Effect of duloxetine in patients with fibromyalgia: fatigue subgroups

Abstracts (271) Bowel function following tapentadol and oxycodone immediate release (IR) Treatment in subjects with end stage joint disease: post-hoc analysis of data from a randomized, double-blind, active- and placebo-controlled study S Kavanagh, W Kwong, G Hammond, D Upmalis, A Okamoto, M Yang; Johnson and Johnson Pharmaceutical Services, Beerse, Belgium Constipation is a common side effect of opioid therapy. Patient-reported bowel function was examined in post-hoc analyses of the Bowel Movement Questionnaire (BMQ) data from a randomized, double-blind, active- and placebo-controlled, parallel-group efficacy and safety study in which end stage joint disease patients (N = 666) were randomly assigned 1:1:1:1 to receive tapentadol immediate release (IR) 50mg, 75mg, oxycodone IR 10mg, or placebo every 4-6 hours for 10 days. BMQ responses were recorded every evening and consisted of 4 questions assessing 1) presence, 2) consistency, 3) completeness, and 4) straining severity of bowel movements. Tapentadol IR 50mg and 75mg had similar proportions of patient days without a bowel movement (95%CI) as placebo [tapentadol 50mg 11% (7-14%); tapentadol 75mg 10% (7-13%); placebo 8% (5-12%); p>0.05 both comparisons vs. placebo] and all were significantly lower than oxycodone [25% (21-28%), p<0.05 all comparisons vs. oxycodone]. Both tapentadol IR doses also had similar proportions of patient days with incomplete bowel movement (95% CI) as placebo [tapentadol 50mg 20% (14-26%); tapentadol 75mg 23% (17-28%); placebo 25% (18-30%); p>0.05 both comparisons vs. placebo], and significantly fewer days with incomplete bowel movement than oxycodone [36% (31-42%), p<0.05 all comparisons vs. oxycodone]. Tapentadol IR patients were significantly less likely to report symptoms of moderate/severe straining [odds ratios (OR) vs. oxycodone (95% CI): tapentadol 50mg 0.49 (0.32-0.77); tapentadol 75mg 0.53 (0.34-0.82)] and hard stools [ORs vs. oxycodone: tapentadol 50mg 0.37 (0.22-0.62); tapentadol 75mg, 0.47 (0.29-0.76)] than oxycodone patients, while differences between tapentadol IR 50mg and placebo were not significant [ORs vs. placebo: moderate/severe straining, 0.90 (0.58-1.41); hard stools, 0.92 (0.52-1.63)]. Consistent with data from the same study that showed tapentadol IR 50 and 75mg provided comparable analgesia to oxycodone IR 10mg and had lower incidence rates of constipation (Afilalo 2008), tapentadol IR also had less bowel function impairment than oxycodone IR. (Funded by Johnson and Johnson Pharmaceutical Services, L.L.C.)

S43 (273) Effect of duloxetine in patients with fibromyalgia: fatigue subgroups L Bradley, A Chappell, M Wohlreich, R Bennett, I Russell, F Wang, D D’Souza, H Moldofsky, J Hall, H Thompson; Eli Lilly and Company, Indianapolis, IN Up to 90% of patients with fibromyalgia (FM) report moderate to severe fatigue. This study tested the hypothesis that baseline ratings of fatigue would negatively impact the efficacy of duloxetine on measures of pain and functional ability in American College of Rheumatology-defined primary fibromyalgia patients. A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in FM was performed. The Fibromyalgia Impact Questionnaire (FIQ) tiredness item (0-10) was used to define fatigue. Results were stratified into 3 subgroups: mild (0-3), moderate (4-6), and severe (7-10) fatigue. Analysis of covariance models and logistic regressions were used to test treatment-by-fatigue subgroup interactions. Across all studies, 796 patients received duloxetine and 533 patients received placebo for approximately 3 months. At baseline, the distribution of fatigue severity in the duloxetine group was 3.64% mild, 16.71% moderate, 79.65% severe; the distribution in the placebo group was 3.75% mild, 15.57% moderate, and 80.68% severe. The rates of clinically significant ($30% and $50%) improvement in Brief Pain Inventory (BPI) average pain were similar across the 3 fatigue subgroups. Fatigue subgrouping did not negatively impact the effects of duloxetine on the patients’ reports of functional ability using the (a) FIQ total score, FIQ measures of physical impairment, interference with work, pain, stiffness, and depression; and (b) the SF-36 mental and physical component summary scores, bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality. Several double-blind, placebo-controlled studies of duloxetine in FM have demonstrated clinically significant improvements in pain and functional ability (FIQ, SF-36). This post hoc analysis shows that the efficacy of duloxetine is not significantly influenced by baseline ratings of fatigue, as defined by the FIQ tiredness rating. This rejection of our hypothesis was unexpected given the prominence of this symptom in most FM patients. (Funding provided by Eli Lilly and Company and Boehringer Ingelheim.)

(272) Relationships between Patient Global Impression of Change (PGIC) and other efficacy assessments in pregabalin fibromyalgia trials

(274) Identification of fibromyalgia patients who may not be appropriate candidates for duloxetine or pregabalin therapy

L Arnold, B Zeiher, L Pauer, K Murphy, E Whalen; University of Cincinnati College of Medicine, Cincinnati, OH Patient Global Impression of Change (PGIC) is a self-rated, 7-point, evaluative instrument for assessment of overall treatment experience and efficacy of chronic pain treatments. A pooled analysis of 3 randomized, placebo-controlled, pregabalin (PGB) fibromyalgia studies was performed to identify potential correlations between endpoint PGIC response and other assessments including mean pain score (MPS), a Fibromyalgia Impact Questionnaire (FIQ) and a MOS-SS sleep disturbance subscale. In the 3 pooled 13-14 week trials assessed, 2228 patients with moderate to severe pain received either PGB (300, 450, or 600 mg/d) or placebo. PGIC results were consistently positive, suggesting dosedependent improvements for patients scoring "much improved" or ‘‘very much improved’’ (placebo: 29.4%; PGB 300 mg/d: 37.2%; PGB 450 mg/d: 42.6%, and PGB 600 mg/d: 44.4%). PGIC correlated moderately with change in MPS (Spearman correlation coefficients: 0.625 placebo, 0.579 PGB-300mg/d, 0.512 PGB-450mg/d, and 0.522 PGB-600 mg/d) and change in FIQ Total Score, (Spearman correlation coefficients: 0.619 placebo, 0.619 PGB-300mg/d, 0.578 PGB-450mg/d, and 0.588 PGB-600 mg/d). PGIC correlated weakly with change in MOS-SS sleep disturbance subscale (Spearman correlation coefficients: 0.394 placebo, 0.400 PGB300mg/d, 0.399 PGB-450mg/d, and 0.418 PGB-600 mg/d). This analysis of 3 pooled pregabalin studies suggests that patient global assessment of change is correlated with reductions in pain and FIQ total score, and to a lesser extent with reductions in sleep disturbance. The most commonly reported adverse events in these trials were dizziness and somnolence. (This research was supported by Pfizer Inc.)

A Sadosky, A Berger, G Zlateva, G Oster; Pfizer Global Outcomes Research, New York, NY This study assessed the prevalence of comorbidities and/or use of selected medications that may contraindicate the use of duloxetine (DLX) and/or pregabalin (PGB) among patients with fibromyalgia (FM). Using the Pharmetrics Patient-Centric Database, we identified all patients, aged $18 years, with $1 medical claims with an ICD-9-CM diagnosis code of FM (729.1) between 7/1/2004 and ending 6/30/2005, and at least one such claim in each of the 2 preceding 12-month periods. We then assessed the prevalence of comorbidities and medication use that could contraindicate DLX and/or PGB. Comorbidities (DLX: narrow angle glaucoma, hepatic insufficiency, pregnancy, severe renal impairment, hypertension; PGB: severe renal impairment, hemodialysis, angioedema) and medications (DLX: monoamine oxidase inhibitors, serotonergic drugs, inhibitors of CYP1A2 or 2D6, drugs metabolized by CYP2D6, phenothiazines, linezolid; PGB: ACE inhibitors, thiazolidinediones) were designated of concern based product labeling and summary reviews. A comorbidity of interest was established for $2 outpatient claims on different days or any inpatient claims with a relevant ICD-9-CM diagnosis code; medication use was established by any pharmacy claims for the medication. A total of 33,176 patients with FM were identified in the study database; mean (6SD) age was 45.5 610.2 years, and 74.5% were women. In patients taking DLX, 32% had comorbidities and/or used medications that might render DLX use inappropriate–predominantly hypertension (17.2%), prescriptions for CYP1A2 or CYP2D6 inhibitors (13.6%), or for serotonergic drugs (11.5%). The corresponding figure for PGB was 8%– predominantly ACE inhibitor use (5.9%) or pregnancy (1.6%). FM patients were four times as likely to have comorbidities and/or to have used other medications that might render them potentially inappropriate candidates for DLX in comparison with PGB. (Supported by Pfizer Inc.)