Burning for relief: long-term real-world outcomes of high-concentration capsaicin patches in painful diabetic neuropathy (CASPAR study)

Aims: To assess the long-term effectiveness and tolerability of repeated applications of high-concentration capsaicin patches (HCCP, 8%) in patients with painful diabetic peripheral neuropathy (pDPN) under real-world conditions.

Methods: In this retrospective cohort study utilizing data from the German Pain e-Registry, 826 adults with pDPN who received at least one HCCP application and had follow-up of 12 months or more were included. Outcomes were analyzed descriptively and included pain intensity (24-h average pain intensity [API] [VAS, 0–100 mm]), duration of analgesic effect (time to re-treatment), adverse events, and treatment persistence. No control group was included. Patients were stratified according to the number of patch treatments (one to four applications).

Results: Significant pain reduction was observed within the first three months (mean API 57.5 → 42.4 mm VAS, corresponding to a 26% decrease). Progressive benefits were seen with successive treatments: patients receiving four patches reported a mean API decrease from 59.0 to 16.0 mm (−43 mm, p<0.001) from baseline to Month 12. By Month 12, a ≥30% pain reduction was achieved in 98.9% of those receiving four patches, 90.8% with three, 67.7% with two, and 22% with one. Importantly, pain intensity gradually returned toward baseline once treatment was discontinued, confirming the reversible nature of the effect. Treatment was generally well tolerated, with mostly mild local reactions (erythema, burning) and no new safety concerns. Moreover, by Month 12, 28.7% of patients receiving four HCCP treatments had discontinued all concomitant pain medications.

Conclusions: Repeated application of HCCP is well-tolerated and effective for long-term management of pDPN in routine practice. These real-world findings suggest that topical capsaicin can provide lasting pain relief without systemic toxicity, especially when oral medications are not tolerated.

Comments. This large real-world dataset offers valuable evidence supporting topical capsaicin for pDPN. Strengths include a large cohort (n=826), extended follow-up (≥12 months), and data from a registry reflecting everyday clinical practice. However, the retrospective, non-randomized design limits causal conclusions and introduces potential selection bias. Key factors such as glycemic control, concomitant medications, or comorbidities were not systematically controlled for. Additionally, the absence of a comparator group prevents direct comparison of efficacy with standard pharmacologic therapies. Despite these limitations, the sustained effect and favorable safety profile are encouraging. The magnitude of pain reduction — over 70% after 12 months in those with four applications — and the clear decline after discontinuation strongly support a treatment-dependent effect. HCCP comprises a patented matrix technology that allows high concentrations of capsaicin to enter the epidermis and activate transient receptor potential vanilloid 1 (TRPV1) receptors on sensory nerve fibers. Exposure to high concentrations of capsaicin leads to reversible desensitization of these fibers involved in neuropathic pain, leading to subsequent pain relief. Interestingly, HCCP may also have disease-modifying effects, with the regeneration of TRPV1-expressing nerve fiber terminals and subsequent restoration of nerve function 1–3 months after a single treatment. However, as diabetes is a chronic condition that continually injures nerve fibers, repeated HCCP treatments are required. Future randomized controlled trials should determine the extent of benefit, identify predictors of response, and evaluate functional outcomes and quality of life. In summary, this study shows that long-term, repeated use of HCCP can maintain pain relief and good tolerability in patients with pDPN. It highlights the role of topical therapy as a useful part of multimodal pain management.

Aleksandra Araszkiewicz

Reference. Überall MA, Kender Z, Quandel T, Engelen S, Guerra LG, Fajri T, Allen SM, Freitas RL, Eerdekens MH. Progressive improvements in patient-reported outcomes with the high-concentration capsaicin patch: A retrospective cohort study in patients with painful diabetic peripheral neuropathy (CASPAR study). J Diabetes Complications. 2025 Sep;39(9):109085. doi: 10.1016/j.jdiacomp.2025.109085. Epub 2025 May 22. PMID: 40499399.

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