Is there a line between ethics and market competition? Lights and shades of the withdrawal of collagenase treatment for Peyronie's disease.

Peyronie's disease treatments is changing again due the interruption of Xiapex® distrubution in Europe. There are many reasons that can be referred to this event. In this editorial we would like to shed light on the current cost items relating to treatment with collagenase clostridium histolyticum (CCH). The inaccessibility of the drug has seen both an increase in surgery for the treatments of both PD and Dupuytren's disease and an interruption of therapies in patients who had not completed their therapeutic cycle. Considering the aforementioned concerns, we would like to invite researchers dealing with PD to conduct studies with the available CCH products in collaboration with the drug companies in order to give again an efficacious treatment for PD.

Health Care Spending in Patients With Stage 3 and Stage 4 Pressure Injuries and Patients With Diabetic Foot Ulcers Treated Early With Clostridial Collagenase Ointment: A Retrospective Data Review.

INTRODUCTION: Clostridial collagenase ointment (CCO) is the only enzymatic agent indicated for debriding chronic dermal ulcers that is approved by the United States Food and Drug Administration. OBJECTIVE: The objective of this study is to estimate health care spending among patients with Stage 3 and Stage 4 pressure injuries (PIs) and patients with diabetic foot ulcers (DFUs) who experienced early (ie, within 30 days of index diagnosis) versus late (31 to 90 days of index diagnosis) initiation of CCO. METHODS: Patients with PIs and DFUs between January 2007 and March 2017 were identified. One-to-one matched cohorts were used to compare all-cause health care spending and disease-related health care spending between the early initiation and late initiation groups. RESULTS: Compared to the early CCO initiation group, all-cause health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. Compared to the early CCO initiation group, disease-related health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. All computations were statistically significant. CONCLUSIONS: Early initiation of CCO provides both all-cause and disease-related health care savings to payers and persons managing patients with PIs or DFUs. Payers, providers, and facilities should consider mechanisms to encourage the early use of CCO to lower costs.

At what cost is collagenase clostridium histolyticum viable for treating Peyronie's disease in a public healthcare system?

BACKGROUND: Collagenase clostridium histolyticum is a recognized non-surgical management for Peyronie's disease, licenced for use in the UK for patients with a palpable plaque and a curvature deformity of at least 30°. However, it is not currently funded for use within the National Health Service. Collagenase clostridium histolyticum has also recently been withdrawn from the European and other markets worldwide, but there is potential for this to be produced off-patent in the future. OBJECTIVES: To determine whether collagenase clostridium histolyticum is cost-neutral when compared to surgical management within a public health care system, using the National Health Service as an example. MATERIALS AND METHODS: Two published protocols for the administration of collagenase in Peyronie's disease were identified-the 'IMPRESS protocol' and the 'London protocol'. Costs were taken from published NHS literature. Surgical intervention rates after collagenase clostridium histolyticum administration and primary penile plication were taken from published literature. The costs of the two published protocols were calculated with costs of any repeat surgical intervention were included within each protocol per patient cost. RESULTS: At the current cost per vial of collagenase to the National Health Service, the IMPRESS protocol per patient costs £3,832.77 (143.7%) more than primary surgery, whilst the London protocol costs £70.77 (2.7%) more than primary surgery. DISCUSSION: At a cost of £548.41 per vial, collagenase administered under the London protocol would be a management option for Peyronie's disease cost neutral to primary corrective surgery. CONCLUSION: Central funding of collagenase in a public healthcare system would enable the management of Peyronie's disease to be moved to the outpatient setting. For this to be done at no additional cost to the NHS, it would require a cost reduction per vial of collagenase of £23.59 (4.1%), to a cost of £548.41.

Comparative Cost-effectiveness of Surgery, Collagenase Clostridium Histolyticum, and Penile Traction Therapy in Men with Peyronie's Disease in an Era of Effective Clinical Treatment.

BACKGROUND: Traditionally, surgery has been considered the gold standard treatment for Peyronie's disease (PD). Less-invasive alternatives, such as collagenase Clostridium histolyticum (CCH) and traction therapy, have been proposed and proven effective. AIM: To compare cost-effectiveness of management options for PD. METHODS: A Markov analytic model was created to compare the cost-effectiveness of treatment with a novel traction device, RestoreX (RXPTT), vs CCH vs surgery. Outcomes were derived from single-institution, prospective data of 63 men treated with RXPTT, 115 with CCH, and 23 with plication or incision and grafting. Costs were based on 2017 Medicare reimbursement and utility values from the literature. MAIN OUTCOME MEASURES: Model outcomes included complications for each treatment arm, as well as the probability of success, which was defined as ≥20% improvement in curvature. Univariable and multivariable sensitivity analyses were performed to test the robustness of the model. RESULTS: Overall success rates were 96% (surgery), 66% (CCH), and 48% (RXPTT). At 10 years after treatment, RXPTT was the most cost-effective, with mean costs per patient of $883 (RXPTT), $11,419 (surgery), and $33,628 (CCH). CCH and surgery both resulted in a gain of quality adjusted life years (QALYs) relative to RXPTT (9.44 and 9.36 vs 9.27, respectively). Sensitivity analysis demonstrated greater cost-effectiveness for surgery if lower (≤46%) rates of postoperative erectile dysfunction or length loss (≤3%). CCH became more cost-effective at lower costs (≤$16,726) or higher success rates (≥76%). On multivariable sensitivity analysis at a willingness to pay threshold of $100,000/QALY, the most cost-effective strategy was RXPTT in 49%, surgery in 48%, and CCH in 3% of simulations. At a willingness to treat threshold of $150,000/QALY, the most cost-effective treatment option was RXPTT in 33%, surgery in 55%, and CCH in 12% of simulations. CLINICAL IMPLICATIONS: In an era of value-based care, this model can guide cost-effective treatment selection on the basis of provider, patient, and payer characteristics. STRENGTHS & LIMITATIONS: The current study represents the first cost-effectiveness comparison of treatment modalities for PD and is strengthened by prospective data collection, large CCH and traction sample sizes, and robust sensitivity analyses. Consistent with cost-effective models, the model is limited by assumptions and may not apply to all scenarios. CONCLUSIONS: RXPTT represents a more cost-effective method for achieving ≥20% curvature improvement compared with surgery or CCH. Depending on treatment goals, rate of surgical complications, and willingness to pay threshold, surgery and CCH may become more cost-effective in select scenarios. Wymer K, Kohler T, Trost L. Comparative Cost-effectiveness of Surgery, Collagenase Clostridium Histolyticum, and Penile Traction Therapy in Men with Peyronie's Disease in an Era of Effective Clinical Treatment. J Sex Med 2019;16:1421-1432.

Comparative cost and clinical effectiveness of clostridial collagenase ointment for chronic dermal ulcers.

Chronic dermal ulcers affect approximately 2.4-4.5 million people in the USA and are associated with loss of function, decreased quality of life and significant economic burden. Debridement is a critical component of wound care involving removal of nonviable tissue from chronic wounds to stimulate the granulation and epithelialization process. Clostridial collagenase ointment has been used as a method of wound debridement for more than 50 years and is currently the only enzymatic debriding ointment with US FDA approval. This review discusses the results of recent real-world studies that build upon the evidence demonstrating the clinical effectiveness, cost-effectiveness and safety of clostridial collagenase ointment across wound types and care settings.

Collagenase clostridium histolyticum for the treatment of Dupuytren's contracture: systematic review and economic evaluation.

BACKGROUND: Dupuytren's disease is a slowly progressive condition of the hand, characterised by the formation of nodules in the palm that gradually develop into fibrotic cords. Contracture of the cords produces deformities of the fingers. Surgery is recommended for moderate and severe contractures, but complications and/or recurrences are frequent. Collagenase clostridium histolyticum (CCH) has been developed as a minimally invasive alternative to surgery for some patients. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of collagenase as an alternative to surgery for adults with Dupuytren's contracture with a palpable cord. DATA SOURCES: We searched all major electronic databases from 1990 to February 2014. REVIEW METHODS: Randomised controlled trials (RCTs), non-randomised comparative studies and observational studies involving collagenase and/or surgical interventions were considered. Two reviewers independently extracted data and assessed risk of bias of included studies. A de novo Markov model was developed to assess cost-effectiveness of collagenase, percutaneous needle fasciotomy (PNF) and limited fasciectomy (LF). Results were reported as incremental cost per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were undertaken to investigate model and parameter uncertainty. RESULTS: Five RCTs comparing collagenase with placebo (493 participants), three RCTs comparing surgical techniques (334 participants), two non-randomised studies comparing collagenase and surgery (105 participants), five non-randomised comparative studies assessing various surgical procedures (3571 participants) and 15 collagenase case series (3154 participants) were included. Meta-analyses of RCTs assessing CCH versus placebo were performed. Joints randomised to collagenase were more likely to achieve clinical success. Collagenase-treated participants experienced significant reduction in contracture and an increased range of motion compared with placebo-treated participants. Participants treated with collagenase also experienced significantly more adverse events, most of which were mild or moderate. Four serious adverse events were observed in the collagenase group: two tendon ruptures, one pulley rupture and one complex regional pain syndrome. Two tendon ruptures were also reported in two collagenase case series. Non-randomised studies comparing collagenase with surgery produced variable results and were at high risk of bias. Serious adverse events across surgery studies were low. Recurrence rates ranged from 0% (at 90 days) to 100% (at 8 years) for collagenase and from 0% (at 2.7 years for fasciectomy) to 85% (at 5 years for PNF) for surgery. The results of the de novo economic analysis show that PNF was the cheapest treatment option, whereas LF generated the greatest QALY gains. Collagenase was more costly and generated fewer QALYs compared with LF. LF was £1199 more costly and generated an additional 0.11 QALYs in comparison with PNF. The incremental cost-effectiveness ratio was £10,871 per QALY gained. Two subgroup analyses were conducted for a population of patients with moderate and severe disease and up to two joints affected. In both subgroup analyses, collagenase remained dominated. LIMITATIONS: The main limitation of the review was the lack of head-to-head RCTs comparing collagenase with surgery and the limited evidence base for estimating the effects of specific surgical procedures (fasciectomy and PNF). Substantial differences across studies further limited the comparability of available evidence. The economic model was derived from a naive indirect comparison and was hindered by a lack of suitable data. In addition, there was considerable uncertainty about the appropriateness of many assumptions and parameters used in the model. CONCLUSIONS: Collagenase was significantly better than placebo. There was no evidence that collagenase was clinically better or worse than surgical treatments. LF was the most cost-effective choice to treat moderate to severe contractures, whereas collagenase was not. However, the results of the cost-utility analysis are based on a naive indirect comparison of clinical effectiveness, and a RCT is required to confirm or refute these findings. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006248. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Resource utilisation associated with single digit Dupuytren's contracture treated with either surgery or injection of collagenase Clostridium histolyticum.

UNLABELLED: The gold standard treatment for Dupuytren's contracture is surgical excision of the cord. A non-surgical treatment with collagenase clostridium histolyticum injection is available but appears costly. OBJECTIVES: To provide data on resource consumption related to surgical and non-surgical treatment for Dupuytren's contracture. DESIGN AND PARTICIPANTS: Twenty patients with a single digit Dupuytren's contracture, 10 treated with surgical excision, and 10 treated with a single injection of collagenase. MEASUREMENTS: Minutes spent in theatre, number of follow-up appointments, time to skin healing, and patients return to normal activities of daily living. RESULTS: The injection group was significantly better regarding theatre time (p < 0.0001), follow-up appointments (p = 0.048), skin healing time (p < 0.001), and return to normal activities of daily living (p = 0.02) than the operated group. CONCLUSIONS: There are significant personal and health economic differences between the two methods of treatment which may influence local choice.

Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren contracture: report of 40 cases.

BACKGROUND: Dupuytren's disease (DD) is a fibroproliferative pathology that affects the palmar aponeurosis causing the development of nodules and collagen cords and the progressive flexion of the fingers. The standard procedure is surgical fasciectomy, followed by high recurrence rates. Collagenase Clostridium histolyticum (CCH) injection represents an innovative noninvasive approach to the treatment of DD. This prospective study was designed to examine the efficacy and safety of CCH injection performed in the outpatient, using local anesthesia. MATERIALS AND METHODS: Forty patients [32 metacarpophalangeal (MP), 8 proximal interphalangeal (PIP)] with Dupuytren's contracture of at least 20° for MP joint and any degree for PIP joint were included. The mean age was 66. All joints were treated with a single vial of collagenase injection and manual breaking of the cord 24 h after. All adverse effects (AEs) were monitored. Patients were checked 7, 30, 90, and 180 days after the injection. Primary endpoint was a reduction in digit contracture within 0°-5° of normal extension. Secondary endpoints were the improvement of range of motion, the evaluation of AEs incidence, and cost-effectiveness of collagenase treatment. RESULTS: About 67.5 % of patients obtained a clinical success. At 6 months, a further 7.5% attained the same result. The mean contracture of treated joints was 5.3º for MP and 6.8° for PIP joints. Twenty-three patients had one or more mild-to-moderate side effects. CONCLUSIONS: The use of collagenase appears to be an effective and safe method for the treatment of Dupuytren's contracture. Therapeutic success was achieved in a significant percentage of patients. The incidence of side effects was higher, but they were local reactions of short duration. The use of a single collagenase vial in patients treated in day surgery appears more cost-effective than surgery.

Use of resources and costs associated with the treatment of Dupuytren's contracture at an orthopedics and traumatology surgery department in Denia (Spain): collagenase clostridium hystolyticum versus subtotal fasciectomy.

BACKGROUND: Our purpose was to analyze and compare the use of direct health resources and costs generated in the treatment of Dupuytren's contracture using two different techniques: subtotal fasciectomy and infiltration with Collagenase Clostridium Histolyticum (CCH) in regular clinical practice at the Orthopedic and Traumatology Surgery (OTS) Department at the Hospital de Denia (Spain). METHODS: Observational, retrospective study based on data from the computerized clinical histories of two groups of patients- those treated surgically using a one or two digit subtotal fasciectomy technique (FSC) and those treated with CCH infiltration, monitored in regular clinical practice from February, 2009 to May, 2012. Demographic (age, sex), clinical (number of digits affected and which ones) and use of resources (hospitalizations, medical visits, tests and drugs) data were collected. Resource use and associated costs, according to the hospital's accounting department, were compared based on the type of treatment from Spain's National Health Service. RESULTS: 91 patients (48 (52.8%) in the FSC group) were identified. The average age and number of digits affected was 65.9 (9.2) years and 1.33 (0.48) digits affected in the FSC group, and 65.1 (9.7) years and 1.16 (0.4) digits in the CCH group.Overall, the costs of treating Dupuytren's disease with subtotal FSC amount to €1,814 for major ambulatory surgery and €1,961 with hospital stay including admission, surgical intervention (€904), examinations, dressings and physiotherapy. As to collagenase infiltration, costs amount to €952 (including minor surgery admission, vial with product, office examination and dressings). Finally, comparing total costs for treatments, a savings of €388 is estimated in favor of CCH treatment in the best-case scenario (patient under MAS system with no need for physiotherapy) and €1,008 in the worst-case scenario (patient admitted to hospital needing subsequent physiotherapy), implying a savings of 29% and 51%, respectively. CONCLUSIONS: This study demonstrates that treating patients with DC by injection with CCH at the OTS department of the Hospital de Denia generates a total savings of 29% and 51% (€388 and €1008) compared with fasciectomy at the time of treatment. Long term evolution of CCH treatment is uncertain and the recurrence rate unknown.

Budget impact analysis in Spanish patients with Dupuytren's contracture: fasciectomy vs. collagenase Clostridium histolyticum.

The aim of this study was to estimate the budget impact of collagenase Clostridium histolyticum (CCH) vs. fasciectomy (FSC) surgery for the treatment of Dupuytren's disease (DD) in Spain. A cost minimization analysis was adopted (effectiveness was assumed to be equivalent for both techniques). DD related costs were considered. CCH costs (including drug, administration and visits) were obtained from clinical trials and a real-life study. FSC costs (including type of admission, visits, operating room, re-admissions, tests, drugs and rehabilitation costs) were collected through a retrospective, observational, local study. Unit costs were obtained from local database systems (e-SALUD and BOT). Results were presented from the NHS perspective for the next 3 years. We assumed that there were 5100 fasciectomies per year (with a 5% annual increase) and that 20%, 30% and 40% of them will annually utilize CCH. In addition, a 10%, 15% and 20% of untreated diagnosed patients were expected to receive CCH. All the data were validated through an expert panel. A sensitivity analysis was performed with the main variables. The average FSC cost was €2250 (72% inpatients), €1703 for outpatients and €2467 for inpatients. The average CCH cost was €1220 (1.5 vial/injection and four visits) and could drop to €898 (1.1 vial/injections and three visits). The accumulated 3years budget impact analysis (BIA) was 45,971€ (K€-2993(1); 3870). According to this study, the inclusion of the CCH should produce a 3-year cumulative budgetary impact of €45,971 (K€-2993; 3870) for the NHS.

▾Xiapex for Dupuytren's contracture.

Dupuytren's contracture is a benign, progressive disabling condition of the hands. Traditionally, surgery (e.g. fasciotomy, fasciectomy, joint fusion and amputation) has been the only effective treatment but it is not an option for every patient. A potential alternative intervention is a formulation of collagenase Clostridium histolyticum (▾Xiapex--Pfizer Limited), which has been licensed for injection directly into the affected joint as treatment for adults with Dupuytren's contracture.5 Here we review the evidence for collagenase C. histolyticum and discuss its place in the management of this condition.