Nanchahal, J., Ball, C., Rombach, I. orcid.org/0000-0003-3464-3867 et al. (9 more authors) (2022) Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial. The Lancet Rheumatology, 4 (6). E407-E416. ISSN 2665-9913
Abstract
Background
Dupuytren'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.
Methods
In 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.
Findings
Between 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.
Interpretation
Intranodular 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.
Funding
Health Innovation Challenge Fund (Wellcome Trust, Department of Health) and 180 Life Sciences.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. (https://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 May 2022 17:32 |
Last Modified: | 04 Nov 2022 16:05 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/s2665-9913(22)00093-5 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:187181 |