Does Duration of Neuropathic Pain Impact the Effectiveness of Pregabalin?

BACKGROUND: Patients with chronic pain conditions such as neuropathic pain frequently experience delays in diagnosis and treatment. Ideally, all patients should be treated in a timely manner, but in those patients with more established disease it is important to know that approved treatments remain effective. METHODS: This was a pooled analysis of 19 randomized placebo-controlled trials of pregabalin for peripheral neuropathic pain conditions, including diabetic peripheral neuropathy, postherpetic neuralgia, and post-traumatic/postsurgical pain. Patients were divided into 5 pain duration categories based on time since onset of pain (< 6 months, 6 months to < 1 year, 1 year to < 2 years, 2 years to < 5 years, and ≥ 5 years). Mean change in pain score at endpoint, vs. placebo, was assessed for each category, together with changes in Patient Global Impression of Change (PGIC) responders ("very much" or "much" improved at endpoint). RESULTS: The analysis included 5,783 patients (n = 3,619 pregabalin; n = 2,164 placebo). Mean baseline pain scores were similar across the pain duration categories (range 6.3 to 6.5). Pregabalin significantly improved pain score at endpoint, vs. placebo, in all patients together (treatment difference [95% confidence interval], -0.59 [-0.67, -0.52], P < 0.0001) and similarly in each pain duration category (P < 0.0001 for each). There were significantly more PGIC responders with pregabalin, vs. placebo, for all patients (45.0% vs. 30.9%, P < 0.0001) and each category separately (P < 0.001 for each). There were no consistent, significant differences in treatment response between the different pain duration categories. CONCLUSIONS: Pregabalin significantly improves pain irrespective of the length of time since onset of neuropathic pain.

Pregabalin Improves Pain Scores in Patients with Fibromyalgia Irrespective of Comorbid Osteoarthritis.

OBJECTIVE: Fibromyalgia (FM) is a chronic pain disorder with patients frequently suffering from comorbid conditions, including osteoarthritis (OA). Data on how FM patients with comorbid OA respond to recommended therapies (such as pregabalin) could help their treatment. DESIGN: This was a pooled exploratory analysis of three randomized placebo-controlled clinical trials of pregabalin in FM patients to assess the impact of comorbid OA on the response to pregabalin. METHODS: Patients were divided into those with and without comorbid OA. Difference in change in least squares (LS) mean pain score at endpoint (assessed by 0-10 numeric rating scale, controlled for baseline pain score) with pregabalin (300 mg/day and 450 mg/day) vs placebo was assessed. Changes in Patient Global Impression of Change (PGIC) responders and Fibromyalgia Impact Questionnaire (FIQ) total score were also assessed. RESULTS: There were 1665 patients in the analysis set (558, placebo; 552, pregabalin 300 mg/day; 555, pregabalin 450 mg/day), including 296 with comorbid OA. Pregabalin 450 mg/day significantly improved the LS mean (95% confidence interval) difference in pain score vs placebo in patients with (0.99 [0.44, 1.55], P < 0.001), and without (0.64 [0.39, 0.89], P < 0.001) OA. Improvements with pregabalin 300 mg/day with (0.31 [-0.25, 0.86], P = 0.276) and without (0.51 [0.25, 0.76], P < 0.001) OA were not consistently significant. Improvements in PGIC and FIQ total score were observed in patients with and without comorbid OA. CONCLUSIONS: FM patients with or without comorbid OA respond to treatment with pregabalin 450mg/day with significant improvements in pain intensity scores. These data could provide guidance to healthcare professionals treating these patients.

The efficacy of pregabalin for the treatment of neuropathic pain in Japanese subjects with moderate or severe baseline pain.

PURPOSE: Although analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP. PATIENTS AND METHODS: Data were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13-16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day. RESULTS: Mean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pregabalin vs placebo (P<0.05). Higher proportions of pregabalin-treated vs placebo-treated subjects shifted to a less severe pain category at endpoint. Consistent with the known safety profile of pregabalin, common adverse events included dizziness, somnolence, weight gain, and peripheral edema. CONCLUSION: Pregabalin demonstrated efficacy for pain relief and sleep improvement with a consistent safety profile in Japanese subjects with either moderate or severe baseline pain severity. CLINICALTRIALSGOV IDENTIFIERS: NCT0039490130, NCT0055347522, NCT0040774524.

The relationship between the reporting of euphoria events and early treatment responses to pregabalin: an exploratory post-hoc analysis.

BACKGROUND: Euphoria is a complex, multifactorial problem that is reported as an adverse event in clinical trials of analgesics including pregabalin. The relationship between the reporting of euphoria events and pregabalin early treatment responses was examined in this exploratory post-hoc analysis. METHODS: Data were from patients with neuropathic or non-neuropathic chronic pain enrolled in 40 randomized clinical trials, who received pregabalin (75-600 mg/day) or placebo. Reports of treatment-emergent euphoria events were based on the Medical Dictionary of Regulatory Activities preferred term "euphoric mood". Prevalence rates of euphoria events overall and by indication were assessed. Post-treatment endpoints included ≥30% improvements in pain and sleep scores up to 3 weeks as well as a ≥1-point improvement in daily pain score up to 11 days after treatment. RESULTS: 13,252 patients were analyzed; 8,501 (64.1%) and 4,751 (35.9%) received pregabalin and placebo, respectively. Overall, 1.7% (n=222) of patients reported euphoria events. Among pregabalin-treated patients, a larger proportion who reported euphoria events achieved an early pain response compared with those who did not report euphoria (30% pain responders in week 1 with euphoria events [43.0%], without euphoria events [24.2%]). Results were similar for weeks 2 and 3. For Days 2-11, a larger proportion of pregabalin-treated patients with (relative to without) euphoria events were 1-point pain responders. Findings were similar in pregabalin-treated patients for sleep endpoints (30% sleep responders in week 1 with euphoria events [50.7%], without euphoria events [36.1%]). Similar results were found for weeks 2 and 3. Patients who received placebo showed similar patterns, although the overall number of them who reported euphoria events was small (n=13). CONCLUSION: In patients who received pregabalin for neuropathic or non-neuropathic chronic pain, those who experienced euphoria events may have better early treatment responses than those who did not report euphoria events.

Comparison of the efficacy and safety of pregabalin for postherpetic neuralgia in Chinese and international patients.

PURPOSE: Pregabalin is indicated for postherpetic neuralgia (PHN) in multiple countries, including China. This analysis compared pregabalin efficacy and safety in Chinese and international patients with PHN. PATIENTS AND METHODS: Data from Chinese and international randomized, double-blind, placebo-controlled trials were compared. Pregabalin was administered at fixed (150, 300, or 600 mg/day) or flexible (150-600 mg/day) doses. The main efficacy measure was mean pain score change at endpoint on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. Secondary efficacy measures included proportions of 30% and 50% pain responders, pain-related sleep interference (PRSI) scores, and proportions of Patient Global Impression of Change (PGIC) responders. The incidences of serious adverse events (SAEs) and adverse events (AEs) were used to assess safety. The effect of baseline pain severity on efficacy was tested. The proportions of patients with severe baseline pain who had moderate or mild pain at endpoint were also assessed. RESULTS: A total of 1166 patients were analyzed: 312 Chinese and 854 international. Overall, results were similar between Chinese and international patients. Pregabalin statistically significantly improved mean pain score versus placebo (least squares mean difference [95% CIs]: Chinese, -0.8 [-1.2, -0.5]; international, -1.3 [-1.6, -1.0]; both p<0.001). Pregabalin was statistically significantly better than placebo in Chinese and international patient groups in the proportions of 30% and 50% pain responders, PRSI scores, and proportions of PGIC responders. Baseline pain severity did not affect efficacy, except for some measures in Chinese patients with moderate baseline pain. Similar proportions of pregabalin-treated patients with severe baseline pain had moderate or mild pain at endpoint in both groups. SAE and AE profiles were comparable in Chinese and international patient groups, except incidences were commonly higher in international patients. CONCLUSION: Chinese and international patients with PHN exhibit comparable pregabalin efficacy and safety, highlighting the utility of pregabalin for diverse PHN patient populations.

Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials.

BACKGROUND: Pregabalin is an effective treatment option for many patients with neuropathic pain. Higher doses of pregabalin have been shown to be more effective in improving pain outcomes but, in practice, failing to appropriately increase the dose can leave patients under-treated. METHODS: This was a pooled analysis of 6 flexible-dose clinical trials of pregabalin in patients with neuropathic pain (diabetic peripheral neuropathy, peripheral herpetic neuralgia, posttraumatic pain, or postsurgical pain). Patients were divided into "dose pathway" groups based on their weekly pregabalin dose from the start of their trial to the first week of their maintenance phase. These were: 150 mg/day only; 150 to 300 mg/day; 150 to 300 to 450 mg/day; 150 to 300 to 450 to 600 mg/day; 150 to 300 to 600 mg/day; 300 to 600 mg/day. Pain outcomes assessed for each group at each new dose were proportion of 30% and 50% responders (≥30% or ≥50% reduction in mean pain score from baseline) and mean change in pain score. Percent change in mean pain score from baseline was assessed using a marginal structural model. RESULTS: Seven hundred and sixty-one patients treated with flexible-dose pregabalin were included in the analysis. For each dose pathway group, there was a notably greater proportion of 30% and 50% responders and change in pain score, at each escalating dose. As assessed by the marginal structural model, higher doses of pregabalin were estimated to result in a significantly greater change in mean pain score at each week. This dose response with flexible-dose pregabalin was consistent with that previously observed with fixed-dose pregabalin. CONCLUSION: Many patients who do not respond to lower doses of pregabalin will respond with notable improvements in pain outcomes when the dose is escalated. These data should encourage physicians treating patients with neuropathic pain to escalate pregabalin to the dose that delivers optimal analgesia and tolerable side effects.

Prior Opioid Use Does Not Impact the Response to Pregabalin in Patients With Fibromyalgia.

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.