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Objective: Fibromyalgia (FM) is a chronic pain disorder for which pregabalin is an approved treatment in the United States. Although opioids are not a recommended treatment option, they continue to be used by many FM patients. The impact of patients' prior opioid use on their subsequent response to pregabalin has not been assessed., Methods: This was a pooled analysis of 4 clinical trials to assess the efficacy of pregabalin in FM patients both with and without prior opioid use. Patients were divided into those using opioids prior to the trial and those who were not. The change in least squares mean pain score (assessed by 0 to 10 numeric rating scale) with pregabalin compared with placebo was assessed together with FM symptoms, anxiety, and depression., Results: There were 2062 patients in the analysis set, including 371 patients with prior opioid use. Equal numbers of patients were treated with placebo, pregabalin 300 mg/d, and pregabalin 450 mg/d. Pregabalin significantly improved the least squares mean (95% confidence interval) difference in pain score compared with placebo in patients both with and without prior opioid use 0.87 (0.34-1.41) and 0.41 (0.17-0.65), respectively, at 300 mg/d and 0.91 (0.39-1.44) and 0.72 (0.48-0.96) at 450 mg/d (P≤0.001 for all). FM symptoms, anxiety, and depression were also improved with pregabalin compared with placebo, regardless of prior opioid use., Discussion: FM patients respond to treatment with pregabalin with significant improvements in pain scores irrespective of prior opioid use. These data could inform treatment decisions for FM patients with prior use of opioids.

Objectives: To evaluate pregabalin's efficacy and safety versus placebo to reduce pain in patients with diabetic peripheral neuropathy (DPN) using a concomitant nonsteroidal anti-inflammatory drug., Materials and Methods: In a randomized, double-masked, 14-week, 2-period, crossover study, patients with painful DPN using a nonsteroidal anti-inflammatory drug for non-DPN-related pain received 150 to 300 mg/d pregabalin or placebo (period 1); 14-day washout; then, the opposite therapy (period 2). Endpoints included weekly change in DPN pain score, sleep interference, adverse events, and patient-reported outcomes., Results: Patients with similar baseline characteristics were randomized (period 1) to 1 of the 2 following possible sequences: pregabalin→placebo (n=154) or placebo→pregabalin (n=147). Results of the primary efficacy measure, mean weekly DPN pain at endpoint, showed no significant difference between pregabalin and placebo. However, 1 sensitivity analysis (mixed-model repeated measures) found greater pain score reductions with pregabalin than placebo at weeks 2 to 4 and overall (all P<0.05). One secondary endpoint analysis, mean treatment difference in DPN-related sleep interference, favored pregabalin over placebo (P=0.0009). Other sensitivity and secondary analyses were nonsignificant. Treatment-emergent adverse events were consistent with the known safety profile of pregabalin., Discussion: Pregabalin (vs. placebo) showed overall improvements in sleep, pain reduction in 1 sensitivity analysis, and was well tolerated. Potential factors that may have confounded the ability to detect a treatment difference in DPN pain reduction (high placebo response, carryover effect, short washout period, or pregabalin dose) are discussed in the context of future studies.

Objectives: This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking., Methods: Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures., Results: Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients., Discussion: Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

Objectives: This study used a randomized withdrawal design to evaluate the efficacy of pregabalin versus placebo for pain relief in patients with painful diabetic peripheral neuropathy inadequately treated by other therapies., Methods: A total of 665 patients received pregabalin in a 6-week single-blind phase. Two hundred ninety-four patients who achieved a ≥ 30% pain response were randomized to receive pregabalin or placebo in a double-blind phase for a further 13 weeks. The primary endpoint was the change in mean pain score from single-blind baseline to double-blind endpoint for pregabalin versus placebo (last observation carried forward [LOCF]). Secondary endpoints included a baseline observation carried forward (BOCF) analysis of mean pain score; time to loss of pain response; and other assessments of pain, sleep, function, and quality of life (QOL)., Results: Pregabalin numerically improved all measures assessed during the single-blind phase. At the end of the double-blind withdrawal phase, there was no significant difference in the primary endpoint of mean pain score (LOCF) between pregabalin and placebo (least squares mean difference, -0.32), although there was a significant difference in the BOCF analysis (least squares mean difference, -0.51). Pregabalin was associated with a significantly longer time to loss of pain response versus placebo during double-blind treatment, and some aspects of sleep and QOL also showed significant improvements with pregabalin., Discussion: This is the first reported placebo-controlled trial of pregabalin in patients with inadequately treated painful diabetic peripheral neuropathy. Although the primary endpoint was not met, pregabalin was associated with clinically relevant improvements versus placebo in this difficult-to-treat population.

Objective: To determine the incidence and duration of response of clinically meaningful improvements with pregabalin across several key symptoms of fibromyalgia (FM)., Methods: This was a post hoc analysis of data from a multicenter, double-blind, placebo-controlled, randomized, withdrawal study, originally designed to evaluate the efficacy of pregabalin monotherapy for durability of effect on FM pain based on pain and Patient Global Impression of Change (PGIC) criteria. Responder criteria for Fibromyalgia Impact Questionnaire total score (≥16-point change), Medical Outcomes Study Sleep Scale Sleep Disturbance subscale (≥15.8-point change), and the 36-item Short-Form Health Survey Vitality scale (≥10-point change) were used to evaluate the incidence and duration of improvements in function, sleep, and fatigue for pregabalin versus placebo among pain and PGIC responders. A composite responder index consisting of pain, PGIC, function, and sleep endpoints was used to explore multidimensional response., Results: Approximately 80% of patients meeting pain and PGIC improvement criteria at randomization had clinically meaningful improvement in fatigue, sleep, or function. Higher proportions of patients in the pregabalin group maintained a clinically meaningful response, and pregabalin-treated patients had a significantly longer time to loss of therapeutic response compared with the placebo group. Composite responder Kaplan-Meier analysis, performed with patients demonstrating clinically meaningful improvements in pain, PGIC, function, and sleep at randomization showed a significantly longer median time to loss of therapeutic response for pregabalin-treated patients., Discussion: The results from this post hoc analysis indicate that pregabalin provides long-term effects across multiple domains of FM (ClinicalTrials.gov registry ID: NCT00151489).