396) Pregabalin is effective irrespective of antidepressant class in fibromyalgia patients currently receiving antidepressant medication for comorbid depression

s The Journal of Pain S75 (396) Pregabalin is effective irrespective of antidepressant class in fibromyalgia patients currently receiving antidepressant medication for comorbid depression L Arnold, P Sarzi-Puttini, P Arsenault, T Khan, P Bhadra Brown, A Clair, J Driscoll, J Landen, and L Pauer; University of Cincinnati College of Medicine, Cincinnati, OH In a 2-way crossover, double-blind, placebo-controlled trial in patients with fibromyalgia (FM) and comorbid depression receiving antidepressant medication, pregabalin significantly reduced mean pain score (0–10 NRS) vs. placebo (LS mean difference [95% CI], -0.61 [-0.91,-0.31]; P=0.0001). However, pregabalin efficacy by antidepressant class has not been evaluated to date. Treatment comprised two 6-week periods; 197 patients were randomized 1:1 to pregabalin/placebo or placebo/pregabalin twice-daily (300 or 450mg/d). Patients received a single, stable antidepressant medication (SSRI or SNRI) for $2 months prior to randomization and throughout the study. 181 patients received $1 dose of pregabalin, and 177 placebo. At baseline, the mean (range) time since depression diagnosis was 12.3 (0.3–45.8) years and mean (SD) Hospital Anxiety and Depression – Depression (HADS-D) score was 8.0 (3.6). 84 (43.5%) patients had major depressive disorder, 101 (52.3%) depression not otherwise specified, and 8 (4.2%) dysthymia. 101 (52.3%) patients were receiving an SSRI and 92 (47.7%) an SNRI for their depression; the most common antidepressants were duloxetine (31.6%), citalopram (16.6%) and venlafaxine (13.5%). Mean (SD) pain scores at baseline were similar in those receiving an SSRI (pregabalin: 6.55 [1.14]; placebo: 6.79 [1.21]) or an SNRI (pregabalin: 6.87 [1.23]; placebo: 6.75 [1.41]). At endpoint, mean (SE) pain scores were significantly lower in pregabalinvs. placebo-treated patients irrespective of antidepressant class (SSRI: 4.63 [0.21] vs. 5.12 [0.21], P=0.0211; SNRI: 5.08 [0.22] vs. 5.84 [0.22], P=0.0012). Treatment difference appeared greater for patients receiving an SNRI (-0.76 [-1.21,-0.31]) vs. an SSRI (-0.48 [-0.89,-0.07]), and those receiving an SSRI had significantly lower endpointmean pain scores (4.88 vs. 5.45; P=0.0359). The safety profile in the overall population was consistent with previous studies. Irrespective of antidepressant class, pregabalin significantly improved mean pain score in FM patients with depression receiving antidepressant medication. This study was funded by Pfizer Inc. (397) Improvement in pain severity category following treatment with pregabalin in patients with fibromyalgia C Argoff, A Clair, and B Emir; Pfizer Inc, New York, NY Pregabalin is FDA-approved for the treatment of fibromyalgia, a complex, chronic pain condition. To further characterize the clinical benefit of pregabalin, this analysis examined shifts in pain intensity severity categories with pregabalin among patients with fibromyalgia. Data were pooled from 5 placebo-controlled trials of pregabalin for fibromyalgia (protocols 1008-105, A0081056, A0081077, A0081100, A0081208) encompassing 937 placebotreated patients and 1623 patients treated with either fixed(300 mg/d or 450 mg/d) or flexible-dose (300-450 mg/d) pregabalin. Pain intensity scores on an 11-point numeric rating scale were classified as mild (0 to <4), moderate (4 to <7) or severe ($7 to 10) and patients with moderate-to-severe pain intensity (average score$4 at baseline)were randomized to treatment. The percentage of patients shifting from moderate or severe pain intensity at baseline to mild, moderate or severe pain intensity at endpoint (baseline observation carried forward) was calculated for pregabalin and placebo. Shifts in pain intensity scores were analyzed using a modified ridit transformation with the Cochran-Mantel-Haenszel procedure. A significantly higher proportion of patients treated with pregabalin shifted to a less severe pain category (baseline to endpoint) compared with placebo (p=0.0001). The percentage of patients improving by 1 pain category (severe-to-moderate or moderate-to-mild) was 30.2% for pregabalin and 27.2% for placebo. An improvement of 2 pain categories (severe-to-mild) was seen for 9.5% of pregabalin-treated and 6.1% of placebo-treated patients. In total, 56.7% (pregabalin) and 61.1% (placebo) of patients did not shift pain categories and 3.6% (pregabalin) and 5.5% (placebo) of patients shifted to a more severe pain category. Combined, more patients shifted to improved pain categories when treated with pregabalin compared with placebo. Overall, these data suggest that relative to placebo, treatment with pregabalin is more often associated with clinically meaningful improvements in pain intensity in patients with fibromyalgia. Sponsored by Pfizer Inc. (398) Potential drug-drug interactions and opioid use among Medicarememberswith fibromyalgia and newly initiated on pregabalin or duloxetine A Sadosky, J Ellis, L Ten Eyck, J Cappelleri, B Parsons, P Mudumby, C Brown, and B Suehs; Comprehensive Health Insights, Louisville, KY This study examined the prevalence of potential drug-drug interactions (pDDIs), the impact of pDDIs on healthcare utilization and costs, and post-index use of opioid analgesics among fibromyalgia (FM) Medicare members newly initiated on pregabalin (PGB) or duloxetine (DLX). Members included those with a PGB or DLX prescription claim between 07/01/2008-06/30/2012 (index event), $1 inpatient or $2 outpatient medical claims with FM diagnosis between 01/01/2008-12/31/2012, and $12 months pre-index and $6 post-index enrollment. Propensity score matching (nearest neighbor approach) was used to help balance the PGB and DLX cohorts on baseline demographic and comorbidity characteristics. pDDIs were defined based onMicromedex 2.0 software and were identified by prescription claims. Six month post-index healthcare utilization and costs were measured by medical and pharmacy claims. Continuous and categorical comparisons were conducted using Wilcoxon rank sum tests and chi-square tests, respectively. No significant differences in baseline demographics or comorbidities were found between matched PGB (n=794) and DLX members (n=794). pDDI prevalence was significantly greater (p<0.0001) among DLX members (71.9%) than among PGB members (4.0%). Therewere no significant differences in all-cause healthcare utilization or costs between PGB members with and without a pDDI. By contrast, DLX members with a pDDI had higher median all-cause costs ($4,719 versus $3,519; p<0.0001) and median number of outpatient visits/member (14.0 versus 12.0; p=0.0009) in comparison to DLX members without a pDDI. Over 12% of potential DLX interactions involved anticoagulants (n=268). There was a trend toward a difference between PGB and DLX members in their respective preversus-post differences in use of long-acting opioids (1.6% and 3.4%, respectively; p=0.077). The significantly higher prevalence of pDDIs and potential cost impact found in FM DLX users, relative to PGB, underscore the importance of considering DDIs when selecting a treatment. This study was funded by Pfizer Inc and Humana Inc. (399) Emergence of new responders to treatment and new adverse events in clinical trials of pregabalin in patients with neuropathic pain due to spinal cord injury B Parsons and B Emir; Pfizer Inc, New York, NY Patients with spinal cord injury (SCI) commonly experience chronic neuropathic pain for which pregabalin is currently the only FDA-approved treatment. A greater understanding of when these patients first respond to treatment and when adverse events (AEs) emerge or worsen could aid design of new proofof-concept studies and help guide treatment of patients. This was a pooled analysis of two 12and 16-week, randomized, placebo-controlled, doubleblind trials of pregabalin (150-600mg/day) in SCI patients with neuropathic pain (n=356). New responders were classified as having a 30% and/or 50% reduction in mean pain score from baseline; once a patient responded they were not scored subsequently (and were then excluded from the responder analysis). Most responders emerged within the first 3 weeks with pregabalin, but were more uniformly distributed with placebo. Proportion of 30% responders by week (from week 1 to 6) was 19.0%, 16.3%, 21.1%, 12.8%, 12.5%, 4.8% with pregabalin, and 6.9%, 10.2%, 6.5%, 9.1%, 1.9%, 6.0% with placebo. Proportion of 50% responders by week was 8.6%, 5.7%, 6.9%, 6.9%, 5.9%, 2.8% with pregabalin, and 0.6%, 3.6%, 2.5%, 2.1%, 3.7%, 3.9% with placebo. Somnolence, dizziness, dry mouth and fatigue were the most common AEs (incidence of 35.7%, 20.9%, 11.0% and 11.0%, respectively). These AEs were recorded weekly for the first 6 weeks; a new AE was scored when it first appeared, and also if it increased in severity. Incidencewith pregabalin by week was: somnolence, 18.7%, 7.3%, 6.9%, 4.7%, 1.8%, 0.6%; dizziness, 11.0%, 3.4%, 2.3%, 3.6%, 1.2%, 0.0%; dry mouth, 2.8%, 2.8%, 1.7%, 1.8%, 0.6%, 0.6%; fatigue, 5.0%, 3.4%, 0.6%, 3.0%, 1.2%, 0.6%. These data suggest that the majority of new responders and AEs appear within 3 weeks of pregabalin initiation. These findings could advise the design of new proof-of-concept studies and guide clinical management. Sponsor: Pfizer Inc. F14 Novel Therapeutic Agents.