Noncancer Pain Patients Research Articles

The Role of Opioids in Chronic Non-Cancer Pain Management.

Chronic pain is prevalent in Asia as well as worldwide, and physicians must carefully consider which pharmacologic or non-pharmacologic analgesic strategy is appropriate based on its availability, adverse effects, abuse liability, potential drug-drug interactions, onset of action, tolerability, cost, and—above all—effectiveness. NSAIDs increase the pain threshold by inhibiting cyclooxygenase (COX) and are the first step of the World Health Organization “pain ladder,” but they have been associated with gastrointestinal complications, possible renal failure, and hypertension. Acetaminophen (paracetamol) is an effective pain reliever for mild to moderate pain, but is associated with liver toxicity at high doses. Opioids are effective pharmacologic treatment and standard therapy for moderate to severe cancer pain, but their long-term use for non-cancer pain is controversial. Opioid-associated side effects may be transient, treatable, or treatment limiting. Not all chronic non-cancer pain patients are candidates for opioid therapy, particularly if there are risk factors for misuse or abuse. Combining an opioid and a nonopioid (such as acetaminophen or NSAID) in combination therapy can create synergistic analgesic effect and reduce the patient’s total opioid consumption while still achieving good analgesic results. Adjuvant agents such as anticonvulsants or tricyclic antidepressants can be useful to deal with multimechanistic pain, including pain with a neuropathic component, frequently observed in chronic non-cancer pain patients.

Automated Prediction of Risk for Problem Opioid Use in a Primary Care Setting

Identification of patients at increased risk for problem opioid use is recommended by chronic opioid therapy (COT) guidelines, but clinical assessment of risks often does not occur on a timely basis. This research assessed whether structured electronic health record (EHR) data could accurately predict subsequent problem opioid use. This research was conducted among 2,752 chronic noncancer pain patients initiating COT (≥70 days' supply of an opioid in a calendar quarter) during 2008 to 2010. Patients were followed through the end of 2012 or until disenrollment from the health plan, whichever was earlier. Baseline risk indicators were derived from structured EHR data for a 2-year period prior to COT initiation. Problem opioid use after COT initiation was assessed by reviewing clinician-documented problem opioid use in EHR clinical notes identified using natural language processing techniques followed by computer-assisted manual review of natural language processing–positive clinical notes. Multivariate analyses in learning and validation samples assessed prediction of subsequent problem opioid use. The area under the receiver operating characteristic curve (c-statistic) for problem opioid use was .739 (95% confidence interval = .688, .790) in the validation sample. A measure of problem opioid use derived from a simple weighted count of risk indicators was found to be comparably predictive of the natural language processing measure of problem opioid use, with 60% sensitivity and 72% specificity for a weighted count of ≥4 risk indicators. PerspectiveAn automated surveillance method utilizing baseline risk indicators from structured EHR data was moderately accurate in identifying COT patients who had subsequent problem opioid use.

Sensitivity of an opiate immunoassay for detecting hydrocodone and hydromorphone in urine from a clinical population: analysis of subthreshold results.

Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former scenario, it is vital to determine whether the drug is present in the urine, even at low concentrations, because failure to detect the drug may lead to accusations of opioid abuse or diversion. Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine. Although many opiate immunoassays also detect hydrocodone (HC) and/or hydromorphone (HM), sensitivities for these analytes are often much lower, increasing the possibility of negative screening results when the drug is present in the urine. We selected 112 urine specimens from patients who had been prescribed HC or hydromorphone but were presumptive negative by the Roche Online DAT Opiate II™ urine drug screening assay, which is calibrated to 300 ng/mL morphine. Using a GC/MS confirmatory method with a detection limit of 50 ng/mL both for HC and for HM, one or both of these opiates were detected in 81 (72.3%) of the urine specimens. Examination of the raw data from these presumptive negative opiate screens revealed that, in many cases, the turbidity signal was greater than the signal obtained for the negative control, but less than the signal for the 300 ng/mL (morphine) threshold calibrator. A receiver operating characteristic curve generated for the reciprocal of the ratio of turbidity measurements in the patient specimens and negative (drug-free) controls, against the presence or absence of HC and/or HM by confirmatory analyses, produced an area under the curve of 0.910. We conclude that this opiate immunoassay has sufficient sensitivity to detect HC and/or HM in some urine specimens that screen presumptive negative for these commonly prescribed opiates at the established threshold.

Characteristics of chronic noncancer pain patients assessed with the opioid risk tool in a Canadian tertiary care pain clinic.

The Opioid Risk Tool (ORT) is a screening instrument for assessing the risk of opioid-related aberrant behavior in chronic noncancer pain (CNCP) patients. This study aims to compare patient characteristics documented in the original ORT study with those identified in CNCP patients assessed using a physician-administered ORT in a tertiary care pain clinic in Toronto, Canada. This was a descriptive cross-sectional study of 322 consecutive new patients referred over 12 months. Data extraction included ORT scores, demographics, pain ratings, opioid, and other medication use at point of entry, diagnosis, and other variables. Characteristics were compared with those described in the original ORT study. The total mean ORT scores of patients in this study were related to several demographic (gender, age, marital status, and country of birth) and nondemographic variables (employment status, cigarette smoking, and contribution of biomedical and/or psychological factors to presentation). Prevalence of characteristics noted in this patient sample differed substantially from that found in Webster and Webster as the basis for ORT scores. Significant differences existed between this study population and the patient sample from which the ORT was derived. Limitations of this study are discussed. We concur with the authors of the original study that the ORT may not be applicable in different pain populations and settings. Based on our findings, we encourage caution in interpreting the ORT in general CNCP settings until further studies are performed.

Lubiprostone for Treatment of Opioid-induced Constipation: Analysis of Influencing Factors

Introduction: Opioid-induced constipation (OIC) frequently results from chronic opioid treatment. Lubiprostone (LUB) efficacy was evaluated in 3 similar phase 3, randomized, double-blind, placebocontrolled, 12-week studies in chronic, non-cancer pain patients with OIC (<3 spontaneous bowel movements [SBMs]/week) at baseline. Two studies enrolled methadone users: 1 met the primary endpoint of change from baseline (CFB) in SBM frequency at Week 8, the other did not. Despite similar design, mean morphine equivalent daily dose (MEDD) of methadone in LUB-treated subjects in the latter study was 32% higher than in the successful study. Unknown at the time of these studies, methadone dosedependently inhibits the ClC-2-mediated secretory effect of LUB (Cuppoletti et al., Cell Biochem Biophys 2013;66:53-63). Methods: Post-hoc sensitivity analyses were used to evaluate the impact of high-dose methadone on CFB in SBM frequency at Week 8 in the intent-to-treat (ITT) population excluding all subjects taking methadone, and separately, excluding subjects taking high-dose (≥200 mg MEDD) methadone. A final sensitivity analysis used a median group replacement simulation for this endpoint. In this analysis, group median values for non-methadone patients and patients taking <200 mg MEDD methadone replaced Week 8 CFB values of methadone and high-dose methadone patients, respectively. Results: Excluding methadone-treated subjects from analysis resulted in clearly improved observed treatment effects in favor of LUB in both studies (Table). Though the second study did not achieve statistical significance in this analysis, clinical effect size was similar across the studies and thus the results were corroborative. In the replacement simulation, highly statistically and clinically significant improvements were observed for both trials for all simulations (p≤0.001). Adverse events were generally mild to moderate, and primarily gastrointestinal. Conclusion: LUB appears effective and well-tolerated in OIC patients with chronic, non-cancer pain taking non-methadone-type opioids. Disclosure - Ms. Losch-Beridon - Employee and holder of stock options: Sucampo Pharma Americas, LLC; Dr. Lichtlen - Consultant to Sucampo; Mr. Wang - Employee of Sucampo Pharma Americas, LLC. This research was supported by an industry grant from Sucampo Pharma Americas, LLC; Takeda Pharmaceuticals International, Inc.Table 1: Methadone Sensitivity Analyses: Change From Baseline, SBM Frequency, Week 8

Doctors and patients in pain: Conflict and collaboration in opioid prescription in primary care

Use of chronic opioid therapy (COT) for chronic noncancer pain has dramatically increased in the United States. Patients seek compassionate care and relief while physicians struggle to manage patients’ pain effectively without doing harm. This study explores the narratives of chronic noncancer pain patients receiving chronic opioid therapy and those of their physicians to better understand the effects of COT on the doctor–patient relationship. A mixed method study was conducted that included in-depth interviews and qualitative analysis of 21 paired patients with chronic pain and their physicians in the following groups: patients, physicians, and patient–physician pairs. Findings revealed that patients’ narratives focus on suffering from chronic pain, with emphasis on the role of opioid therapy for pain relief, and physicians’ narratives describe the challenges of treating patients with chronic pain on COT. Results elucidate the perceptions of ideal vs difficult patients and show that divergent patterns surrounding the consequences, utility, and goals of COT can negatively affect the doctor–patient relationship. The use of paired interviews through a narrative lens in this exploratory study offers a novel and informative approach for clinical practice and research. The findings have significant implications for improving doctor–patient communication and health outcomes by encouraging shared decision making and goal-directed health care encounters for physicians and patients with chronic pain on COT. PerspectiveThis study found patterns of understanding pain, opioid pain medications, and the doctor–patient relationship for patients with chronic pain and their physicians using a narrative lens. Thematic findings in this exploratory study, which include a portrayal of collaborative vs conflictual relationships, suggest areas of future intervention and investigation.

Changes in Quality of Life after 3 months of Usual Care in a Large Sample of Patients with Noncancer Pain: The "QOOL: Quality of Life and Pain" Study.

Large-scale observational studies can provide useful information on changes in health outcomes over time. The aim of this study was to investigate the effect of 3 months of usual care on quality of life (QOL) and pain outcomes in noncancer chronic pain patients managed by pain specialists and to examine factors associated with changes in QOL. This was assessed using the EQ-5D and pain outcomes using the Brief Pain Inventory (BPI). Changes in QOL and pain were studied for the overall sample and in subgroups defined by baseline pain severity. Multivariate regression was used to investigate factors associated with change on EQ-5D. Three thousand and twenty-nine patients were included for analysis. After 3 months of usual care, a mean of 40.9% of patients showed improvement on individual EQ-5D dimensions, with the highest rates of improvement seen on the pain/discomfort (50.8%) and anxiety/depression (48.3%) dimensions. The EQ-5D Index increased from a mean (SD) of 0.35 (0.2) to 0.58 (0.21) points between baseline and month 3, and the thermometer from 41.5 (19.4) to 58.7 (17.8), indicating a large effect. Improvements in QOL were larger in those with severe baseline pain. The BPI severity summary score improved from a mean (SD) of 6.5 (1.4) to 4.1 (1.7) and the interference summary score from 6.6 (1.5) to 4.2 (1.9). Changes on the BPI severity and interference scores were associated with changes in the EQ-5D Index and thermometer. In conclusion, 3 months of usual care in noncancer pain patients led to substantial improvements in QOL and pain outcomes.

Risk assessment of opioid misuse in italian patients with chronic noncancer pain.

Objective. Opioid therapy in patients with chronic noncancer pain must be preceded by evaluation of the risk of opioid misuse. The aim of this study was to evaluate the predictive validity of the Italian translation of the Pain Medication Questionnaire (PMQ) and of the Diagnosis Intractability Risk and Efficacy Score (DIRE) in chronic pain patients. Design. 75 chronic noncancer pain patients treated with opioids were enrolled and followed longitudinally. Risk of opioid misuse was evaluated through PMQ, DIRE, and the physician's clinical evaluation. Pain experience and psychological characteristics were assessed through specific self-report instruments. At follow-ups, pain intensity, aberrant drug behaviors, and presence of the prescribed opioid and of illegal substances in urine were also checked. Results. PMQ demonstrated good internal consistency (Cronbach's α = 0.77) and test-retest reliability (r = 0.86). Significant correlations were found between higher PMQ scores and the number of aberrant drug behaviors detected at 2-, 4-, and 6-month follow-ups (P < 0.01). Also the DIRE demonstrated good predictive validity. Conclusions. The results obtained with specific tools are more reliable than the clinician's evaluation alone in predicting the risk of opioid misuse; regular monitoring and psychological intervention will contribute to improving compliance and outcome of long-term opioid use.

The Subjective Psychoactive Effects of Oral Dronabinol Studied in a Randomized, Controlled Crossover Clinical Trial for Pain

Many cannabinoid medications are approved in North America or in phase III trials, such as dronabinol, nabilone, or nabiximols. Little is known about their subjective psychoactive effects when used for pain management. We hypothesized that when used for pain, dronabinol has psychoactive effects in a dose-response relationship, whose peak effects are comparable with smoking marijuana. This was a randomized controlled trial of single dose placebo, 10 or 20 mg dronabinol in 30 chronic noncancer pain patients taking opioids and not using marijuana. Participants completed the Addiction Research Center Inventory (ARCI) hourly for 8 hours during 3 monitored sessions. Comparison sample was the ARCI ratings in participants with no pain (N=20), monitored every 30 minutes after smoking a 1.99% THC (low) and a 3.51% (high strength) marijuana cigarette. The 10 and 20 mg dronabinol doses had significantly elevated scores over time on 4/5 subscales versus placebo (P<0.05). Average daily morphine use, total pain relief (TOTPAR), age, sex, and baseline pain level were not significant covariates. ARCI peak effects at 2 hours were similar to peak effects of smoked marijuana at 30 minutes (P=0.80, 10 mg=low strength, 20 mg=high strength). In pain patients, oral dronabinol has similar psychoactive effects to smoking marijuana. This risk must be considered in any decision to prescribe cannabinoid medications for pain.

Physicians' Beliefs and Likelihood of Prescribing Opioid Tamper-Resistant Formulations for Chronic Noncancer Pain Patients

Tamper-resistant opioid formulations (TRFs) have recently been the target of active development in an effort to deter opioid misuse and abuse. To understand factors that are predictive of physicians' likelihoods of prescribing TRFs to patients with chronic noncancer pain (CNCP). A cross-sectional survey was conducted, utilizing a questionnaire of clinicians' attitudes and opinions about opioids for CNCP (Clinicians' Attitudes about Opioids Scale) to explore beliefs about and likelihood of prescribing TRFs. A nationally representative sample of 1,535 practicing physicians throughout the United States. A stepwise hierarchical multiple linear regression analysis was conducted to estimate if physician characteristics, opinions, or geographic region categorized according to state rates of mortality by drug overdose and milligrams of opioids prescribed by state were predictive of the likelihood of prescribing TRFs. Board certification in Pain Medicine and prescribing opioids to a higher volume of CNCP patients were significantly predictive of a reported likelihood of prescribing TRFs, in addition to concerns about possible misuse and abuse of opioids, beliefs in the effectiveness of opioids for CNCP, and greater satisfaction with education and training in pain management this set of factors accounted for 21% of the model variance. Rates of mortality by drug overdose and opioid prescription volume by location were not predictive of TRF usage. Reducing physician concerns about potential misuse and abuse of opioids through additional education in pain management and dissemination of information about the potential benefits and availability of TRFs should influence physicians' attitudes about and the adoption of TRFs.

(447) Symptom improvement following naloxegol treatment in noncancer pain patients with opioid-induced constipation

(447) Symptom improvement following naloxegol treatment in noncancer pain patients with opioid-induced constipation

Effectiveness of opioid analgesics in chronic noncancer pain.

There is general agreement about the need to perform a screening test to assess the risk of opioid misuse prior to starting a long-term opioid treatment for chronic noncancer pain. The evidence supporting the effectiveness of opioid long-term treatment is weak, and no predictors of its usefulness have been assessed. The aim of this study was to assess the effect on pain and quality of life of chronic opioid treatment, and detect the possible predictors of its effectiveness. This observational, prospective study was conducted in 2 Italian Pain Relief Units on 77 patients affected by intractable chronic pain. Patients were submitted to psycho-logical tests, investigating the individual pain experience, risk of opioid misuse, mood states, quality of life, and personality characteristics prior to starting treatment and at 2,4, and 6-month follow-up. Both maximum and habitual pain, as measured with VAS, underwent a statistically significant reduction at 2, 4, and 6-month follow-up. In multivariate analysis, lower scores in the Pain Medication Questionnaire (PMQ) were predictive of a major reduction in maximum VAS (P = 0.005). Both low PMQ and MMPI-cynicism scores were predictive of habitual VAS decrease (P = 0.012 and P = 0.028, respectively). The results indicate that pain relief significantly improved over a 6-month period of opioid treatment, together with quality of life. The outcome was better in patients with a pretreatment low risk of opioid misuse, low scores in the Cynicism scale of MMPI-2, and no aberrant drug behaviors at follow-up. Therefore, a psychological screening and support is crucial for a good outcome of opioid therapy for chronic noncancer pain patients.

Pain, kinesiophobia and quality of life of low back pain patients

BACKGROUND AND OBJECTIVES: Chronic low back pain is a musculoskeletal problem with high prevalence and frequent associated conditions, which causes major impact on patients' daily life and quality of life. This study aimed at evaluating pain perception, fear of movement and adherence to treatment of patients with low back pain and surgical indication. METHODS: This is a prospective study with convenience sample made up of low back pain patients, called test group: chronic non-cancer pain patients who were randomly selected and were waiting for surgery. Control group was made up of patients screened by the Pain Clinic, with low back pain, however asymptomatic. Tools were the visual analog scale, the Morisky & Green questionnaire to check adherence to treatment and the Roland-Morris questionnaire to evaluate functional incapacity. Fear of movement was evaluated by the Tampa Scale for Kinesiophobia and quality of life by the Study Short form 12 Health Survey (SF-12) (Medical Outcomes). RESULTS: Mean age of the test group was 38.8±6.5 years with prevalence of females, impaired labor situation and mean education of 8.5±3.8 years. Both mental and physical components had lower quality of life scores in the test group, in addition to more severe pain, functional incapacity and fear of movement. Non-adherence to treatment was seen in 65% of test group patients. CONCLUSION: Fear of movement, functional incapacity and pain observed in test group may have implications in the quality of life of low back pain patients who will be submitted to surgery and may be predictors for the incorporation of different strategies to contribute to more effective approaches.

Prevalence and impact of constipation and bowel dysfunction induced by strong opioids: a cross-sectional survey of 520 patients with cancer pain: DYONISOS study

Objective:To describe the prevalence of opioid-induced constipation (OIC) in patients with cancer pain according to the Knowles-Eccersley-Scott symptom score (KESS), the different symptoms of opioid-induced bowel dysfunction (OIBD), and to assess the impact of OIBD on patient’s quality-of-life.Methods:A cross-sectional observational study, using the KESS questionnaire and the physician’s subjective assessment of constipation, and other questionnaires and questions on constipation, OIBD, and quality-of-life, carried out on 1 day at oncology day centres and hospitals.Results:Five hundred and twenty patients were enrolled at 77 centres in France; 61.7% of patients (n = 321) showed a degree of constipation that is problematic for the patient according to KESS (between 9–39). Even more patients, 85.7% (n = 438), were considered constipated according to the physician’s subjective assessment—despite laxative use (84.7% of patients). Quality-of-life was significantly reduced in constipated vs non-constipated patients for both PAC-QoL (p < 0.0001 for total score and each dimension) and the SF-12 questionnaires (statistically significant for all dimensions except physical state and role physical). OIC and OIBD led to hospitalization (16% of patients), pain (75% of patients), and frequent changes in opioid and laxative treatment.Key limitations:This cross-sectional study, in a selected population of cancer patients, has measured prevalence and impact of OIBD. Further confirmation could be sought through the use of longitudinal studies, and larger populations, such as non-cancer pain patients treated with opioidsConclusions:Cancer patients taking opioids for pain are very frequently constipated, even if they are prescribed laxatives. This leads to relevant impairments of quality-of-life.

Further validation of the psychometric properties of the Bowel Function Index for evaluating opioid-induced constipation (OIC)

Objective:The BFI (Bowel Function Index) is a 3-item questionnaire for assessing opioid-induced constipation (OIC). The aim of this study was to contribute to the validation of the psychometric properties of the BFI by confirming a constipation threshold, and through correlation with other validated tools: KESS (Knowles Eccersley Scott Symptom) score and generic (12-Item Short Form Health Survey, SF-12) and specific (Patient Assessment of Constipation–Quality of Life, PAC-QoL) quality-of-life scores.† BFI Copyright 2002, Mundipharma GmbH, City, Country; BFI is subject of European Patent Application Publication No. EP 1,860,988 and corresponding patents and applications in other countries.* PAC-QOL, Janssen Global Services, LLC, City, State, Country, USA.Methods:A survey on opioid-requiring cancer-patients was carried out in France. A questionnaire was filled out for all patients that recorded their demographic characteristics, an assessment of their constipation using BFI and KESS scores, and included a self-assessment of quality-of-life using PAC-QoL and SF-12. Correlation of BFI with KESS, PAC-QoL, and SF-12 was investigated.Results:Five hundred and twenty patients participated in the entire data collection with no loss. BFI was shown to be statistically correlated (r = 0.571; p < 0.0001) with the KESS score and matches up with PAC-QoL and to a lesser extent with the SF-12 generic quality-of-life questionnaire. A BFI threshold of 27–29 to discriminate constipated from non-constipated patients was confirmed.Key limitations:This cross-sectional study in a selected population of cancer pain patients has validated the psychometric properties of the BFI. Further confirmation of the validity of the BFI could be sought through the use of longitudinal studies, and larger populations, such as non-cancer pain patients treated with opioids.Conclusion:This study contributes to the validation of the psychometric properties of the BFI. It confirms the BFI as an easy-to-use tool to assess constipation and its impact on quality-of-life in chronic pain patients.

All-cause Mortality in Placebo-controlled Clinical Trials of Methylnaltrexone: A Pooled Analysis

Purpose: To evaluate all-cause mortality and baseline cardiovascular risk factors in patients enrolled in placebo (PBO)-controlled trials conducted with the peripheral mu-opioid antagonist, methylnaltrexone (MNTX). Methods: This analysis assessed all-cause mortality in patients enrolled in Phase 2 and Phase 3 PBO-controlled trials of MNTX for the treatment of opioid-induced constipation (advanced illness and noncancer pain patients) and postoperative ileus. The probability of death was calculated using the Cox proportional-hazards model, with a 2-sided test and significance level of 0.05, to compare the time to death for patients treated with MNTX versus PBO. Baseline cardiovascular risk factors were also assessed. Results: Overall, 3,491 patients were treated with either MNTX (n=2,413) or PBO (n=1,078). Demographic characteristics were comparable in the MNTX (33.9% ≥60 years of age, 54.7% female, 38.9% with BMI ≥30) and PBO groups (38.7% ≥ 60 years of age, 54.5% female, 36.5% with BMI ≥30). Cardiovascular history and risk factors across all patients in the analysis included: hypertension (MNTX: 44.3%, PBO: 45.5%), hyperlipidemia/hypercholesterolemia (26.2%, 23.5%), diabetes (22.3%, 23.9%), angina (11.2%, 13.2%), myocardial infarction (13.2%, 13.1%), and stroke (11.3%, 12.2%). Some subjects had multiple risk factors. There were 25 deaths (rate=13.7 events per 100 person-years of exposure) in the MNTX group and 21 deaths (rate=31.4 events per 100 person-years of exposure) in the PBO group. The hazard ratio for risk of death in the MNTX group relative to the PBO group was 0.46 (p=0.007), corresponding to a relative reduction in risk of death of 54%. Conclusion: In a pooled analysis of all-cause mortality in PBO-controlled trials of MNTX, a lower risk of mortality was observed in MNTX-treated patients. Kaplan-Meier Curve of All-Cause Mortality in Placebo-Controlled Studies with Methylnaltrexone. Disclosure - Lynn Webster: Consultant for AstraZeneca, Covidien Mallinckrodt, Nektar Therapeutics, Jazz Pharmaceuticals, CVS, Boehringer Ingelheim, Neura Therapeutik, Orexo, Quintiles, Theravance Darren Brenner: Consultant and speaker for Salix, Consultant for Perrigo, Speaker Bureau for Ironwood/Forrest Robert L. Rolleri: employee of and holds stock in Salix Pharmaceuticals, Inc. Andrew C. Barrett: employee of and holds stock in Salix Pharmaceuticals, Inc. Enoch Bortey: employee of and holds stock in Salix Pharmaceuticals, Inc. Craig Paterson: employee of and holds stock in Salix Pharmaceuticals, Inc. William P. Forbes: officer and employee of and holds stock in Salix Pharmaceuticals, Inc.Figure

Spontaneous Bowel Movement Frequency Is Improved Over 12 Weeks of Lubiprostone Therapy in Opioid-induced Constipation Patients Regardless of Gender, Age, or Race: Pooled Analysis of Three Well-controlled Studies

Purpose: To evaluate impact of demographic characteristics (gender, age, and race) on overall spontaneous bowel movement (SBM) frequency rates with 12-week oral lubiprostone (24 mcg BID) therapy in non-cancer pain patients with opioid-induced constipation (OIC). Methods: Data were pooled from three multicenter, double-blind trials in which adult patients with OIC (i.e., <3 SBMs/wk) were randomized to receive lubiprostone 24 mcg (n=659) or placebo (n=641) BID for 12 weeks. Overall change from baseline (CFB) in SBM frequency across the entire treatment period was assessed for the pooled population, as well as for select demographic categories (i.e., by gender, age, and race) to determine whether these factors impacted treatment response. Results: The mean age of enrolled subjects was 50.5 years (range: 20-89 years); 62.5% of the patients were women and 82.1% were white. The mean overall CFB in SBM frequency was statistically significantly improved for all patients treated for up to 12 weeks with lubiprostone as compared with placebo (2.8 vs 2.2 SBMs/wk, respectively; p<0.001). Overall SBM frequency changes were also statistically significantly improved with lubiprostone treatment in subgroup analyses of men and women (p≤0.004 for both populations). Although statistical significance was not achieved in elderly patients (≥65 years), likely due to the small size of this population (n=110), the absolute treatment difference between the lubiprostone and placebo arms in elderly was identical to the reported difference for the non-elderly population (+0.6 SBM/wk treatment advantage for lubiprostone vs placebo in both age subsets; p<0.001 for nonelderly). For the same endpoint, a larger treatment difference was observed for non-white patients treated with lubiprostone vs placebo overall (3.2 vs 2.5 SBMs/wk; n=224) relative to white patients overall (2.7 vs 2.2 SBMs/wk), though statistical significance was only achieved for the white population (n=1027; p<0.001). Conclusion: Over a 12-week treatment period, changes from baseline in SBM frequency were consistently higher with lubiprostone therapy versus placebo treatment regardless of patient gender, age, or race. Statistical separation between the lubiprostone and placebo arms was achieved overall, and for populations of men, women, white patients, and patients aged <65 years. Non-white patients and those ≥65 years of age reported the same or better response to lubiprostone therapy than their white and nonelderly counterparts, though statistical significance was not achieved due to relatively small patient numbers in these groups. This research was funded by Sucampo Pharma Americas, LLC, Bethesda, MD, and Takeda Pharmaceuticals International, Inc., Deerfield, IL. Disclosure - Byron Cryer has consulting relationships with AstraZeneca, Inc., Horizon Therapeutics, PLx Pharma, Pfizer Inc., POZEN, Inc., Ritter Pharma, and Sucampo Pharmaceuticals, Inc. Shadreck Mareya is an employee of Sucampo Pharma Americas, LLC. Taryn Joswick is an employee of Sucampo Pharma Americas, LLC. Gayle Dolecek is an employee of Sucampo Pharma Americas, LLC. Yijun Sun is an employee of Sucampo Pharma Americas, LLC. Ryuji Ueno is a Director of Sucampo AG, is an employee of Sucampo Pharma Americas, LLC, and is a shareholder of Sucampo Pharmaceuticals, Inc. This research was supported by an industry grant from Sucampo Pharma Americas, LLC; Takeda Pharmaceuticals International, Inc.

Self‐Critical Perfectionism Predicts Outcome in Multidisciplinary Treatment for Chronic Pain

Self-critical perfectionistic personality features have been shown to influence the onset and perpetuation of pain symptoms. However, no study to date has investigated whether these personality features are associated with treatment response in chronic pain. Using a naturalistic pre-post design, the present study examined the effect of self-critical perfectionism on treatment outcome in terms of self-reported pain. The study was conducted in a sample of 53 chronic non-cancer pain patients who followed Multidisciplinary Pain Education Program (MPEP), a brief, 2-week cognitive-behaviorally based psycho-educational intervention for chronic pain that was recently found to be effective in reducing pain severity. Pre- and post-treatment pain intensity levels were assessed with the visual analog scale of the McGill Pain Questionnaire-Short Form. Pretreatment self-critical perfectionism was significantly associated with negative treatment outcome, even after taking into account pretreatment levels of depression. Results suggest that self-critical perfectionistic personality features may negatively interfere with treatment response in patients with chronic pain. Thus, findings indicate that chronic pain patients with high levels of self-critical perfectionism may benefit less from brief interventions such as MPEP, and therefore may need more intensive and tailored treatment.

Infectious Complications Related to Intrathecal Drug Delivery System and Spinal Cord Stimulator System Implantations at a Comprehensive Cancer Pain Center

Background: Intrathecal drug delivery (IDD) and spinal cord stimulator (SCS) systems are implantable devices for the management of both chronic and cancer pain. Although these therapies have favorable long-term outcomes, they are associated with occasional complications including infection. The incidence of infectious complications varies from 2 - 8% and frequently requires prolonged antibiotics and device revision or removal. Cancer patients are particularly susceptible to infectious complications because they are immunocompromised, malnourished, and receiving cytotoxic cancer-related therapies. Objective: Determine if cancer pain patients have a higher incidence of infectious complications following implantation of IDD or SCS systems than non-cancer pain patients. Study Design: Retrospective chart review. Setting: Single tertiary comprehensive cancer hospital. Methods: Following local Institutional Review Board (IRB) approval, we collected data on infectious complications for IDD and SCS systems implanted at MD Anderson Cancer Center for the treatment of cancer and chronic pain. The examined implants were performed from July 15, 2006, to July 14, 2009. In addition, we obtained data regarding patient comorbidities and perioperative risk factors to assess their impact on infectious complications. Results: One hundred forty-two devices were implanted in 131 patients during the examined period. Eighty-three of the devices were IDD systems and 59 were SCS systems. Eighty percent of the patients had a diagnosis of cancer. Four infectious complications were noted with an overall infectious risk of 2.8%. The infection rate was 2.4% for IDD systems versus 3.4% for SCS systems (P = 1). All infections were at the implantable pulse generator (IPG) or pump pocket site. The rate of infection was 2.7% for cancer patients and 3.3% for non-cancer patients (P = 1). Neither the perioperative administration of prophylactic antibiotics (P = 0.4) nor the National Nosocomial Infection Surveillance (NNIS) risk level for individual patients (P = 0.15) were statistically associated with infectious complication. The mean surgical time was longer for cases with infection at 215 ± 93 minutes versus 132 ± 52 minutes for those without infection which was statistically significant (P = 0.02). Limitations: The major limitation of this study is that it was a retrospective analysis. An additional limitation is that 51(38.9%) of our patients either died or were lost to follow-up during the year following implantation which may have led to an underestimation of our infection rates. Conclusions: The experience of this tertiary cancer pain center demonstrates that infectious complications following implantation of IDD and SCS systems are relatively rare events in cancer patients. Contrary to our initial hypothesis, no difference was found in the infection rate between cancer and non-cancer patients. The main factor associated with increased risk of infectious complications was increased surgical time, indicating a need to minimize patient time in the operating room. The low infectious complication rate seen in this series compared to previous reports in non-cancer patients is likely multifactorial in nature. Key Words: Spinal cord stimulation, intrathecal drug delivery, implantable pain therapies, neuromodulation, pain procedures, pain, complications, infection, surgical site infection

Su2042 Time to Onset of Lubiprostone Treatment Effect in Chronic Non-Cancer Pain Patients With Opioid-Induced Constipation: Data From Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Trials

Su2042 Time to Onset of Lubiprostone Treatment Effect in Chronic Non-Cancer Pain Patients With Opioid-Induced Constipation: Data From Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Trials