P-023 - An evaluation of effectiveness with HCCTS across RCT vs RWE data for one year treating painful diabetic peripheral neuropathy

Abstract Title: An evaluation of effectiveness with HCCTS across RCT vs RWE data for one year treating painful diabetic peripheral neuropathy


Background: Positive evidence from double-blind, randomized controlled trials (RCT) is a standard requirement for the approval of new medical therapies. Such trials provide reliable evidence of efficacy and safety for a given treatment, but often raise concerns about how well the results generalize to clinical practice¹. Additionally, especially when long-term treatment effects (≥12 weeks) are investigated, it is difficult to conduct double-blind trials.

The PACE study was an open-label, Phase III, randomized, 3-arm, multinational clinical trial, designed to assess the long-term (1-year) effects of repeat administration of high concentration capsaicin (8%) topical system (HCCTS) plus standard of care (SOC) vs. SOC alone in patients with painful diabetic peripheral neuropathy (pDPN)^2,3. Although this RCT suggested that repeated application of HCCTS is associated with sustained efficacy and safety in addition to improvements in quality of life, the question of generalizability remains.

A real-world evidence (RWE) study (CASPAR) was conducted to assess the effect of ongoing treatment with HCCTS in clinical practice. This was a non-interventional, retrospective cohort study using anonymized routine medical care data from the German Pain eRegistry of patients with pDPN for 12 months, up to 4 treatments, following index treatment. The results represent real-world experience with HCCTS in clinical practice⁴.

Purpose/Objectives: The presented analysis is part of a larger study with the goal to correlate responder rates to baseline characteristics in patients with peripheral neuropathic pain treated with HCCTS.

The current data compares the following results for treatment with HCCTS for pDPN between the PACE (RCT) and CASPAR (RWE) studies:

• Pain intensity


• Responder rate


• Pain related sleep disturbance

The analysis provides a side-by-side comparison of the reported results from treatment with HCCTS for one year via a RCT (PACE) vs. RWE (CASPAR) to assess generalizability.


Methods: In CASPAR and PACE, assessments were captured to measure pain intensity, responder rate and sleep disturbances with repeated applications of HCCTS. A comparison between outcomes from both studies assess if results from the RCT (PACE) can be applied to clinical practice via analysis of the RWE (CASPAR).


Results: Both studies included patients with pDPN with similar demographic characteristics [mean (SD)] of age [60.4 (10.5); 66.1 (13.3) years], BMI [30.44, (4.8); 31.5 (7.2)], duration of pDPN [4.3 years (3.72); 4.6 (3.6)] in PACE and CASPAR respectively. The average daily pain intensity mean (SD) at baseline was 56.0 (1.32) BPI-DN, and 61.4 (18.5) VAS, in PACE and CASPAR respectively. Pain intensity reduced to 36.0 (18.4) and 8.8 (6.4) in PACE and CASPAR respectively after one year, resulting in a 35.7% and 85.7% reduction.

The responder rate, defined as a ≥ 30% pain reduction in average daily pain increased to 77.1% (PACE) and 100% (CASPAR) at 12 months. A decrease in pain-related sleep disturbance was observed over time in both PACE and CASPAR. Sleep disturbance decreased from 56.0 (24.3) to 35.0 (24.3) and 64.6 (24.2) to 10.1 (8.0) resulting in 37.5% and 84.4% reduction at 12 months, in PACE and CASPAR respectively. In both studies, the tolerability profile was similarly characterized with mostly application site reactions.

Conclusions/Implications for future research and/or clinical care: In a population with overall similar baseline characteristics in both PACE (RCT) and CASPAR (RWE), similar trends regarding effectiveness were observed after one year of HCCTS treatment for pDPN. In both studies a decrease was observed in average pain intensity, increasing responder rates with successive treatments and overall improvements in sleep. The magnitude of the changes was larger in CASPAR compared to PACE. This might be reflective both of how RWE more easily generalizes to clinical practice and how RCTs are restrictive with multiple inclusion criteria. Although RWE may be more generalizable, the analysis is restricted due to lack of control group for comparison. In both studies HCCTS was well tolerated. The benefit of ongoing treatments with HCCTS established in an RCT has been confirmed in clinical practice with data from this RWE study.


References:

1. Flather M, Delahunty N, Collinson J. Generalizing results of randomized trials to clinical practice: reliability and cautions. Clinical Trials. 2006;3(6):508-512.


2. 2. Vinik AI, et al. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomized, 52-week, open-label, safety study. BMC Neurol. 2016 Dec 6;16(1):251.


3. Vinik AI, et al. Repeat treatment with capsaicin 8% patch (179mg capsaicin cutaneous patch): Effects on pain, quality of life, and patient satisfaction in painful diabetic peripheral neuropathy: an open-label, randomized controlled clinical trial. J Curr Med Res Opin. 2019;2:388-401.


4. CASPAR German Pain eRegistry Study. Data on file.