➢ Data from randomized controlled trials showed that 130 (64%) of 203 joints (including 102 [77%] of 133 metacarpophalangeal joints and twenty-eight [40%] of seventy proximal interphalangeal joints) that were treated with as many as three injections of collagenase clostridium histolyticum obtained reduction of contracture to ≤5°.
➢ Common adverse events following collagenase treatment include swelling, ecchymosis, pain, pruritus, and lymphadenopathy, with 98% (243) of 249 patients experiencing at least one adverse event.
➢ Severe adverse events following collagenase treatment include flexor tendon and pulley ruptures, which are seen at a rate of 0.56 to 1.5 per 1000 injections.
➢ The rate of recurrence following collagenase treatment (defined as a ≥20° increase in contracture in the presence of a palpable cord, or further medical or surgical treatment of the joint) was 35% (217 of 623 joints) at the time of the three-year follow-up (27% [121 of 451] for metacarpophalangeal joints and 56% [ninety-six of 172] for proximal interphalangeal joints).
➢ Recurrence rates are lower in patients with reduction of contracture to <5° following collagenase injection compared with those with only partial correction.
Dupuytren disease is a benign fibroproliferative disorder of collagen that affects the palmar fascia of the hands, resulting in nodules and cords. These pathological cords contain myofibroblastic cells that contract, producing progressively disabling fixed flexion deformities1. The metacarpophalangeal and proximal interphalangeal joints, and the ring and small fingers, are most often affected. Despite the recent surge in scientific research regarding this common disease, the exact pathogenesis and etiology remain unclear. However, there is general agreement that this is a genetic disorder with variable penetrance2-4 as there is an increased incidence among the relatives of patients with Dupuytren disease. In addition, other studies have demonstrated that Dupuytren disease is associated with diabetes5,6, human immunodeficiency virus (HIV)7, tobacco use5,8,9, and alcohol consumption5,9,10. There is not consistent evidence to support an association between Dupuytren disease and occupations involving manual labor. A study of >97,000 miners seeking compensation for Hand-Arm Vibration Syndrome in the United Kingdom demonstrated no association between the prevalence of Dupuytren disease and the number of years of exposure to vibratory manual work after carefully controlling for patient age5. The associations between Dupuytren disease and some conditions, such as epilepsy11, are controversial, and there is no evidence to suggest that modification of factors such as smoking or drinking will change the natural history in affected patients.
Dupuytren disease primarily affects older white males of Northern European descent. Analyses of emigration patterns have shown a higher prevalence of Dupuytren disease in countries such as Australia to which Vikings and Northern Europeans emigrated12. Conversely, Dupuytren disease is rare in Africa and China. A population study of 15,950 citizens in a small Norwegian town demonstrated a 9.4% prevalence in men, compared with 2.8% in women. The authors showed a clear relationship between prevalence and age as well as equalization of the male-to-female ratio with aging13. Although the prevalence of Dupuytren disease is lower in females, the presentation and the response to operative treatment with regard to recurrence and complications were statistically similar to those in men14.
There is no known cure for Dupuytren disease, and all treatment modalities are aimed at reducing contractures and improving hand function. Operative treatment currently remains the standard treatment, with subtotal palmar fasciectomy being the most commonly performed procedure, although needle aponeurotomy has been gaining in popularity. Prospective studies have shown the functional benefits of surgery for the treatment of Dupuytren disease as measured with the Sollerman hand score15, which is a validated outcome measure based on the performance of twenty common tasks such as pouring a cup or turning a key, with 80 being the highest possible score16,17. Other nonoperative and operative adjuvant treatments that have been investigated include intralesional hyaluronidase, trypsin, gamma interferon, triamcinilone18-21, intraoperative topical 5-fluorouracil22, external beam radiation23, and verapamil/nifedipine (in vitro testing for potential intralesional use)24. Despite the generally poor results associated with these treatments, the appeal of a nonoperative solution persists because of the morbidity, complications, and lengthy recovery period typically associated with limited fasciectomy25,26.
There is good evidence to support the idea of Dupuytren diathesis, a more aggressive form of the disease. Factors associated with Dupuytren diathesis include family history, bilateral disease, ectopic lesions, male sex, and an age of less than fifty years at the time of onset. The presence of all of these factors increases the risk of recurrence by 71%, compared with 23% for patients with none of the factors27. Certain diathesis features such as plantar fibromatosis, knuckle pads, and radial side involvement have been shown to have a stronger influence on recurrence and extension than bilateral hand involvement and an early age of onset28. In addition to diathesis features, preoperative proximal interphalangeal joint contractures of >60° also have been shown to be prognostic of recurrence after operative treatment29.
Until the recent approval of collagenase clostridium histolyticum (CCH), sold under the trade name Xiaflex (Auxilium Pharmaceuticals, Malvern, Pennsylvania) and approved by the U.S. Food and Drug Administration (FDA) in February 2010, there was no other effective nonoperative option. The present report reviews the current best evidence regarding injectable collagenase for the treatment of Dupuytren disease and compares it with evidence regarding surgical options. Graded recommendations for treatment based on the best available evidence are provided.
Evidence on Injectable Collagenase
Enzymatic fasciotomy was first introduced by Bassot in 1965 when he injected a mixture of trypsin, α-chymotrypsin, hyaluronidase, thiomucase, and lidocaine into two patients with Dupuytren disease18. He reported full correction of the contractures. Enzymatic fasciotomy was later studied by Hueston19 in 1971. Using an injection of trypsin, hyaluronidase, and lidocaine, he was able to achieve full correction at the metacarpophalangeal joint in twelve patients, with limited efficacy at the proximal interphalangeal joint. The main complications were hand swelling and skin tears. Hueston saw a role for enzymatic fasciotomy particularly in elderly patients and in those with medical comorbidities precluding even regional anesthesia. McCarthy, in a study of fourteen patients who were followed for a mean of 6.5 years, was the first to present long-term data on the use of the Hueston enzymatic fasciotomy formula30. Seven of the ten patients who were available for evaluation had recurrence within two to three years, and one small finger was amputated because of infection. The author concluded that enzymatic fasciotomy offered no advantage over surgical fasciotomy but that it was associated with greater morbidity. The first proof-of-concept in vitro study of collagenase for the treatment of Dupuytren disease was performed in 1995 with use of excised cords from patients who had been managed with fasciectomy31. That study led to further clinical studies by Hurst and Badalamente and their colleagues at the State University of New York at Stony Brook that eventually brought injectable collagenase to the market32-35.
Mechanism of Action
Collagenase clostridial histolyticum contains two distinct enzymes, class-I clostridial collagenase (Aux-I) and class-II collagenase (Aux-II). These two metalloproteinase enzymes are complementary and synergistic in their ability to digest the highly stable and degradation-resistant triple helical collagen structure. The enzymes act primarily against fibrillar collagen types, including the relevant subtypes seen in Dupuytren cords (types I and III), and lack clinically relevant activity against type-IV collagen, which is found in the basement membrane of nerves, vessels, and skin36.
No drug interactions are known to occur in association with clostridial collagenase. Although tetracycline and its derivatives inhibit the action of matrix metalloproteinases (MMPs), it is unknown whether there is any effect with clinical use37,38. Similarly, anthracyclines such as daunomycin and doxorubicin have shown anticollagenase effects and potentially could reduce the efficacy of collagenase treatments39. There is no contraindication to the use of collagenase in patients receiving anticoagulants; however, we are not aware of any studies that have assessed the safety of collagenase use in this population. Because vascular leakage and ecchymosis are commonly seen following CCH injection, caution is advised with regard to its use in patients taking anticoagulants other than low-dose aspirin (<150 mg) or nonsteroidal anti-inflammatory medications within seven days after injection.
Two Phase-III multicenter, randomized, double-blinded, placebo-controlled clinical trials led to FDA approval of injectable collagenase. These two studies, named Collagenase Option for the Reduction of Dupuytren (CORD) I and CORD II, were from sixteen sites in the United States and five sites in Australia, respectively32,40. Both studies included patients who were more than eighteen years of age and who had at least one metacarpophalangeal contracture between 20° and 100° or at least one proximal interphalangeal contracture between 20° and 80° due to a palpable cord. All patients had a positive tabletop test (the inability to place the affected fingers and palm flat on a table) (Fig. 1). The studies excluded breast-feeding and pregnant women, patients with bleeding disorders, patients who had had a recent stroke, patients who had had recent treatment of the affected joint, patients who had used tetracycline derivative within fourteen days before collagenase injection, and patients with chronic neuromuscular disorders affecting the hands. One joint was treated at a time. The primary end point was a reduction of contracture of the affected joint to within 0° to 5° of full extension thirty days after the last injection. Each cord could undergo as many as three injection and manipulation cycles. In CORD I, which enrolled 308 patients, 130 (64%) of 203 joints that were randomized to the active drug group met the primary end point, compared with seven (6.8%) of 103 joints that were randomized to the placebo (control) group (treated with 10-mM TRIS per 60-mM sucrose reconstituted in diluent) (p < 0.002)32. The success rate was 77% (102 of 133) for metacarpophalangeal joints and 40% (twenty-eight of seventy) for proximal interphalangeal joints. When broken down by severity, the success rate was 89% for metacarpophalangeal joint contractures of ≤50°, compared with 58% for those of >50°. Similarly, the success rate was 81% for proximal interphalangeal joint contractures of ≤40°, compared with 22% for those of >40°. Two patients had flexor tendon ruptures, and one had complex regional pain syndrome. Mild adverse side effects (including edema, pain, ecchymosis, lymphadenopathy, pruritus, skin tear, and skin blister) were seen in almost all patients who were managed with collagenase.
The CORD II study40 enrolled sixty-six patients with use of the same protocol used in the CORD I study. Overall, twenty (44%) of forty-five joints in the collagenase group were successfully treated, compared with one (4.8%) of twenty-one joints in the placebo group (p < 0.001). The success rates for metacarpophalangeal and proximal interphalangeal joints treated with collagenase were 65% and 25%, respectively. One flexor pulley rupture was encountered.
The Joint I and Joint II studies were nine-month, open label trials of CCH that were conducted at fourteen United States sites (Joint I) and twenty international sites (Joint II)41. A total of 879 joints in 587 patients were managed with as many as three injections per joint (maximum, five injections per patient). Reduction of contracture to <5° was obtained in 497 joints (57%), including 369 (70%) of the metacarpophalangeal joints and 128 (37%) of the proximal interphalangeal joints. At least one adverse event (most commonly edema, contusion, or pain) was seen in 97% of the patients. Serious adverse events were seen in two patients; these events included one case of deep venous thrombosis and one case of tendinitis near the injection site. There were no tendon or pulley ruptures.
The patient was a seventy-two-year old, right-hand-dominant man with history of progressive contracture in both hands. At the time of evaluation, the patient had a 68° contracture of the right small metacarpophalangeal joint (Figs. 1 and 2). After the treatment options and risks were discussed, the patient chose CCH injection. The day after the injection, the hand demonstrated mild swelling and a blood blister at the proximal digital flexion crease (Fig. 3). After the finger was anesthetized with lidocaine and bupivacaine, a manipulation was performed, resulting in cord rupture (Video 1). Two months later, the patient had a CCH injection for the treatment of a left ring metacarpophalangeal contracture of 40°, and, at the time of the latest follow-up, sixteen months after treatment, the patient maintained full range of motion with no evidence of recurrence (Fig. 4).
The CORD I and CORD II studies clearly demonstrated the efficacy of collagenase compared with placebo, but long-term durability was not evaluated. Recently, Peimer et al. reported three-year recurrence data from the Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study (CORDLESS)42. This five-year study enrolled patients who had been included in any of the previous Phase-III clinical trials. Of a total of 950 eligible patients, 643 patients (1080 joints) participated. Recurrence was defined as a ≥20° worsening of contracture in the presence of a palpable cord in a joint with initial treatment success. There was an overall recurrence rate of 35% (217 of 623) among joints that were successfully treated, with a rate of recurrence of 27% (121 of 451) at the metacarpophalangeal and of 56% (ninety-six of 172) at the proximal interphalangeal joint. Among patients who had obtained partial correction (≥20° correction but not to 0° to 5°), the overall rate of nondurable response (defined as a ≥20° worsening of contracture in the presence of a palpable cord) at three years was 50% (150 of 301 joints), with a rate of 38% at the metacarpophalangeal and 62% at the proximal interphalangeal joint. These three-year data showed that patients who had achieved successful correction of Dupuytren contractures to 0° to 5° had a lower recurrence rate compared with those who had had partial correction. The joints that were successfully treated had a 65% chance of maintaining the correction at three years, and only 7% (forty-three of 623) required another CCH injection or surgical correction during that period42. The study also revealed two very different groups of patients: those in whom the contracture progressed linearly over the three-year follow-up and those in whom it remained essentially stable (Fig. 5). In both metacarpophalangeal and proximal interphalangeal joints, recurrences occur slowly, and at three years the joints have not returned to their pre-injection contracture whether fully or partially corrected. Joints without recurrence maintained the correction over three years, with only minimum change in contracture. That study did not offer any means of distinguishing between these two treatment groups.
The longest-term study of collagenase evaluated the rate of recurrence at eight years but only included eight patients from an earlier Phase-II clinical trial43. Patients in that dose-response study received either 0.145 mg, 0.29 mg, or the currently approved dose of 0.58 mg of collagenase. Recurrence was noted in four of the six patients with metacarpophalangeal contractures and both of the patients with proximal interphalangeal contractures. The recurrent metacarpophalangeal contractures generally were less severe than the initial contractures. In contrast, the recurrent proximal interphalangeal contractures progressed to become more severe than the initial contractures. The two proximal interphalangeal contractures were 35° and 55° initially and improved to 0° and 15° at one week but progressed to 50° and 70° by the time of the eight-year follow-up. No patient had further interventions following the initial single collagenase injection, although seven (88%) of the eight patients in the study stated that they would pursue further injections if needed.
Adverse Events and Complications
The most comprehensive data regarding the safety of injectable collagenase is found in the FDA Briefing Document that included safety data on all patients who had received at least one 0.58-mg dose in the twelve pre-release clinical studies44. A total of 1082 patients received 2630 injections. Minor self-limiting adverse events, most frequently edema, contusion, and pain, were seen in 98% (243) of 249 patients in the placebo-controlled trials. Serious adverse events related to the mechanism of action of the drug included three tendon ruptures and one pulley rupture (rate, 1.5 per 1000 injections). One-year post-marketing adverse events reported to the manufacturer of collagenase demonstrated a similar safety profile to that seen during clinical development. Approximately 5400 injections were performed from February 2010 to February 2011, with two reported flexor tendon ruptures and one flexor pulley injury (rate, 0.56 per 1000 injections). There were no reports of systemic or anaphylactic reactions and no reports of nerve injury45. Frequent adverse events (i.e., edema and ecchymosis) (Fig. 6) are common to almost all collagenase injections as a result of the biologically active peptide fragments produced as a result of collagen lysis. These collagen breakdown products stimulate mast cell degranulation with resultant edema, vascular leakage, and neutrophil chemotaxis46,47.
Patients managed with injectable collagenase routinely develop antibodies to both collagenase subtypes. Cross-reaction of these antibodies with human endogenous MMPs theoretically could lead to fibrotic complications, including joint stiffness, swelling, and soft-tissue pain. In a recent in vitro study, blood samples from seventy-one patients who had been managed with collagenase were studied for cross-reactivity to five MMPs, with no cross-reactivity being found between the two anti-clostridial collagenase antibodies and the five studied MMPs48. In addition, there have been no findings of adverse events related to the inhibition of endogenous MMPs across the clinical trials of clostridial collagenase.
Recently, Swanson et al. reported on a case of skin graft loss in a digit treated with collagenase49. The patient, who had been managed with dermofasciectomy eight years previously, received injections of collagenase into two central proximal interphalangeal cords through native skin. The patient was first seen again for manipulation seven days after the injection, at which time graft dehiscence was noted. No mention was made regarding possible superficial extravasation of collagenase at the time of injection. The senior author of the present review (F.T.D.K.) has used collagenase in patients who had skin grafts in proximity to the injection site and has not seen this complication. Until additional studies elucidate the risk of this complication, caution is warranted with regard to the use of collagenase near or under a skin graft.
Efficacy in the Thumb
The CORD I and CORD II trials excluded thumb treatment, and limited data exist on the efficacy of collagenase on thumb and first web space contractures. The only published report of which we are aware included five thumbs in four patients who were followed for three months50. All four patients had successful cord rupture and reported an increased range of movement and function, with no short-term serious complications.
Use of Collagenase in the Small Finger
In the twelve pre-release clinical studies, all three flexor tendon ruptures occurred following treatment for small finger proximal interphalangeal contracture. As a result, a “safe zone” for injection was introduced32, with the recommendation that injections not be placed in the cord >4 mm distal to the proximal digital flexion crease as the cord becomes closer to the flexor sheath distally in the digit. Peimer et al., in a report on the twelve-month post-marketing safety data for CCH, noted two flexor tendon ruptures and one pulley injury45. Only one of the events (a flexor rupture) followed injection for the treatment of a small finger proximal interphalangeal cord. The other two events followed treatment of ring metacarpophalangeal cords. Because of the small number of tendon ruptures, it is not yet clear whether there is an increased pattern of risk for tendon injury in the treatment of small finger proximal interphalangeal joint contracture; however, it is prudent to adhere to the manufacturer’s injection instructions and to avoid extravasation of collagenase outside of the cord during all injections.
Efficacy of Collagenase After Operative Treatment
Pooled data from twelve collagenase clinical trials involving a total of 1082 patients demonstrated no difference in terms of efficacy or safety between the 206 hands that had had previous operative treatment and the 196 hands that had not51. Injection of CCH in patients who had had previous operative treatment resulted in a 75% and 52% improvement in fixed flexion contracture at the metacarpophalangeal and proximal interphalangeal joints, respectively. This group of patients represents a possible cohort in which collagenase may have a unique advantage over revision fasciectomy as the risks of digital nerve and artery division have been reported to be as high as 58% (fifteen of twenty-six patients) during revision procedures, compared with 3.9% (three of seventy-seven patients) during primary procedures26.
Use of Collagenase in Multiple Cords
Currently, CCH is FDA-approved for the treatment of one cord per visit. In the previously mentioned CORD I and II studies, a single injection was performed, with additional injections being separated by thirty days. In a recent study, twelve patients who had at least three palpable cords were followed prospectively during two treatment sessions separated by one month52. During the first treatment session, a single cord was injected and manipulated. During the second treatment session, two different cords were injected concurrently in the same hand. Metacarpophalangeal and proximal interphalangeal joint correction were not significantly different, and no serious adverse events occurred in association with either one or two injections. In addition, no detectable systemic levels in the blood were seen in association with two concurrent injections. Although the sample size was low, these data suggest that treating two cords concurrently is safe and efficacious and allows for a more rapid return of hand function. The authors concluded that treating two cords concurrently would be a substantial advantage for both the patient and the physician.
Comparison of Injectable Collagenase with Operative Treatment
Operative treatment is the mainstay for Dupuytren disease and has been the only effective treatment for many years. In one of the few high-quality therapeutic studies on the operative treatment of Dupuytren disease, 166 rays were randomized to either percutaneous needle fasciotomy (also known as needle aponeurotomy) or limited fasciectomy53. Patients were followed for six weeks with regard to improvement in the total passive extension deficit; the Disabilities of the Arm, Shoulder and Hand (DASH) score; and complications. The total passive extension deficit improved by 79% in the limited fasciectomy group, compared with 63% in the percutaneous needle fasciotomy group (p = 0.001). When broken down by Tubiana grades54, percutaneous needle fasciotomy was shown to be less effective beyond grade II (defined as a total passive extension deficit of >90°). The rate of serious complications (including infection, hematoma, and digital nerve transection) was 0% for percutaneous needle fasciotomy and 5% for limited fasciectomy. Patients recovered faster following percutaneous needle fasciotomy. In that group, the DASH scores at week one were not significantly different from the preoperative scores. In contrast, following limited fasciectomy, it took five weeks for the DASH scores to improve to the preoperative levels. The authors concluded that percutaneous needle fasciotomy is a good treatment alternative to limited fasciectomy for patients with milder disease because of significantly quicker recovery and fewer major complications.
Evaluation of the same group from the Netherlands five years later provided the recurrence rate and long-term patient satisfaction data55. The authors defined recurrence as worsening of the total passive extension deficit of ≥30° for a treated finger. At five years, the rate of recurrence was 85% in the percutaneous needle fasciotomy group (167 joints), compared with 21% in the limited fasciectomy group (125 joints) (p < 0.001). Recurrence also occurred significantly sooner in the percutaneous needle fasciotomy group than in the limited fasciectomy group (at an average of 2.3 years compared with 3.7 years, p = 0.001). Younger patients (those less than fifty years old) had more aggressive disease and a higher rate of recurrence. The average patient satisfaction score was significantly higher following limited fasciectomy because of the better durability of the correction (p < 0.001). The authors concluded that percutaneous needle fasciotomy is best suited for well-informed elderly patients with mild contractures who are willing to accept a higher risk of recurrence in exchange for a lower rate of complications and a faster recovery. In comparison with the CORDLESS data, injectable collagenase was associated with an overall recurrence rate of 35% at three years, which was higher than that for limited fasciectomy but lower than that for percutaneous needle fasciotomy.
Pess et al. retrospectively reviewed the results of 1013 percutaneous needle aponeurotomy treatments in 474 patients56. Follow-up data on 91% of the patients demonstrated successful correction of the contracture to within 0° to 5° of full extension in 98% of the metacarpophalangeal joints and 67% of the proximal interphalangeal joints. The mean metacarpophalangeal joint contracture improved from 35° ± 19° to 1° ± 4°, and the mean proximal interphalangeal joint contracture improved from 50° ± 22° to 6° ± 11°. Complications were rare and included skin tears (prevalence, 3.4%), temporary neurapraxia (1.2%), and a presumed laceration of the ulnar digital nerve of the small finger (0.1%). The authors reported recurrence of contracture of ≤20° in 80% of the metacarpophalangeal joints and 35% of the proximal interphalangeal joints. Extrapolating from these findings, we can define recurrence as a worsening of contracture of ≥21° in order to allow for comparisons with the previous CORD studies. Therefore, there is a roughly 20% rate of recurrence at the metacarpophalangeal joint and a 65% rate of recurrence at the proximal interphalangeal joint. The authors also noted significantly greater maintenance of correction at both the metacarpophalangeal and proximal interphalangeal joints in patients more than fifty-five years old. This finding agrees with the conclusion by van Rijssen et al. that percutaneous needle fasciotomy was best suited for the older patient given the higher recurrence rate in young patients55. Both percutaneous needle fasciotomy and collagenase have been shown to be safe, with very few serious adverse events. The major complication associated with percutaneous needle fasciotomy is iatrogenic nerve division, which had a prevalence of only 0.1% in the series of Pess et al. An earlier retrospective report on 211 patients demonstrated a similar nerve division rate of 0.4% in association with percutaneous needle fasciotomy and a 3.2-year recurrence rate of 58%57. In contrast, the major complication associated with collagenase is flexor tendon or pulley rupture, which occurred in four of 1082 patients in clinical studies58.
It is unknown whether the results of enzymatic fasciotomy with use of collagenase will be similar to those of surgical fasciotomy or needle aponeurotomy. When the data reported in the CORD I study are compared with data reported by Pess et al., the primary end point of <5° contracture was successfully reached in 77% of metacarpophalangeal joints and 40% of proximal interphalangeal joints that were treated with collagenase, compared with 98% of metacarpophalangeal joints and 67% of proximal interphalangeal joints that were treated with aponeurotomy. Recurrence rates following CCH were similar to those following percutaneous needle fasciotomy at three years (27% compared with 20% for metacarpophalangeal joints and 56% compared with 65% for proximal interphalangeal joints). On the average, the patients in the study by Pess et al. had milder metacarpophalangeal and proximal interphalangeal joint contractures (35° and 50°) as compared with those in the CORD I study (48° and 55°) and therefore direct comparisons must be made with caution.
A cost-utility analysis based on a survey administered to fifty participants between fifty and eighty years of age was performed to determine the utilities and associated possible outcomes of different treatments (limited fasciectomy, percutaneous needle fasciotomy, and collagenase injection)59. The quality-adjusted life years for each possible outcome was calculated on the basis of the mean utility assigned by the participants and the mean direct cost of that treatment as based on 2009 Medicare data. Using the traditional threshold for cost effectiveness of $50,000 per quality-adjusted life year gained, the authors concluded that limited fasciectomy is not cost effective, percutaneous needle fasciotomy is cost effective if the success rate is high, and collagenase is cost effective when priced under $945.
Any new treatment method should be approached with initial skepticism and caution until it has demonstrated consistent effectiveness, tolerability, and value. Numerous well-performed clinical studies have clearly demonstrated the efficacy and safety of injectable collagenase, with data showing that 64% of joints were able to achieve reduction of contracture to within 5° of full extension. Correction was maintained in two-thirds of joints at the time of the three-year follow-up. Collagenase appears to be less durable than limited fasciectomy but better tolerated and associated with less serious complications. The value of collagenase is dependent on the cost of injection and the number of injections required. Collagenase has only been compared directly with placebo, and we are not aware of any studies in which collagenase has been compared with limited fasciectomy or percutaneous needle fasciotomy. There is a need for prospective outcome studies comparing injectable collagenase with other treatment methods (Table I).
Source of Funding: No external funding was utilized for this review.
Investigation performed at the Indiana Hand to Shoulder Clinic, Indianapolis, Indiana
Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.
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