With the publication of the IMPRESS I and II trials demonstrating the efficacy of CCh and subsequent approval of this medication for the treatment of PD by a variety of national health regulatory bodies, CCh became a popular and important non-surgical treatment option for patients diagnosed with PD. Despite CCh being recommended as a first line therapy by the CUA and AUA [5, 6], Xiaflex® has been removed from Australian, Asian, European, and Canadian European markets. Our study aimed to assess insurance approval rates and usage of CCh in Canada as a potential factor for discontinuation of the medication.
Overall, our study demonstrated high insurance approval rates for use of CCh in Peyronie’s disease, with 92.9% of requests being approved in Canada. Applications were more likely to be accepted for PD compared to DP, however prescriptions for PD patients were less likely to be filled. A potential explanation is the out-of-pocket expense associated with Xiaflex may act as a barrier for patients to access this medication, even with insurance approval. Interestingly, higher volume prescribers were more likely to have accepted applications. However, it is possible that this is due to the fact that providers who have received prior acceptances are more likely to submit more applications and know how to appropriately complete the required application. Although significant interprovincial variation was present, overall insurance coverage application approvals were high for the country as a whole. Once approved, patients were likely to proceed with CCh treatment, with 91.2% of all approved prescriptions being filled.
Despite CCh being the only approved medical therapy for PD, it was unfortunately removed from multiple countries including Canada. With a lack of effective non-surgical options, this will surely lead to increased surgical intervention rates as the authors of this paper have anecdotally noted. Although a cost-effectiveness analysis by Cordon et al. demonstrated that the cost of penile plication was significantly less than that of the CCh protocol utilized in IMPRESS I and II [11], other considerations should be taken into account. The primary outcome assessed in their study was improvement in curvature [11], and CCh still has utility as a primary non-surgical option not only for achieving a functionally straight penis, but also as a tool to help improve patient satisfaction. Further investigation of alternative CCh protocols were able to demonstrate significantly improved cost effectiveness, with cost being comparable to primary surgery [12]. Additionally, limited operating room time in a single-payer system such as Canada is another consideration that was not accounted for in the US and UK [11, 13] cost effectiveness studies. Aside from the additional stress on the already limited resources of a universal healthcare system, there are several patient factors to consider. Not all patients may be ideal candidates for surgery, and regardless of candidacy, there are inherent risks of surgery as well as post-operative complications that must be discussed with the patient. Among surgical candidates, secondary effects of surgery, such as approximately 2cm of penile shortening associated with penile plication. In contrast, a recent study combining CCh with RestoreX traction device demonstrated 1.9cm improvement in length in addition to curvature improvements [14]. This ~ 4cm difference in penile length between correcting a curve with plication versus CCh + RestoreX traction is dramatic for many patients and must be considered when evaluating patient outcomes and cost-effectiveness. For other techniques such as plaque incision and grafting, a 50% [15] risk of worsening erectile dysfunction is also considered as a non-acceptable risk for many men and leads to a lifetime of adjuvant ED therapies, accruing further expenses. Ultimately, although immediate outcomes for surgical repair are good, patients may express concerns in the long term regarding their quality of life such as satisfaction with penile cosmesis, off-target effects of surgery and new onset ED [16, 17].
The potential effects of the discontinuation of CCh in the Canadian healthcare system was addressed in our prior study, which sought to understand the perception of Canadian providers regarding this issue [9]. A large majority of the survey participants felt that the discontinuation of CCh would be a significant loss for Canadian PD patients. In addition, few Canadian providers would offer alternative intralesional therapies in the future and would be more likely to offer surgical management for PD. The sentiment among Canadian providers to not offer alternative intralesional therapy may result in a large proportion of PD patients who are not suitable for surgical management to remain untreated. Furthermore, many patients who are unwilling to proceed with surgery due to personal preferences will also remain untreated. This has significant implications given the prevalence of PD as well as its negative impact on mental health [18, 19], with approximately one third of men with PD may suffer from clinical depression [19]. Additionally, PD has been associated with significant emotional and psychosocial distress in domains such as quality of life, self-esteem, social isolation, relationship strain, and stigmatization [18]. Given the mental health difficulties faced by many PD patients, the lack of non-surgical options may further dissuade patients from proceeding with therapy for their condition. This will unfortunately lead to further worsening of both the patient’s physical and mental health.
Intralesional interferon has also been discontinued for treatment of Peyronie’s disease in Canada, leaving traction therapy and intralesional verapamil as the only recommended non-surgical options. However, intralesional verapamil has heterogeneous results in the literature [20] and lacks high level data as well as a well-established protocol. Mechanical traction devices may be undesirable to many patients as well, as many treatment regimens recommend use for multiple hours daily. The significant limitations on the efficacy of non-surgical treatments are an important consideration when treating a population where depression is a significant issue [18, 19]. In the future, individuals with Peyronie’s disease may be further dissuaded from proceeding with therapy, putting patients at further risk for worsening of their condition and psychosocial status.
This study is not without limitations. Our data was limited to what could be provided by the Canadian distributer, Bioscript Solutions. While relatively granular data was obtained regarding insurance application, acceptance, amount of coverage, and more, data regarding certain baseline information was lacking including age, comorbidities, socioeconomic status, and employment status. Most importantly, detailed explanations for insurance coverage rejection were not available. Additionally, this data is likely biased towards Canadian individuals with extended health coverage, and it is possible that a significant number of patients without extended health benefits did not attempt applying for Xiaflex approval. Given that 0.5% of men seek assessment and management of their PD with a healthcare professional, and 11–13% of men likely have PD [21], the total number of prescriptions over a ~ 2-year period of 748 suggests that a significant number of Canadian men suffering with PD are not seeking healthcare evaluation or are not choosing CCH as a treatment method. This reinforces the notion that better public awareness for PD is necessary to engage men suffering in silence and reducing barriers to treatment.