Impact of the Advent of Collagenase Clostridium histolyticum on the Surgical Management of Peyronie’s Disease: A Population-Based Analysis

This retrospective observational cohort study was performed using data from the Kaiser Permanente Southern California health care system, an integrated network serving ∼4.7 million patients across 15 medical centers. The Kaiser Permanente Southern California system delivers health care services to a racially, ethnically, and socioeconomically diverse population that reflects the broader demographic composition of the population in Southern California.¹¹ Information about the medical care Kaiser Permanente Southern California patients receive is captured through an electronic medical record (EMR). The Kaiser Permanente Southern California EMR was the primary data source for patient identification, characterization, and evaluation. The EMR-based datasets’ information includes sociodemographic and pharmacy and health care use data.^12,13

From January 1, 2004, to December 31, 2020, the authors identified patients diagnosed with PD and monitored the trends of PD management longitudinally using the EMR. To be included in the study, patients must have been ≥ 18 years of age, diagnosed with PD, and started on either injection therapy (CCH), surgical therapy (penile plication or excision with grafting), or oral therapy (vitamin E, colchicine, or pentoxifylline).¹⁴ Patients who were undergoing penile prosthetic surgery for concurrent erectile dysfunction were excluded.

Being diagnosed with PD as a Kaiser Permanente patient > 18 years of age between 2004 and 2020 was the primary exposure. The diagnosis of PD must have occurred during the years 2004–2020 and been made by a practitioner. Demographic information, including age, sex, race, and ethnicity, was collected from the EMR. Kaiser Permanente’s EMR collects self-reported race and ethnicity data and includes stratifications of Asian or Pacific Islander, Black, Hispanic, White, unknown, and other. Comorbidities for patients with PD, including hypertension, erectile dysfunction, type 2 diabetes mellitus, and hyperlipidemia, were identified from the EMR and were identified as potential confounders.

Primary outcomes included the annual incidence of PD from 2004 to 2020 among men ≥ 18 years of age, as well as annual rates of CCH therapy, surgical therapy, and oral medication, including pentoxifylline, colchicine, and vitamin E. Events of PD were identified using International Statistical Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 607.85 and International Statistical Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) code N48.6.^15,16 Initiation of the type of therapy was ascertained using Current Procedural Terminology (CPT) codes, which were linked and used alongside pharmacy records obtained from the Healthcare Common Procedure Coding System to identify the type of therapies initiated. Injection therapy was identified using CPT codes 54200 and 54205, in addition to identifying the usage of CCH per the inpatient and outpatient pharmacy databases.^15,16 Surgical therapy was identified using CPT codes 54110, 54112, and 54360.¹⁶ The use of oral therapy was identified using pharmacy databases. The American Urological Association guidelines on PD in 2015 reported that vitamin E was found to have no significant efficacy for the treatment of PD, and the present study aimed to evaluate whether changes in prescription corresponded to these guidelines.¹⁷

The annual incidence of PD was reported for all years from 2004 to 2020 and was reported using the annual new onset of PD among males in Kaiser Permanente Southern California ≥ 18 years of age as the numerator and the annual number of males ≥ 18 years of age as the denominator. Similar methods were utilized to calculate and assess the change in surgical treatment (grafting/plication), CCH injection use, and oral medication as treatment for PD. The change in incidence of PD and treatment for PD from 2004 to 2020 was assessed using slope estimates and 95% confidence intervals (CIs), with corresponding P values.

Baseline characteristics between treatment groups (surgical vs injection) for PD were compared using the Chi-squared test for categorical variables and the Kruskal–Wallis test for continuous variables. Descriptive and multivariable logistic regression modeling was also implemented to ascertain which demographic or comorbidity recorded, in addition to time-to-follow-up, were more likely to influence whether patients received injection vs surgical therapy for their PD.

A total of 11,706 patients with PD were identified (mean age = 56.0 years, standard deviation = 11.58); 6384 (54.5%) were White, 3527 (30.1%) Hispanic, 383 (3.3%) Asian/Pacific Islander, 836 (7.1%) Black, and 577 (4.9%) other or unknown. Of the 11,706 patients with PD, 2544 (21.7%) had erectile dysfunction, 3877 (33.1%) had hypertension, and 1578 (13.5%) had type 2 diabetes mellitus (Table 1). Among all patients, 253 (2.2%) received injection therapy and 356 (3.04%) received surgical therapy. Those who received injection therapy had an average follow-up in 790.7 days, whereas those who received surgical therapy had a shorter follow-up, on average 413.0 days (P < .05). Neither group had significant differences in average age or comorbidities; the mean age for the injection group was 57.5 (9.09) years and the surgical group 56.2 (10.09) years, P > .05. However, stratification of age into subgroups (< 45, 45–54, 55–64, and ≥ 65 years) showed that a larger number of older patients received surgical therapy vs injection therapy, P < .05 (Table 1).

From 2004 to 2020, 11,706 patients presented for PD management, and the average incident rate was 52.8 per 100,000 eligible members. The rate of new PD diagnosis per 100,000 patients increased by 0.37 every year, P < .05 (Figure 1). Over the study period, the incident rate of surgical management per 1000 eligible patients declined on average at a rate of 0.40 each year (P < .001), although there was an increase rate of 1.19 (P < .001) for CCH injection therapy (Table 2). Following the FDA approval of CCH in 2013, the average incident rate (per 1000 eligible patients) for surgical therapy between 2014 and 2020 declined by 2.8 (P < .001) compared to that in 2004–2013, whereas it significantly increased by 5.1 (P < .001) for injection therapy (Figure 2). Average rates of oral colchicine and vitamin E significantly decreased (P < .001), although average rates of prescribing pentoxifylline significantly increased (P < .001) from 2016 to 2020 compared to 2004 to 2015 (Figure 3). Patients presenting in the post-CCH era were approximately 2 times significantly more likely to receive injection therapy (adjusted odds ratio = 2.08; P < .001; 95% CI = 1.47–2.94). On multivariable modeling, patients more likely to receive injection therapy as primary treatment for PD were 45–54 years of age (adjusted odds ratio = 2.77; P = .002; 95% CI = 1.34–5.73).

In this retrospective analysis, the authors found the incidence of new PD diagnosis per 100,000 patients to increase by 0.366 (P < .05) every year, suggesting a slight overall increase in the incidence of PD. When comparing oral therapies for PD, this study found colchicine to be the most prescribed oral treatment from 2004 to mid-to-late 2012, at which point pentoxifylline became the most prescribed oral treatment up until 2020. The American Urological Association’s 2015 guidelines stated that vitamin E lacked efficacy for the treatment of PD, and the present study’s results indicate the average usage of vitamin E to be –8.6 (P < .05) from 2016 to 2020 vs 2004 to 2015, suggesting that the guidelines played a role in the reduction of oral therapy. Moreover, the present study’s results illustrate an increased average rate of 9.9 (P < .05) in CCH injection use as a treatment of PD after its FDA approval, followed by a subsequent reduction in annual rates of surgery by 1.5 (P < .05). This study’s regression analysis illustrates that post-CCH era patients and those 44–55 years of age were 2.8 times more likely to receive injection therapy, highlighting the impact of the FDA approval of CCH, as well as the individual-level patient and physician shared decision-making that may have accounted for the differences in the treatment of PD across the age groups.

Although the present study adjusted for confounders for logistic regression, this study’s results could have been impacted by unknown confounders. Moreover, the present study assessed only changes in trends of PD incidence and treatment patterns and hence did not evaluate or illicit individual changes among patients or situations where multiple therapies may have been used. This study also had some degree of overlap with the COVID-19 period, which may have accounted for the changes seen from 2019 to 2020; however, the authors could not quantify that impact. Lastly, although the present study discussed changes in the trends of treatment for PD, it did not provide information on whether these trends were supported by changes in outcomes for PD.

Other studies with similar methodology have shown that patients who receive injection therapy were more likely to be younger and more likely to have sought treatment in the post-CCH era as opposed to those who receive surgical therapy.¹⁸ The present study’s results concur with those results, as the authors likewise found that patients were more likely to receive injection therapy in the post-CCH era, and with a greater magnitude. Another study looking at data from 2007 to 2018 found that the estimated annual incidence of PD increased from 61 to 77 per 100,000, and they found that the most common oral treatment was initially colchicine around 2007 but that pentoxifylline treatment became more common around 2018, and CCH became the most common injection treatment after its FDA approval.¹⁹ They also identified how the implementation of CCH injections drove the increase in the cost to treat PD by ~500%.¹⁹ The present study agrees with these results, as the authors also found colchicine to be the most prescribed oral treatment until mid-to-late 2012, at which point pentoxifylline became the most prescribed oral treatment up until 2020. Additionally, the present study also supports the increase in CCH injections used for the treatment of PD after its December 2023 FDA approval, although further analysis would be needed to understand the changes in the cost to treat PD among this population.

The data utilized in this study came from Kaiser Permanente Southern California, which is an integrated health care model. Although Kaiser Permanente Southern California data represent diverse populations, the present study results may not apply to areas not in the Kaiser Permanente Southern California region and to hospitals and clinics that do not utilize an integrated health care model.