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Prediction of pain response by severity of sleep interference in neuropathic pain
P48
The Journal of Pain
Abstracts
(288) Clinical characteristics, pharmacotherapy and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants
(290) Prediction of pain response by severity of sleep interference in neuropathic pain
A Chandran, G Zlateva, D Leslie, K Tai, and M Gore; Avalon Health Solutions, Philadelphia, PA
Identification of baseline patient characteristics that predict response to a particular drug would enhance the therapeutic choices of an individual drug in the treatment of painful diabetic neuropathy (PDN) or postherpetic neuralgia (PHN). Emerging evidence suggests a bi-directional relationship between pain and sleep interference: sleep deprivation increases pain sensitivity and pain interferes with sleep. The objective of this post hoc analysis was to examine the relationship of pain interference with sleep at baseline and the pain reduction with pregabalin. Data from 11 double-blind trials involving 2902 patients with PDN and PHN receiving pregabalin or placebo for 5-8 weeks were pooled. Change in pain at endpoint for treatment differences by disease groups were analyzed using an analysis of covariance (ANCOVA) interaction model. Among PDN patients with mild, moderate to severe sleep disturbance [rating of <4, 4 to 7 or $7, respectively, on the Daily Sleep Interference (DSI) scale], pain improved significantly with pregabalin compared with placebo at endpoint: mild sleep disturbance; pain improvement (-0.59, P <.0094); moderate -0.84, P<0.0001; severe -1.50, P< 0.0001). The treatment difference between the pain responses with different levels of sleep interference was significant (p <0.0083). Among patients with PHN, pain improved significantly with pregabalin compared with placebo at endpoint regardless of baseline sleep interference: (mild -0.94 P<0.0001, moderate -0.99 P<0.0001, severe-1.40 P<0.0001). Among PDN patients, pregabalin reduces pain in proportion to the degree of sleep interference. Among PHN patients, pregabalin improvements in pain are similar in magnitude among the mild or moderate sleep interference patients; however, higher improvements among the severe baseline interference patients were observed (P<0.0001). High levels of pain interference with sleep may be useful for identifying patients with PDN or PHN likely to respond well to pregabalin. Supported by Pfizer Inc.
The objective of this study was to evaluate treatment patterns and costs among patients with fibromyalgia (FM) newly prescribed pregabalin or tricyclic antidepressants (TCAs) in clinical practice. Using the LifeLinkÔ Health Plan Claims Database, patients with FM (ICD-9-CM code 729.1X) newly prescribed TCAs (n=898; mean age 48.569.9 years) were identified and propensity scorematched (PSM) with patients initiated on pregabalin (n=898; mean age 47.969.6 years). Comorbidities, pain-related pharmacotherapy and healthcare resource use/costs were examined during the 12-months preceding (pre-index) and following (follow-up) the date of the first pregabalin or TCA prescription. Both cohorts had multiple comorbidities and a substantial pain medication burden in both the pre-index and follow-up periods. Among pregabalin patients, use of non-selective NSAIDs (43.3% vs. 39.8%), other anticonvulsants (28.6% vs. 23.3%), and tetracyclic/misc antidepressants (28.5% vs. 25.8%) significantly decreased and COX-2 inhibitors (7.7% vs. 10.4%), TCAs (4.8% vs. 7.9%) and topical agents (10.8% vs. 15.1%) increased in the follow-up period; all p-values <0.05. Among TCA patients, there were significant decreases for muscle relaxants (42% vs. 38.4%) and sedative hypnotics (27.4% vs. 23.9%) and increases for Cox-2s (5.8% vs. 7.9%) and anticonvulsants (25.1% vs. 33.7%); all p-values <0.05. There were significant increases (p<.0001) in pharmacy costs in both cohorts and in total healthcare costs in the pregabalin cohort from pre-index to follow-up. Median total costs were higher (p<0.05) in the pregabalin group relative to TCAs in both the pre-index ($9,935 vs. $8,771) and follow-up periods ($10,689 vs. $8,379). Patients with FM prescribed pregabalin and TCAs were characterized by a considerable comorbidity and pain medication burden. Medication use and costs increased in the follow-up period for both cohorts. Despite our attempts to control for bias through PSM, the higher pre-index total costs in the pregabalin cohort suggest a potential channeling of more severe patients to pregabalin.
A Vinik, B Emir, and R Cheung; Eastern Virginia Medical School, Norfolk, VA
(289) Identification of sensory symptom clusters in patients with neuropathic pain based on the neuropathic pain symptom inventory questionnaire
(291) Objective and subjective benefits of pregabalin on measures of sleep efficiency in patients with fibromyalgia and sleep maintenance disturbance
R Freeman, R Baron, D Bouhassira, B Emir, R Cheung, and K Murphy; Pfizer Inc., New York, NY
M Resnick, T Roth, D Lankford, P Bhadra, and E Whalen; Pfizer Inc., New York, NY
Neuropathic pain (NeP) presents with a heterogeneous clinical phenotype that includes a variety of sensory symptoms and pain qualities. The current analyses were conducted to identify whether patterns of sensory symptoms exist, based on baseline responses on the Neuropathic Pain Symptom Inventory (NPSI) questionnaire, and to evaluate whether these symptom clusters have impact on the response to pregabalin. The self-administered NPSI includes 10 different pain symptom descriptors (eg, burning, stabbing, electric shock, etc) and 2 temporal items, and allows for discrimination and quantification of 5 distinct clinically relevant dimensions of NeP. This analysis was based on data from 4 randomized, double-blind, placebo-controlled clinical studies of pregabalin (150-600 mg/day) in patients with NeP syndromes: central post-stroke pain, post-traumatic peripheral pain, painful HIV neuropathy, and painful diabetic peripheral neuropathy. The NPSI questionnaire was used in all trials. Three of the 4 trials failed to show a significant treatment effect for pregabalin versus placebo at endpoint. Quantile normalization was used to reduce inter-study variations in the NPSI ratings. To identify symptom constellations and select the number of clusters, a Partitioning Around Medoids algorithm and silhouette plots were used. Preliminary analyses suggested 5 symptom clusters, but additional analyses to assess the number and types of symptom clustering will be done to identify more clinically-relevant clusters. The different sensory symptom clusters, independent of etiology, may reflect common underlying pain mechanisms across these NeP syndromes and therefore may share a response to drug treatment. Grouping patients based on sensory symptom clusters may improve clinical trial design and trial outcomes. This study was funded by Pfizer Inc.
Sleep problems are common among fibromyalgia patients and contribute towards fibromyalgia-related fatigue and pain. This randomized, double-blind, placebo-controlled, 2-period crossover study sought to assess the effect of pregabalin on objective and subject rated measures of sleep, and subject-rated daily pain (from 0 [’no pain’] to 10 [’worst possible pain’]) in patients with fibromyalgia. Patients $18y with fibromyalgia and sleep maintenance difficulties were enrolled and randomized (1:1) to pregabalin (300-450 mg/d) or placebo for crossover Period 1; and vice versa for Period 2. Subjects were required to meet subjective and objective sleep disturbance criteria prior to randomization. Each crossover period had a dose-adjustment (to Day 14 of period) and dose maintenance (to Day 29 of period) phase, with a 2-week taper/washout between periods. Total Sleep Time (TST) was recorded by polysomnography at baseline and during 2 consecutive nights at end of Period 1[Day 31] and 2[cumulative Day 73], subject-rated measures of sleep efficacy were recorded daily via IVRS (subjective-TST[sTST]) and Sleep Quality (11-point scale from 0[’very poor’] to 10[’excellent’]). Objective- and subject -rated endpoints were analyzed using a linear mixed-effects model. Of 119 subjects randomized (103 [86.6%] female; 104[87.4%] white; mean 48.4y), 102(85.7%) completed both Periods. Mean duration of FM at baseline was 4.2y (range 0–26.3y). Subjects recorded sleep disturbance at baseline. Baseline pain score was 6.761.63 (placebo–>pregabalin) and 6.661.62 (pregabalin–>placebo). Treatment with pregabalin increased PSG-recorded TST by >25 mins vs. treatment with placebo (LS mean 396.2 vs. 370.6 mins; P<0.0001). During all treatment weeks, pregabalin treatment increased sTST vs. placebo treatment (Week 4 LS mean difference [95%CI]:+25.4 [15.0,35.9];P<0.0001), and Sleep Quality (0.89 [0.51, 1.26];P<0.0001). Pain scores reduced during all treatment weeks with pregabalin (Week 4 difference vs. placebo: 0.52[ 0.90, 0.14];P=0.008). Fibromyalgia subjects treated with pregabalin recorded clinically-meaningful improvements in measures of sleep efficiency and quality, and reported reduced pain. Supported by Pfizer Inc.
The Journal of Pain
Abstracts
(288) Clinical characteristics, pharmacotherapy and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants
(290) Prediction of pain response by severity of sleep interference in neuropathic pain
A Chandran, G Zlateva, D Leslie, K Tai, and M Gore; Avalon Health Solutions, Philadelphia, PA
Identification of baseline patient characteristics that predict response to a particular drug would enhance the therapeutic choices of an individual drug in the treatment of painful diabetic neuropathy (PDN) or postherpetic neuralgia (PHN). Emerging evidence suggests a bi-directional relationship between pain and sleep interference: sleep deprivation increases pain sensitivity and pain interferes with sleep. The objective of this post hoc analysis was to examine the relationship of pain interference with sleep at baseline and the pain reduction with pregabalin. Data from 11 double-blind trials involving 2902 patients with PDN and PHN receiving pregabalin or placebo for 5-8 weeks were pooled. Change in pain at endpoint for treatment differences by disease groups were analyzed using an analysis of covariance (ANCOVA) interaction model. Among PDN patients with mild, moderate to severe sleep disturbance [rating of <4, 4 to 7 or $7, respectively, on the Daily Sleep Interference (DSI) scale], pain improved significantly with pregabalin compared with placebo at endpoint: mild sleep disturbance; pain improvement (-0.59, P <.0094); moderate -0.84, P<0.0001; severe -1.50, P< 0.0001). The treatment difference between the pain responses with different levels of sleep interference was significant (p <0.0083). Among patients with PHN, pain improved significantly with pregabalin compared with placebo at endpoint regardless of baseline sleep interference: (mild -0.94 P<0.0001, moderate -0.99 P<0.0001, severe-1.40 P<0.0001). Among PDN patients, pregabalin reduces pain in proportion to the degree of sleep interference. Among PHN patients, pregabalin improvements in pain are similar in magnitude among the mild or moderate sleep interference patients; however, higher improvements among the severe baseline interference patients were observed (P<0.0001). High levels of pain interference with sleep may be useful for identifying patients with PDN or PHN likely to respond well to pregabalin. Supported by Pfizer Inc.
The objective of this study was to evaluate treatment patterns and costs among patients with fibromyalgia (FM) newly prescribed pregabalin or tricyclic antidepressants (TCAs) in clinical practice. Using the LifeLinkÔ Health Plan Claims Database, patients with FM (ICD-9-CM code 729.1X) newly prescribed TCAs (n=898; mean age 48.569.9 years) were identified and propensity scorematched (PSM) with patients initiated on pregabalin (n=898; mean age 47.969.6 years). Comorbidities, pain-related pharmacotherapy and healthcare resource use/costs were examined during the 12-months preceding (pre-index) and following (follow-up) the date of the first pregabalin or TCA prescription. Both cohorts had multiple comorbidities and a substantial pain medication burden in both the pre-index and follow-up periods. Among pregabalin patients, use of non-selective NSAIDs (43.3% vs. 39.8%), other anticonvulsants (28.6% vs. 23.3%), and tetracyclic/misc antidepressants (28.5% vs. 25.8%) significantly decreased and COX-2 inhibitors (7.7% vs. 10.4%), TCAs (4.8% vs. 7.9%) and topical agents (10.8% vs. 15.1%) increased in the follow-up period; all p-values <0.05. Among TCA patients, there were significant decreases for muscle relaxants (42% vs. 38.4%) and sedative hypnotics (27.4% vs. 23.9%) and increases for Cox-2s (5.8% vs. 7.9%) and anticonvulsants (25.1% vs. 33.7%); all p-values <0.05. There were significant increases (p<.0001) in pharmacy costs in both cohorts and in total healthcare costs in the pregabalin cohort from pre-index to follow-up. Median total costs were higher (p<0.05) in the pregabalin group relative to TCAs in both the pre-index ($9,935 vs. $8,771) and follow-up periods ($10,689 vs. $8,379). Patients with FM prescribed pregabalin and TCAs were characterized by a considerable comorbidity and pain medication burden. Medication use and costs increased in the follow-up period for both cohorts. Despite our attempts to control for bias through PSM, the higher pre-index total costs in the pregabalin cohort suggest a potential channeling of more severe patients to pregabalin.
A Vinik, B Emir, and R Cheung; Eastern Virginia Medical School, Norfolk, VA
(289) Identification of sensory symptom clusters in patients with neuropathic pain based on the neuropathic pain symptom inventory questionnaire
(291) Objective and subjective benefits of pregabalin on measures of sleep efficiency in patients with fibromyalgia and sleep maintenance disturbance
R Freeman, R Baron, D Bouhassira, B Emir, R Cheung, and K Murphy; Pfizer Inc., New York, NY
M Resnick, T Roth, D Lankford, P Bhadra, and E Whalen; Pfizer Inc., New York, NY
Neuropathic pain (NeP) presents with a heterogeneous clinical phenotype that includes a variety of sensory symptoms and pain qualities. The current analyses were conducted to identify whether patterns of sensory symptoms exist, based on baseline responses on the Neuropathic Pain Symptom Inventory (NPSI) questionnaire, and to evaluate whether these symptom clusters have impact on the response to pregabalin. The self-administered NPSI includes 10 different pain symptom descriptors (eg, burning, stabbing, electric shock, etc) and 2 temporal items, and allows for discrimination and quantification of 5 distinct clinically relevant dimensions of NeP. This analysis was based on data from 4 randomized, double-blind, placebo-controlled clinical studies of pregabalin (150-600 mg/day) in patients with NeP syndromes: central post-stroke pain, post-traumatic peripheral pain, painful HIV neuropathy, and painful diabetic peripheral neuropathy. The NPSI questionnaire was used in all trials. Three of the 4 trials failed to show a significant treatment effect for pregabalin versus placebo at endpoint. Quantile normalization was used to reduce inter-study variations in the NPSI ratings. To identify symptom constellations and select the number of clusters, a Partitioning Around Medoids algorithm and silhouette plots were used. Preliminary analyses suggested 5 symptom clusters, but additional analyses to assess the number and types of symptom clustering will be done to identify more clinically-relevant clusters. The different sensory symptom clusters, independent of etiology, may reflect common underlying pain mechanisms across these NeP syndromes and therefore may share a response to drug treatment. Grouping patients based on sensory symptom clusters may improve clinical trial design and trial outcomes. This study was funded by Pfizer Inc.
Sleep problems are common among fibromyalgia patients and contribute towards fibromyalgia-related fatigue and pain. This randomized, double-blind, placebo-controlled, 2-period crossover study sought to assess the effect of pregabalin on objective and subject rated measures of sleep, and subject-rated daily pain (from 0 [’no pain’] to 10 [’worst possible pain’]) in patients with fibromyalgia. Patients $18y with fibromyalgia and sleep maintenance difficulties were enrolled and randomized (1:1) to pregabalin (300-450 mg/d) or placebo for crossover Period 1; and vice versa for Period 2. Subjects were required to meet subjective and objective sleep disturbance criteria prior to randomization. Each crossover period had a dose-adjustment (to Day 14 of period) and dose maintenance (to Day 29 of period) phase, with a 2-week taper/washout between periods. Total Sleep Time (TST) was recorded by polysomnography at baseline and during 2 consecutive nights at end of Period 1[Day 31] and 2[cumulative Day 73], subject-rated measures of sleep efficacy were recorded daily via IVRS (subjective-TST[sTST]) and Sleep Quality (11-point scale from 0[’very poor’] to 10[’excellent’]). Objective- and subject -rated endpoints were analyzed using a linear mixed-effects model. Of 119 subjects randomized (103 [86.6%] female; 104[87.4%] white; mean 48.4y), 102(85.7%) completed both Periods. Mean duration of FM at baseline was 4.2y (range 0–26.3y). Subjects recorded sleep disturbance at baseline. Baseline pain score was 6.761.63 (placebo–>pregabalin) and 6.661.62 (pregabalin–>placebo). Treatment with pregabalin increased PSG-recorded TST by >25 mins vs. treatment with placebo (LS mean 396.2 vs. 370.6 mins; P<0.0001). During all treatment weeks, pregabalin treatment increased sTST vs. placebo treatment (Week 4 LS mean difference [95%CI]:+25.4 [15.0,35.9];P<0.0001), and Sleep Quality (0.89 [0.51, 1.26];P<0.0001). Pain scores reduced during all treatment weeks with pregabalin (Week 4 difference vs. placebo: 0.52[ 0.90, 0.14];P=0.008). Fibromyalgia subjects treated with pregabalin recorded clinically-meaningful improvements in measures of sleep efficiency and quality, and reported reduced pain. Supported by Pfizer Inc.