Different collagenase delivery for Dupuytren’s disease in public hospitals

Section: Hand Abstract Background: The delivery protocol of collagenase Clostridium histolyticum (collagenase) injection for Dupuytren’s disease is variable, due to limited evidence for any one approach and widespread ‘off-label’ delivery occurring in Australia. As such, this preliminary study aimed to assess whether different collagenase delivery protocols for treating Dupuytren’s disease have an impact on effectiveness and safety. It was hypothesised that different collagenase delivery would affect outcomes.


Introduction
Dupuytren's disease is a common, benign fibrotic disease resulting in finger flexion contractures. 1 It can lead to significant functional hand impairment, 2 with patients therefore seeking treatment. 3 Treatment focuses on four characteristics identified by Tubiana in 1975: 'to correct deformity, avoid complications, shorten postoperative recovery, and prophylactically prevent recurrences. ' 4 Surgical correction of Dupuytren's disease via fasciotomy, fasciectomy and dermofasciectomy has been the mainstay of therapy over recent decades. 5,6 Minimally invasive techniques include percutaneous needle aponeurotomy and collagenase injections. Percutaneous needle aponeurotomy is advantageous due to rapid recovery times and the ability for outpatient management. 7 However, recurrence rates are higher compared with fasciectomy and dermofasciectomy. 8 These two surgical options are associated with a lengthier recovery time and a lower recurrence rate but an increased complication profile. 5 In 2013, collagenase was licensed by the Therapeutic Goods Administration in Australia for the treatment of Dupuytren's disease. The drug is not Medicare indexed, limiting its accessibility for patients.
The aim of this study was to assess differences in effectiveness and safety that may arise due to different collagenase delivery protocols. It was hypothesised that different protocols would have an impact on the effectiveness and safety of collagenase delivery.

Adverse effects
Adverse effects were recorded by asking or observing patients for any side effects that they had experienced. These were recorded as a percentage of the participant cohort that developed the side effects. Complications were analysed as a total sum across all digits and joints. Complications were classified as treatment-related and serious treatment-related adverse effects.
A p-value less than 0.05 was deemed statistically significant.

Study population
At Institute I and Institute II, 49 and 18 participants, respectively, were recorded at initial visit, manipulation and first review (six weeks posttreatment).
Clinic design comparison Table 1 shows the key constituents of each clinic design. This is a qualitative tabulation of how collagenase is delivered at each clinic.  The change in total passive extension deficit (TPED) at first review following collagenase was found to be statistically significant in both cohorts (Figure 1). As shown in tables 2 and 3, in both cohorts the fourth and fifth digit had a better response to treatment.

Demographic data
To determine whether differences existed between the TPED at each clinic a Mann-Whitney U-test was used. Nil statistically significant difference in the median TPED values from the two clinics (p=0.09) (Figure 1) was recorded.

A statistically significant reduction in all three
PROMs occurred within Institutes I and II at six weeks post-collagenase treatment (    was no statistically significance difference in each PROM (URAM, Southampton score and PSFS) reduction that occurred when comparing the two, as shown in Table 3.

Safety
Adverse effects following collagenase treatment at both clinics were comparable with results from the CORD I and II studies (

Discussion
This study explored the application of collagenase as a therapeutic for people with Dupuytren's disease within two public hospital clinics using different delivery protocols. The preliminary data show that collagenase is a safe and effective treatment for people with Dupuytren's disease, irrespective of clinic design and delivery of collagenase.

Ethics approval
This study was approved by both clinics' human research ethics and governance committees with reference numbers LRR17PH7 and 13226, respectively. Informed consent was obtained for data and photographs collected for this study.

Disclosure
The authors received no financial support for the research, authorship and/or publication of this article.
David J Hunter-Smith and Warren M Rozen were consultants for Actelion (previous distributor of XIAFLEX® in Australia). The authors have no other conflicts of interest to declare.