Progressive Response of Repeated Treatment with High-Concentration (179 mg) Capsaicin Patch in Peripheral Neuropathic Pain After Surgical or Traumatic Nerve Injury: Findings from the 12-Month German CASPAR Registry Study

Abstract

Introduction: Peripheral neuropathic pain after nerve injury (PNI) caused by surgery or trauma can severely impact daily life. The high-concentration capsaicin patch (HCCP, 179 mg) is a topical therapy approved for peripheral neuropathic pain, including PNI. This study utilizes data from the German Pain e-Registry (GPeR) to investigate the real-world effectiveness of HCCP in managing PNI across multiple treatments over 1 year.

Methods: CASPAR is a retrospective, non-interventional cohort study investigating patients with peripheral neuropathic pain treated with HCCP. The present analysis included 499 patients with PNI who received ≥ 1 HCCP with ≥ 12 months of follow-up. Key measures included pain intensity, quality of life (QoL), affective distress, sleep disturbances, and overall functioning. Furthermore, analgesic use and adverse events associated with HCCP treatment were evaluated.

Results: The mean average daily pain intensity (API) decreased from 52.5 mm on the visual analog scale (VAS) at baseline to 21.5 mm at month 12 in patients receiving four HCCPs. At month 12, a ≥ 30% reduction in API was observed in 25.8%, 44.9%, 85.3%, and 97.8% of patients receiving one, two, three, and four HCCP treatments, respectively. Significant improvements were also noted in physical and mental QoL, sleep, mood, and daily functioning. Patients receiving three or four HCCP treatments maintained pain relief and symptom improvements over the 12-month period, whereas those who discontinued treatment after one or two treatments experienced symptom rebound. In addition, repeated HCCP treatments were associated with a marked reduction in concomitant analgesic use and an increase in days of normal activities. Adverse events were mild-to-moderate application-site reactions, consistent with the well-established safety profile of HCCP.

Conclusions: HCCP treatment is associated with reductions in pain intensity and improvements in sleep, mood, and overall QoL in patients with PNI. These benefits are amplified with continued treatment and are accompanied by reduced use of concomitant analgesics and more days of usual activities, although a direct causal relationship cannot be confirmed within the context of this observational study.

Clinical trial registration: EU PAS number: EUPAS1000000106.

Keywords: High-concentration capsaicin patch; Peripheral nerve injury; Peripheral neuropathic pain; Real-word data; Topical treatment.

Fig. 1

Study design. Between 1 January 2015 and 31 December 2021, a total of 27,679 patients with PNP were documented in the GPeR. Of the 2574 patients eligible for inclusion in the CASPAR study, 499 had PNI and formed the full analysis cohort. All 499 patients with PNI received at least one treatment with HCCP during the 12-month follow-up period. Among them, 402 received a second treatment, 264 a third, and 135 a fourth. Based on the number of total treatments within the study period, 97 patients received one treatment, 138 received two, 129 received three, and 135 received four treatments. Assessments were conducted at baseline (prior to the first treatment) and after each HCCP treatment or just before the next treatment at 3-month intervals (± 2 weeks). EoS end of study (month 12), GPeR German Pain e-Registry, HCCP high-concentration capsaicin patch, PNI peripheral nerve injury, PNP peripheral neuropathic pain, QoL quality of life. ^#Number of patients receiving a first, second, third, and fourth treatment. ^*Number of patients with a total of one, two, three, and four treatments, respectively, during the observation period (12 months). ^‡Categorized in postherpetic neuralgia (PHN), peripheral nerve injury (PNI), painful diabetic peripheral neuropathy (PDPN), and others

Fig. 2

Impact of repeated HCCP treatment on pain intensity and sleep disturbances in patients with PNI. A, B Changes in average API score (A) and average mPDI-6 sleep score (B) in patient subgroups receiving one to four consecutive HCCP treatments with follow-up throughout the study period. The dotted lines in A and B indicate the points of HCCP treatment discontinuation. C Proportion of patients achieving ≥ 30% and ≥ 50% pain reduction, stratified by the number of HCCP treatments received (one to four treatments). API average 24-h pain intensity, BL baseline, CI confidence interval, HCCP high-concentration capsaicin patch, mPDI modified pain disability index, PNI peripheral nerve injury, VAS visual analog scale

Fig. 3

Changes in pain phenotype according to PDQ-7. A Change in individual (0–5, where 0 = never and 5 = very strongly) and overall (total score, 0–35) PDQ-7 pain phenotype scores in patient subgroups receiving one to four consecutive HCCP treatments throughout the study. B Absolute change in neuropathic pain symptoms in patients with PNI who received four consecutive HCCP treatments (n = 135) compared with baseline. Relative changes (effect sizes) and p-values are shown below each bar. CI confidence interval, HCCP high-concentration capsaicin patch, PDQ-7 7-item painDETECT^® questionnaire, PNI peripheral nerve injury

Fig. 4

Changes in affective distress and emotional health following HCCP treatment. A−C Mean change from baseline in self-reported depression (A), anxiety (B), and stress (C) scores, as measured by the DASS-21, in patient subgroups receiving one to four consecutive HCCP treatments over the study period. The dotted lines in A−C indicate the points of HCCP treatment discontinuation. D Proportion of patients with PNI reporting suicidal ideation (rated as “sometimes” or “frequently/often”) across four consecutive HCCP treatments (n = 135). BL baseline, CI confidence interval, DASS-21 21-item Depression, Anxiety and Stress Scale, HCCP high-concentration capsaicin patch, NRS numeric rating scale, PNI peripheral nerve injury

Fig. 5

Pain-related quality of life impairments and daily activity limitations. A Changes in pain-related QoL impairment according to the QLIP sum score over the course of one to four consecutive HCCP treatments. Scores ≤ 20 (black dotted line) indicate clinically relevant QoL limitations due to pain. The dotted lines in the score evaluation indicate the points of HCCP treatment discontinuation. B Number of days with impaired daily activities over the past 3 months, assessed using the von Korff scale. Data are shown for patients stratified by the number of HCCP treatments received. BL baseline, CI confidence interval, HCCP high-concentration capsaicin patch, NRS numeric rating scale, QoL quality of life, QLIP quality of life impairment by pain inventory

Fig. 6

Use of systemic concomitant medication. A Proportion of patients using pain-related concomitant antidepressants, antiepileptics, and high-potency opioids in patient subgroups receiving one to four consecutive HCCP treatments over the 12-month study period. B Absolute and relative changes in the number of systemic analgesic co-medications from baseline to month 12 in patient subgroups receiving one to four consecutive HCCP treatments. HCCP high-concentration capsaicin patch