Pregabalin in painful diabetic peripheral neuropathy using an NSAID for other pain conditions

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SCIENCE
Pregabalin in painful diabetic peripheral neuropathy using an NSAID for other pain conditions
Key Take-Away: 

Pregabalin shows significant improvement over placebo in reduction of sleep interference associated with Diabetic peripheral neuropathy (DPN) pain.

According to the United States Centers for Disease Control and Prevention, approximately 60% to 70% of people in the United States who have diabetes also have mild to severe forms of comorbid neuropathy; among those who are ≥ 40 years of age, nearly 30% have reported paresthesia in their extremities. Diabetic peripheral neuropathy (DPN) can have several symptoms, including deep lancinating or severe unremitting pain, and can significantly reduce a patient’s quality of life (QoL).

ABSTRACT: 
Background: 

According to the United States Centers for Disease Control and Prevention, approximately 60% to 70% of people in the United States who have diabetes also have mild to severe forms of comorbid neuropathy; among those who are ≥ 40 years of age, nearly 30% have reported paresthesia in their extremities. Diabetic peripheral neuropathy (DPN) can have several symptoms, including deep lancinating or severe unremitting pain, and can significantly reduce a patient’s quality of life (QoL).

Patients with neuropathic pain have been reported to be more likely to use nonsteroidal anti-inflammatory drugs (NSAID) than medications such as pregabalin with proven efficacy for painful DPN. In one study, nearly 50% of patients with painful DPN reported using prescription NSAIDs specifically for their painful DPN. However, current neuropathic pain treatment guidelines either do not recommend or do not address NSAIDs for neuropathic pain. This study was conducted to assess the pain response to pregabalin (up to 300 mg/day) compared with placebo in subjects who were using NSAID primarily for non-DPN pain.

Rationale behind research

  1. Prior studies evaluate nearly 50% of patients with painful DPN reported using prescription NSAIDs but treatment guidelines either do not recommend or do not address NSAIDs for neuropathic pain
  • Objective

To evaluate Pregabalin efficacy and safety versus placebo to reduce pain in subjects with diabetic peripheral neuropathy (DPN) using a concomitant nonsteroidal anti-inflammatory drug (NSAID).

Methods: 

 

Study outcomes

  • Primary outcome: DPN pain score reported using a 11-point NRS (0 = “no pain” and 10 = “worst possible
  • Secondary outcomes: DPN-related sleep interference and adverse events
  • Time-points
  •  Efficacy: Baseline and weekly up to 6 weeks on period 1
  • Adverse Events: Baseline and weekly up to  6weeks on period 1
Results: 

  • Baseline : Subjects 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)
  • Primary outcome:
  • There were no significant difference between pregabalin and placebo at weekly mean DPN pain score. However, one sensitivity analysis (mixed model repeated measures) found greater pain score reductions with pregabalin than placebo at weeks 2-4 and overall (all P < 0.05)
  • Secondary outcome:
  • The reduction of DPN pain interference with sleep was in favor of pregabalin treatment over placebo at weeks 2-6 (all P < 0.05), except week 1 (P = 0.1659)
  • Other sensitivity and secondary analyses were non-significant. Treatment-emergent AEs were consistent with the known safety profile of pregabalin.
Conclusion: 

Pregabalin did not demonstrate a significant reduction in change in DPN pain scores, future research would be required to determine the potential confounding impact of the crossover study design in different chronic pain populations. Pregabalin did, however, show a significant improvement over placebo in reduction of sleep interference associated with DPN pain and its safety results were consistent with its known safety profile.

This study has evaluated the effect of pregabalin vs placebo on DPN pain and DPN pain on walking. A statistically significant difference was found between pregabalin and placebo in Period 1 only (but not in Period 2 or overall). Subjects, who experienced an efficacy response (change in pain scores) to pregabalin in Period 1, continued to respond in Period 2 inspite of being switched to placebo. A similar carryover effect was not observed in subjects who received placebo during Period 1. One could hypothesize that variability in the placebo response during Period 2 could be a confounding factor that could contribute to a carryover effect. In terms of safety, pregabalin was well tolerated. Most adverse events (AEs) were mild or moderate and no treatment-related serious AEs arose. Additional research would be required to determine which dose would have improved the therapeutic response in this population. Another consideration is that a broad use of pregabalin and other DPN treatments over time in this indication may have caused a potentially more refractory study population.

Clin J Pain. 2015 May 8
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