- Email: [email protected]
(255) A response profile for fentanyl buccal tablet (FBT) in opioid-tolerant patients with breakthrough pain (BTP)
Abstracts
P39
(252) Risk factors for delayed opioid cessation following surgery
(254) Impact of fentanyl buccal tablet on both patient and clinician ratings of patient function
I Carroll, C Wang, J Wang, M Gillespie, P Barelka, K Humphreys, J Trafton, F Dirbas, S Goodman, R Whyte, W Cannon, G Yang, J Pollard, S Mackey; Stanford University, Stanford, CA Prescription drug abuse is a growing problem. Little is known about factors leading to more persistent opioid use following acute injury. We proposed to use the peri-operative setting to identify psychological risk factors for prolonged opioid use. We conducted a prospective, longitudinal observational study among 77 patients undergoing either: (1) thoracotomy, (2) mastectomy, (3) lumpectomy, (4) total hip replacement, or (5) total knee replacement. Patients were recruited before their surgery and asked to complete a battery of questionnaires as a baseline assessment of various psychological and substance-abuse related factors previously implicated in opioid abuse. Factors included depression, anxiety, fear of pain, family and personal history of substance abuse, and selfperceived susceptibility to addiction, among others. Patients were then called daily post-operatively to record opioid use and Brief Pain Inventory (BPI) pain scores until the patient reached the endpoint of reporting both discontinuation of opioids and zero average pain for five consecutive days. Our primary endpoint for this study was time-to-opioidcessation as defined by five consecutive days of zero opioid use. Cox proportional hazards regression of data from more than three thousand phone calls showed a median time to opioid cessation of 35 days (95% CI 23-40) Multivariate Cox regression analysis showed that pain duration (p ⫽ 0.001), depression (p ⫽ 0.002), and self-perceived addiction susceptibility (p ⫽ 0.025) were each independently and significantly associated with delayed opioid cessation. We have established that the surgical setting is ideal for establishing psychological factors that lead to more persistent opioid use following acute injury. These data may help improve understanding of how pain, psychological impairment and opioid use lead to chronic opioid use and abuse over time.
J Farrar, E Michna, J Messina, F Xie; University of Pennsylvania School of Medicine, Philadelphia, PA We evaluated the effects of Fentanyl Buccal Tablet (FBT) over a 12-week treatment period, with secondary assessments of patient function. Opioid-tolerant adults with chronic non-cancer pain and BTP (1-4 episodes/ day) were titrated to a single successful FBT dose (100-800 mcg providing adequate analgesia without unacceptable AEs) and then entered a 4-week open-label period (at the successful dose) followed by doubleblind, randomized treatment for 9 BTP episodes (6 FBT, 3 placebo). The open-label/double-blind sequence was repeated twice. Patient function was assessed using the Brief Pain Inventory-Short Form (BPI-SF) and three questionnaires based on the functional component of the BPI-SF. Patients and clinicians rated the level of change on items related to functioning since starting the study as a global assessment after week 12 or early withdrawal (endpoint). Evaluations included the Goal Attainment Scale (GAS; patients rated change in 3 of 7 functional factors they selected a priori as important), Patient Assessment of Function questionnaire (PAF; 7 questions rated on a 7-point scale, very much worsened to very much improved), and Clinician Assessment of Patient Function questionnaire (CAPF; 5 questions rated on a 7-point scale, very much worsened to very much improved). BPI-SF: evaluations showed little change from baseline to endpoint. GAS: 44/59 (75%) patients reported an improvement in their general activity, with similar results for other functional factors, e.g., mood (82%), sleep (63%). PAF: ⬎50% of patients reported some improvement in 5/7 areas of functioning, including a majority who reported an improvement in the ability to perform at work (77%), participate in social events (74%), and enjoy life (76%). CAPF: Clinicians reported some improvement in each area of functioning for ⬎60% of patients. AEs were generally typical of opioids. In conclusion, FBT had consistently positive effects on function in opioidtolerant patients with BTP. Sponsored by Cephalon, Inc.
(253) Fentanyl buccal tablets effective for pediatric patient with episodic pain secondary to ulcerative colitis
(255) A response profile for fentanyl buccal tablet (FBT) in opioid-tolerant patients with breakthrough pain (BTP)
M Holtsman, L Wania-Galicia, D Williamson; UC Davis Medical Center, Sacramento, CA A sixteen year-old 49 kg. female with a four month history of ulcerative colitis was admitted to the pediatric ward with persistent nausea and severe episodic pain associated with bowel movements. Her ulcerative colitis was refractory to treatment with Infliximab and steroids. On admission, she was initially treated with 12.5 mcg/hr Transdermal Fentanyl System and intravenous morphine 1-2 mg every three hours as needed for pain with minimal relief. The Pain Service was then consulted to optimize her analgesia. Given the crampy and episodic character of her abdominal pain, hyoscyamine 0.125 mg PO/SL was recommended which provided modest improvement of her episodic pain. In addition, the patient was started on a morphine PCA with which she used approximately 1 mg/hr intravenous morphine. A trial of oral morphine 10 –20 mg for episodic pain was attempted. The morphine PCA was continued for pain not controlled by oral morphine. However, the patient’s episodic pain increased so rapidly that her oral morphine regimen was ineffective. As the patient’s long-acting analgesic (Transdermal Fentanyl) had been titrated up to 25 mcg/hr for one week, Fentanyl Buccal Tablet 100 mcg was initiated for her severe episodic pain. The Fentanyl Buccal Tablet provided effective pain reduction with the patient utilizing up to four doses per day. The Fentanyl Transdermal System was eventually titrated to a final dose of 37.5 mcg/hr change every three days. Her abdominal pain has remarkably improved. The patient’s analgesic regimen on discharge included: Fentanyl Transdermal System 37.5 mcg/hr change every three days, Fentanyl Buccal Tablets 100 mcg one tab every four hours as needed for pain not to exceed four doses per day, Hyoscyamine 0.25 mg PO/SL every four hours as needed. The patient has continued on this regimen for two months now with stable pain control.
J Farrar, E Michna, J Messina, F Xie; University of Pennsylvania School of Medicine, Philadelphia, PA FBT has been effective and generally well tolerated in short-term studies of opioid-tolerant patients with BTP.1-3 We evaluated the FBT response profile in a longer-term study of BTP with 3 equally spaced withinpatient double-blind periods using various response measures. Opioidtolerant adults with chronic non-cancer pain experiencing 1-4 BTP episodes/day were enrolled. Patients who titrated to a successful dose of FBT (single dose 100-800 mcg providing adequate analgesia without unacceptable AEs) then received open-label FBT (at the successful dose) for 4 weeks followed by double-blind, randomized treatment for 9 episodes (6 FBT, 3 placebo). The open-label/double-blind sequence was repeated twice. During the double-blind evaluation periods (after 4, 8, and 12 weeks of treatment), patients rated BTP intensity (PI, 0 –10 scale) predose and during the observation period 5–120 min postdose, and were to record when any pain relief (APR) and meaningful pain relief (MPR) were achieved. Measures of clinically relevant response included % of episodes with ⱖ33% and ⱖ50% improvement in PI, and patientassessed APR and MPR. Of 148 patients titrated, 105 (71%) achieved a successful dose and, of these, 81/105 (77%) completed the study. Following week 12, significant differences between FBT and placebo were seen during the observation period for % episodes with ⱖ33% improvement in PI (54% vs 31%, OR 2.61, P⬍0.0001) and ⱖ50% improvement in PI (42% vs 22%, OR 2.51, P⬍0.0001). Patients reported APR at rates of 74% for FBT vs 52% for placebo (OR 2.63, P⬍0.0001). Similarly, rates of MPR were 58% vs 34% (OR 2.71, P⬍0.0001). AEs were generally typical of opioids. In conclusion, responses to FBT were consistent across clinically meaningful measures after 12 weeks of treatment in opioid-tolerant patients with BTP. Sponsored by Cephalon, Inc. (1. Slatkin, J Support Oncol, 2007; 2. Portenoy, Curr Med Res Opin, 2007; 3. Simpson, Clin Ther, 2007.)
P39
(252) Risk factors for delayed opioid cessation following surgery
(254) Impact of fentanyl buccal tablet on both patient and clinician ratings of patient function
I Carroll, C Wang, J Wang, M Gillespie, P Barelka, K Humphreys, J Trafton, F Dirbas, S Goodman, R Whyte, W Cannon, G Yang, J Pollard, S Mackey; Stanford University, Stanford, CA Prescription drug abuse is a growing problem. Little is known about factors leading to more persistent opioid use following acute injury. We proposed to use the peri-operative setting to identify psychological risk factors for prolonged opioid use. We conducted a prospective, longitudinal observational study among 77 patients undergoing either: (1) thoracotomy, (2) mastectomy, (3) lumpectomy, (4) total hip replacement, or (5) total knee replacement. Patients were recruited before their surgery and asked to complete a battery of questionnaires as a baseline assessment of various psychological and substance-abuse related factors previously implicated in opioid abuse. Factors included depression, anxiety, fear of pain, family and personal history of substance abuse, and selfperceived susceptibility to addiction, among others. Patients were then called daily post-operatively to record opioid use and Brief Pain Inventory (BPI) pain scores until the patient reached the endpoint of reporting both discontinuation of opioids and zero average pain for five consecutive days. Our primary endpoint for this study was time-to-opioidcessation as defined by five consecutive days of zero opioid use. Cox proportional hazards regression of data from more than three thousand phone calls showed a median time to opioid cessation of 35 days (95% CI 23-40) Multivariate Cox regression analysis showed that pain duration (p ⫽ 0.001), depression (p ⫽ 0.002), and self-perceived addiction susceptibility (p ⫽ 0.025) were each independently and significantly associated with delayed opioid cessation. We have established that the surgical setting is ideal for establishing psychological factors that lead to more persistent opioid use following acute injury. These data may help improve understanding of how pain, psychological impairment and opioid use lead to chronic opioid use and abuse over time.
J Farrar, E Michna, J Messina, F Xie; University of Pennsylvania School of Medicine, Philadelphia, PA We evaluated the effects of Fentanyl Buccal Tablet (FBT) over a 12-week treatment period, with secondary assessments of patient function. Opioid-tolerant adults with chronic non-cancer pain and BTP (1-4 episodes/ day) were titrated to a single successful FBT dose (100-800 mcg providing adequate analgesia without unacceptable AEs) and then entered a 4-week open-label period (at the successful dose) followed by doubleblind, randomized treatment for 9 BTP episodes (6 FBT, 3 placebo). The open-label/double-blind sequence was repeated twice. Patient function was assessed using the Brief Pain Inventory-Short Form (BPI-SF) and three questionnaires based on the functional component of the BPI-SF. Patients and clinicians rated the level of change on items related to functioning since starting the study as a global assessment after week 12 or early withdrawal (endpoint). Evaluations included the Goal Attainment Scale (GAS; patients rated change in 3 of 7 functional factors they selected a priori as important), Patient Assessment of Function questionnaire (PAF; 7 questions rated on a 7-point scale, very much worsened to very much improved), and Clinician Assessment of Patient Function questionnaire (CAPF; 5 questions rated on a 7-point scale, very much worsened to very much improved). BPI-SF: evaluations showed little change from baseline to endpoint. GAS: 44/59 (75%) patients reported an improvement in their general activity, with similar results for other functional factors, e.g., mood (82%), sleep (63%). PAF: ⬎50% of patients reported some improvement in 5/7 areas of functioning, including a majority who reported an improvement in the ability to perform at work (77%), participate in social events (74%), and enjoy life (76%). CAPF: Clinicians reported some improvement in each area of functioning for ⬎60% of patients. AEs were generally typical of opioids. In conclusion, FBT had consistently positive effects on function in opioidtolerant patients with BTP. Sponsored by Cephalon, Inc.
(253) Fentanyl buccal tablets effective for pediatric patient with episodic pain secondary to ulcerative colitis
(255) A response profile for fentanyl buccal tablet (FBT) in opioid-tolerant patients with breakthrough pain (BTP)
M Holtsman, L Wania-Galicia, D Williamson; UC Davis Medical Center, Sacramento, CA A sixteen year-old 49 kg. female with a four month history of ulcerative colitis was admitted to the pediatric ward with persistent nausea and severe episodic pain associated with bowel movements. Her ulcerative colitis was refractory to treatment with Infliximab and steroids. On admission, she was initially treated with 12.5 mcg/hr Transdermal Fentanyl System and intravenous morphine 1-2 mg every three hours as needed for pain with minimal relief. The Pain Service was then consulted to optimize her analgesia. Given the crampy and episodic character of her abdominal pain, hyoscyamine 0.125 mg PO/SL was recommended which provided modest improvement of her episodic pain. In addition, the patient was started on a morphine PCA with which she used approximately 1 mg/hr intravenous morphine. A trial of oral morphine 10 –20 mg for episodic pain was attempted. The morphine PCA was continued for pain not controlled by oral morphine. However, the patient’s episodic pain increased so rapidly that her oral morphine regimen was ineffective. As the patient’s long-acting analgesic (Transdermal Fentanyl) had been titrated up to 25 mcg/hr for one week, Fentanyl Buccal Tablet 100 mcg was initiated for her severe episodic pain. The Fentanyl Buccal Tablet provided effective pain reduction with the patient utilizing up to four doses per day. The Fentanyl Transdermal System was eventually titrated to a final dose of 37.5 mcg/hr change every three days. Her abdominal pain has remarkably improved. The patient’s analgesic regimen on discharge included: Fentanyl Transdermal System 37.5 mcg/hr change every three days, Fentanyl Buccal Tablets 100 mcg one tab every four hours as needed for pain not to exceed four doses per day, Hyoscyamine 0.25 mg PO/SL every four hours as needed. The patient has continued on this regimen for two months now with stable pain control.
J Farrar, E Michna, J Messina, F Xie; University of Pennsylvania School of Medicine, Philadelphia, PA FBT has been effective and generally well tolerated in short-term studies of opioid-tolerant patients with BTP.1-3 We evaluated the FBT response profile in a longer-term study of BTP with 3 equally spaced withinpatient double-blind periods using various response measures. Opioidtolerant adults with chronic non-cancer pain experiencing 1-4 BTP episodes/day were enrolled. Patients who titrated to a successful dose of FBT (single dose 100-800 mcg providing adequate analgesia without unacceptable AEs) then received open-label FBT (at the successful dose) for 4 weeks followed by double-blind, randomized treatment for 9 episodes (6 FBT, 3 placebo). The open-label/double-blind sequence was repeated twice. During the double-blind evaluation periods (after 4, 8, and 12 weeks of treatment), patients rated BTP intensity (PI, 0 –10 scale) predose and during the observation period 5–120 min postdose, and were to record when any pain relief (APR) and meaningful pain relief (MPR) were achieved. Measures of clinically relevant response included % of episodes with ⱖ33% and ⱖ50% improvement in PI, and patientassessed APR and MPR. Of 148 patients titrated, 105 (71%) achieved a successful dose and, of these, 81/105 (77%) completed the study. Following week 12, significant differences between FBT and placebo were seen during the observation period for % episodes with ⱖ33% improvement in PI (54% vs 31%, OR 2.61, P⬍0.0001) and ⱖ50% improvement in PI (42% vs 22%, OR 2.51, P⬍0.0001). Patients reported APR at rates of 74% for FBT vs 52% for placebo (OR 2.63, P⬍0.0001). Similarly, rates of MPR were 58% vs 34% (OR 2.71, P⬍0.0001). AEs were generally typical of opioids. In conclusion, responses to FBT were consistent across clinically meaningful measures after 12 weeks of treatment in opioid-tolerant patients with BTP. Sponsored by Cephalon, Inc. (1. Slatkin, J Support Oncol, 2007; 2. Portenoy, Curr Med Res Opin, 2007; 3. Simpson, Clin Ther, 2007.)