Determining clinically important changes in range of motion in patients with Dupuytren's Contracture: secondary analysis of the randomized, double-blind, placebo-controlled CORD I study.

ABSTRACT

BACKGROUND AND OBJECTIVE: Injectable collagenase Clostridium histolyticum is efficacious in correcting Dupuytren's contracture as assessed by changes in the angle of contracture and range of motion (ROM). However, clinically important changes in ROM have not been evaluated in depth. The objective of this secondary analysis of the CORD I trial was to identify severity levels using baseline ROM, estimate a clinically important difference (CID) for ROM, and link the results to collagenase treatment and patient satisfaction. METHODS: In the CORD I trial, patients with Dupuytren's disease and joint contractures ≥20° were randomized to receive a maximum of three collagenase 0.58 mg or placebo injections into the cord of the affected hand at 30-day intervals. The primary endpoint was reduction in contracture to ≤5° 30 days after the last injection (day 30). The secondary endpoints, which are reported in this analysis, were ROM, physician- and patient-rated severity ('normal', 'mild', 'moderate', 'severe') and improvement, and treatment satisfaction. Linear regression was used to model data for severity classification and CID estimation for ROM based on physician and patient ratings. RESULTS: At baseline, mean ROM was 43.9° in the collagenase-treated joints (n = 197) and 45.3° in the placebo-treated joints (n = 102). On day 30, mean ROM was 80.7° in the collagenase-treated joints and 49.5° in the placebo-treated joints. The mean increase in ROM was 36.7° in the collagenase-treated joints (p < 0.001) and 4.0° in the placebo-treated joints (not significant). The estimated CID for ROM was 13.5° (95% CI 11.9, 15.1), reflecting a one-category change in severity. The mean increase in ROM exceeded the CID in the collagenase-treated joints but not in the placebo-treated joints; the difference between collagenase treatment and placebo in the mean increase in ROM also exceeded the CID, implying that the improvement with collagenase was clinically relevant. The severity classification for ROM was ≥67.0° ('normal'), ≥54.3 and <67.0° ('mild'), ≥41.6 and <54.3° ('moderate'), and <41.6° ('severe'). More collagenase- than placebo-treated patients achieved 'normal' (81% vs 25%; p < 0.0001) status, and more collagenase- than placebo-treated patients reported being 'very/quite satisfied' (87% vs 32%; p < 0.001). CONCLUSION: Injectable collagenase significantly improves ROM and treatment satisfaction versus placebo. ROM improvements are clinically relevant as well as statistically significant. These data support the potential need to include ROM and physician- and patient-rated severity and satisfaction as standard assessments for Dupuytren's contracture treatment outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT00528606; other study identification number AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).