Impact of Adhesion on Patient Satisfaction, Medication Switching and Discontinuation With Lidocaine Topical Patches Based on FDA Adverse Event Reporting and Patient Surveys

Impact of Adhesion on Patient Satisfaction, Medication Switching and Discontinuation With Lidocaine Topical Patches Based on FDA Adverse Event Reporting and Patient Surveys

Background:

FDA recognizes adhesion as a key quality component in topical patches, critical for consistent drug delivery, therapeutic effect, and patient compliance.  In a 2021 industry guidance document, FDA communicated guidelines for adhesion testing of all new and generic transdermal systems, recommending that at least 75% of a patch’s total surface area should be adhered during the entire use period.  For long-wear products, topical systems should also be tested under water stress conditions such as bathing and showering to mimic use in real world settings. Despite these FDA standards, adhesion is seldom a driving factor in the selection of topical lidocaine patches. 

ZTLido^® (lidocaine topical system 1.8%) (LTS) is a prescription lidocaine patch approved for the treatment of post-herpetic neuralgia (PHN). A comparative pharmacokinetic study established bioequivalence between ZTlido and Lidoderm^® (lidocaine 5% patch) (LP). While LTS and LP deliver the same amount of lidocaine through the skin, the novel design of LTS allows for better adhesion. Across three head-to-head adhesion studies, the mean percentage adherence for LTS was 89-93% compared to 63% for LP (brand) and 27% for LP (generic).

Purpose/Objectives:

Through analysis of the FDA Adverse Events Reporting System (FAERS), we evaluated the volume and proportion of product adhesion and product quality events reported for LTS and LP.  Two internet surveys conducted in 2016 and 2022 measured the impact of adhesion on patient satisfaction, switching, discontinuation and ability to function.

Method:

FAERS Analysis

We queried the FAERS database for all adverse event cases related to LTS (ZTLido) and LP (Lidoderm, lidocaine 5% patch generic) covering the timeframe from market approval to March 31, 2023.  For each product, we quantified the volume of cases, % of cases with “product adhesion” in the event term, and % cases with “product quality” in the event term. 

On-line Surveys

The first of two on-line surveys was conducted by a third party market research organization (Harris Poll) in May 2016 and included patients > 18 years with a PHN diagnosis within two years and who were treated with LP. This survey pre-dated the FDA approval of LTS, thus the only lidocaine patches represented in this survey was LP (brand and generic).  The second on-line survey was conducted by the manufacturer of LTS between March 2022-January 2023 and included patients who were treated with LTS daily for at least 30 days. Patients were incentivized to respond to the survey with a small token of appreciation for their time. The surveys queried patients on their satisfaction with their patch, and impact of patch adhesion on switching, discontinuations and patient ability to function.

Results:

As of March 31, 2023, FDA has received 4,949 adverse event cases for LP, of which 2826 (57%) were related to Product Adhesion issues and 2687 (54%) were related to Product Quality issues.  Comparatively, FDA has received 107 adverse event cases for LTS, of which only 9 (8%) were related to Product Adhesion and 4 (3.74%) were related to Product Quality. 

A total of 153 patients participated in the May 2016 survey of lidocaine 5% patch, while 100 patients participated in the 2022-2023 survey of LTS. The mean age was slightly younger in the 2016 survey (45.2 years compared to 53.9 years) and there were a higher proportion of male patients (50% compared to 26%). 

Only 30% of patients treated with LP responded that they were highly satisfied (“Very satisfied”) compared to 89% of patients treated with LTS who responded positively (“Completely satisfied/mostly satisfied”). While 62% of patients treated with LP expressed frustration with patch adhesion, 96% of patients treated with LTS responded that their patch “Always stayed on “or “Stayed on most of the time”.  Adhesion issues caused 24% of patients treated with LP to request a different brand of patch and 16% discontinued patch therapy altogether.  By contrast, 88% of patients treated with LTS stated that they were able to do more of the things they wanted to do.  When queried on what they liked most about LTS, the top three responses were: 1) “I have less pain than before” (76%); 2) “It stuck better than other lidocaine patches I have tried” (63%); and 3) “I can do more of what I want” (36%). 

Conclusions: LTS has demonstrated significantly improved adhesion compared to LP in head-to-head clinical studies; the high proportion of product adhesion and product quality adverse events reported for LP affirms this finding. In addition, an on-line patient survey demonstrated that the impact of poor adhesion results in poor patient satisfaction leading to product switches and even patch discontinuations, whereas better adhesion resulted in improved patient satisfaction, better pain control and enabled the patients to be more functional.

References: Gudin J, Argoff C, Fudin J, et al. J Pain Res. 2020;13:1485-1496.
Gudin J, Webster LR, Greuber E, Vought K, Kuritzky L. J Pain Research. 2021:14:513-526.