Hand Surgery Department, University Hospital, Uppsala, Sweden.
Clin Drug Investig. 2011 Nov 1;31(11):791-8. doi: 10.1007/BF03256918.
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.
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.
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).
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.
ClinicalTrials.gov Identifier: NCT00528606; other study identification number: AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).
注射用胶原酶组织溶纤维蛋白酶治疗掌腱膜挛缩症，疗效可通过挛缩角度和活动度（ROM）的变化来评估。然而，ROM 的临床重要变化尚未得到深入评估。本 CORD I 试验的次要分析旨在使用基线 ROM 确定严重程度水平，估计 ROM 的临床重要差异（CID），并将结果与胶原酶治疗和患者满意度联系起来。
在 CORD I 试验中，患有掌腱膜挛缩症且关节挛缩≥20°的患者被随机分配接受最多 3 次胶原酶 0.58mg 或安慰剂注射，间隔 30 天。主要终点是末次注射后 30 天（第 30 天）挛缩程度≤5°。本分析报告的次要终点是 ROM、医生和患者评定的严重程度（“正常”、“轻度”、“中度”、“重度”）和改善程度以及治疗满意度。使用线性回归对数据进行建模，根据医生和患者的评分，对严重程度分类和 ROM 的 CID 估计进行建模。
在基线时，胶原酶治疗关节的平均 ROM 为 43.9°（n=197），安慰剂治疗关节的平均 ROM 为 45.3°（n=102）。第 30 天，胶原酶治疗关节的平均 ROM 为 80.7°，安慰剂治疗关节的平均 ROM 为 49.5°。胶原酶治疗关节的 ROM 平均增加 36.7°（p<0.001），安慰剂治疗关节的 ROM 平均增加 4.0°（无统计学意义）。ROM 的估计 CID 为 13.5°（95%CI 11.9，15.1），反映了严重程度的一级变化。胶原酶治疗关节的 ROM 平均增加超过 CID，但安慰剂治疗关节没有；胶原酶治疗与安慰剂治疗在 ROM 平均增加方面的差异也超过了 CID，这意味着胶原酶治疗具有临床相关性。ROM 的严重程度分类为：≥67.0°（“正常”）、≥54.3°且<67.0°（“轻度”）、≥41.6°且<54.3°（“中度”）和<41.6°（“重度”）。与安慰剂治疗相比，更多的胶原酶治疗患者达到“正常”状态（81%比 25%；p<0.0001），更多的胶原酶治疗患者报告“非常/相当满意”（87%比 32%；p<0.001）。
与安慰剂相比，注射用胶原酶可显著改善 ROM 和治疗满意度。ROM 的改善具有临床意义，且具有统计学意义。这些数据支持将 ROM 以及医生和患者评定的严重程度和满意度作为掌腱膜挛缩症治疗结果的标准评估纳入的潜在需要。
ClinicalTrials.gov 标识符：NCT00528606；其他研究识别号：AUX-CC-857（Auxilium Pharmaceuticals， Inc.）。
