John Sasaki

Prevention of Mechanical Failures in Implanted Spinal Cord Stimulation Systems

Introduction.  Spinal cord stimulation (SCS) is an effective procedure for the treatment of neuropathic extremity pain, with success rates approaching 70%. However, mechanical failures, including breakage and migration, can significantly limit the long‐term effectiveness of SCS. A systematic analysis of surgical techniques was undertaken by a consensus group, coupled with extensive in vivo and in vitro biomechanical testing of system components.

Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain

ABSTRACT Objective: To assess the long-term efficacy, tolerability and safety of polymer-coated extended- release morphine sulfate (P-ERMS) (KADIAN*) compared with controlled-release oxycodone HCl (CRO) (OxyContin†) in treating chronic, nonmalignant, moderate to severe pain in a community- based outpatient population. * KADIAN is a licensed trademark of Alpharma Branded Products Division Inc., Piscataway, NJ, USA † OxyContin is a registered trademark of Purdue Pharma L.P., Stamford, CT, NJ, USA Design: Phase IV, prospective, randomized, open-label. Participants: Adults (N = 112) with chronic, nonmalignant, moderate to severe pain with visual numeric scale (VNS) scores ≥ 4 (0 = no pain; 10 = worst pain). Interventions: Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24‐week treatment period. Upward titration of dose and switching P-ERMS to BID or CRO to thrice-daily (TID) dosing was allowed Weeks 2–24. Main outcome measures: Quality of life (Physical [PCS] and Mental [MCS] Component Summary scores of the SF-36v2 Health Survey), pain and sleep scores (0–10), and patient and clinician assessments of current therapy (–4 to +4). Results: Patients in both treatment groups experienced significant improvements in PCS scores (P-ERMS, +2.6; CRO, +3.1; p < 0.05 vs. baseline); patients taking CRO also demonstrated improvements in MCS scores (+4.7, p < 0.05 vs. baseline). Both groups attained significant reductions from baseline to 24 weeks in pain (P-ERMS, –2.0; CRO, –1.4; p ≤ 0.001 vs. baseline); the reduction with P-ERMS was clinically meaningful (as defined by at least a 2‐point reduction in VNS score). Patients attained significant improvement in sleep scores (P-ERMS, –2.6; CRO, –1.6; p < 0.001 vs. baseline; p < 0.05, P-ERMS vs. CRO). At Week 24, both groups indicated significantly increased patient (P-ERMS, +2.6; CRO, +1.7; p < 0.001 vs. baseline) and clinician (P-ERMS, +4.0; CRO, +3.1; p < 0.001 vs. baseline) global assessments of therapy. After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID). Most common adverse events were constipation, nausea, and somnolence, with no significant difference between treatment groups. Conclusions: P-ERMS and CRO both relieved chronic nonmalignant pain in this community-based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID).

Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules.

ABSTRACT Objective: To demonstrate the efficacy and tolerability of polymer-coated extended-release morphine sulfate (P-ERMS) (KADIAN*) for the treatment of chronic, moderate-to-severe, non-malignant pain in a community-based outpatient population not satisfactorily relieved with their current therapies. * KADIAN is a registered trademark of Alpharma Branded Products Division Inc., Piscataway, NJ Design: Phase IV, prospective, randomized, open-label, blinded endpoint. Participants: Adults (N = 1428) with chronic, moderate-to-severe, non-malignant pain with visual numeric scale scores ≥ 4 (0 = no pain; 10 = worst pain). Interventions: Patients were randomized to P‐ERMS once daily in am or pm for a 4‐week treatment period. Dose increases were allowed; however, switching to twice-daily dosing was reserved until week 2. Main outcome measures: Improvement from baseline in pain and sleep scales (0–10) (after weeks 2 and 4), quality of life (physical and mental component summary scores of the SF-36v2 Health Survey) (week 4), and patient (weeks 2 and 4) and clinician (week 4) assessments of current therapy (–4 to +4). Patient satisfaction was assessed again 1 month after the study. Results: Approximately 70% of patients completed the study, with 2.4% (n = 34) discontinuing due to lack of efficacy, and 9.6% (n = 136) discontinuing due to an adverse event. Improvements were seen in pain and sleep scores, physical and mental component scores of the SF-36v2, and patient and clinician global assessment scores ( p < 0.0001, all assessments). Patients attained similar results regardless of am vs. pm dosing. More than half (55.4%) of patients were maintained on once-daily therapy, with the remainder on a twice-daily regimen, in accordance with the prescribing information. Most adverse events (71.6%) were mild to moderate in severity, the most common being constipation (11.6%) and nausea (9.2%). One‐month follow-up indicated continued satisfaction with P‐ERMS vs. previous medication ( p < 0.0001). Conclusions: P‐ERMS was efficacious and well tolerated in patients with chronic, moderate-to-severe, non-malignant pain when used once or twice daily.

Assessment of Patient Preference for Constant Voltage and Constant Current Spinal Cord Stimulation

Objectives:  Spinal cord stimulation devices control energy by generating either constant voltage (CV) pulses or constant current (CC) pulses. This study aimed to investigate: 1) whether patients feel differences between CV and CC stimulation; 2) if patients prefer CV or CC stimulation.

Effectiveness of polymer-coated extended-release morphine sulfate capsules in older patients with persistent moderate-to-severe pain: A subgroup analysis of a large, open-label, community-based trial

UNLABELLED Abstract. BACKGROUND Opioid analgesics may offer benefits over nonopioids in some older patients, especially those with moderate-to-severe pain. Polymer-coated extended-release morphine sulfate (P-ERMS) has been found to be efficacious and well tolerated in patients with chronic, moderate-to-severe, nonmalignant pain when used QD or BID. OBJECTIVE The purpose of this analysis was to determine the effectiveness of P-ERMS in older patients (aged >65 years) with persistent, moderate-to-severe, inadequately controlled, nonmalignant pain. METHODS This was a subgroup analysis of the older population from an openlabel trial in community-based pain clinics in which patients underwent treatment with P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant pain (≥4 on a scale of 0-10). Patients received P-ERMS at a dose determined by the investigator based on their previous analgesic regimen, QD (morning or evening) for a 4-week treatment period. Dose increases were permitted after weeks 1 and 2; switching to BID was allowed after week 2, if needed. Measurements included changes in pain and sleep scores (0-10 scale), quality of life (QOL) scores (physical and mental component summaries [PCS and MCS, respectively] of the 36-Item Short-Form Health Survey instrument), and patient and clinician assessments of current treatment based on a 9-point scale ranging from -4 to +4. RESULTS One hundred forty-eight older patients (mean [SD]age, 73.4 [5.5] years) began treatment with P-ERMS; 86 (58.1%) of those patients completed the study. Pain and sleep scores significantly improved (decreased) from baseline to week 4 (7.4 vs 5.0 and 5.0 vs 3.2, respectively; both, P < 0.001). PCS and MCS scores significantly improved (increased) from baseline (27.7 vs 31.6 and 37.6 vs 40.8, respectively; both, P < 0.05), as did patient and clinician global assessments (-1.2 vs 1.1 and -1.5 vs 1.4; both, P < 0.001). Results found in these older patients were similar to those observed in the younger patients (aged ≤65 years). A majority (71.4%) of the older patients remained on QD administration and took significantly lower mean daily doses than younger patients (77.0 vs 105.2 mg/d, respectively; P = 0.001). The dropout rate for the subgroup was 41.1%, which was similar to that reported in previous studies in mixed-age populations taking other extended-release morphine formulations. Of the patients who discontinued (n = 60), adverse events (AEs) were the most prevalent reason (n = 29). The most common treatment-related AEs were constipation (19.6%) and nausea (9.5%). CONCLUSIONS This subgroup analysis of a previously published study revealed that the older patients in that study who were receiving P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant pain who completed the study attained significant improvements in pain, sleep, and QOL scores compared with baseline. Patient and clinician satisfaction with treatment increased significantly from baseline to study end. Older patients utilized significantly lower mean daily doses than younger patients (P < 0.001), and >70% remained on a QD administration regimen for the duration of the study.

Spinal Cord Stimulation (SCS)—The Implantable Systems Performance Registry (ISPR)

The Implantable Systems Performance Registry (ISPR) was created to monitor the product performance of Medtronic Spinal Cord Stimulation (SCS) and implanted intrathecal drug infusion systems available in the United States.

Comment and Reply on:Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain

We are writing in response to the study entitled ‘Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain’, published in the August 2006 issue of Current Medical Research and Opinion by Nicholson et al.. We agree with the authors that for patients with chronic pain, opioids should be administered around-theclock to achieve continuous pain relief, and modifiedrelease dosage forms of morphine and oxycodone provide additional options to appropriate patients with moderate to severe chronic pain. The stated purpose of this study was ‘to compare the efficacy, tolerability and safety’ of polymer-coated extended-release morphine sulfate (P-ERMS; Kadian*) to that of controlledrelease oxycodone HCl (CRO; OxyContin†) ‘in the long-term treatment of chronic, moderate to severe, nonmalignant pain in a community-based outpatient population’. While we commend the stated aim of the study, the method of the study and conclusions lead to concerning and misleading inferences regarding the dosing and administration of CRO Tablets. First, we would like to address this statement in the ‘Introduction’ section: ‘Clinicians have reported that effective pain relief with CRO may require dosing three times daily (TID) or even four times daily (QID) ’. The three references cited in support of this statement are not well-controlled clinical studies evaluating the safety and efficacy of dosing CRO more frequently than q12h, but rather are two retrospective chart reviews and a patient-reported utilization survey. These reviews and survey did not evaluate patients’ pain control or tolerability of the medication with more frequent dosing schedules and therefore, from a safety and efficacy standpoint, are not adequate references to support CRO dosing at less than q12h intervals. Next, we would like to comment on the titration protocol presented in Figure 1 of the ‘Study design/ methodology’ section. We are perplexed with the rationale for the titration design where ‘after Weeks 2, 4, 8 and 12 clinicians were allowed to up-titrate the dose of study medication (if not increased during the previous visits) or to switch to BID dosing of P-ERMS or TID dosing of CRO (if the dose was increased at the previous visit). After Week 12, if necessary, the clinician could adjust the patient’s dosing as clinically indicated during the interim.’ While it is not clear what is meant by ‘the clinician could adjust the patient’s dosing as clinically indicated’, the titration scheme to increase the CRO dosing frequency is not consistent with the recommended dosing for CRO. As stated in the prescribing information for CRO, it is most appropriate to increase the q12h dose, not the dosing frequency. There are no well-controlled clinical studies on dosing intervals shorter than q12h. The efficacy and safety of CRO q12h has been well substantiated by numerous controlled clinical trials in various chronic pain states.