Incidence of Tendon Rupture After Collagenase Clostridium Histolyticum Injection for Treatment of Dupuytren Contracture in Adults: A Postmarketing Safety Analysis.

Purpose: Based, in part, on the clinical study reports of tendon rupture events after collagenase clostridium histolyticum (CCH) (Xiaflex, Endo Pharmaceuticals Inc) treatment for Dupuytren contracture (DC), a Risk Evaluation and Mitigation Strategy program was instituted in 2010 by Auxilium Pharmaceuticals (now Endo Pharmaceuticals Inc) to ensure that the benefits of CCH injection outweighed the risks when treating DC. Using the postmarketing surveillance data collected in this program, a retrospective analysis was conducted to evaluate the incidence of flexor tendon rupture after CCH treatment for DC in the clinical practice setting. Methods: The Endo Pharmaceuticals Inc safety database was searched for cases of tendon rupture reported between February 2, 2010, and October 8, 2015. Total number of CCH treatments for DC and incidence of tendon rupture were estimated using CCH dosing derived from clinical trial experience (1.7 CCH vials/treatment) or clinical practice evidence (1.08 CCH vials/treatment). Results: Over the 5.8-year surveillance period, 97,609 vials of CCH were distributed for the treatment of DC, equivalent to an estimated total of 57,416 treatments (at 1.7 CCH vials/treatment) or 90,378 treatments (at 1.08 CCH vials/treatment). Although CCH distribution increased during the surveillance period, reports of tendon rupture were infrequent (approximately 13 cases/y; total cases: flexor tendon, n = 57; ligament/pulley, n = 2), corresponding to a 0.10% (1.7 CCH vials/treatment) or 0.06% (1.08 CCH vials/treatment) mean estimated incidence of tendon rupture in patients with DC after CCH treatment. Conclusions: This retrospective analysis showed that flexor tendon rupture occurred infrequently in patients with DC who were treated with CCH in real-world practice settings between 2010 and 2015. On the basis of these findings and other favorable safety evidence, the Risk Evaluation and Mitigation Strategy program requirement for CCH for the treatment of DC was ended by the US Food and Drug Administration in November 2016. Type of study/level of evidence: Therapeutic IV.

Relationship between Fracture of the Ulnar Styloid Process and DRUJ Instability: A Biomechanical Study.

Background There has been clinical question in the treatment of ulnar styloid fracture with distal radius fracture, surgical fixation of the styloid fragment, or ignorance of the fragment. We examined relationship between size of the ulnar styloid fracture and distal radioulnar joint (DRUJ) stability biomechanically to answer the above clinical question. Methods Changes in the dorsopalmar stiffness of the DRUJ after experimentally simulating in four types of ulnar styloid fractures were examined in cadavers. After tip, middle, base-horizontal, and base-oblique type of styloid fractures were made sequentially, changes in dorsopalmar DRUJ stiffness were measured using the MTS machine in the intact wrist, for each fracture, at 60 degrees pronation, neutral, and 60 degrees supination, respectively. Additional cutting of the radioulnar ligament (RUL) at the fovea was also simulated with the base-horizontal fracture. Results The tip and middle type fractures did not demonstrate significant loss of stiffness compared with the intact. The base-horizontal fracture demonstrated only significant loss of stiffness in the dorsal direction (radius palmar; ulnar dorsal) with forearm in neutral rotation. The base-oblique fracture demonstrated significant loss of dorsopalmar stiffness of the DRUJ. Additional section of the RUL with the base-horizontal fracture induced significant loss of stiffness of the DRUJ compared with the intact. Conclusions Because the RUL originates from the fovea as well as from the base of the ulnar styloid, these results suggest that DRUJ instability closely correlates with how much of the bony fragment includes the originating portions of the RUL. The findings further suggest that larger base-oblique and base-horizontal fragments with resultant DRUJ instability must be reattached, but that even base-horizontal fragment as well as tip and middle ulnar styloid fragment can be ignored when there is no instability.

Anesthesia for collagenase clostridium histolyticum injection in patients with dupuytren disease: A cohort analysis.

Procedural pain is one of the most common adverse effects reported by patients with Dupuytren disease (DD) treated with collagenase clostridium histolyticum (CCH). The aim of this study was to assess the effectiveness of wrist block before CCH injection in reducing procedural pain and to analyze its impact on adverse effects. We performed a prospective, single-center study in which we compared two groups of patients in a consecutive cohort. In the first group (NO-BLOCK), wrist block was only performed before finger extension, whereas in the second group (BLOCK), it was performed before CCH injection and finger extension. Pain was assessed on a 10-item numerical rating scale. Our results show that pain scores were clearlylower in the BLOCK group than in the NO-BLOCK group: 4.72 vs. 0.61 for CCH injection and 3.43 vs. 0.82 for finger extension. Patients who rated CCH injection pain with a score of 4 or higher were 11 times more likely to experience pain during extension. There was a weak correlation between the use of wrist block for CCH injection and the occurrence of skin lacerations (Spearman's rho = -0.222, p < 0.01) and the presence of pruritus (Spearman's rho = 0.183, p < 0.07). In conclusion, wrist block before CCH injection is an effective measure of decreasing perceived pain throughout the different stages of CCH treatment in patients with DD.

Skin Laceration in Collagenase Clostridium histolyticum Treatment for Dupuytren's Contracture.

BACKGROUND: Dupuytren's contracture produces a progressive flexion contracture of the affected fingers. Collagenase Clostridium histolyticum produces breakdown of the cord in the hand and/or finger(s) that tightens as a result of the disease creating a contracture, allowing manual traction and cord rupture. One of the side effects is spontaneous skin laceration when the finger is extended. OBJECTIVES: To evaluate the development of skin lacerations in Dupuytren's contracture treated with collagenase Clostridium histolyticum, to determine predisposing factors, and evaluate the effectiveness of 2 different treatments (antiseptic and non-antiseptic dressings). PARTICIPANTS: Included 157 patients diagnosed with Dupuytren's contracture and treated with collagenase Clostridium histolyticum. METHODS: Analysis of variables and logistic regression model were applied to determine their possible relationship with skin lacerations. The effectiveness of the type of treatment used was evaluated by comparing the amount of time required for healing. RESULTS: Skin lacerations were present in 33.1% (n = 52) of patients, with an average laceration length of 1.12 (SD: 0.70) cm. Characteristics that were significant predisposing factors for lacerations were disease bilateralism (p = .002), previous surgical intervention (p = .003), and initial matacarpophalangeal joint contracture (p < .001). Worse initial contracture (Z = 5.94; p < .001) had a greater risk of laceration as did those who had prior hand surgery, or whose little finger was affected. Average treatment length of healing was 11.24 days (SD: 8.13). All wounds healed successfully. There were no significant differences (p = .511) in healing between different dressings evaluated. CONCLUSIONS: Skin lacerations as a consequence of treating Dupuytren's contracture with collagenase Clostridium histolyticum occur often and are moderately serious. For all cases, evolution is satisfactory in less than 2 weeks, and the type of treatment does not appear to make any difference in healing time.

Treatment of Recurrent Dupuytren Contracture in Joints Previously Effectively Treated With Collagenase Clostridium histolyticum.

PURPOSE: Collagenase Clostridium histolyticum (CCH) is approved for the treatment of adults with Dupuytren contracture with a palpable cord. This open-label, phase 4 study evaluated the safety and efficacy of CCH for the retreatment of recurrent contractures in joints that were previously effectively treated with CCH. METHODS: Patients participating in a long-term follow-up study who had contracture recurrence (increased ≥ 20° with a palpable cord) after successful treatment in the previous study were eligible. Recurrent joint contractures were treated with up to 3 CCH injections (∼ 1 month apart). Patients were followed for 1 year to evaluate safety. Assessments included change in joint contracture, range of motion, and the percentage of joints that achieved contracture of 5° or less at day 30 after the last injection. RESULTS: The efficacy analysis included 51 patients with 1 treated joint per patient (31 metacarpophalangeal, 20 proximal interphalangeal). A total of 35 joints (69%) received 1 injection, 12 (24%) received 2 injections, and 4 (8%) received 3 injections. Fifty-seven percent of joints achieved contracture of 5° or less (29 of 51). Overall, 86% (43 of 50) patients had a 20° or greater increase in range of motion. The adverse event profile was consistent with previous studies. One ligament injury was reported. CONCLUSIONS: At a short-term follow-up of 1 year, recurrent contracture in joints previously successfully treated with CCH may be effectively retreated with up to 3 injections of CCH. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Pain Associated With Treatment of Dupuytren Contracture With Collagenase Clostridium histolyticum.

PURPOSE: The primary objective of this study was to quantify the degree of pain associated with collagenase Clostridium histolyticum (CCH) injection and to determine whether it is related to other factors in the intervention. METHODS: A prospective study of 135 patients was performed to evaluate pain at 3 points during treatment: (1) after CCH injection, using a numerical rating scale (NRS), (2) a binary (positive/negative) assessment before manipulation 24 hours after CCH and after removing the bandage, and (3) after joint manipulation performed with wrist block anesthesia. RESULTS: The average NRS for pain during infiltration was 4.7. Pain was present before manipulation in 52.6% of patients. Pain from manipulation showed an average NRS score of 3.6. The amounts of pain at CCH infiltration, pain after 24 hours, and pain from the manipulation were correlated because patients who experienced pain during CCH infiltration were more likely to report experiencing pain during manipulation. CONCLUSIONS: Collagenase Clostridium histolyticum injection for treating Dupuytren contracture can be a painful process. There is a clear relationship between a patient's level of pain during injection of CCH and the likelihood that the patient will experience pain during manipulation, even with the use of local anesthesia. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Dupuytren Contracture Recurrence Following Treatment With Collagenase Clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data.

PURPOSE: Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study was a 5-year noninterventional follow-up study to determine long-term efficacy and safety of collagenase clostridium histolyticum (CCH) treatment for Dupuytren contracture. METHODS: Patients from previous CCH clinical studies were eligible. Enrolled patients were evaluated annually for contracture and safety at 2, 3, 4, and 5 years after their first injection (0.58 mg) of CCH. In successfully treated joints (≤ 5° contracture following CCH treatment), recurrence was defined as 20° or greater worsening (relative to day 30 after the last injection) with a palpable cord or any medical/surgical intervention to correct new/worsening contracture. A post hoc analysis was also conducted using a less stringent threshold (≥ 30° worsening) for comparison with criteria historically used to assess surgical treatment. RESULTS: Of 950 eligible patients, 644 enrolled (1,081 treated joints). At year 5, 47% (291 of 623) of successfully treated joints had recurrence (≥ 20° worsening)-39% (178 of 451) of metacarpophalangeal and 66% (113 of 172) of proximal interphalangeal joints. At year 5, 32% (198 of 623) of successfully treated joints had 30° or greater worsening (metacarpophalangeal 26% [119 of 451] and proximal interphalangeal 46% [79 of 172] joints). Of 105 secondary interventions performed in the successfully treated joints, 47% (49 of 105) received fasciectomy, 30% (32 of 105) received additional CCH, and 23% (24 of 105) received other interventions. One mild adverse event was attributed to CCH treatment (skin atrophy [decreased ring finger circumference from thinning of Dupuytren tissue]). Antibodies to clostridial type I and/or II collagenase were found in 93% of patients, but over the 5 years of follow-up, this did not correspond to any reported clinical adverse events. CONCLUSIONS: Five years after successful CCH treatment, the overall recurrence rate of 47% was comparable with published recurrence rates after surgical treatments, with one reported long-term treatment-related adverse event. Collagenase clostridium histolyticum injection proved to be an effective and safe treatment for Dupuytren contracture. For those receiving treatment during follow-up, both CCH and fasciectomy were elected options. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Collagenase clostridium histolyticum for dupuytren contracture: patterns of use and effectiveness in clinical practice.

PURPOSE: To collect data on the real-world effectiveness of collagenase clostridium histolyticum (CCH) during its first year of use following U.S. Food and Drug Administration approval and compare those results with clinical trial efficacy data. METHODS: This retrospective chart review was conducted at 10 U.S. community and academic practice sites with major experience using CCH. Charts of patients treated with CCH between February and December 2010 were abstracted, and anonymized data were analyzed. Clinical use, including number of injections per cord and effectiveness outcomes (joint contracture and range of motion) were compared with results from 2 registration trials. RESULTS: Data were collected from 501 patients (74% male; 48% employed; mean [SD] age, 65 [10] y); 463 patients had sufficient data for analysis. We found that 1.08 CCH injections were used per treated joint, compared with a mean of 1.7 injections in registration trials. Ninety-three percent of joints received only 1 injection. The mean (SD) number of visits per injection was 2.92 (1.0). Mean (SD) contracture was reduced by 75% from 49° (21) at baseline to 12° (17), similar to the 71% to 79% reduction in clinical trials. Mean (SD) range of motion was improved by 37° from 44° (20) at baseline to 81° (14), similar to the increase of 35° and 37° in the 2 clinical trials; and 67% of first injections resulted in full correction to 0° to 5°, compared with the clinical trial rate of 39%. CONCLUSIONS: Despite a lower injection rate, correction of joint contracture and range of motion was similar to findings from clinical trials. Effectiveness reports using this kind of surveillance design could provide patients, physicians, and payers with the information needed to make better treatment and reimbursement decisions. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS study): 3-year data.

PURPOSE: To evaluate long-term efficacy and safety of collagenase clostridium histolyticum (CCH) after the third year of a 5-year nontreatment follow-up study, Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study. METHODS: This study enrolled Dupuytren contracture patients from 5 previous clinical studies. Beginning 2 years after their first CCH injection, we re-evaluated patients annually for joint contracture and safety. Recurrence in a previously successfully treated joint (success = 0° to 5° contracture after CCH administration) was defined as 20° or greater worsening in contracture in the presence of a palpable cord or medical/surgical intervention to correct new or worsening contracture. We assessed partially corrected joints (joints reduced 20° or more from baseline contracture but not to 0° to 5°) for nondurable response, also defined as 20° or greater worsening of contracture or medical/surgical intervention. RESULTS: Of 1,080 CCH-treated joints (648 metacarpophalangeal [MCP]; 432 proximal interphalangeal [PIP]; n = 643 patients), 623 (451 MCP, 172 PIP) had achieved 0° to 5° contracture in the original study. Of these joints, 35% (217 of 623) recurred (MCP 27%; PIP 56%). Of these recurrences, an intervention was performed in 7%. Of the 1,080 CCH-treated joints, 301 were partially corrected in the original study. Of these, 50% (150 of 301; MCP: 38% [57 of 152]; PIP: 62% [93 of 149]) had nondurable response. We identified no new long-term or serious adverse events attributed to CCH during follow-up. Anti-clostridial type I collagenase and/or anti-clostridial type II collagenase antibodies were reported for 96% or more of patients who received 2 or more CCH injections and 82% who received 1 injection. CONCLUSIONS: The recurrence rate, which is comparable to other standard treatments, and the absence of long-term adverse events 3 years after initial treatment indicate that CCH is an effective and safe treatment for Dupuytren contracture. Most successfully treated joints had a contracture well below the threshold for surgical intervention 3 years after treatment. Recurrence rates among successfully treated joints were lower than nondurable response rates among partially corrected joints. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Vertical locking of the metacarpophalangeal joint in young adults.

Locking of the metacarpophalangeal joints has been occasionally reported in older adults, but reports of this problem are rare in younger individuals. We report 8 young adult patients with a metacarpophalangeal joint locked in 90° flexion after minor trauma. The cases included 6 little fingers and 2 thumbs in 1 male and 7 female patients aged 16 to 39 years. All were easily reduced closed. We postulate the mechanism of injury.

Ulnar coronoid process anatomy: possible implications for elbow instability.

Ulnar coronoid process fractures are relatively uncommon injuries usually occurring with elbow dislocations and contributing to elbow instability. Recent evidence suggests coronoid tip fractures have a role in the instability. We sought to quantify the capsular and brachialis attachments of the ulnar coronoid process to better understand why instability occurs. We prepared eight fresh-frozen cadaveric specimens to ascertain the specific attachment locations. After dissection, we isolated and resected the proximal ulna, including the coronoid process and its soft tissue attachments. We then embedded, sectioned, and stained the specimens. The average distance from the tip of the coronoid to the proximal capsule was 2.36 +/- 0.39 mm. The average distance from the tip of the coronoid to the proximal brachialis insertion was 10.13 +/- 1.6 mm. Most coronoid tip fractures included disruption of the anterior capsule, which potentially explains why instability can be associated with these fractures.

Flexor superficialis abductor transfer with carpal tunnel release for thenar palsy.

PURPOSE: In patients with advanced chronic carpal tunnel syndrome (CTS) the ability of the thumb to abduct and perform functional opposition is impaired greatly, primarily because of denervation and paralysis of the abductor pollicis brevis muscle. The purpose of this study was to evaluate the results of transfer of the flexor digitorum superficialis to the abductor pollicis brevis for restoration of thumb abduction in thenar paralysis caused by advanced chronic CTS. METHODS: Fifty patients (51 hands) with advanced CTS and loss of thumb abduction had a flexor digitorum superficialis transfer (37 small, 10 ring, 4 middle finger donors) to the abductor pollicis brevis with simultaneous carpal tunnel release (49 of 51 endoscopic). Thirty patients (60%) were women with an average age of 70 years (range, 35-90 y). Forty-three patients (84%) were in their sixth through eighth decades. We analyzed retrospectively preoperative and postoperative abduction, abduction strength, thenar muscle recovery and function, and patient satisfaction and complications. RESULTS: All patients reported improved thumb and hand function. Thumb abduction increased almost 20 degrees and 3 British Medical Research Council strength grades. Abduction was improved by the transfer in all patients, with some thenar recovery found in 35 of 40 cases followed-up longer than 12 months. Harvest of the flexor digitorum superficialis from the ring and middle fingers was associated with donor finger proximal interphalangeal joint contracture, although harvest from the small finger was not. CONCLUSIONS: Carpal tunnel release with simultaneous flexor digitorum superficialis-to-abductor pollicis brevis transfer provides satisfactory results for patients with profound CTS and thenar paralysis. The use of the small finger superficialis as the donor motor has minor morbidity compared with other methods and has predictable improvement and patient satisfaction. This transfer method is combined easily with endoscopic carpal tunnel release (as in 49 of our 51 cases), 2-portal, or open method releases.

Sonographically guided percutaneous carpal tunnel release: an anatomic and cadaveric study.

Minimally invasive techniques have become the standard of care for multiple procedures. This paper demonstrates both the surgeons' capacity to perform an accurate anatomic evaluation of the hand and forearm (n=10) and the use of this anatomic information to accurately perform sonographically guided, percutaneous carpal tunnel release using a single-portal endoscope without direct or indirect visualization in a cadaver model (n=6). Open dissection was then performed to confirm complete ligament transection and to evaluate the surrounding structures for injury. In all 6 cadavers, the transverse carpal ligament was transected completely without injury to any surrounding structures. With further investigation, this novel technique may offer a less invasive, office-based method for the surgical treatment of carpal tunnel syndrome that may offer patients an expedited recovery.