Elsevier

The Journal of Hand Surgery

Volume 40, Issue 10, October 2015, Pages 1963-1971
The Journal of Hand Surgery

Scientific article
The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study

Data from this paper were presented at the American Society for Surgery of the Hand Annual Meeting, September 18–20, 2014, Boston (Hurst L, et al. J Hand Surg Am. 2014;39[9 Suppl]:e32–e33).
https://doi.org/10.1016/j.jhsa.2015.06.099Get rights and content

Purpose

To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the same hand with Dupuytren fixed flexion contractures (FFCs).

Methods

Patients with 2 or more contractures in the same hand caused by palpable cords participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same hand (1 injection per affected joint) during the same visit. Finger extension was performed approximately 24, 48, or 72 or more hours later. Changes in FFC and range of motion, incidence of clinical success (FFC ≤ 5°), and adverse events (AEs) were summarized.

Results

The study enrolled 715 patients (725 treated joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98° to 27°. Mean total range of motion increased from 90° to 156°. The incidence of clinical success was 65% in metacarpophalangeal joints and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild to moderate, resolving without intervention; the most common were swelling of treated extremity, contusion, and pain in extremity. The incidence of skin lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of time to finger extension.

Conclusions

Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint, with the exception of skin laceration. The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint. Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints, and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment.

Type of study/level of evidence

Therapeutic III.

Section snippets

Study design

This 60-day prospective, open-label, phase 3b study was conducted from September 2012 through July 2013 at 56 sites in the United States, Australia, New Zealand, and Europe. The study protocol was approved by local ethics committees, and research was carried out in compliance with the Declaration of Helsinki as currently amended. All participants provided written informed consent before the initiation of any study-specific procedures and were free to discontinue at any time.

Patients

Eligible patients

Efficacy

Total FFC and total ROM data by joint subgroup are summarized in Table 2. Improvements in FFC for joint pairs ranged from 84% in the 2 MCP joint subgroup to 60% in the 2 PIP joint subgroup. The 2 MCP/PIP joint subgroups (same finger and different fingers) were 72% and 68%, respectively. Improvement in ROM showed similar results for 4 subgroups. Improvement for FFC (Fig. 1) and ROM (Fig. 2) were similar regardless of finger extension time. Clinical success (FFC ≤ 5°) was reached in 65% of MCP

Discussion

CCH is an approved treatment that provides an alternative to surgical interventions for patients with Dupuytren contracture. Its short- and long-term efficacy and safety have been demonstrated in a 5-year follow-up study13 and several clinical trials.7, 8, 14 The protocols for those clinical trials, however, did not address some issues that arise in clinical practice settings—namely, concurrent treatment of more than 1 joint on the same hand and ability to vary the time between injection and

Acknowledgment

The authors thank Sherri D. Jones, PharmD, of MedVal Scientific Information Services, LLC, for providing medical writing and editorial assistance. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: The GPP2 Guidelines.” Funding to support this study and the preparation of this manuscript was provided by Auxilium Pharmaceuticals, Inc.

References (17)

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Cited by (39)

  • Risk Factors for Skin Tears Following Collagenase Clostridium histolyticum to Treat Dupuytren Contractures

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    Because the largest proportion of adult dermal tissue is composed of type I collagen, there could be a direct effect of CCH to cleave dermal collagen strands, creating the potential for skin tear during manipulation, especially in the setting of superficial injections in which some CCH is deposited in the dermis itself. Furthermore, based on these results and previous studies showing that 2 simultaneous doses of CCH may result in a greater incidence of skin tear,6,17 there may be a dose–response relation between the dose of CCH and the effect on cleavage of type I collagen in the dermal tissue. The use of CCH in patients receiving active anticoagulation remains controversial.

  • Needle Aponeurotomy Versus Collagenase Injections for Dupuytren Disease: A Review of the Literature and Survey of Patient-Reported Satisfaction, Recurrence, and Complications After Needle Aponeurotomy

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    The 5-year data from the Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study indicates that CI is both effective and safe with a reduction in disease and low complication rates.22 Moreover, Pess et al20 demonstrated that collagenase injections were effective in improving contracture at both the metacarpophalangeal and proximal interphalangeal joints at all stages of disease, and Gaston et al18 determined that collagenase injections were safe and effective treating contractures in multiple joints in the same hand. Similar studies looked at the effectiveness and safety of an NA.

  • Adverse effects associated with collagenase clostridium histolyticum in Dupuytren disease: A prospective study

    2018, Orthopaedics and Traumatology: Surgery and Research
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    Considering the above mechanisms of action, one could logically wonder whether the adverse effects reported for CCH are truly adverse effects. If treatment effects directly related to the mechanisms of action of CCH were removed from this equation, or perhaps even better, if only effects that truly affect a patient's quality of life [7,22,32] were considered, then the rate of adverse effects attributable to CCH would be considerably lower. A common and perfectly reasonable question asked by non-experts in this area is “Are we really using a drug with an adverse affect rate of close to 100% to treat a benign disease?”

  • Anesthesia for collagenase clostridium histolyticum injection in patients with dupuytren disease: A cohort analysis

    2018, Journal of Plastic, Reconstructive and Aesthetic Surgery
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    Skin laceration rates are more common when the extension is performed by a surgeon. Surgeons are more comfortable with the procedure and they are not afraid of causing lacerations, as they know that the they will heal well in the vast majority of cases.13,23,24 Surgeons take a secondary role when patients with moderate contractures perform the extension by themselves.

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The authors received research and manuscript preparation funding for this study from Auxilium. R.G.G. is on the speakers bureau of and receives research support from Auxilium, receives royalties from Biomet, is a consultant to Biomet and Smith & Nephew, and is an advisor for BioMedical Enterprises, MiMedx. G.M.P. is on the speakers bureau of and receives research support from Auxilium and receives royalties from Biomet. S.C. receives research support from Auxilium. B.D., B.M.C., G.J.K., and J.P.T. are employees of Auxilium; and L.C.H. receives a partial Xiaflex royalty from BioSpecifics Technologies and research support from Auxilium.

All authors contributed equally, and each was involved in study design, data acquisition, or data analysis/interpretation and in drafting or critically revising the manuscript. All authors reviewed the final manuscript and gave approval for submission.

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