Human Factors Results for Fentanyl Iontophoretic Transdermal System (ITS) With Enhanced Controller for Postoperative Pain Management.

PURPOSE: The purpose of this analysis was to conduct summative usability evaluations, including behavioral and subjective evaluations, for the fentanyl iontophoretic transdermal system (ITS). DESIGN: Four usability studies were conducted in representative users. METHODS: The first three studies were conducted with (1) health care professionals (HCPs; N = 31), (2) patients who received placebo fentanyl ITS (N = 30), and (3) healthy volunteers (N = 30), and focused on the understanding and use of fentanyl ITS. The fourth study included HCPs (N = 31) and healthy volunteers (N = 30), and focused on the effectiveness of formal training regarding the use of fentanyl ITS. FINDINGS: Overall, user groups found the fentanyl ITS easy to use. There were no use errors that could potentially have safety implications. In the three early studies, there were some minor difficulties experienced; however, the introduction of a structured training reduced these difficulties. CONCLUSIONS: Patients, nurses, and pharmacists were able to use fentanyl ITS with ease.

Liposomal Bupivacaine Use in Third Molar Impaction Surgery: INNOVATE Study.

The analgesic efficacy and safety of liposomal bupivacaine (LB) in third molar extraction was evaluated in this phase 3, double-blind, placebo-controlled study of subjects undergoing bilateral third molar extraction. Subjects were randomized 2 : 1 to infiltration with LB (133 mg/10 mL) or placebo, and received opioid rescue medication as needed. Primary efficacy measure was cumulative area under the curve (AUC) of numeric rating scale (NRS) pain severity scores through 48 hours (AUC of NRS0-48) postsurgery. Other measures included AUC of NRS0-24, AUC of NRS0-72, and AUC of NRS0-96, and incidence of adverse events. There were 150 subjects in the primary efficacy population (n = 99 LB, n = 51 placebo) and 89 in the per-protocol population (n = 59 LB, n = 30 placebo). Least-squares mean for AUC of NRS0-48 was 172.3 LB versus 194.7 placebo (P = .227) in the primary efficacy population and 120.8 LB versus 183.3 placebo (P = .023) in the per-protocol population. At all time points, between-group differences in AUC of NRS scores were significant in the per-protocol population (LB lower than placebo, P < .05) but not in the primary efficacy population. The adverse event profile was similar between groups. LB produced significantly lower cumulative pain scores versus placebo at all time points in the per-protocol analysis but not in the primary efficacy analysis because of protocol violations. This study indicates significant improvement in pain scores in the third molar model, but because of extensive protocol violations additional studies are warranted to demonstrate effectiveness.

Meta-Analysis of the Ease of Care From a Patients' Perspective Comparing Fentanyl Iontophoretic Transdermal System Versus Morphine Intravenous Patient-Controlled Analgesia in Postoperative Pain Management.

PURPOSE: The purpose of this meta-analysis was to evaluate patients' assessment of fentanyl iontophoretic transdermal system (ITS) and morphine intravenous patient-controlled analgesia (IV PCA) ease of care (EOC) using a validated patient EOC questionnaire. Fentanyl ITS is a preprogrammed, needle-free PCA system used for the management of acute pain in postoperative patients. METHODS: This meta-analysis assessed the patient EOC of fentanyl ITS and morphine IV PCA using data from three randomized, active-comparator trials in adult postoperative patients with moderate-to-severe pain. All three studies utilized a validated patient EOC questionnaire which consists of 23 items grouped into seven subscales (confidence with device, comfort with device, movement, dosing confidence, pain control, knowledge/understanding, and satisfaction). Each item is scored on a six-point Likert scale. The weighted mean difference between treatments was calculated for the overall EOC and for each of the seven subscales. RESULTS: The EOC analyses were based on responses to questionnaires from 1,943 patients treated with either fentanyl ITS (n = 961) or morphine IV PCA (n = 982). There was a statistically significant advantage in favor of fentanyl ITS over morphine IV PCA in terms of overall EOC (weighted mean difference = 0.28; 95% confidence interval (0.22 to 0.34); P < 0.0001). Five of the seven subscales (confidence with device, comfort with device, movement, dosing confidence, and knowledge/understanding) on the patient EOC questionnaire showed a statistically significant advantage for fentanyl ITS versus morphine IV PCA. The two subscales that did not show any difference were pain control (P = 0.7303) and satisfaction (0.0561). CONCLUSION: In this meta-analysis, fentanyl ITS is associated with some advantages in terms of an EOC profile from a patients' perspective when compared with morphine IV PCA.

Meta-Analysis of the Ease of Care From the Nurses' Perspective Comparing Fentanyl Iontophoretic Transdermal System (ITS) Vs Morphine Intravenous Patient-Controlled Analgesia (IV PCA) in Postoperative Pain Management.

PURPOSE: The aim of this meta-analysis was to compare the ease of care (EOC) of fentanyl iontophoretic transdermal system (ITS) vs the morphine intravenous patient-controlled analgesia (IV PCA) as assessed by the nurse. DESIGN: Meta-analysis of three phase 3B randomized active-comparator trials. METHODS: This meta-analysis according to Cochrane's approach assessed EOC using a validated nurse questionnaire (22 items grouped into three subscales, which include time efficiency, convenience, and satisfaction) in adult patients treated with fentanyl ITS or morphine IV PCA for postoperative pain management. The weighted mean difference (WMD) between treatments was calculated. FINDING: EOC analyses were based on responses to questionnaires from 848 (fentanyl ITS) and 761 (morphine IV PCA) nurses. Fentanyl ITS was reported to provide significant advantages compared with morphine IV PCA in terms of nurses' overall EOC (WMD = -0.57, P < .0001) and each of the subscales: time efficiency (WMD = -0.58, P < .0001), convenience (WMD = -0.57, P < .0001), and satisfaction (WMD = -0.47, P < .0001). CONCLUSIONS: In this meta-analysis, fentanyl ITS is associated with a superior EOC profile from the nurses' perspective than morphine IV PCA.

Durable control of metastases in an HLA-A2+ patient with refractory melanoma after low-dose radiotherapy in combination with MAGE-A4 T cell therapy: a case report.

There is no currently approved adoptive cellular therapy for solid tumors. Pre-clinical and clinical studies have demonstrated that low-dose radiotherapy (LDRT) can enhance intratumoral T cell infiltration and efficacy. This case report describes a 71-year-old female patient with rectal mucosal melanoma that had developed metastases to liver, lung, mediastinum, axillary nodes, and brain. After systemic therapies had failed, she enrolled in the radiation sub-study of our phase-I clinical trial exploring the safety and efficacy of afamitresgene autoleucel (afami-cel), genetically engineered T cells with a T cell receptor (TCR) targeting the MAGE-A4 tumor antigen in patients with advanced malignancies (NCT03132922). Prior to the infusion of afami-cel, she received concurrent lymphodepleting chemotherapy and LDRT at 5.6 Gy/4 fractions to the liver. Time to partial response was 10 weeks, and duration of overall response was 18.4 weeks. Although the patient progressed at 28 weeks, the disease was well controlled after high-dose radiotherapy to liver metastases and checkpoint inhibitors. As of the last follow-up, she remains alive over two years after LDRT and afami-cel therapy. This report suggests that afami-cel in combination with LDRT safely enhanced clinical benefit. This provides evidence for further exploring the benefit of LDRT in TCR-T cell therapy.

A Prospective, Randomized, Open-Label Study Comparing an Opioid-Sparing Postsurgical Pain Management Protocol With and Without Liposomal Bupivacaine for Full-Arch Implant Surgery.

PURPOSE: Mild to moderate pain is common following dental implant surgeries, although severe pain is reported in some patients. This randomized, open-label trial was designed to determine the efficacy and safety of an opioid-sparing postsurgical pain management protocol with or without local infiltration of liposomal bupivacaine for full-arch implant surgery. This procedure is used in edentulous and/or failing dentition patients and involves securing four or more implants to the maxilla and/or mandible to serve as anchors for dental prostheses. MATERIALS AND METHODS: Patients scheduled to undergo full-arch implant surgery were randomly assigned to receive an opioid-sparing postsurgical pain management protocol with or without liposomal bupivacaine 266 mg at the end of surgery. All patients received infiltration with ≤ 40 mL lidocaine 2% with epinephrine at the beginning of surgery and bupivacaine 0.5% with epinephrine near the end of surgery and oral opioid or nonopioid analgesics (oxycodone 5 mg tablets or ibuprofen 600 mg), as needed, postsurgically. Pain severity at the surgical site was assessed using a verbal 0 to 10 numeric rating scale (0 [no pain] to 10 [worst pain imaginable]). Patients separately assessed pain in their mandible and maxilla. Reports of treatment-emergent adverse events were collected. RESULTS: Sixty-nine patients were randomized to the liposomal bupivacaine 266 mg (n = 34) or control group (n = 35). At all time points postsurgery for both the mandible (all P ≤ .0112) and the maxilla (all P ≤ .0083), the liposomal bupivacaine group reported significantly less cumulative pain than the control group. At the conclusion of the 7-day follow-up, patients in the liposomal bupivacaine group experienced one-third less cumulative postsurgical pain than patients in the control group. Seventy-seven percent of patients in the liposomal bupivacaine group and 80% in the control group experienced a treatment-emergent adverse event. A higher percentage of patients in the liposomal bupivacaine versus control group reported itching (15% vs 9%) and constipation (38% vs 23%). CONCLUSION: Patients receiving an opioid-sparing postsurgical pain management protocol with liposomal bupivacaine 266 mg experienced a statistically significant reduction of postsurgical pain and clinically relevant reduction in opioid consumption. The overall incidence of treatment-emergent adverse events was comparable in patients receiving an opioid-sparing postsurgical pain management protocol with or without liposomal bupivacaine.

Design and functionality of a smart fentanyl iontophoretic transdermal system for the treatment of moderate-to-severe postoperative pain.

Fentanyl iontophoretic transdermal system (ITS) is a patient-controlled analgesia system used for the management of acute postoperative pain. The first-generation fentanyl ITS was an integrated one-piece system; however, corrosion that could limit reliability was detected in a small number of systems. A second-generation fentanyl ITS was designed to separate the hydrogels in the Drug Unit from the electronic circuit of the Controller during manufacture and storage, removing the primary cause of corrosion and thereby improving reliability. No evidence of corrosion has been observed in over 10,000 systems tested in real-time aging studies for the second generation fentanyl ITS. The second generation fentanyl ITS design features combine to ensure safe operation of the system with high reliability.

A comparison of opioid-related adverse events with fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia in acute postoperative pain.

OBJECTIVE: This analysis compared opioid-related adverse events (ORADEs) observed with fentanyl iontophoretic transdermal system (ITS) versus morphine intravenous (iv.) patient-controlled analgesia (PCA) in the management of postoperative pain. METHODS: Safety data from four Phase IIIB randomized, active-comparator trials were pooled for this analysis (n = 1288 fentanyl ITS and 1313 morphine iv. PCA patients). Treatment-emergent adverse events were collected via spontaneous report. In this post hoc analysis, ORADEs were defined as apnea, confusion, constipation, dyspnea, hypotension, hypoventilation, hypoxia, ileus, nausea, pruritus, somnolence, tachycardia, urinary retention and vomiting. Odds ratios (OR) and 95% CI were calculated for all ORADEs and p-values were based on logistic regression with treatment as effect. RESULTS: There were fewer patients in the fentanyl ITS group compared with the morphine iv. PCA group who experienced at least one ORADE (52.7 vs 59.1%, respectively; OR: 0.772: 95% CI: 0.661-0.901; p = 0.0011). The ORADEs that occurred less frequently in the fentanyl ITS group than in the morphine iv. PCA group included hypotension (3.7 vs 5.5%, respectively; OR: 0.667; 95% CI: 0.459-0.969; p = 0.0338), hypoventilation (0.9 vs 1.9%, respectively; OR: 0.444; 95% CI: 0.217-0.906; p = 0.0256), nausea (40.3 vs 44.5%, respectively; OR: 0.842; 95% CI: 0.721-0.984; p = 0.0310), pruritus (5.5 vs 9.4%, respectively; OR: 0.559; 95% CI: 0.413-0.757; p = 0.0002) and tachycardia (1.6 vs 2.8%, respectively; OR: 0.489; 95% CI: 0.277-0.863; p = 0.0136). No ORADEs occurred more frequently in the fentanyl ITS group compared with the morphine iv. PCA group. CONCLUSION: Fentanyl ITS, in the management of acute postoperative pain, offered safety advantages in terms of ORADEs compared with morphine iv. PCA.

Fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia for pain management following orthopedic surgery: A pooled analysis of randomized, controlled trials.

OBJECTIVE: To compare the efficacy and safety of patient-controlled pain management following orthopedic surgery using either fentanyl iontophoretic transdermal system (ITS) or morphine intravenous (i.v.) patient-controlled analgesia (PCA). SETTING: Acute Care Hospital. PATIENTS: Three-open-label, multicenter, randomized, active-controlled, parallel-group phase 3B studies (N = 2095) were conducted that compared fentanyl ITS with morphine i.v. PCA for postoperative pain in hospitalized postoperative patients. A subgroup of orthopedic surgery patients (N = 1,216) was pooled for this analysis; of which 819 completed treatment. INTERVENTIONS: A total of 590 patients received fentanyl ITS (40 µg/dose) and 626 patients received morphine i.v. PCA (1 mg/dose) for up to 72 hours. MAIN OUTCOME MEASURES: Efficacy measures included the patient global assessment (PGA) and the investigator global assessment (IGA) of the method of pain control. RESULTS: Patients had a mean age of about 60 years, were predominantly Caucasian (90.5 percent), and the majority underwent hip replacement (80.3 percent). There were more patients treated with fentanyl ITS who rated their pain control method as "excellent" compared to morphine i.v. PCA at 24 hours postsurgery (44.8 percent vs 33.0 percent, respectively; p < 0.001), 48 hours (37.5 percent vs 25.3 percent, respectively; p < 0.001), and at the last assessment (54.3 percent vs 39.6 percent, respectively; p < 0.001). There were more investigators who rated treatment with fentanyl ITS as "excellent" compared to morphine i.v. PCA at the last assessment (57.4 percent vs 36.9 percent, respectively; p < 0.001). CONCLUSIONS: Following orthopedic surgery, patients and investigators more frequently reported global assessment of pain control as "excellent" on the PGA and IGA assessments with fentanyl ITS than with morphine i.v. PCA.

Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain.

Opioids are commonly used in the management of moderate-to-severe postoperative pain. Patient-controlled analgesic techniques are recognized as preferred administration methods. Previously, research has focused on intravenously administered opioids via a programmable pump. More recently, an iontophoretic transdermal system (ITS), which is patient controlled, has been developed. The focus of this review is on pain management using the fentanyl ITS during the 24-72-hour time period immediately following surgery. Fentanyl ITS offers a needle-free alternative to traditional intravenous (IV) patient-controlled analgesia (PCA) system that is as effective and safe as IV PCA. This system is easy to use for both patients and nurses. The use of fentanyl ITS is generally associated with a better ease-of-care profile, including a greater ease of mobility, from a patients' perspective when compared with morphine IV PCA.

Development of the fentanyl iontophoretic transdermal system (ITS) for patient-controlled analgesia of postoperative pain management.

The fentanyl iontophoretic transdermal system (ITS) is a needle-free, patient-activated drug delivery system used for patient-controlled analgesia in adult hospitalized patients with postoperative pain. The system design has been updated to a separated system consisting of a Controller and a Drug Unit, and has had regulatory submissions in USA and Europe in 2014. Fentanyl ITS has been shown to be therapeutically equivalent to morphine intravenous (iv.) patient-controlled analgesia. One of the advantages of fentanyl ITS is that patients have better mobility as there is no need for an iv. pump, iv. lines and pole. The introduction of the updated fentanyl ITS will add a versatile tool to the postoperative pain management armamentarium.

Meta-analysis of the efficacy of the fentanyl iontophoretic transdermal system versus intravenous patient-controlled analgesia in postoperative pain management.

OBJECTIVE: This meta-analysis was conducted to analyze and compare the efficacy outcomes associated with the fentanyl iontophoretic transdermal system (ITS) and morphine intravenous (IV) patient-controlled analgesia (PCA) in the management of postoperative pain. RESEARCH DESIGN AND METHODS: This meta-analysis assessed the efficacy of the fentanyl ITS versus morphine IV PCA using data from four randomized, active-controlled trials (n = 1271 fentanyl ITS and 1298 morphine IV PCA patients). Main outcome measures were patient global assessment (PGA) of the method of pain control at 24 h. RESULTS: Fentanyl ITS and morphine IV PCA did not significantly differ regarding 'good' and 'excellent' ratings on the PGA of the method of pain control at 24 h (odds ratio = 0.95, p = 0.66), however, fentanyl ITS was superior in terms of 'excellent' PGA ratings at that time point (odds ratio = 1.53, p < 0.0001). No significant differences were found in weighted mean pain intensity scores at 24, 48 and 72 h. CONCLUSIONS: In this meta-analysis, fentanyl ITS was as efficacious as morphine IV PCA and may offer additional benefits as demonstrated by its 'excellent' PGA ratings.

Fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia for pain management following gynecological surgery: a meta-analysis of randomized, controlled trials.

AIM: To compare the efficacy and safety of patient-controlled fentanyl iontophoretic transdermal system (ITS) with morphine intravenous (i.v.) patient-controlled analgesia (PCA) for pain management following gynecological surgery. METHODS: Two-open-label, multicenter, randomized, active-controlled, parallel-group studies (n = 1142) were conducted that compared fentanyl ITS with morphine iv. PCA for postoperative pain. The subgroup of gynecological surgery patients from each trial was utilized for this meta-analysis (n = 604). Of these patients, 295 received fentanyl ITS (40 µg/dose) and 309 received morphine i.v. PCA (1 mg/dose) for up to 72 h. Efficacy measures included the patient global assessment (PGA) and the investigator global assessment (IGA) of the method of pain control. RESULTS: Gynecological surgery patients (n = 604) included in this meta-analysis had a mean age of 45 years, were predominantly Caucasian (65%) and had a mean body mass index of 29 mg/kg2. There were statistically significantly more patients treated with fentanyl ITS and more investigators who rated their pain control method as 'excellent' on the PGA at 24 h (49.3 vs 37.4%, respectively; p = 0.0029) and IGA at the last assessment (59.5 vs. 38.0%, respectively; p < 0.0001), respectively, compared with morphine iv. PCA at the last assessment. CONCLUSION: Following gynecological surgery, patients and investigators were more satisfied (had a higher percent of an 'excellent' rating on the PGA and IGA, respectively) with fentanyl ITS than morphine iv. PCA as a method of pain control.