Risk of harm in synthetic and biological intervention trials in patients with inflammatory arthritis: protocol for a metaepidemiological study focusing on contextual factors.


Journal

BMJ open
ISSN: 2044-6055
Titre abrégé: BMJ Open
Pays: England
ID NLM: 101552874

Informations de publication

Date de publication:
06 09 2021
Historique:
entrez: 7 9 2021
pubmed: 8 9 2021
medline: 16 9 2021
Statut: epublish

Résumé

Inflammatory arthritis (IA) conditions, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, are characterised by inflammatory infiltration of the joints. Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively, reduce the effects of proinflammatory cytokines and immune cells to ameliorate disease. However, immunosuppression can be associated with high rates of serious adverse events (SAEs), including serious infections, and maybe an increased risk of malignancies and cardiovascular events. Currently, there is no empirical evidence on the extent to which contextual factors and risk of bias (RoB) domains may modify these harm signals in randomised trials. We will search MEDLINE (via PubMed) for systematic reviews published since April 2015 and all Cochrane reviews. From these reviews, randomised trials will be eligible if they include patients with an IA condition with at least one group randomly allocated to bDMARD and/or tsDMARD treatments. A predefined form will be used for extracting data on population characteristics (eg, baseline characteristics or eligibility criteria, such as medication background) and specific harm outcome measures, such as number of withdrawals, numbers of patients discontinuing due to adverse events and number of patients having SAEs. RoB in individual trials will be assessed using a modified Cochrane RoB tool. We will estimate the potentially causal harm effects related to the experimental intervention compared with control comparator as risk ratios, and heterogeneity across randomised comparisons will be assessed statistically and evaluated as inconsistency using the I Ethics approval is not required for this study. Results will be disseminated through publication in international peer-reviewed journals. CRD42020171124.

Identifiants

pubmed: 34489286
pii: bmjopen-2021-049850
doi: 10.1136/bmjopen-2021-049850
pmc: PMC8422485
doi:

Substances chimiques

Antirheumatic Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e049850

Informations de copyright

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Esben Malm (E)

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

Sabrina Mai Nielsen (SM)

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

Johannes Berg (J)

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

John P A Ioannidis (JPA)

3Department of Medicine, Department of Epidemiology and Population Health, Department of Biomedical Data Science, Department of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.

Daniel Furst (D)

Division of Rheumatology, Department of Medicine, University of California at Los Angeles, LA, CA, USA.

Josef S Smolen (JS)

Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria.

Peter C Taylor (PC)

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Lars Erik Kristensen (LE)

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Simon Tarp (S)

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Torkell Ellingsen (T)

Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

Robin Christensen (R)

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark robin.christensen@regionh.dk.
Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

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