Therapie des Morbus Dupuytren mit Injektion von Kollagenase in Deutschland – Ergebnisse und Komplikationen an 110 Gelenken

Zusammenfassung

Hintergrund Seit 2011 steht in Deutschland mit der Injektion von mikrobieller Kollagenase (Xiapex®, Fa. Pfizer) ein neues minimalinvasives Verfahren zur Therapie des Morbus Dupuytren zur Verfügung.

Ziel Wir berichten über die aktuelle Situation, Ergebnisse und Komplikationen nach Injektion von mikrobieller Kollagenase zur Therapie des Morbus Dupuytren in Deutschland.

Patienten und Methoden In unserer Studie wurde 78 Patienten (61 Männer, 17 Frauen) mit 87 Injektionen an 87 Strahlen (Kleinfinger n = 40, Ringfinger n = 37, Mittelfinger n = 8 und Zeigefinger n = 2) behandelt, und wir konnten davon 39 Patienten (32 Männer, 7 Frauen) über einen Zeitraum von 6 Monaten prospektiv beobachtet. Wir dokumentierten Kontrakturgrade prätherapeutisch, nach 6 Wochen und nach 6 Monaten.

Ergebnisse Am MCP-Gelenk (n = 26) erfolgte eine Korrektur von durchschnittlich 51° auf 0° (p < 0,05). Nach 6 Monaten konnte die Kontraktur am MCP-Gelenk (n = 16) von durchschnittlich 52° auf 0° reduziert werden (p < 0,05). Die initiale Korrektur am PIP-Gelenk (n = 28) belief sich von durchschnittlich 63° auf 15° (p < 0,05). Nach 6 Monaten zeigte sich am PIP-Gelenk (n = 12) eine durchschnittliche Reduktion von 70° auf 40° (p < 0,05). Bei kombinierten Kontrakturen von MCP- und PIP-Gelenk (n = 33) ergab sich eine Korrektur von 96° auf 13° (p < 0,05). Nach 6 Monaten zeigte sich bei den kombinierten Kontrakturen (n = 16) eine Korrektur von 91° auf 61° (p < 0,05). Als häufige Nebenwirkungen registrierten wir lokale Schwelllungen (n = 36), gefolgt von Hämatomen (n = 25), temporären lividen Verfärbungen (n = 17) und Hautrissen (n = 16). Es kam zu keinen schweren Komplikationen wie Beugesehnen-, Gefäß- oder Nervenverletzungen. Die schwersten Komplikationen waren 4 kleine Hautdefekte, die jedoch im Verlauf mit konservativer Wundbehandlung abheilten.

Schlussfolgerung Verglichen mit internationalen Studien präsentieren wir vergleichbare Resultate. Hervorzuheben sind die guten Ergebnisse mit nur einer Injektion bei hohen prätherapeutischen Kontrakturgraden am MCP-Gelenk und respektable Erfolge bei kombinierten Kontrakturen an beiden Gelenken mit nur einer Injektion. Es traten keine schwerwiegenden Komplikationen auf. Die Nebenwirkungen entsprechen dem Spektrum vergleichbarer Studien. Wir sind der Meinung, dass die Injektion von mikrobieller Kollagenase eine komplikationsarme und erfolgversprechende Therapieoption zur Behandlung des M. Dupuytren darstellt. Endgültige Aussagen zur Effektivität im Vergleich zur perkutanen Nadelfasziotomie (PNF) und partiellen Aponeurektomie müssen weitere Langzeitstudien untersuchen.

Abstract

Background Since 2011, a new minimally-invasive treatment for Dupuytren’s disease has been available in the form of injectable collagenase (Xiapex®, Pfizer).

Purpose Our aim is to report about the results and adverse effects of injectable collagenase for the treatment of Dupuytren’s disease in Germany.

Patients and Methods We treated 78 patients (61 male, 17 female) with 87 injections in 87 digits (little finger n = 40, ring finger n = 37, middle finger n = 8 and index n = 2). We documented the range of motion before treatment, after 6 weeks and after 6 months. We were able to include 39 patients (32 male, 7 female) in the 6-month follow-up.

Results The initial correction in MCP joints (n = 26) was from an average 51° to 0° (p < 0.05). After 6 months there was an average reduction of contracture in MCP joints (n = 16) from 52° to 0° (p < 0.05). The initial correction in PIP joints (n = 28) was from an average of 63° to 15° (p < 0.05). After 6 months, PIP joints (n = 12) exhibited an average correction from 70° auf 40° (p < 0.05). In combined contractures of MCP und PIP joints (n = 33), there was a mean reduction from 96° to 13° (p < 0.05). In the 6-month follow-up, the correction of combined contractures (n = 16) was from 91° to 61° (p < 0.05). Common adverse effects were local oedema (n = 36), followed by haematoma (n = 25), temporary livid discolouration (n = 17) and skin tears (n=16). There were no severe complications such as tendon ruptures, vessel or nerve injuries. The most severe complications comprised 4 little skin defects that healed with conservative wound care.

Conclusion Our results are comparable with previous international studies. Very good success has been achieved with single injection treatment for high-grade preoperative contractures in MCP joints, while treatment success for combined contractures of MCP and PIP joints has been satisfactory. There have been no severe complications. Common adverse effects have been similar to previous studies. In our opinion, collagenase injection is a safe and efficient treatment for Dupuytren’s disease. Further studies are needed to compare long-term efficacy with percutaneous needle aponeurotomy und partial fasciectomy.

Schlüsselwörter

M. Dupuytren - Kollagenase

Key words

Dupuytren’s disease - collagenase

• Literatur

• 1 Felici N, Marcoccio I, Giunta R. et al. Dupuytren contracture recurrence project: reaching consensus on a definition of recurrence. Handchir Mikrochir Plast Chir 2014; 46: 350-354
• 2 Hurst LC, Badalamente MA, Hentz VR. et al. Injectable collagenase clostridium histolyticum for Dupuytren’s contracture. N Engl J Med 2009; 361: 968-979
• 3 Spanholtz TA, Holzbach T, Wallmichrath J. et al. Treatment of Dupuytren’s contracture by means of injectable collagenase: first clinical experiences. Handchir Mikrochir Plast Chir 2011; 43: 275-280
• 4 Watt AJ, Curtin CM, Hentz VR. Collagenase injection as nonsurgical treatment of Dupuytren’s disease: 8-year follow-up. J Hand Surg Am 2010; 35: 534-539 539 e531
• 5 Knobloch K, Kraemer R, Papst S. et al. German version of the brief Michigan Hand Outcomes Questionnaire: implications for early quality of life following collagenase injection in dupuytren contracture. Plast Reconstr Surg 2012; 129: 886e-887e
• 6 Hallock GG. Skin laceration as a serious adverse sequela of injectable collagenase for Dupuytren contracture. Plast Reconstr Surg 2012; 129: 205e-206e
• 7 Knobloch K, Vogt PM. Beware of the small finger and/or the proximal interphalangeal joint? Skin lacerations following collagenase injection in dupuytren contracture. Plast Reconstr Surg 2012; 130: 202e-204e author reply 204e–205e
• 8 Spiers JD, Ullah A, Dias JJ. Vascular complication after collagenase injection and manipulation for Dupuytren’s contracture. J Hand Surg Eur Vol 2014; 39: 554-556
• 9 Rozen WM, Edirisinghe Y, Crock J. Late complications of clinical clostridium histolyticum collagenase use in Dupuytren’s disease. PLoS One 2012; 7: e43406
• 10 King IC, Belcher HJ. Cold intolerance following collagenase Clostridium histolyticum treatment for Dupuytren contracture. J Hand Surg Am 2014; 39: 808-809
• 11 Hay DC, Louie DL, Earp BE. et al. Surgical findings in the treatment of Dupuytren’s disease after initial treatment with clostridial collagenase (Xiaflex). J Hand Surg Eur Vol 2014; 39: 463-465
• 12 Peimer CA, Wilbrand S, Gerber RA. et al. Safety and tolerability of collagenase Clostridium histolyticum and fasciectomy for Dupuytren’s contracture. J Hand Surg Eur Vol 2015; 40: 141-149
• 13 Alberton F, Corain M, Garofano A. et al. Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren contracture: report of 40 cases. Musculoskelet Surg 2014; 98: 225-232
• 14 Warwick D, Arner M, Pajardi G. et al. Collagenase clostridium histolyticum in patients with Dupuytren’s contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes. J Hand Surg Eur Vol 2015; 40: 124-132
• 15 Witthaut J, Jones G, Skrepnik N. et al. Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: short-term results from 2 open-label studies. J Hand Surg Am 2013; 38: 2-11
• 16 Binter A, Neuwirth M, Rab M. Treatment of Dupuytren’s disease with collagenase – a 1-year follow-up of 37 patients. Handchir Mikrochir Plast Chir 2014; 46: 355-360
• 17 Arora R, Kaiser P, Kastenberger TJ. et al. Injectable collagenase Clostridium histolyticum as a nonsurgical treatment for Dupuytren’s disease. Oper Orthop Traumatol 2016; 28: 30-37
• 18 Sood A, Therattil PJ, Paik AM. et al. Treatment of dupuytren disease with injectable collagenase in a veteran population: a case series at the department of veterans affairs new jersey health care system. Eplasty 2014; 14: e13
• 19 Peimer CA, Blazar P, Coleman S. et al. 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. J Hand Surg Am 2015; 40: 1597-1605
• 20 Skirven TM, Bachoura A, Jacoby SM. et al. The effect of a therapy protocol for increasing correction of severely contracted proximal interphalangeal joints caused by dupuytren disease and treated with collagenase injection. J Hand Surg Am 2013; 38: 684-689
• 21 Hayton MJ, Bayat A, Chapman DS. et al. Isolated and spontaneous correction of proximal interphalangeal joint contractures in Dupuytren’s disease: an exploratory analysis of the efficacy and safety of collagenase Clostridium histolyticum. Clin Drug Investig 2013; 33: 905-912
• 22 Badalamente MA, Hurst LC, Benhaim P. et al. Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in dupuytren contracture: combined analysis of 4 phase 3 clinical trials. J Hand Surg Am 2015; 40: 975-983
• 23 Nydick JA, Olliff BW, Garcia MJ. et al. A comparison of percutaneous needle fasciotomy and collagenase injection for dupuytren disease. J Hand Surg Am 2013; 38: 2377-2380
• 24 Stromberg J, Ibsen-Sorensen A, Friden J. Comparison of Treatment Outcome After Collagenase and Needle Fasciotomy for Dupuytren Contracture: A Randomized, Single-Blinded, Clinical Trial With a 1-Year Follow-Up. J Hand Surg Am 2016; 41: 873-880
• 25 Vollbach FH, Walle L, Fansa H. Dupuytren’s disease – patient satisfaction and functional results one year after partial fasciectomy and injection of collagenase. Handchir Mikrochir Plast Chir 2013; 45: 258-264
• 26 Zhao JZ, Hadley S, Floyd E. et al. The Impact of Collagenase Clostridium histolyticum Introduction on Dupuytren Treatment Patterns in the United States. J Hand Surg Am 2016; 41: 963-968
• 27 Mehta S, Belcher HJ. A single-centre cost comparison analysis of collagenase injection versus surgical fasciectomy for Dupuytren’s contracture of the hand. J Plast Reconstr Aesthet Surg 2014; 67: 368-372
• 28 Povlsen B, Shields AM, Bhabra GS. Resource utilisation associated with single digit Dupuytren’s contracture treated with either surgery or injection of collagenase Clostridium histolyticum. Hand Surg 2014; 19: 205-209
• 29 Gaston RG, Larsen SE, Pess GM. et al. The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study. J Hand Surg Am 2015; 40: 1963-1971
• 30 Gajendran VK, Hentz V, Kenney D. et al. Multiple collagenase injections are safe for treatment of Dupuytren’s contractures. Orthopedics 2014; 37: e657-660