Background Collagenase Clostridium histolyticum (CCH), recently approved in Europe is an efficacious, minimally invasive, and well tolerated treatment for Dupuytren’s contracture (DC).
Objectives To report efficacy/safety and recurrence rates 3 years after CCH treatment from the ongoing, 5-year follow-up CORDLESS study of DC patients who participated in Phase III trials of CCH and had ≥1 fixed-flexion contracture (FFC) measurement.
Methods CORDLESS enrolled DC patients from all 5 Phase III studies of CCH. Patients were evaluated annually for recurrence starting 2 years after CCH injection. Detailed history, examinations, additional treatments for DC and complications were recorded. Recurrence was defined as: (1) increase in contracture ≥20° and a palpable cord or (2) the joint received further CCH/surgical treatment. A post hoc analysis defined recurrence as a ≥30° increase in joint contracture, a commonly used clinical threshold for secondary surgical intervention. Recurrence by baseline disease severity was also calculated. Low severity was defined as FFC ≤50° for metacarpophalangeal (MP) joints and ≤40° for proximal interphalangeal (PIP) joints, and high severity was defined as FFC >50° for MP and >40° for PIP joints.
Results 602 patients (84% male, mean±SD age, 66±9 y) were evaluable at Year 3. Of 1080 treated joints, 623 (58%) achieved clinical success (FFC of affected joint improved to 0-5°). By Year 3, 35% (217/623) of successfully treated joints had recurrence (≥20°), in 27% (120/451) of MP and 56% (97/172) of PIP joints. By Year 3, 22% met the ≥30° definition of recurrence; rates were 16% in MP joints and 38% in PIP joints. In successfully treated joints, lower baseline severity was associated with lower recurrence rates in PIP (50% low vs 71% high) but not in MP joints (28% low vs 18% high). Mean FFC for nonrecurring joints (MP 2.8°; PIP 7.8°) was nearly the same as mean FFC at time of initial success (MP 1.2°; PIP 1.7°). Mean FFC for the recurrent joints at Year 3 (MP 32.8°; PIP 36.7°) was below the pretreatment levels (MP 36.5°; PIP, 40.1°). About 7% of joints underwent CCH treatment or surgical intervention for recurrence by Year 3. No new long-term adverse events (AEs) or serious AEs related to previous CCH treatment were observed.
Conclusions CCH is efficacious and well tolerated in DC patients 3 years after initial treatment, and treatment response is durable. Using ≥20° and ≥30° definitions, overall recurrence rate by Year 3 was 35% and 22%, respectively. Recurrence was more common in PIP than MP joints, consistent with published surgical literature. Less severe PIP contracture at baseline resulted in better outcomes. The absence of new or serious AEs at indicates a good long-term tolerability profile for CCH.
Disclosure of Interest M. Boeckstyns: None Declared, D. Boyce: None Declared, J. Vasenius: None Declared, F. T. Kaplan: None Declared, C. Peimer: None Declared, P. Blazar: None Declared, D. Gilpin: None Declared, T. Smith Employee of: Auxilium Pharmaceuticals, J. Tursi Employee of: Auxilium Pharmaceuticals, B. Cohen Employee of: Auxilium Pharmaceuticals, P. Szczypa Employee of: Pfizer Ltd, R. Gerber Employee of: Pfizer Inc
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