XIAPEX (Clostridium collagenase histolyticum, also known as AA4500) was developed as a targeted therapy for the treatment of Dupuytren's contracture that presents some palpable cord.
XIAPEX is composed of two different collagenases isolated and purified from the bacterium Clostridium histolyticum. The pharmacological activity of the AA4500 involves the selective lysis of the collagen at the injection site (ie, in the Dupuytren cord). Therefore, the therapeutic activity of the AA4500 is localized, so the AA4500 does not require a systemic exposure to be effective.
The two collagenases work in a complementary way to hydrolyze the collagen chains and interrupt the pathological collagen cords that cause contractures of Dupuytren.
The AUX-I (a class of collagenase I) split the final portions of the collagen chain, while the AUX-II (a class of collagenase II) split the inner segment of the collagen chain.
The Dupuytren strings are mainly composed of type I and III collagen. Other soft tissues of the hand, including ligaments and tendons, are also susceptible to the action of XIAPEX, causing the physician who uses it for the treatment of Dupuytren to understand the mechanism of action and the appropriate procedure of administration of XIAPEX.
Inclusion and exclusion criteria
- Inclusion criteria.
- ≥18 years of age.
- Dupuytren's contracture in at least one finger other than the thumb.
- Contracture of at least 20º and not more than 100º (MF) or 80º (IFP) caused by a palpable string.
- Bleeding disorders or recent stroke.
- Other disorders that affect the hands.
- Treatment during the 90 days before the start of the study.
- Use of tetracycline derivatives in the previous 14 days.
- Use of anticoagulants in the previous 7 days (except the low dose of aspirin).
- Allergy to collagenase or its excipients.
Infiltration systematics of the Xiapex
Once the patient is selected, on the day of the infiltration the patient goes on an empty stomach.
It is important to feel the rope and once its extension is determined, the cord infiltrates with the needle slowly infiltrating the product. The flange is punctured in three points with some rules depending on whether it is a metacarpophalangeal flange or IFP.
After the extension of the finger, we can:
Place a compressive bandage and start immediate mobilization of the fingers if the affectation is unimportant - Place a plaster splint for a week and keep it at night and between exercises for 2-3 months to avoid recurrence and the new digital retraction if the affectation is important.
It is a therapeutic procedure that is not free from risks. It is important to know the anatomy and the product to optimize the results and reduce complications.
If there is a cord that affects the MF and the IFP of the long fingers, 1º the MF will be done and the IFP one month.
It is a procedure that can be used in recurrences of dupuytren whenever there is a palpable cord.
Do not close doors to surgery if there is a recurrence of the disease in the future.
We conducted a prospective study of patients treated for Dupuytren's disease with collagenase in the period between May 2012 and September 2013.
This is a series of 71 affected patients, with an average age of 63'8 years (33-84 years). 62 men (87%) and 9 women (13%), with a mean follow-up of 9 months (15-3 months). 15 patients are included in a multi-center Phase IV clinical trial. 10 patients were younger than 45 years old (14.1%), the rest being patients older than that age limit (61 patients).
Of the 71 patients included, all were right-handed, and there were no large differences between the involvement of the right and left hand, since 33 patients had involvement of their right hand (46%) and 38 patients of their left hand (54%).. A very striking fact is bilaterality, ie the involvement of both hands by the dupuytren (62%). 38% of patients had a family history of Dupuytren's disease. We value the manual activity of the patients and classify it as Mild, moderate and high, evidencing that 35% have mild activity, 40% moderate and 25% high. We value influential habits such as tobacco and alcohol, obtaining the following results; Tobacco: 73.2% of patients are non-smokers, 15.5% smoke less than 10 cigarettes / day and 11.3% smoke more than 10 cigarettes per day. In relation to alcohol, 38 patients (53.5%) were non-drinkers, 24 patients (33.8%) mild alcohol users and 9 (12.7%) moderate-important consumers.
When assessing predisposing factors, we found that 28% of patients have diabetes Mellitus, 4% are patients with chronic obstructive pulmonary disease and there was no association with epilepsy or liver disease. Regarding the association with other types of fibromatosis, we see that 7% had lederhoose disease, 7% Peyronie's disease and 4% Garrod's nodules.
Of the 71 patients, 4 patients were treated with palpable cord recurrence. 23% of the patients had suffered prior Dupuytren's disease intervention in the other hand or in another location. When assessing the concomitant pathology to dupuytren (STC, osteoarthritis, spring finger ...), we see the following findings: 9/71 patients also had STC, 8/71 had osteoarthritis and 4/71 had or had suffered a springy finger.
When we assess the duration of the disease , we see that 23% had more than 10 years, 32% between 7-10 years, 25% between 3-7 years and 20% less than 20 years.
When we value the affection finger we see that the most frequently affected is the 5th finger in 54%, followed by the 4th finger in 42% and the 3rd finger in 4%.
The severity of the disease was determined by Tubiana classification. The majority of patients were in stage II / III.
Infiltration was performed in the office, as well as stretching at 24 h.
28 cases exclusively affected the MTF, 11 only the PFI and 32 cases the MTF with PFI.
The degree of contracture of IFP was higher than that of MTF (65'4% vs 35'5% respectively).
The result to the extension of pure MTF was satisfactory maintaining the degree of extension below 5º per year. However, in IFP, this does not happen. The initial full extension is not obtained, with a residual flexo of about 10º that is gradually lost.
The results are spectacular in MTF, not in IFP where, being the 5th finger, and being the degree of shrinkage worse, the results are worse.