Background
Dupuytren’s contracture is caused by nodules and cords which pull the fingers towards the palm of the hand. Treatments include limited fasciectomy surgery, collagenase injection and needle fasciotomy. There is limited evidence comparing limited fasciectomy with collagenase injection.
Objectives
To compare whether collagenase injection is not inferior to limited fasciectomy when treating Dupuytren’s contracture.
Design
Pragmatic, two-arm, unblinded, randomised controlled non-inferiority trial with a cost-effectiveness evaluation and nested qualitative and photographic substudies.
Setting
Thirty-one National Health Service hospitals in England and Scotland.
Participants
Patients with Dupuytren’s contracture of ≥ 30 degrees who had not received previous treatment in the same digit.
Interventions
Collagenase injection with manipulation 1–7 days later was compared with limited fasciectomy.
Main outcome measures
The primary outcome was the Patient Evaluation Measure score, with 1 year after treatment serving as the primary end point. A difference of 6 points in the primary end point was used as the non-inferiority margin. Secondary outcomes included: Unité Rhumatologique des Affections de la Main scale; Michigan Hand Outcomes Questionnaire; recurrence; extension deficit and total active movement; further care/re-intervention; complications; quality-adjusted life-year; resource use; and time to function recovery.
Randomisation and blinding
Online central randomisation, stratified by the most affected joint, and with variable block sizes allocates participants 1 : 1 to collagenase or limited fasciectomy. Participants and clinicians were not blind to treatment allocation.
Results
Between 31 July 2017 and 28 September 2021, 672 participants were recruited (n = 336 per group), of which 599 participants contributed to the primary outcome analysis (n = 285 limited fasciectomy; n = 314 collagenase).
At 1 year (primary end point) there was little evidence to support rejection of the hypothesis that collagenase is inferior to limited fasciectomy. The difference in Patient Evaluation Measure score at 1 year was 5.95 (95% confidence interval 3.12 to 8.77; p = 0.49), increasing to 7.18 (95% confidence interval 4.18 to 10.88) at 2 years. The collagenase group had more complications (n = 267, 0.82 per participant) than the limited fasciectomy group (n = 177, 0.60 per participant), but limited fasciectomy participants had a greater proportion of ‘moderate’/‘severe’ complications (5% vs. 2%). At least 54 participants (15.7%) had contracture recurrence and there was weak evidence suggesting that collagenase participants recurred more often than limited fasciectomy participants (odds ratio 1.39, 95% confidence interval 0.74 to 2.63).
At 1 year, collagenase had an insignificantly worse quality-adjusted life-year gain (−0.003, 95% confidence interval −0.006 to 0.0004) and a significant cost saving (−£1090, 95% confidence interval −£1139 to −£1042) than limited fasciectomy with the probability of collagenase being cost-effective exceeding 99% at willingness to pay thresholds of £20,000–£30,000 per quality-adjusted life-year.
At 2 years, collagenase was both significantly less effective (−0.048, 95% confidence interval −0.055 to −0.040) and less costly (−£1212, 95% confidence interval −£1276 to −£1147). The probability of collagenase being cost-effective was 72% at the £20,000 threshold but limited fasciectomy became the optimal treatment at thresholds over £25,488. The Markov model found the probability of collagenase being cost-effective at the lifetime horizon dropped below 22% at thresholds over £20,000.
Semistructured qualitative interviews found that those treated with collagenase considered the outcome to be acceptable, though not perfect.
The photography substudy found poor agreement between goniometry and both participant and clinician taken photographs, even after accounting for systematic differences from each method.
Limitations
Impacts of the COVID-19 pandemic resulted in longer waits for Dupuytren’s contracture treatment, meaning some participants could not be followed up for 2 years. This resulted in potential underestimation of Dupuytren’s contracture recurrence and/or re-intervention rates, which may particularly have impacted the clinical effectiveness and long-term Markov model findings.
Conclusions
Among adults with Dupuytren’s contracture, collagenase delivered in an outpatient setting is less effective but more cost-saving than limited fasciectomy. Further research is required to establish the longer-term implications of both treatments.
Future work
Recurrence and re-intervention usually occur after 1 year, and therefore follow-up to 5 years or more could resolve whether the differences observed in the Dupuytren’s interventions surgery versus collagenase trial to 2 years worsen.
Study registration
Current Controlled Trials ISRCTN18254597.
Funding
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/102/04) and is published in full in Health Technology Assessment; Vol. 28, No. 78. See the NIHR Funding and Awards website for further award information.
