Brief Pain Inventory Average Pain Research Articles

Home-based EEG neurofeedback for the treatment of chronic pain: A randomized controlled clinical trial

This parallel, two-arm, blinded, randomized controlled superiority trial examined whether, when added to usual care, active- electroencephalography neurofeedback (EEG NFB) was safe and more effective than sham control-EEG NFB for chronic pain. 116 participants with chronic pain were randomly assigned (1:1) to usual care plus ≥ 32 sessions of active-EEG NFB upregulating relative alpha power over C4 or usual care plus ≥ 32 sessions of sham control-EEG NFB. Per protocol analyses revealed no significant between-group differences in the primary outcome, brief pain inventory (BPI) average pain (mean difference [95% CI]: -0.04 [-0.39 to 0.31], p=0.90), or any secondary outcomes. However, 44% of participants in the active-EEG NFB group and 45% in the control-EEG NFB group reported at least a moderate (≥30%), clinically important improvement in BPI average pain. The number of treatment emergent adverse events were similar in both groups (p = 0.83), and none were serious. Post-hoc analyses revealed similar upregulated relative alpha power in both groups during training, with concordant positive rewards delivered to the active-EEG group 100% of the time and the control-EEG group ~25% of the time, suggesting a partially active sham intervention. When added to usual care, the active-EEG NFB intervention used in this study was not superior to the sham control-EEG NFB intervention. However, a large proportion of participants in both groups reported a clinically important reduction in pain intensity. A partially active sham intervention may have obscured between-group differences. The intervention was free of important side effects, with no safety concerns identified. PerspectivesThis study is the first attempt at an appropriately blinded, randomized, sham-controlled trial of alpha EEG NFB for the treatment of chronic pain. The findings may interest people living with chronic pain, clinicians involved in chronic pain management, and may inform the design of future EEG NFB trials. Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000667819.

Abstract PO1-11-06: Evaluating Symptom Clusters in Patients with Breast Cancer Experiencing Aromatase Inhibitor-Associated Musculoskeletal Symptoms

Abstract Background: Although treatment with an aromatase inhibitor (AI) for 5-10 years decreases 10-year breast cancer mortality by about 40%, up to 25% of patients will stop treatment early because of treatment-related, intolerable joint and muscular pain and stiffness, called aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). We previously identified that nociplastic pain, or chronic pain in the absence of tissue damage or inflammation, is associated with increased likelihood of developing AIMSS. Other studies have found that symptom clusters, such as the SPPADE symptoms (sleep disturbance, pain, physical function impairment, anxiety, depression, and low energy/fatigue) are prevalent and co-occur in patients with cancer. Here we examine the prevalence of SPPADE symptoms for patients experiencing AIMSS and willing to enroll on a clinical trial examining use of cannabidiol (CBD) to treat their symptoms. Methods: Patients with stage 0-3 hormone receptor-positive breast cancer experiencing AIMSS (defined as worst joint pain ≥4/10 during prior 7 days that developed or worsened since starting AI therapy) were eligible for enrollment in this single arm, single center phase 2 open label clinical trial (NCT04754399). Enrolled patients completed validated questionnaires at baseline and then received CBD (Epidiolex) for 15 weeks. Patient-reported outcomes (PRO) data was collected serially, including the following questionnaires which addressed SPPADE symptoms: Brief Pain Inventory (BPI) to assess pain, PROMIS Profile 29+2 v2.1 to assess multiple symptoms, and Fibromyalgia Survey (FMS) to assess nociplastic pain. Results: 39 patients enrolled on this clinical trial. The median age at enrollment was 57 (range 37-59) and 21% of patients were over age 70. The majority of patients were white (92%) and average BMI was 31 (SD 6.6). Anastrozole was the most used aromatase inhibitor (74%), followed by exemestane (18%), and letrozole (8%). 5 patients (13%) required concomitant GnRHa therapy. Baseline PRO data was obtained from 37 patients. BPI average pain score over the week prior to enrollment was 5.1 (SD 1.5) and worst pain score was 7.2 (SD 1.3). Pain interference reported on the BPI was 4.1 (SD 2.1). Compared to the general population, enrolled patients reported better physical function (T-score 60.2, SE 3.7), less depression (T-score 45.5, SE 4.7) and fatigue (T-score 46.7, SE 5.1), and similar levels of anxiety (T-score 51, SE 7.1) and sleep disturbance (T-score 49.5, SE 5.9) on the PROMIS Profile. On the FMS, 62% of patients had evidence of nociplastic pain, with average score 13.3 (SD 5.7). The median number of sites of pain in the body reported by patients was 8 (range 1-16). Conclusions: While patients enrolling on an AIMSS clinical trial reported a high degree of daily pain that regularly interferes with their activities, for most patients these symptoms did not appear to have a negative impact on mood, affect, or other symptoms that typically cluster with pain. Though it is difficult to extrapolate results from a small population, the unexpected absence of co-occurring symptoms in this population raises additional questions about the interplay of AIMSS and other symptoms commonly reported in interventional AIMSS studies. Follow-up PRO data will be obtained in this clinical trial, allowing us to examine the impact of CBD use on pain, pain interference, and other patient-reported symptoms, as well as to explore which patients are more likely to obtain benefit from CBD treatment. Funding support provided by Conquer Cancer, the ASCO Foundation and the Rising Tide Foundation for Clinical Cancer Research. Citation Format: Fleege Nicole, N. Lynn Henry. Evaluating Symptom Clusters in Patients with Breast Cancer Experiencing Aromatase Inhibitor-Associated Musculoskeletal Symptoms [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-06.

Measurement of the Association of Pain with Clinical Characteristics in Oral Cancer Patients at Diagnosis and Prior to Cancer Treatment.

Oral cancer patients suffer pain at the site of the cancer, which degrades quality of life (QoL). The University of California San Francisco Oral Cancer Pain Questionnaire (UCSFOCPQ), the only validated instrument specifically designed for measuring oral cancer pain, measures the intensity and nature of pain and the level of functional restriction due to pain. The aim of this study was to compare pain reported by untreated oral cancer patients on the UCSFOCPQ with pain they reported on the Brief Pain Inventory (BPI), an instrument widely used to evaluate cancer and non-cancer pain. The correlation between pain measured by the two instruments and clinical characteristics were analyzed. Thirty newly diagnosed oral cancer patients completed the UCSFOCPQ and the BPI. Pain severity measurements made by the UCSFOCPQ and BPI were concordant; however, the widely used BPI average pain over 24 hours score appeared less sensitive to detect association of oral cancer pain with clinical characteristics of patients prior to treatment (nodal status, depth of invasion, DOI). A BPI average score that includes responses to questions that measure both pain severity and interference with function performs similarly to the UCSFOCPQ in detection of associations with nodal status, pathologic T stage (pT stage), stage and depth of invasion (DOI). Pain assessment instruments that measure sensory and interference dimensions of oral cancer pain correlate with biologic features and clinical behavior.

The Pain Clinic for Older People.

Multidisciplinary pain clinics have an established role in the management of persistent pain, but there is little evidence to support this approach in an older population. This study describes the characteristics and pain outcomes of patients attending a pain clinic designed exclusively for older people. A retrospective audit was performed of outcomes of the Pain Clinic for Older People (PCOP) in 2015-2019. Response to treatment was determined by change in Brief Pain Inventory (BPI) scores at initial attendance and after a treatment program. Clinically meaningful improvement was defined by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus criteria of ≥30% improvement in average pain and one-point improvement in pain interference. Results were compared with the national benchmark collated by the electronic Persistent Pain Outcomes Collaboration (ePPOC), which reports the combined results from 67 participating Australian and New Zealand pain services. Patients attending the PCOP had a mean age of 80.5 years and had high rates of frailty (84%), cognitive impairment (30%), and multimorbidity. Significant reductions in BPI average pain and BPI pain interference scores were achieved. Clinically meaningful improvement in BPI average pain was achieved in 63% of patients attending the PCOP who were 65-74 years of age and in 46% of patients who were ≥75 years of age, which met the national benchmark set by ePPOC of 40% for both age groups. Clinically meaningful improvement in BPI pain interference was achieved in 69% of those attending the PCOP who were 65-74years of age and in 66% of those who were ≥75 years of age, comparable to the ePPOC benchmark of 71% and 65% for the respective age groups. PCOP clients achieved significant and meaningful improvements in their pain outcomes that satisfied the national benchmark. Advanced age, cognitive impairment, frailty and multimorbidity should not be regarded as barriers to benefit from a pain clinic specifically designed for older people.

Abstract PD12-03: Predictors of pain reduction in trials of interventions for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS)

Abstract Background: Up to half of AI-treated breast cancer patients experience AIMSS, and 20-30% have severe symptoms that lead to treatment discontinuation. Multiple interventions have been examined in randomized clinical trials, including in SWOG S0927 (omega-3 fatty acids vs placebo), S1202 (duloxetine vs placebo), and S1200 (true acupuncture vs sham acupuncture vs wait list control). We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from these trials. Methods: The S0927, S1200, and S1202 clinical trials had similar eligibility criteria, and all used the same patient-reported outcomes measures to assess arthralgias and endocrine symptoms. The Brief Pain Inventory (BPI) examines average pain, worst pain, and pain interference; higher numbers reflect more symptoms. Endocrine symptoms were assessed with the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), which includes subscales for functional and physical well-being; higher scores reflect better function. We also used validated measures to assess joint symptoms in the knees/hips (WOMAC) and hands (M-SACRAH), where higher scores indicate greater symptom severity. We analyzed the subset of patients enrolled on these three trials who had a baseline BPI average pain score of at least 4/10 (S0927, n=185; S1200, n=158; S1202, n=240). The primary outcome was 50% reduction in BPI average pain from baseline to week 12. Variable cut-point selection was performed on each continuous variable to identify a binary cut-point that optimally distinguished high versus low levels of pain reduction. Logistic regression was performed for each variable. A risk model was built by summing the number of statistically significant baseline predictors and categorizing patients by low vs. medium vs. high likelihood of pain reduction. All analyses were stratified by study and adjusted for treatment arm. Results: Of the 583 analyzed patients, median age was 60 years (range 27-84), median body mass index was 30 kg/m2 (range 18-84), and 208 patients (35.7%) had at least a 50% reduction in BPI average pain. Factors significantly associated with at least a 50% reduction in pain included lower pain and pain interference and better physical and functional status at study enrollment (Table). Patients with 2-4 of the 7 statistically significant factors were twice as likely to experience pain reduction compared to those with fewer than 2 factors (37.8% vs. 22.5%; odds ratio [OR] 2.08, 95% CI 1.38-3.13, p<.001). Those with 5-7 factors were more than 5 times more likely to experience pain reduction (61.2% vs. 22.5%; OR 5.66, 95% CI 3.21-9.98, p<.001). Conclusions: Patients with AIMSS who have lower pain and better functional status are more likely to experience meaningful pain reduction in intervention trials for AIMSS. These findings suggest early intervention for treating AIMSS may be important. Baseline pain and functional status should be considered as stratification factors in future interventional trials. Funding: NIH/NCI Grant Award CA189974; and in part by the Hope Foundation for Cancer Research. Association of baseline characteristics with 50% reduction in average pain from baseline to 12 weeksFactorRates of pain reductionOdds Ratio (95% CI)P valueAge: <70 vs ≥70 years37.1% vs. 26.3%1.66 (0.96-2.86)0.07BMI: <30 vs. ≥30 kg/m237.9% vs. 33.6%1.27 (0.90-1.79)0.17BPI average pain: 4 vs. ≥548.6% vs. 31.7%1.93 (1.30-2.86)0.001BPI worst pain: <6 vs. ≥649.0% vs. 32.8%1.95 (1.26-3.02)0.003BPI pain interference: <3 vs. ≥347.8% vs. 31.9%2.21 (1.47-3.32)0.0001FACT-ES Functional Well-Being: ≥24 vs. <2449.3% vs. 33.9%1.97 (1.18-3.30)0.01FACT-ES Physical Well-Being: ≥12 vs. <1238.6% vs. 21.1%2.45 (1.44-4.18)0.001FACT-ES Endocrine Subscale: ≥42 vs. <4236.7% vs. 29.7%1.44 (0.84-2.47)0.19WOMAC: <50 vs. ≥5049.0% vs. 26.0%2.63 (1.85-3.74)<.001M-SACRAH: <33 vs. ≥3345.6% vs. 27.4%2.18 (1.54-3.10)<.001 Citation Format: N. Lynn Henry, Joseph M Unger, Cathee Till, Katherine D Crew, Michael J Fisch, Dawn L Hershman. Predictors of pain reduction in trials of interventions for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-03.

Clinical pain management by a multidisciplinary palliative care team: Experience from a tertiary cancer center in China.

To investigate the effect of multidisciplinary interventions on pain management in cancer inpatients.Four hundred thirty eight patients with cancer pain, who performed the multidisciplinary intervention were recruited. Before and after intervention, the Brief Pain Inventory (BPI) and the MD Anderson Symptom Inventory (MDASI) score as the primary endpoints and QOL scores as the secondary endpoint were all evaluated. To investigate the factors that led to different responses to multidisciplinary interventions, patients were classified as non-responders or responders.Finally, 92 patients (63 male and 29 female) scheduled for cancer pain management by inter-professional team were studied. After individualized multidisciplinary therapy, both pain and symptom severity was improved, as demonstrated by lowered BPI worst and average pain scores, as well as symptom severity score measured by MDASI (P = .017, P = .003, and P = .011, respectively). The proportion of patients with mild pain increased regarding the BPI worst and average pain at baseline and after treatment (P < .05). The QOL analyses showed multidisciplinary interventions could significantly improve the function and symptom scores (P < .001). More patients in responder group received chemotherapy (58, 70.7%, P = .003), while fewer received mini-invasive therapy (6, 7.32%, P = .011).Multidisciplinary interventions had certain beneficial effect on cancer pain management, especially in patients with moderate or severe pain.

Episodic Cancer Pain: Patient Reporting, Prevalence, and Clinicodemographic Associations at Initial Cancer Pain Clinic Assessment.

Background Better understanding of the episodic cancer pain (CP) spectrum, including pains that occur in addition to its conventionally defined breakthrough CP (BTcP) and incident CP (IcP) components, may inform CP assessment and management. This study aimed to determine the prevalence of episodic patient-reported CP and the prevalence and associations of study-defined BTcP (S-BTcP) and IcP (S-IcP) in patients with CP. Methods In a cross-sectional study at their first CP clinic attendance, participants with CP had the following assessments: Brief Pain Inventory (BPI); Pain Management Index (PMI), with PMI-negative status indicating undertreatment; standardized neuropathic pain component (NPC) status; S-BTcP (no trigger identified) and S-IcP (trigger identified) status, based on a preceding 7-day history of transitory pain flares distinct from background pain, and BPI-Worst or BPI-Now pain intensity ≥ 4. Clinicodemographic variables' association with S-BTcP and S-IcP was examined in logistic regression analyses. Results Of 371 participants, 308 (83%) had episodic CP by history alone; 140 (37.7%) and 181 (48.8%) had S-BTcP and S-IcP, respectively. Multivariable analyses demonstrated significant (p < 0.05) associations (odds ratios: 95% CIs) for 6 variables with S-BTcP: head and neck pain location (2.53; 1.20–5.37), NPC (2.39; 1.34–4.26), BPI average pain (1.64; 1.36–1.99), abdominal pain (0.324; 0.120–0.873), S-IcP (0.207; 0.116–0.369), and PMI-negative status (0.443; 0.213–0.918). Similar independent associations (p < 0.05) occurred for S-IcP with NPC, BPI average pain, and PMI-negative status, in addition to radiotherapy, S-BTcP, soft tissue pain, and sleep interference. Conclusions Episodic or transient patient-reported CP flares often do not meet the more conventional criteria that define BTcP and IcP, the principal episodic CP types. Both BTcP and IcP occur frequently and both are associated with a NPC, higher pain intensity, and less opioid underuse in the management of CP. Further studies are warranted to both better understand the complex presentations of episodic CP and inform its classification.

Relationship Between Pain Reduction and Improvement in Health-Related Quality of Life in Patients with Knee Pain Due to Osteoarthritis Receiving Duloxetine: Exploratory Post Hoc Analysis of a Japanese Phase 3 Randomized Study.

PurposeThis post hoc analysis of a Japanese phase 3 randomized study (ClinicalTrials.gov identifier: NCT02248480) investigated relationships between changes in pain severity and changes in health-related quality of life (HRQoL) in duloxetine-treated patients with knee osteoarthritis (OA).Patients and MethodsPatients with knee OA and Brief Pain Inventory (BPI) average pain score ≥4 received duloxetine 60 mg/day or placebo for 14 weeks. Spearman rank correlation coefficients were calculated for change in pain severity, as assessed by the BPI, and change in HRQoL, as assessed by the items of the (i) 36-item Short-Form Health Survey (SF-36; a generic measure of HRQoL) and (ii) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; an OA-specific measure of HRQoL).ResultsAfter 14 weeks of treatment, there was a significantly greater improvement (p<0.001) for duloxetine (n=177) vs placebo (n=176) in BPI average pain severity score and significantly greater improvements (p<0.01) for duloxetine vs placebo for 5 of the 8 SF-36 domains (including the Role-Physical, Bodily Pain, and Physical Functioning domains) and all 24 individual WOMAC items. The correlation between BPI change from baseline and SF-36 item change from baseline was statistically significant (p<0.05) for 2 of the 8 SF-36 items (Bodily Pain, Physical Functioning) in duloxetine-treated patients. The correlation between BPI change from baseline and WOMAC item change from baseline was statistically significant for 22 of the 24 WOMAC items in duloxetine-treated patients.ConclusionThis post hoc analysis suggested that the pain reduction observed in duloxetine-treated patients with knee OA was associated with improvements in OA-specific aspects of HRQoL, ie, pain and physical functioning.

Efficacy and safety of duloxetine versus placebo in adolescents with juvenile fibromyalgia: results from a randomized controlled trial

BackgroundCurrently, there are no medications approved for the treatment of juvenile fibromyalgia (JFM). We evaluated the safety and efficacy of duloxetine 30/60 mg once daily (QD) versus placebo in adolescents with JFM.MethodsIn this Phase 3b, multisite (US, Argentina, Puerto Rico, and India) trial, patients aged 13–17 years with JFM and a score of ≥4 on the Brief Pain Inventory-Modified Short Form: Adolescent Version (BPI) 24-h average pain severity score were randomized to duloxetine or placebo for the 13-week double-blind period. The starting duloxetine dose was 30 mg, with a target dose of 60 mg QD, as tolerated. The primary endpoint was the mean change in 24-h average pain severity of the Brief Pain Inventory (BPI) from baseline to Week 13, analyzed using mixed-model repeated measures (MMRM) technique. Secondary measures were BPI severity and interference scores; treatment response (≥30%, ≥50% reductions on BPI average pain severity); Pediatric Pain Questionnaire; Clinical Global Impression of Severity: Overall and Mental Illness scales; Functional Disability Inventory: child and parent versions; Children’s Depression Inventory; Multidimensional Anxiety Scale for Children; and safety and tolerability. Continuous secondary efficacy measures were analyzed using analysis of covariance or MMRM, and categorical data using Cochran-Mantel-Haenszel test and Fisher’s exact test, where appropriate.ResultsA total of 184 patients with JFM received duloxetine (N = 91) or placebo (N = 93), of which 149 patients (81.0%) completed the 13-week double-blind treatment period. Baseline characteristics were comparable between groups; majority of the patients were Caucasian (77.17%) and females (75.0%), with a mean age of 15.53 years. For the primary measure, BPI average pain severity, the mean change was not statistically different between duloxetine and placebo (− 1.62 vs. -0.97, respectively; p = .052). For secondary efficacy outcomes, statistically significantly more duloxetine- versus placebo-treated patients had a treatment response (≥30% and ≥50% reductions on BPI average pain severity) and improvement of the general activity and relationships items on the BPI interference subscale. The percentage of patients reporting at least 1 treatment-emergent adverse event was higher in the duloxetine versus placebo groups (82.42% vs. 62.37%, respectively; p = .003). The overall safety profile of duloxetine in this study was similar to that reported previously in duloxetine pediatric trials of other indications.ConclusionsThe primary study outcome, mean change in 24-h BPI average pain severity rating from baseline to Week 13, did not significantly improve with duloxetine compared to placebo in patients with JFM. However, significantly more patients on duloxetine compared to placebo had a ≥30% and ≥50% reduction in pain severity. There were no new safety concerns related to duloxetine in the study population.Trial registrationClinicalTrials.gov Identifier: NCT01237587. Registered 08 November, /2010.

Maintenance of effect of duloxetine in Chinese patients with pain due to osteoarthritis: 13-week open-label extension data

BackgroundThe objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data.MethodsThis was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed.ResultsOf 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event.ConclusionThe analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase.Trial registrationClinicalTrials.gov identification number NCT01931475. Registered 29 August 2013.

Abstract P1-11-04: Association between body mass index (BMI) and response to duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS)

Abstract Background: AIMSS occurs often in women treated with AI therapy for early stage breast cancer and can negatively impact adherence and persistence with therapy. Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat mood disorders and chronic pain. In SWOG S1202, patients with AIMSS treated with duloxetine reported statistically significant improvement in pain by 12 weeks compared to placebo. Obesity is a predictor of increased likelihood of developing AIMSS, and a prior study of omega 3 fatty acid versus placebo for AIMSS showed a potential differential response to therapy by BMI. In this exploratory analysis of S1202, we investigated the association between baseline BMI and response to therapy. Methods: In S1202, 299 postmenopausal women with stage I-III hormone receptor-positive breast cancer on AI therapy who developed new or worsening average pain of 4-10 on a numerical rating scale were enrolled, randomized 1:1 to duloxetine or placebo with randomization stratified by baseline pain (4-6 vs. 7-10) and prior taxane therapy (yes vs. no). Patients were treated for 12 weeks. Patient-reported outcomes including Brief Pain Inventory (BPI) were obtained at baseline and weeks 2, 6, 12, and 24. Patients were categorized into BMI&amp;lt;30 kg/m2 (non-obese) or BMI≥30 kg/m2 (obese). The pre-specified aim of this secondary analysis was to examine whether the effect of intervention on BPI average pain at 12 weeks differed between obese and non-obese patients. Multiple linear regression was used, adjusting for the stratification factors and the baseline score. We tested whether the interaction of BMI status and intervention effect was statistically significant at α=.05. Results: 289 patients were eligible for the analysis, 54% of whom were obese. The cohorts were well balanced other than by race. The difference by intervention arm in the 12-week mean BPI scores between baseline and follow-up scores was substantially different for the obese versus non-obese cohorts. In the patients with BMI&amp;lt;30, the reduction in observed mean average pain score was similar in the duloxetine- and placebo-treated patients (-2.46 points vs. -2.34 points, p=.75). In contrast, in the patients with BMI≥30 the reduction in pain score was statistically significantly greater for the duloxetine-treated compared to the placebo-treated patients (-2.73 points vs. -1.64 points, p=.003; interaction p-value=.02). Differences in intervention effects between obese and non-obese groups were even stronger at 2-weeks (interaction p-value=.001) and 6-weeks (interaction p-value&amp;lt;.0001). Similar findings were evident for other pain-related patient-reported outcomes. Conclusions: In the placebo-controlled S1202 trial, obese patients with AIMSS obtained more analgesic benefit from duloxetine. Additional studies are warranted to determine the biologic basis for these findings, such as a different mechanism underlying development of AIMSS or pain expression in patients with obesity, or other confounding variables related to analgesic response to duloxetine relative to placebo. Support: NIH/NCI grants CA189974, CA189821, CA180820; and in part by Damon Runyon-Lilly Clinical Investigator Award #CI-53-10 [to NLH], and in part by Lilly USA, LLC. Citation Format: Henry NL, Unger JM, Till C, Schott AF, Crew KD, Lew DL, Fisch MJ, Moinpour CM, Wade JL, Hershman DL. Association between body mass index (BMI) and response to duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-04.

Preoperative ultrasound-guided multilevel paravertebral blocks reduce the incidence of postmastectomy chronic pain: a double-blind, placebo-controlled randomized trial.

PurposeChronic postsurgical pain is a challenging problem after breast cancer surgery. This prospective, randomized, double-blinded, parallel-group, placebo-controlled trial was conducted to evaluate the influence of preoperative ultrasound-guided multilevel paravertebral blocks (PVBs) on chronic pain following mastectomy.Patients and methodsOne hundred eighty-four women were randomized to receive ultrasound-guided multilevel (T1–T5) PVBs with 5 mL of ropivacaine 0.5% or normal saline per level. The primary end point was the incidence of chronic pain at 3 months following mastectomy assessed by the brief pain inventory (BPI), while the secondary end points were the acute postoperative pain, the number of patients requiring rescue analgesia, postoperative nausea and vomiting (PONV), side effects, and chronic pain at 6 months after surgery assessed by the BPI.ResultsA total of 172 patients completed the study. Ultrasound-guided multilevel PVBs significantly decreased immediate postoperative pain for the first 12 hours (P<0.001). Additionally, fewer patients in the PVB group required rescue analgesia in the first 48 hours post-operatively compared to the control group (5/86 vs 28/86, OR =0.128, 95% CI: 0.047–0.351, P<0.001). No statistically significant difference was tested between the two groups (9.3% vs 17.4%, OR =0.419, 95% CI: 0.162–1.087, P=0.068) in the incidence of PONV. At 3 months, the incidence of chronic pain (BPI average pain score ≥3) was 34.5% and 51.2% (OR =0.511, 95% CI: 0.277–0.944, P=0.031) in the PVB and control groups, respectively, and at 6 months, the incidence was 22.1% and 37.2% (OR =0.479, 95% CI: 0.245–0.936, P=0.03), respectively. No complications occurred during the study.ConclusionThis study indicated that perioperative ultrasound-guided multilevel PVBs with ropivacaine improved acute postoperative pain and decreased postmastectomy chronic pain at 3 and 6 months postoperatively.

Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927).

Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I-III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0-10). Among the 249 participants, 139 had BMI < 30kg/m2 (56%) and 110 had BMI ≥ 30kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively). In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

Efficacy of duloxetine by prior NSAID use in the treatment of chronic osteoarthritis knee pain: A post hoc subgroup analysis of a randomized, placebo-controlled, phase 3 study in Japan

BackgroundA previously conducted placebo-controlled, randomized, phase 3 study of 353 Japanese patients with knee osteoarthritis (OA) showed significant improvements for duloxetine vs placebo in pain and health-related quality of life (HRQoL) (ClinicalTrials.gov Identifier: NCT02248480). Reported here are post hoc subgroup analyses evaluating the efficacy of duloxetine according to the pattern of prior nonsteroidal anti-inflammatory drug (NSAID) use. MethodsPatients with knee OA pain received once-daily duloxetine or placebo for 14 weeks. Pain was evaluated using the Brief Pain Inventory (BPI) and HRQoL was evaluated using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Patients were divided into four subgroups based on their prior NSAID use: (i) no prior NSAID use; (ii) low-frequency NSAID use (<14 days/month); (iii) high-frequency transdermal NSAID use (transdermal NSAIDs only; ≥14 days/month for the 3 months before study entry); and (iv) high-frequency other NSAID use (eg, oral NSAIDs only, both oral and transdermal NSAIDs; ≥14 days/month for the 3 months before study entry). ResultsIn each of the four prior NSAID use subgroups, there were greater reductions in BPI average pain severity score for duloxetine vs placebo at all timepoints during the 14-week treatment period; the treatment*prior NSAID use interaction was not statistically significant. In each subgroup, the proportion of patients achieving a ≥50% reduction in BPI average pain severity score was higher for duloxetine vs placebo. In each subgroup, there were greater reductions in WOMAC total score for duloxetine vs placebo at all timepoints; the treatment*prior NSAID use interaction was not statistically significant. In each subgroup, there were greater reductions at Week 14 in WOMAC pain, stiffness, physical function, and total scores for duloxetine vs placebo. ConclusionsDuloxetine was consistently effective with respect to pain relief and HRQoL in Japanese patients with knee OA pain, regardless of the pattern of prior NSAID use.

Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study.

PurposeDuloxetine is efficacious for chronic low back pain (CLBP). This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919) assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation) have enhanced responses to duloxetine.Patients and methodsPatients (N = 456) with CLBP for ≥6 months and Brief Pain Inventory (BPI) average pain severity score of ≥4 were randomized (1:1) to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction). Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4) and early TR-AESIs (with or without TR-AESIs by Week 2). Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL), and response rate (≥30% or ≥50% pain reduction at Week 14).ResultsPatients with ≥30% early pain reduction (n = 108) or early TR-AESIs (n = 50) had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226), whereas patients with 10%–30% (n = 63) or <10% (n = 48) pain reduction did not; patients without early TR-AESIs (n = 180) had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction) were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.ConclusionEarly pain reduction or TR-AESIs may predict which CLBP patients are most likely to respond to duloxetine with improvements in pain and QOL.

Patient-reported outcomes after surgical stabilization of spinal tumors: symptom-based validation of the Spinal Instability Neoplastic Score (SINS) and surgery

Background ContextNeoplastic spinal instability is movement-related pain or neurologic compromise under physiologic loads with the Spinal Instability Neoplastic Score (SINS) developed to facilitate diagnosis. There is a paucity of evidence that mechanical instability correlates with patient-reported symptoms and that surgical stabilization significantly improves these patient-reported outcomes (PROs). PurposeThe objective of this study was to determine if SINS correlates with patient-reported preoperative pain and disability, and if surgical stabilization significantly improves PRO. Study DesignA single-institution prospective cohort study was carried out. Patient SampleA total of 131 patients who underwent stabilization for metastatic spinal tumor treatment between July 2014 and August 2016 were included. Outcomes MeasuresPreoperative baseline and mean difference in perioperative PROs as assessed by the Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory (MDASI) were the outcome measures. MethodsThe SINS was analyzed as a continuous, ordinal, and categorical variable (Stable: 0–6, Indeterminate: 7–12, Unstable: 13–18). Statistical analysis was performed using Spearman rank coefficient (rho), the Kruskal-Wallis test, and an extension of the Cochran-Armitage trend test. The SINS and association between the mean differences in post- and preoperative PRO scores was analyzed using the Wilcoxon signed-rank test. ResultsThere was a statistically significant positive correlation between increasing SINS and severity of preoperative pain with BPI average pain (rho=0.20; p=.03) and MDASI pain (rho=0.19; p=.03). Increasing SINS correlated with severity of preoperative disability with BPI walking (rho=0.19; p=.04), MDASI activity (rho=0.24; p=.006), and MDASI walking (rho=0.20; p=.03). Similar associations were noted when SINS was analyzed as an ordinal categorical variable. Stabilization significantly improved nearly all PRO measures for patients with indeterminate and unstable SINS. Significant correlations persisted when controlling for neurologic status and were not affected based on the technique of surgical stabilization used. ConclusionsPatient-related outcome-based validation of SINS confirms this scoring system for diagnosing neoplastic spinal instability and provides surgeons with a tool to determine which patients will benefit from stabilization. Surgical stabilization of cancer patients with SINS consistent with mechanical instability provides significant reduction in pain and improves patient mobility independent of neurologic status and stabilization technique.

Duloxetine 60 mg for chronic low back pain: post hoc responder analysis of double-blind, placebo-controlled trials.

IntroductionDuloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP.Patients and methodsThis was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12–14 weeks) in adult patients with CLBP. Primary outcome was proportion of patients with ≥30% reduction in Brief Pain Inventory (BPI) average pain (“pain reduction”) at 12–14 weeks. The proportion of patients with ≥30% and ≥50% (secondary outcome) pain reduction in duloxetine and placebo groups was compared. Variables for responder analyses were early improvement (≥15% pain reduction at Week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites according to the Michigan Body Map (≥2 vs 1 [isolated CLBP]; 1 trial); relative risk (RR) and 95% confidence interval (CI) were calculated.ResultsCompared with placebo (n = 653), a greater proportion of duloxetine-treated patients (n = 642) achieved ≥30% (59.7% vs 47.8%; P < 0.001) and ≥50% pain reduction (48.6% vs 35.1%; P < 0.001). Among duloxetine-treated patients, early improvement was associated with greater likelihood of ≥30% (RR [95% CI], 2.91 [2.30–3.67]) or ≥50% (3.24 [2.44–4.31]) pain reduction. Women were slightly more likely than men to achieve ≥30% (RR [95% CI], 1.14 [1.00–1.30]) or ≥50% (1.17 [0.99–1.38]) pain reduction. Response rates were similar between age, CLBP duration, and baseline BPI average pain score subgroups. Patients with ≥2 painful sites were more likely to respond to duloxetine 60 mg relative to placebo than patients with isolated CLBP (RR, duloxetine vs placebo [95% CI]: ≥30% reduction, ≥2 painful sites 1.40 [1.18–1.66], isolated CLBP 1.07 [0.78–1.48]; ≥50% reduction, ≥2 painful sites 1.51 [1.20–1.89], isolated CLBP 1.23 [0.81–1.88]).ConclusionEarly pain reduction was indicative of overall response. Patients with multiple painful sites had more benefit from duloxetine than patients with isolated CLBP.

Abstract S5-06: Randomized, placebo-controlled trial of duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) in early stage breast cancer (SWOG S1202)

Abstract Background: Adherence to AI therapy for adjuvant treatment of hormone receptor-positive breast cancer is poor, primarily because of AIMSS. Premature discontinuation of AI therapy can lead to increased likelihood of breast cancer recurrence. Duloxetine (dulox) is a serotonin norepinephrine reuptake inhibitor that is FDA-approved for treatment of multiple chronic pain disorders. Phase II data from an open label trial of dulox for treatment of AIMSS demonstrated a 61% improvement in pain. We hypothesized that treatment of AIMSS with dulox would improve average joint pain compared to placebo (plac). Methods: Postmenopausal women with stage I-III breast cancer who had been taking AI therapy for between 3 wks and 36 mo were enrolled. To be eligible, patients were required to have average pain of ≥4/10 using the Brief Pain Inventory (BPI) that developed or worsened since AI therapy initiation, and not have any contraindications to dulox therapy. Patients were randomized 1:1 to dulox 30 mg daily for 7 d then 60 mg daily for 11 wks then 30 mg daily for 7 d, or to matching plac, stratified by baseline pain (4-6 vs 7-10) and prior taxane use (yes vs no). Pain, depression, and quality of life (QoL) were assessed after 2, 6, and 12 wks of therapy, as well as at the 24 wk time point. The primary analysis used linear mixed models to examine average pain through 12 wks by arm, adjusting for the stratification factors and assessment time. Clinically significant change in average pain was defined as a ≥2-point decrease from baseline. Results: 299 patients were randomized between June 2013 and October 2015, 10 of whom were ineligible. 127 dulox-treated and 128 plac-treated patients were evaluable for the primary analysis. No sizeable imbalances in baseline factors were noted by arm. Seventeen pts reported grade 3 adverse events (AEs) (dulox: 12/138 (8.7%), plac: 5/141 (3.5%)), and 40 pts discontinued treatment because of AEs (dulox: 21 (52.5%), plac: 19 (47.5%)). Mean observed average pain, the proportion of pts experiencing clinically significant change in average pain from baseline, and percent reduction in average pain all indicated greater improvement for dulox compared with plac through 12 wks, but were similar by arm at wk 24 (12 wks after completion of intervention; see Table). In multivariable linear mixed model analysis, the BPI average pain was reduced on average by 0.82 points more on dulox compared to plac over the first 12 wks (95% CI -1.24 to -0.40, p=0.0002). Similar patterns were observed for worst pain, pain interference, joint pain, stiffness, and functioning, and QoL. Table: Observed Average Pain Scores by Assessment TimeTime PointBaseline2 weeks6 weeks12 weeks24 weeksduloxplacduloxplacduloxplacduloxplacduloxplacAverage pain5.445.493.514.412.953.962.913.453.373.42Percent reduction--34%20%46%28%46%36%37%37%Patients with clinically significant change--54%44%69%49%69%60%60%59% Conclusions: Treatment with duloxetine was superior to placebo for the treatment of AIMSS among women with early stage breast cancer, was well tolerated, and was associated with improvements in QoL. Clinicaltrials.gov NCT01598298. Citation Format: Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow D, Sharer CW, Lew DL, Moseley A, Fisch MJ, Moinpour C, Hershman DL, Wade III JL. Randomized, placebo-controlled trial of duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) in early stage breast cancer (SWOG S1202) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-06.

Effectiveness of Duloxetine Compared With Pregabalin and Gabapentin in Diabetic Peripheral Neuropathic Pain

This study aimed to compare the effectiveness of duloxetine (DLX) and the anticonvulsants pregabalin (PGB) and gabapentin (GBP) for the treatment of diabetic peripheral neuropathic pain (DPNP) in routine clinical care. Data from a 6-month, noninterventional study involving 2575 patients in whom treatment of DPNP was initiated with or changed to DLX, PGB, or GBP (n=1523) were analyzed post hoc; patients treated with other medications or combinations were excluded from this analysis. Propensity scoring was used to compare patient groups, assessing Brief Pain Inventory (BPI), Clinical and Patient Global Impression (CGI/PGI), the Hospital Anxiety and Depression Scale (HADS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF 12). Mean median daily dosage over 6 months was 53.9 mg for DLX (N=931), 173.5 mg for PGB (N=248), and 727.8 mg for GBP (N=351). BPI average pain severity (last observation carried forward, mean [SD]) decreased by 2.3 [2.30] points for DLX patients, and by 1.9 [2.22] in PGB, and 1.1 [2.15] in GBP patients. This difference remained statistically significant (DLX vs. PGB: P=0.029; DLX vs. GBP: P<0.001) after adjustment by propensity scores. Similar findings were also seen for the BPI interference score, CGI and PGI, the HADS anxiety score, the HADS depression score. When compared with DLX, the low doses of PGB and GBP used in this noninterventional study might have contributed to the lower effectiveness found for both anticonvulsants in the treatment of patients with DPNP.

Inadequate pain relief and large functional loss among patients with knee osteoarthritis: evidence from a prospective multinational longitudinal study of osteoarthritis real-world therapies.

Objective. To estimate the prevalence of inadequate pain relief (IPR) among patients with symptomatic knee OA prescribed analgesic therapy and to characterize patients with IPR.Methods. Patients ≥50 years old with physician-diagnosed knee OA who had taken topical or oral pain medication for at least 14 days were recruited for this prospective non-interventional study in six European countries. Pain and function were assessed using the Brief Pain Inventory (BPI) and the WOMAC; quality of life (QoL) was assessed using the 12-item short form. IPR was defined as an average pain score of >4 out of 10 on BPI question 5.Results. Of 1187 patients enrolled, 68% were female and the mean age was 68 years (s.d. 9); 639 (54%) met the definition of IPR. Patient responses for the BPI average pain question were well correlated with responses on the WOMAC pain subscale (Spearman r = 0.64, P < 0.001). In multivariate logistic regression, patients with IPR had greater odds of being female [adjusted odds ratio (adjOR) 1.90 (95% CI 1.46, 2.48)] and having OA in both knees [adjOR 1.48 (95% CI 1.15, 1.90)], higher BMI, longer OA duration, depression or diabetes. Patients with IPR (vs non-IPR) were more likely to have worse QoL, greater function loss and greater pain interference.Conclusion. IPR is common among patients with knee OA requiring analgesics and is associated with large functional loss and impaired QoL. Patients at particular risk of IPR, as characterized in this study, may require greater attention towards their analgesic treatment options.Trial registration: https://clinicaltrials.gov/ (NCT01294696).