This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.
This review aimed to compare injections of collagenase clostridium histolyticum with standard surgical treatments for Dupuytren’s contracture. Unfortunately existing trials are small and there are no head to head trials of surgery vs collagenase, so it is not possible to determine which therapy is more effective in the short or longer term - nor which is likely to be the more cost-effective. However, collagenase was clinically successful in 63% of cases, compared to just 6% for placebo. Draft guidance from NICE recommends against the use of collagenase clostridium histolyticum for Dupuytren’s, except in the context of research.
Why was this study needed?
In Dupuytren's disease connective tissue in the palm of the hand thickens, forming fibrous cords which can cause one or more fingers to bend in towards the palm of the hand – this is called Dupuytren’s contracture. The condition isn't life-threatening, but it can get steadily worse over time and make normally daily activities difficult. Most people with mild Dupuytren’s disease don’t need or seek treatment.
Surgery is commonly used to treat moderate and severe contractures by removing the thickened tissue to release the tightness in the hand. Recurrence rates are high; it is not clear whether this is due to progression of the disease or to post surgical scarring. There were 18,222 hospital admissions for Dupuytren’s contracture in England between April 2012 and March 2013.
A recently developed alternative to surgery is an injection of the enzyme collagenase clostridium histolyticum. The collagenase initially weakens the cords over about 24 hours, after which the finger is straightened to help the cord to break. Mobilisation is encouraged and return to activity may be quicker than after open surgery. The aim of this review was to assess the effectiveness of collagenase for adults with Dupuytren's contracture compared with surgery.
What did this study do?
This was a systematic review that included a variety of study types. Five randomised controlled trials compared collagenase with placebo. The results of these were pooled in meta-analysis where possible. Two non-randomised trials compared collagenase with surgery, but no higher quality evidence was found. Six of these trials were from the USA and one was from Australia: all but one had fewer than 100 participants. Fifteen observational case series of people who had received collagenase were also included to investigate longer-term outcomes.
An economic model was developed using estimates of the costs of collagenase and the risks and benefits of each procedure. However, few studies have directly compared collagenase with surgery, and so there was considerable uncertainty about many of the assumptions used in the model.
The results need to be treated with caution. There were no randomised controlled trials comparing collagenase with surgery, and included trials were small and sponsored by companies involved in the development of collagenase.
What did it find?
- Joints treated with collagenase were ten times more likely to achieve clinical success compared to those treated with placebo – 63% versus 6% (relative risk 10.21, 95% confidence interval 5.29 to 19.69). Clinical success was defined as a reduction in contracture to between 0° to 5° of normal, 30 days after the last injection. This was from a meta-analysis of three trials. The knuckle joints where the fingers meet the hand, improved more than the other small joints of the fingers.
- Nearly all participants, 97%, treated with collagenase experienced an adverse event compared with around a quarter receiving placebo, most of which were mild or moderate (e.g. swelling, pain, injection site bleeding and itching). Four serious adverse events were observed in the collagenase group: three tendon ruptures and one case of severe, persistent pain.
- Recurrence rates varied widely. For the knuckle joints they varied from 0% at one year to 27% at three years, whereas those for the first finger joints varied from 0% at one year to 56% at three years.
- The two non-randomised controlled trials comparing collagenase with surgery gave mixed results and had a high risk of bias. This included making no attempt to take account of differences in patient characteristics between those given the alternative treatments.
What does current guidance say on this issue?
A NICE technology appraisal is currently being undertaken for collagenase clostridium histolyticum for Dupuytren's contracture. The expected publication date is unknown. The draft guidance recommends against the use of collagenase clostridium histolyticum for treating Dupuytren’s contracture, except in the context of research.
What are the implications?
The main limitation of this review was the lack of high quality trials directly comparing collagenase with surgery. Long-term data on rate of recurrence, complications and impact of repeated treatment after collagenase were also lacking.
While collagenase was significantly more effective than placebo, there was no evidence that collagenase was better or worse than surgical treatments. Two costing studies, conducted in the USA and Canada, suggest that the cost of collagenase needs to be significantly reduced if it is to offer a cost-effective alternative to surgery. The economic model produced by this study also indicated that surgery was more cost-effective than collagenase. It was estimated that one treatment with collagenase would have a total cost of around £1,739. However, due to various uncertainties these results should be treated with caution.
Brazzelli M, Cruickshank M, Tassie E, et al. Collagenase clostridium histolyticum for the treatment of Dupuytren's contracture: systematic review and economic evaluation. Health Technol Assess. 2015 Oct;19(90):1-202.
This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 13/05/01).
Baltzer H, Binhammer PA. Cost-effectiveness in the management of Dupuytren’s contracture. A Canadian cost–utility analysis of current and future management strategies. Bone Joint J. 2013;95–B(8):1094–100.
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