Efficacy and safety of Capsaicin 8% patch in painful diabetic peripheral neuropathy: a double-blind, randomized placebo-controlled study

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Efficacy and safety of Capsaicin 8% patch in painful diabetic peripheral neuropathy: a double-blind, randomized placebo-controlled study
Key Take-Away: 

This study showed that Capsaicin 8% patch provides modest and statistically significant improvements in pain relief and sleep quality compared with a placebo patch in patients with painful diabetic peripheral neuropathy (PDPN). 

A devastating condition that has shown to affect approximately one-quarter of patients with type 2 diabetes mellitus is PDPN. There is lack of data regarding the optimal management of PDPN which has led to variable clinical control with antidepressants, anticonvulsants, or opioid medications. These medications have side effects and are also discontinued due to significant adverse effects, lengthy dose titration, drug-drug interactions, the need for frequent, repeat administration, and the risk of addiction, abuse, and withdrawal symptoms. 

ABSTRACT: 
Background: 

A devastating condition that has shown to affect approximately one-quarter of patients with type 2 diabetes mellitus is PDPN. There is lack of data regarding the optimal management of PDPN which has led to variable clinical control with antidepressants, anticonvulsants, or opioid medications. These medications have side effects and are also discontinued due to significant adverse effects, lengthy dose titration, drug-drug interactions, the need for frequent, repeat administration, and the risk of addiction, abuse, and withdrawal symptoms.

Recent studies have suggested Capsaicin 8% patch as a second-line option. Capsaicin is a potent, highly selective vanilloid receptor subtype one agonist that causes depolarization of the neuron. The Capsaicin 8% patch is enhanced for fast delivery of a high concentration of Capsaicin directly to the skin. The advantage of minimal systemic absorption reduces the possibility for drug-drug interactions, removes the requirement for dose adjustment in the old patients or patients with kidney or liver problem, and diminishes the risk of systemic AEs. The ELEVATE study explained that treatment with Capsaicin 8% patch provided better pain relief with a quick onset of action, less systemic side effects, and higher patient satisfaction as compared to pregabalin in nondiabetic patients with PNP.

Rationale behind research

  • The effectiveness and safety of the Capsaicin 8% patch in patients with PDPN has not been fully explained.
  • The present study was the first to assess the efficacy and safety of the Capsaicin 8% patch versus placebo in this population.

Objective

To assess the effectiveness and safety of Capsaicin 8% patch versus placebo patch in PDPN.

Methods: 

Note: This was a placebo-controlled, multicenter trial

Study outcomes

  • Primary outcomes: The primary efficacy endpoint was the percentage change in the numeric pain rating scale (NPRS) average daily pain score. The score was evaluated over the previous 24 hours according to question 5 of the Brief Pain Inventory (BPI)-Diabetic Neuropathy (BPI-DN) from baseline to the mean score over weeks 2 through 8.
  • Secondary outcomes: Secondary efficacy endpoints were:
  • Percentage change in NPRS average daily pain score (question 5 of the BPI-DN) from baseline to the mean score over weeks 2 through 12
  • Percentage change and mean change in average daily pain scores each week throughout the study to week 12
  • Occurrence of  ≥30% and ≥50% decrease in average daily pain score from baseline compared with the mean score over weeks 2 through 8 and 2 through 12
  • Percentage change in sleep interference NPRS score from baseline compared with the mean score over weeks 2 through 8 and 2 through 12
  • Percentage change in sleep interference according to the NPRS score each week
  • Time to treatment response, defined as the first of 3 consecutive days on which the patient reported ≥30% decrease in average daily pain score from baseline
  • Overall patient status using Patient Global Impression of Change at weeks 2, 8, and 12
  • Treatment satisfaction using the Self-Assessment of Treatment II questionnaire at baseline, weeks 8 and 12
  • Change in EuroQol in 5 dimensions from baseline to weeks 2, 8 and 12.
  • Time Points: Baseline and week 2, 8 and 12
Results: 

 

Outcomes

Baseline characteristics: There were no notable differences in the baseline characteristics amongst the study groups.

Primary Outcomes:

Average Daily Pain (between weeks 2 through 8): There was a modest and statistically significant reduction in average daily pain from baseline to between weeks 2 through 8 in the Capsaicin 8% patch group versus placebo patch (-27.4% vs. -20.9%).

Figure1: Mean percentage change in average daily pain from baseline to between weeks 2 through 8

Secondary Outcomes:

  • Average Daily Pain (between weeks 2 through 12): Analysis of change in average daily pain score from baseline to between weeks 2 through 12 showed that this reduction in average daily pain was maintained (-28.0% vs. -21.0%).

Figure 2: Mean percentage change in average daily pain from baseline to between weeks 2 through 12

  • Both groups achieved at least a 30% reduction in average daily pain score from baseline to between weeks 2 through 8 (Capsaicin 8% patch, 39.8%; placebo, 32.8%). Analysis between weeks 2 through 12 indicated that more patients were responders in the Capsaicin 8% patch group during this period (40.9% vs. 31.7%). Similar proportions of patients in both groups achieved at least a 50% reduction in average daily pain score from baseline to weeks 2 through 8 (21.0% vs. 18.0%) and weeks 2 through 12 (22.0% vs. 19.1%)
  • The median time to treatment response was shorter with the Capsaicin 8% patch versus placebo patch, with 50% of patients achieving at least a 30% reduction in average daily pain after 19 days in the Capsaicin 8% patch group versus 72 days in the placebo group
  • A greater mean percentage reduction in BPI-DN sleep interference NPRS score was seen in the Capsaicin 8% patch group versus the placebo patch group from baseline to between weeks 2 through 8 and weeks 2 through 12
  • Numerically more patients in the Capsaicin 8% patch group reported being ‘‘very much improved’’ or ‘‘much improved’’ in Patient Global Impression of Change status compared with placebo at week 8 (39.4% vs 30.2%) and week 12 (40.5% vs. 29.7%;).
  • No prominent differences observed at any time point for the change from baseline in EuroQol in 5 Dimensions total score.

Adverse events: Apart from application site reactions, treatment-emergent adverse events were similar between groups. 

Conclusion: 

This study reported that the Capsaicin 8% patch provided moderate and statistically significant improvements in pain relief and improved sleep quality as compared to placebo patch in patients with PDPN. These findings are of similar magnitude to the effects of other treatments with known efficacy in neuropathic pain.

Percentage change in average daily pain from baseline to between weeks 2 through 8 which is the primary endpoint of the current study, has not been previously evaluated. Results from ELEVATE study showed superior efficacy of Capsaicin 8% over pregabalin in providing pain relief in non-diabetic patients with PNP. The study also described that the Capsaicin 8% patch was linked with a faster onset of action, higher patient satisfaction with treatment, and fewer systemic side effects, replicating the safety profile seen in this and previous studies with the Capsaicin 8% patch.

The overall results of this study suggest that the effectiveness of Capsaicin 8% patch is similar to that of other drugs for neuropathic pain, but with a lack of systemic AEs, and that is the reason it should be considered for a place in treatment of PDNP.

The Journal of Pain, Vol 18, No 1 (January), 2017: pp 42-53
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