Dupuytren's disease is a slowly progressive condition affecting the layer of connective tissue in the palm of the hand and the fingers (the palmar fascia).2 Dupuytren's disease starts in the palm of the hand with the appearance of a number of nodules, made of cells that can produce collagen.2 As the disease progresses, excess collagen continues to build up and may eventually form into a rope-like cord under the skin.2 The cord extends from the palm into the finger and can gradually contract the finger permanently toward the palm; this is known as Dupuytren's contracture.2 A small number of patients with Dupuytren's disease will go on to develop Dupuytren's contracture.
The mainstay of treatment for Dupuytren's contracture is hand surgery and approximately 12,000 patients undergo surgery for the condition in the UK each year.3 Collagenase clostridium histolyticum is the first injectable treatment to be developed for Dupuytren's contracture and offers an alternative treatment option to surgery for some patients in the UK.1
"Dupuytren's contracture can significantly impact a person's quality of life, interfering with everyday tasks, including dressing, washing, driving and shaking hands. Patients can be reluctant to have surgery due to the possibility of scarring and prolonged time of recovery. Therefore a new treatment that provides an alternative option to surgery is important news for people in the UK living with Dupuytren's," said Chris Bainbridge, Consultant Hand Surgeon, Pulvertaft Centre for Hand Surgery, Royal Derby Hospital.
Collagenase clostridium histolyticum has been the subject of two pivotal studies which led to European authorisation, Collagenase Option for Reduction of Dupuytren's (CORD I and CORD II).4,5 The primary endpoint of CORD I was the percentage of patients achieving a reduction in contracture of the selected primary joint to 5 degrees or less, approximately 30 days after the last injection of that joint.4 Results showed that 64% of primary joints treated with collagenase clostridium histolyticum met the primary endpoint, compared with 6.8% of those injected with placebo (P <0.001).4 The most commonly reported adverse events in CORD I were localised swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness.4 Three treatment-related serious adverse events were reported: two tendon ruptures and one case of complex regional pain syndrome.4 No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed.4
In CORD II, primary endpoint was the percentage of patients achieving a reduction in contracture of their primary treated joint to 5 degrees or less, approximately 30 days after the last injection.5 Statistically significantly more cords injected with collagenase than placebo met the primary end point (44.4% vs 4.8%; P <0.001).5 In addition, patient satisfaction and physician ratings of improvement after treatment with collagenase clostridium histolyticum were significantly higher than with placebo treatment.5 No joint met the criteria for recurrence of contracture by the end of the 12 month study.5 The most common reported adverse reactions were similar to those reported in CORD I.4,5 In addition there were two cases of treatment related serious adverse events; one patient had a flexion pulley rupture and one patient experienced cord proliferation and sensory abnormality in the treated hand requiring surgical intervention.5 No arterial, nerve or tendon injuries or severe systemic allergic reactions were reported.5
"The development of a new treatment like Xiapex is an important step forward for patients with Dupuytren's contracture. Its availability in the UK is testament to Pfizer's continued commitment to bring new innovative medicines to patients and is good news for patients and physicians alike", said, Jonathan Jones, Medical Director of the Speciality Care Business Unit at Pfizer Limited.
Collagenase clostridium histolyticum is administered by local injection directly into the palpable Dupuytren's cord, a procedure which can be carried out in an outpatient setting,1 to break down the structure of the cord. 24 hours after injection, a finger extension procedure can be carried out as necessary to break the cord and allow extension of the finger.1
Collagenase clostridium histolyticum should only be administered by an appropriately trained hand surgeon and Pfizer is providing training on its administration and use to hand surgeons in the UK.
Notes
About Dupuytren's contracture
Dupuytren's disease is found more frequently in people of white northern European descent6 and the highest prevalence has been seen in northern Scotland, Iceland and Norway.7,8 The condition is more common in men who also tend to be more severely affected by Dupuytren's disease than female patients.9 A small number of patients with Dupuytren's disease will go on to develop Dupuytren's contracture.
Dupuytren's disease can affect up to 20% of men who are over 60 years of age, and 20% of women who are over 80 years of age.2 This means that as the ageing population increases, so does the incidence of Dupuytren's disease.10
About Xiapex (Collagenase clostridium histolyticum)
Collagenase clostridium histolyticum is a formulation of two purified collagenases (collagenase is an enzyme capable of breaking down collagen), derived from the bacterium Clostridium histolyticum.1 It is the first pharmacological treatment to be indicated for Dupuytren's contracture and may be an alternative to invasive and often complicated surgery for some patients.1
If contracture remains four weeks after treatment with collagenase clostridium histolyticum, another injection can be administered into the same cord, and the finger extension procedure can be carried out again if necessary (the cord may also break on its own). Injections and finger extension procedures may be administered up to three times per cord, at approximately four-week intervals.1
For full prescribing information, see the Summary of Product Characteristics.
Pfizer has the marketing rights to collagenase clostridium histolyticum in Europe and Auxilium Pharmaceuticals Inc. (NASDAQ: AUXL) has the rights in the rest of the world. Collagenase clostridium histolyticum has been authorised by the European Medicines Agency in February 2011 for the treatment of Dupuytren's contracture in adult patients with a palpable cord.11 In the US by the Food and Drug Administration (tradename in the US Xiaflex®) for treatment of adult patients with Dupuytren's contracture.12
References
1. Xiapex SmPC. Available here.
2. NHS Choices website. Dupuytren's contracture. Available here. Last accessed 19.01.11
3. Dias J, Braybrooke J. Dupuytren's Contracture: An Audit of the Outcomes of Surgery. J Hand Surg 2006; 31(5): 514-521
4. Hurst LC, Badalamente MA, Hentz VR et al. Injectable collagenase clostridium histolyticum for Dupuytren's contracture (CORD I). NEJM 2003; 361: 968-79
5. Gilpin D, et al. Injectable Collagenase Clostridium Histolyticum: A New Nonsurgical Treatment for Dupuytren's Contracture. J Hand Surg 2010; 35(12): 2027-2038
6. Townley WA, et al. Dupuytren's contracture unfolded. BMJ 2006; 332: 397-400
7. Hart MG, Hooper G. Clinical associations of Dupuytren's disease. Postgrad Med J 2005; 81: 425-428
8. Trojian TH, Chu SM. Dupuytren's disease: diagnosis and treatment. Am Fam Physician 2007; 76: 86-9
9. Gudmundsson KG, et al. Epidemiology of Dupuytren's disease: clinical, serological, and social assessment. The Reykjavik Study. J Clin Epidemiology 2000; 53: 291-6
10. Bayat A and McGrouther DA. Management of Dupuytren's disease -clear advice for an elusive condition. Ann R Coll Surg Engl 2006; 88: 3-8
11. European Medicine Agency website. Available here.
12. US Food and Drug Administration press release, 2nd February 2010.
Source:
Pfizer Inc.