Adverse Effects of Collagenase in the Treatment of Dupuytren Disease: A Systematic Review.
BACKGROUND
Collagenase clostridium histolyticum (CCH) has proven to be both safe and effective in the treatment of Dupuytren disease (DD). The medium-term outcomes are similar to those achieved with surgery, and most adverse effects are self-limiting and considered to be mild or moderate.


OBJECTIVE
Our objective was to conduct a systematic review of the adverse effects of CCH in DD since the release of the drug to evaluate the incidence, severity, classification, and definitions of these effects.


METHODS
We analyzed the literature in terms of modifications to the original treatment protocol and grouped adverse effects according to their pathophysiological origin.


RESULTS
We included 28 clinical studies and five case reports or case series analyzing 4456 patients with a mean age of 63.6 years. Mean follow-up was 7.07 months (range 3-24); the mean number of patients per study was 148 (range 5-1082). The studies did not classify the adverse effects they reported into groups. The most common effects were peripheral edema (54.4%), bruising (42.9%), and upper limb pain (28.3%). Significant biases were observed for use of terminology, demarcation of sites of involvement, severity criteria, and assessment methods.


CONCLUSIONS
A simpler and clearer consensus-based classification system would enable better evaluation and comparison of the adverse effects of CCH in the treatment of DD. Consideration of inflammatory phenomena as part of the drug's mechanism of action would significantly reduce overall rates of adverse effects.
Orthopedics and Traumatology Surgery, Hospital de Denia, Partida Beniadlà, S/N, Denia, 03700, Alicante, Spain. sanjuan.rafcer@gmail.com.|University of Granada, Granada, Spain. sanjuan.rafcer@gmail.com.
Rafael
http://orcid.org/0000-0002-1958-0987
R
Sanjuan-Cerveró
Pharmacy Service, Hospital Dr Moliner, Porta Coeli s/n Serra, 46118, Valencia, Spain.
Francisco J
FJ
Carrera-Hueso
University of Granada, Granada, Spain.|Ophthalmologic Department, Hospital Virxen da Xunqueira, Cee, A Coruña, Spain.
Pedro
P
Vazquez-Ferreiro
University of Granada, Granada, Spain.|Pharmacy Service, Hospital Nisa Rey Don Jaime, Castellón, Spain.
Diego
D
Gomez-Herrero
D004387:Dupuytren Contracture / Q000188:drug therapy*; D006801:Humans; D003012:Microbial Collagenase / Q000009:adverse effects*; D009626:Terminology as Topic
D003012:Microbial Collagenase