Authors' objectives: 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. To compare whether collagenase injection is not inferior to limited fasciectomy when treating Dupuytren’s contracture. Dupuytren’s disease affects over 2 million UK adults. Cords pull the fingers down towards the palm. This interferes with hand function and dexterity, impacting on quality of life. Current treatments to remove, dissolve or break the cords include surgical correction [limited fasciectomy (LF)], collagenase injection (an enzyme injected into the cord), and percutaneous needle fasciotomy (a needle is used to puncture, weaken and cut the cord). None of these treatments cure the tendency to develop Dupuytren’s contracture (DC) and so the cords and contracture can recur over time. Collagenase has some benefits over LF surgery including shorter recovery and no dependence on operating theatre availability for delivery of the intervention. There is, however, limited robust evidence comparing surgical correction and collagenase injection in terms of clinical effectiveness, cost-effectiveness, and in terms of patient’s experiences and preferences. The primary objective was to compare whether collagenase injection is not inferior to LF in the treatment of DC. Secondary objectives included investigation of recurrence at 1 and 2 years after treatment and cost-effectiveness. A qualitative substudy explored patients’ views of collagenase and LF, and a photography substudy investigated whether measurements of extension and flexion made on photographs taken by patients reflect goniometric measurements to assess recurrence.

Authors' results and conclusions: 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. 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. Clinical effectiveness In total 672 participants (64.6%) were recruited and randomised; 336 to receive collagenase injection and 336 to receive LF. Baseline characteristics were similar across groups. Of the 672 randomised participants, 621 (92.4%) received treatment as part of the trial. Cross-over was limited: one participant (0.3%) allocated to collagenase received LF; seven participants allocated to LF received collagenase (2.1%). On average participants received collagenase by 12.1 weeks [standard deviation (SD) 13.7] and LF in 17.7 weeks (SD 16.5) after randomisation. Most participants (n = 315, 95.2%) had just one digit treated. No participants required an unplanned inpatient admission following treatment and 62.0% (n = 201) collagenase participants and 78.3% (n = 224) LF participants had full correction following treatment. At 1 year (primary time-point) the difference in PEM scores showed that collagenase was inferior to LF; difference 5.95 [95% confidence interval (CI) 3.12 to 8.77; p = 0.49]. The benefit of LF over collagenase continued to increase to 2 years (7.18, 95% CI 4.18 to 10.88; p = 0.82). There were no material changes in these results for any of the sensitivity or additional analyses undertaken. The primary analysis therefore shows that there is little evidence to support rejection of the hypothesis that collagenase is inferior to LF at 1 and 2 years post treatment. Indeed, the observed data are highly compatible with LF being superior to collagenase with regard to the primary outcome measure at both these time points. Patient Evaluation Measure overall assessment scores corresponded with the primary outcome analyses and participants in both groups reported positive experiences of treatment. The estimated difference in URAM scores followed those of PEM, increasing in favour of LF over time from 3 months (0.82, 95% CI −0.21 to 1.84; p = 0.12) to 5.37 (95% CI 3.85 to 6.88; p ≤ 0.00005) at 2 years. At 1 year MHQ scores were higher (better) in the LF group (1 year: −4.69, 95% CI −7.27 to −2.12; p = 0.0004) and this continued at 2 years (2 years: −6.71, 95% CI −9.60 to −3.82; p ≤ 0.00005). Return to function was better in the short term for the collagenase group (week 2: 14.93, 95% CI 11.66 to 18.19; p ≤ 0.00005; 6 weeks: 5.00, 95% CI 2.29 to 7.70; p = 0.003) but by 1 year function was superior after LF (−4.93, 95% CI −7.63 to −2.22; p = 0.0004). At 1 year participants who received LF were more likely to respond as being ‘cured’ or ‘much better’ than participants who received collagenase [odds ratio (OR) 3.01, 95% 2.15 to 4.23; p ≤ 0.00005]. Passive extension deficit was similar between the groups at baseline (mean: 45.8°; SD 17.0). Following collagenase treatment, extension deficit seemed to be worse at all time points ranging from a difference of 5.73° (95% CI 2.88 to 8.59; p = 0.0001) at 3 months to 10.10° (95% CI 6.46 to 13.73; p ≤ 0.00005) at 1 year and increasing again up to 2 years. Results when imputed data were included were similar. Increases in reference joint passive range of movement (RoM) were similar between the two groups following treatment. However, from 6 months there was strong evidence that collagenase resulted in poorer passive RoM (−7.42°, 95% CI −11.54 to −3.29; p = 0.0004) and this difference increased further over time. Measurements of active extension deficit were similar between the two groups at baseline (mean: 51.9°, SD 16.1). Like passive extension deficit, active extension deficit was worse following collagenase treatment at all time points, ranging from a difference at 3 months of 5.57° (95% CI 3.02 to 8.12; p ≤ 0.00005) to 11.52° (95% CI 8.13 to 14.91; p 

Authors' recommendations: Follow-up to 5 years or more would establish the evolution of differences observed at 2 years, particularly in relation to recurrence and re-intervention, which usually occurs after 1 year. Also, the data collection in the DISC trial has been used as the basis for planning the data collection for the ongoing HAND-2 trial [NIHR: 127393; ISRCTN: 18254597], which will allow for a network meta-analysis of all key interventions for DC. The results from the qualitative substudy provide direction on planning further research to understand behavioural trends that influence a patient’s decision to seek care and return to care after initial intervention.

Authors' methods: Pragmatic, two-arm, unblinded, randomised controlled non-inferiority trial with a cost-effectiveness evaluation and nested qualitative and photographic substudies. Thirty-one National Health Service hospitals in England and Scotland. Patients with Dupuytren’s contracture of ≥ 30 degrees who had not received previous treatment in the same digit. Collagenase injection with manipulation 1–7 days later was compared with limited fasciectomy. 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. 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. Design The Dupytren's interventions surgery vs collagenase (DISC) trial was a multicentre, pragmatic, parallel two-arm randomised controlled non-inferiority trial with a cost-effectiveness evaluation, and nested qualitative and photography substudies. Participants were randomised on an equal basis to receive either of the two treatment options via a remote randomisation service. Randomisation was blocked, with randomly varying block sizes, and stratified by reference (worst-affected) joint [metacarpophalangeal (MCP) joint or proximal interphalangeal (PIP) joint]. Participants were followed up at 3 months, 6 months, 1 year and 2 years after treatment. Data collection included joint measurements and photography at baseline, and all follow-up time points. Trial recruitment was undertaken in 31 NHS hand units across England and Scotland between June 2017 and September 2021. Patients aged 18 years and over with a discrete, palpable Dupuytren’s cord causing contracture of ≥ 30 degrees and who were appropriate for both study treatments, were eligible for inclusion. Patients were excluded if they had severe contractures (> 135 degrees); had received treatment to the study digit; had other pre-existing disorders affecting hand function; had contraindications to collagenase; had a coagulation disorder; were female and pregnant or breastfeeding; had participated in a study involving another investigational medicinal product within 12 weeks or had another disease or disorder which would put them at risk if participating. The intervention was collagenase Clostridium histolyticum injection, supplied through routine NHS stocks. Collagenase was injected as three aliquots at set anatomical points in line with the current approved summary of product characteristics. After an interval of 1–7 days, participants returned to the clinic, where under local anaesthetic the cord was snapped to correct the contracture. The control group received LF surgery to remove the diseased nodules and cord to correct the contracture. Participants were followed up at routine wound check appointments following intervention.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/15/102/04

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/KGXD8528

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/KGXD8528

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk