinical forms for its data collection; for this reason there is an absence of standardized methodologies and a placebo-controlled group, and some data were missing. Conclusions: Ziconotide IT therapy is a treatment option commonly used for clinical practice in 17 Italian pain therapy and neurosurgery units. It might give relief to patients with refractory chronic pain, and it seems to have a safe profile. Long-term studies and controlled trials are required.: Key words: ziconotide; registry; drug safety; intrathecal; refractory chronic pain, opioid, adverse events, long-term treatment

A Benefit/Risk Assessment of Intrathecal Ziconotide in Chronic Pain: A Narrative Review

“…Regarding the tumor type, the authors included 4 patients affected by breast cancer, 8 patients affected by lung cancer, 4 patients affected by colorectal cancer, and 10 other patients affected by unspecified types of cancers. The study disclosed a good efficacy of Ziconotide in malignant and non-malignant intractable pain [ 22 ]. Pain intensity was tested after one month of treatment and 69.23% of patients reported a pain intensity reduction of at least 30%, with a mean dose of 4.36 μg per day and a treatment period of 53 days [ 22 ].…”

“…The study disclosed a good efficacy of Ziconotide in malignant and non-malignant intractable pain [ 22 ]. Pain intensity was tested after one month of treatment and 69.23% of patients reported a pain intensity reduction of at least 30%, with a mean dose of 4.36 μg per day and a treatment period of 53 days [ 22 ]. Furthermore, 53.84% experienced a 50% pain intensity reduction and almost all patients experienced such reduction within a mean treatment period of 82 days [ 22 ].…”

Intrathecal pain management with ziconotide: Time for consensus?

“…However, in Europe, ITA is practiced in few specialist centers, and most regimens involve morphine rather than ziconotide, although where ziconotide is used the experiences are positive (McDowell et al., 2020). The low adoption of ziconotide ITA in Europe can be traced to key, inter‐related differences between the United States and European practices, in particular: European concerns regarding ziconotide dose selection and tolerability (high starting dose; poor tolerability): these concerns relate to the ziconotide dosing regimen listed in the EU Summary of Product Characteristics (SmPC) (Table 1) Limited recent European‐specific clinical data and formal guidance on ziconotide ITA (Alicino et al., 2012; Dupoiron et al., 2012; Dupoiron et al., 2019; Raffaeli et al., 2011): this clinical literature does not align with the dosing regimen in the EU SmPC …”

A Review of the Clinical and Therapeutic Implications of Neuropathic Pain

“…Despite the underlying rationale, the efficacy of this type of medication greatly differs by the type of drug and the center performing the treatment, and for this reason, the NeuPSIG recommendations have not been able to address this issue [ 29 ]. In our experience, ziconotide has been beneficial in refractory pain with a safe profile [ 35 ]. In this step, we suggest considering other types of therapies, such as transcranial direct-current stimulation, and repetitive transcranial magnetic stimulation that has proven to be effective in the setting of NP refractory to all previously listed therapies [ 36 ].…”