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Economic evaluation plan of a randomised controlled trial of intra-nodular injection of anti-TNF and placebo among patients with early Dupuytren's disease: Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).

ABSTRACT: Dupuytren's disease (DD) is a common fibroproliferative condition of the palmar and digital fascia of the hand; however, there is currently no approved treatment for early stage DD. The objective of this paper is to describe the methods applied to assess the cost-effectiveness of adalimumab injections compared to usual care for controlling the progression of early stage DD in the Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD) trial. Measure of effectiveness and resource use will be obtained from a randomised clinical trial, carried out in three healthcare centres, and recruiting a minimum of 138 patients aged 18 years and above with a diagnosis of early stage DD. Resource use and utility measures (quality-adjusted life years) will be collected at 3, 6, 9, 12 (primary outcome endpoint) and 18 months post-randomisation. A within-trial cost-utility analysis (CUA) will be conducted at 12 months and if the intervention is effective, a decision analytic model will be applied to estimate the lifetime effectiveness and costs. The analysis will be performed from a health system (National Health Service and personal social services) perspective. Sensitivity analysis will be conducted to assess the robustness of the results. RIDD is the first randomised controlled trial with an economic evaluation conducted among patients with early stage DD. The protocol described here records our intent to conduct both a within-trial CUA alongside the RIDD study and a lifetime CUA using decision-analytic modelling.

SUBMITTER: Png ME

PROVIDER: S-EPMC6354323 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Economic evaluation plan of a randomised controlled trial of intra-nodular injection of anti-TNF and placebo among patients with early Dupuytren's disease: Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).

Png May Ee ME Dritsaki Melina M Gray Alastair A Pinedo-Villanueva Rafael R Rivero-Arias Oliver O Nanchahal Jagdeep J

Wellcome open research 20180101

Dupuytren's disease (DD) is a common fibroproliferative condition of the palmar and digital fascia of the hand; however, there is currently no approved treatment for early stage DD. The objective of this paper is to describe the methods applied to assess the cost-effectiveness of adalimumab injections compared to usual care for controlling the progression of early stage DD in the Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD) trial. Measure of effectiveness and resource use will be ...[more]

PMID: 30756094

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Project description:BackgroundDupuytren's disease is a common fibrotic condition that causes the fingers to flex irreversibly into the palm. Treatments for late-stage disease all have limitations, and there is no approved treatment for early-stage disease. We identified tumour necrosis factor as a therapeutic target in Dupuytren's disease, and in a dose ranging trial found 40 mg adalimumab in 0·4 mL to be most efficacious. Here we aimed to assess the effects of intranodular injection of adalimumab in early-stage disease.MethodsIn this phase 2b, randomised, double-blind, placebo-controlled trial adults with early-stage Dupuytren's disease and an established clinically distinct nodule with a clear history of progression in the preceding 6 months were recruited from two clinical centres in the UK and were randomly assigned 1:1 to receive four injections of adalimumab or saline every 3 months. Participants and assessors were masked. The primary outcome was nodule hardness measured with a durometer at 12 months. Data were analysed by linear mixed effects regression models in the intention-to-treat population with multiple imputation for missing primary outcome data. The trial is registered at the ISRCTN registry, ISRCTN 27786905 and is complete.FindingsBetween Feb 17, 2017, and Jan 11, 2019, 284 participants were screened in the UK and 140 were enrolled. 47 (34%) participants were female and 93 (66%) were male. Mean age of participants was 59·7 years (SD 10·0). Primary outcome data were available from 113 participants. Nodule hardness was lower (-4·6 AU [95% CI -7·1 to -2·2], p=0·0002) in the adalimumab compared with the saline group at 12 months. There were no related serious adverse events; the most common adverse events were minor injection site reactions.InterpretationIntranodular injections of adalimumab in participants with early-stage Dupuytren's disease resulted in softening and reduction in size of the nodules. Longer follow-up would be required to assess the effect of tumour necrosis factor inhibition on disease progression, extension deficit and hand function.

Project description:Dupuytren's disease is a chronic, progressive fibroproliferative condition of the hand fascia which results in digital contraction. So far, treatments do not directly interfere with the (myo)fibroblasts that are responsible for the formation of the collagen-rich cords and its contraction. Here we investigated whether verteporfin (VP) is able to inhibit the activation and subsequent differentiation of DD nodular fibroblasts into myofibroblasts. Fibroblasts were isolated from nodules of 7 Dupuytren patients. Cells are treated (1) for 48 h with 5 ng/ml transforming growth factor β1 (TGF-β1) followed by 48 h with/without 250 nM VP in the absence of TGF-β1, or treated (2) for 48 h with TGF-β1 followed by 48 h with/without VP in the presence of TGF-β1. mRNA levels were measured by means of Real-Time PCR, and proteins were visualized by means of Western blotting and/or immunofluorescence. Quantitative data were statistically analyzed with GraphPad Prism using the paired t-test. We found that fibroblasts activated for 48 h with TGF-β1 show a decrease in mRNA levels of COL1A1, COL3A1, COL4A1, PLOD2, FN1EDA, CCN2 and SERPINE1 when exposed for another 48 h with VP, whereas no decrease is seen for ACTA2, YAP1, SMAD2 and SMAD3 mRNA levels. Cells exposed for an additional 48 h with TGF-β1, but now in the presence of VP, are not further activated anymore, whereas in the absence of VP the cells continue to differentiate into myofibroblasts. Collagen type I, fibronectin-extra domain A, α-smooth muscle actin, YAP1, Smad2 and Smad3 protein levels were attenuated by both VP treatments. We conclude that VP has strong anti-fibrotic properties: it is able to halt the differentiation of fibroblasts into myofibroblasts, and is also able to reverse the activation status of fibroblasts. The decreased protein levels of YAP1, Smad2 and Smad3 in the presence of VP explain in part the strong anti-fibrotic properties of VP. Verteporfin is clinically used as a photosensitizer for photodynamic therapy to eliminate abnormal blood vessels in the eye to attenuate macular degeneration. The antifibrotic properties of VP do not rely on photo-activation, as we used the molecule in its non-photoinduced state.

Project description:BackgroundTreatments for Dupuytren's contracture include limited fasciectomy and collagenase injection. Comparisons of the effectiveness of these treatments have been limited.MethodsWe performed an unblinded, multicenter, pragmatic, two-group, randomized, controlled noninferiority trial comparing collagenase injection with limited fasciectomy in persons with moderate Dupuytren's contracture. The primary outcome was the score on the Patient Evaluation Measure-Hand Health Profile (PEM), a questionnaire for assessing hand health as reported by the patient, at 1 year after treatment. Scores on the PEM range from 0 to 100, with higher scores indicating worse outcomes. The prespecified noninferiority margin was 6 points.ResultsA total of 672 persons (336 per group) were assigned to receive collagenase injection or to undergo limited fasciectomy. The primary analysis included 599 persons: 314 in the collagenase group and 285 in the limited-fasciectomy group. The mean score on the PEM at 1 year was 17.8 among the 284 patients with available data in the collagenase group and 11.9 among the 250 patients with available data in the limited-fasciectomy group (estimated difference, 5.9 points; 95% confidence interval [CI], 3.1 to 8.8; one-sided P = 0.49 for noninferiority). Among the patients with available data (229 patients in the collagenase group and 197 patients in the limited-fasciectomy group), the estimated difference in the mean score on the PEM at 2 years was 7.2 points (95% CI, 4.2 to 10.9). Moderate or severe complications of treatment occurred in 1.8% of the patients in the collagenase group and in 5.1% of those in the limited-fasciectomy group; recurrent contracture resulted in reintervention in 14.6% and 3.4%, respectively.ConclusionsCollagenase injection was not noninferior to limited fasciectomy with respect to the score on the PEM at 1 year after treatment. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme; DISC ISRCTN Registry number ISRCTN18254597.).

Project description:Dupuytren's disease is a progressive fibroproliferative disorder of the hand. In the nodular stage of Dupuytren's disease, pain might limit daily hand activities and progress to finger contractures. Focused electromagnetic high-energetic extracorporeal shockwave therapy (ESWT) may reduce pain in Dupuytren's nodules (Tubiana N). In this prospective, randomized, blinded, placebo-controlled single center trial, we enrolled 52 patients (mean age, 58.2 ± 9.2) with painful nodular Dupuytren disease Tubiana N. Randomization was done to either (group A) 3 treatments with focused electromagnetic high-energetic ESWT (2000 shots, 3 Hz, 0.35 mmJ/mm2/hand, Storz Duolith SD1, n = 27) or (group B) placebo ESWT (2000 shots, 3 Hz, 0.01 mJ/mm2/hand, n = 25) in a weekly interval. Primary outcome was the level of pain on a visual analogue scale (VAS 0-10) at 3/6/12/18 months, secondary outcomes were patient-related outcome measures (DASH score, MHQ score, URAM scale), grip strength, patient's satisfaction, and Dupuytren's disease progression over 18 months follow-up. Focused ESWT significantly improved outcomes. Pain was reduced from 3.6 ± 1.8 to 1.9 ± 1.2 at three, to 1.4 ± 0.7 at six, to 1.7 ± 1.6 after 12 months and 1.9 ± 0.8 after 18 months in the intervention group (47% reduction, p < 0.05). In the placebo group, pain on VAS increased from 2.2 ± 1.4 to 3.4 ± 1.7 at three, to 3.4 ± 1.8 at six, to 3.4 ± 1.4 at 12 and 3.1 ± 1.1 at 18 months (35% increase, p < 0.05). Quality-of-life score tended to improve in the intervention group (MHQ, 77 ± 19 to 83 ± 12; DASH, 12 ± 18 to 10 ± 9) while it deteriorated in the placebo group as Dupuytren's disease was progressing (MHQ, 79 ± 15 to 73 ± 17; DASH, 6 ± 10 to 14 ± 13). The strength of the affected hand and fingers did not change significantly in either of the groups. Patients' satisfaction was higher in the intervention group for symptom improvement (56% vs. 12%) and reduction of disease progression (59% vs. 24%). Any Dupuytren-related intervention was performed in 26% in the intervention group and in 36% in the placebo group within 18 months of follow-up (n.s.). Focused electromagnetic high-energetic ESWT can significantly reduce pain in painful nodules in Dupuytren's disease in an 18-month perspective. ( ClinicalTrials.gov Identifier: NCT01184586).

Dataset Information

Economic evaluation plan of a randomised controlled trial of intra-nodular injection of anti-TNF and placebo among patients with early Dupuytren's disease: Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).

Publications

Economic evaluation plan of a randomised controlled trial of intra-nodular injection of anti-TNF and placebo among patients with early Dupuytren's disease: Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).

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