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2015 ; 19
(90
): 1-202
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Collagenase clostridium histolyticum for the treatment of Dupuytren s
contracture: systematic review and economic evaluation
#MMPMID26524616
Brazzelli M
; Cruickshank M
; Tassie E
; McNamee P
; Robertson C
; Elders A
; Fraser C
; Hernandez R
; Lawrie D
; Ramsay C
Health Technol Assess
2015[Oct]; 19
(90
): 1-202
PMID26524616
show ga
BACKGROUND: Dupuytren's disease is a slowly progressive condition of the hand,
characterised by the formation of nodules in the palm that gradually develop into
fibrotic cords. Contracture of the cords produces deformities of the fingers.
Surgery is recommended for moderate and severe contractures, but complications
and/or recurrences are frequent. Collagenase clostridium histolyticum (CCH) has
been developed as a minimally invasive alternative to surgery for some patients.
OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
collagenase as an alternative to surgery for adults with Dupuytren's contracture
with a palpable cord. DATA SOURCES: We searched all major electronic databases
from 1990 to February 2014. REVIEW METHODS: Randomised controlled trials (RCTs),
non-randomised comparative studies and observational studies involving
collagenase and/or surgical interventions were considered. Two reviewers
independently extracted data and assessed risk of bias of included studies. A de
novo Markov model was developed to assess cost-effectiveness of collagenase,
percutaneous needle fasciotomy (PNF) and limited fasciectomy (LF). Results were
reported as incremental cost per quality-adjusted life-year (QALY) gained.
Deterministic and probabilistic sensitivity analyses were undertaken to
investigate model and parameter uncertainty. RESULTS: Five RCTs comparing
collagenase with placebo (493 participants), three RCTs comparing surgical
techniques (334 participants), two non-randomised studies comparing collagenase
and surgery (105 participants), five non-randomised comparative studies assessing
various surgical procedures (3571 participants) and 15 collagenase case series
(3154 participants) were included. Meta-analyses of RCTs assessing CCH versus
placebo were performed. Joints randomised to collagenase were more likely to
achieve clinical success. Collagenase-treated participants experienced
significant reduction in contracture and an increased range of motion compared
with placebo-treated participants. Participants treated with collagenase also
experienced significantly more adverse events, most of which were mild or
moderate. Four serious adverse events were observed in the collagenase group: two
tendon ruptures, one pulley rupture and one complex regional pain syndrome. Two
tendon ruptures were also reported in two collagenase case series. Non-randomised
studies comparing collagenase with surgery produced variable results and were at
high risk of bias. Serious adverse events across surgery studies were low.
Recurrence rates ranged from 0% (at 90 days) to 100% (at 8 years) for collagenase
and from 0% (at 2.7 years for fasciectomy) to 85% (at 5 years for PNF) for
surgery. The results of the de novo economic analysis show that PNF was the
cheapest treatment option, whereas LF generated the greatest QALY gains.
Collagenase was more costly and generated fewer QALYs compared with LF. LF was
£1199 more costly and generated an additional 0.11 QALYs in comparison with PNF.
The incremental cost-effectiveness ratio was £10,871 per QALY gained. Two
subgroup analyses were conducted for a population of patients with moderate and
severe disease and up to two joints affected. In both subgroup analyses,
collagenase remained dominated. LIMITATIONS: The main limitation of the review
was the lack of head-to-head RCTs comparing collagenase with surgery and the
limited evidence base for estimating the effects of specific surgical procedures
(fasciectomy and PNF). Substantial differences across studies further limited the
comparability of available evidence. The economic model was derived from a naive
indirect comparison and was hindered by a lack of suitable data. In addition,
there was considerable uncertainty about the appropriateness of many assumptions
and parameters used in the model. CONCLUSIONS: Collagenase was significantly
better than placebo. There was no evidence that collagenase was clinically better
or worse than surgical treatments. LF was the most cost-effective choice to treat
moderate to severe contractures, whereas collagenase was not. However, the
results of the cost-utility analysis are based on a naive indirect comparison of
clinical effectiveness, and a RCT is required to confirm or refute these
findings. STUDY REGISTRATION: This study is registered as PROSPERO
CRD42013006248. FUNDING: The National Institute for Health Research Health
Technology Assessment programme.
|Adult
[MESH]
|Cost-Benefit Analysis
[MESH]
|Dupuytren Contracture/*surgery/*therapy
[MESH]
|Humans
[MESH]
|Microbial Collagenase/adverse effects/economics/*therapeutic use
[MESH]