Efficacy of Collagenase Clostridium Histolyticum Injection, a Potential Nonsurgical Intralesional Treatment Option for Plantar Fibromatosis: A Randomized, Open-Label, Dose-Ranging Study

Abstract

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Plantar fibromatosis (PFi) is characterized by collagen-containing nodules on the foot along the plantar fascia that can cause pain and functional disability. Current treatments focus on symptom relief, which may become ineffective, or surgery, which can have lengthy recovery times. Collagenase clostridium histolyticum (CCH) is approved for Dupuytren’s and Peyronie’s disease treatment, which are both fibroproliferative disorders that may coexist in patients with PFi. This dose-ranging study assessed the efficacy and safety of CCH treatment of PFi. Methods: In this Phase 1, multicenter study, participants were randomly allocated (1:1:1) to receive 0.6, 1.2, or 2.25 mg/mL CCH. All participants underwent the initial treatment period (ITP) and received 1–2 intralesional injections per nodule on Day 1 with 5 follow-up assessments. Participants with palpable treated nodules could receive additional CCH doses (at 2.25 mg/mL; retreatment period, RP), with follow-up at specified intervals. Assessments included a 5-scale measure of nodule hardness (0 [nonpalpable] to 4 [hard]), and the Foot Function Index-Short Form23 (FFI-SF23) reported as a composite score (0 – 100) of 3 subscale scores (disability, difficulty, and pain subscales). Results: After ITP (n=24), 100% (8/8) of participants receiving 2.25 mg/mL CCH showed improvement in nodule hardness, compared with 87.5% (7/8) and 75% (6/8) of participants receiving 1.2 and 0.6 mg/mL, respectively. FFI-SF23 also showed a negative change from baseline across treatment groups, indicating improvement. Participants that received 2.25 mg/mL reported the largest percent improvement (-83.7%). After RP (n=11), 81.8% (9/11) of participants showed improvement in nodular hardness and an FFI-SF23 score change of -9.3%, indicating further improvement from baseline after ITP. CCH had a consistent safety profile in ITP/RP. Conclusion: CCH caused dose-dependent improvement of nodule hardness after treatment, with 2.25 mg/mL utilized for nodule retreatment; FFI-SF23 scores correlated with this finding, indicating CCH may be a potential nonsurgical intralesional option for PFi treatment.