Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rheumatoid Arthritis: A Systematic Review

Choi, May Y.; Barnabe, Cheryl; Barber, Claire; Bykerk, Vivian P.; Pope, Janet; Hazlewood, Glen

doi:10.1002/acr.23620

Cited by 14 publications

(16 citation statements)

References 23 publications

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“…For an RCT relevant to these issues, an explanatory‐intermediate approach for eligibility and flexibility of adherence might be necessary 6 . However, in line with previous evidence, 31,32 more than one‐third of the protocols in our study did not include any information on the flexibility of adherence. Whether missing information may imply full flexibility remained unclear, illustrating the need for using validated tools to assess pragmatic features before protocol publication 34 …”

Section: Discussionmentioning

confidence: 64%

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Generalizability of randomized controlled trials in primary health care: Applying the PRECIS‐2 tool on published protocols

Papagiannopoulou

Laiou

Tatsi³

et al. 2022

Evaluation Clinical Practice

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Rationale: Pragmatic design may facilitate the generalizability of effectiveness of randomized controlled trials (RCTs) in primary health care (PHC). Aims and Objectives:The aim of this study was to investigate whether published protocols in PHC were designed pragmatically and to explore whether specific trial characteristics may be related to a pragmatic design.Methods: Using the Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2), we assessed pragmatism for 123 published RCT protocols. For each domain, we calculated the mean score with the 95% confidence interval (95% CI).Interrater reliability was assessed by weighted κ-coefficient with 95% CI. We examined potential associations of published protocol characteristics with overall pragmatism by performing univariate and multivariate analyses. Results:We observed the highest score for primary analysis (4.66, 95% CI: 4.51, 4.82). The eligibility score was intermediate (3.16, 95% CI: 3.01, 3.32). Domains with scores towards the explanatory side included organization (2.50, 95% CI: 2.36, 2.63), flexibility of delivery (2.74, 95% CI: 2.60, 2.88) and flexibility of adherence (3.00, 95% CI: 2.83, 3.17). Interrater agreement was good (κ = 0.61; 95% CI: 0.34, 0.80; p < 0.001). Higher sample sizes were correlated to a pragmatic design (odds ratio: 6.86, 95% CI: 1.64, 28.75; p = 0.04). Conclusion:Most RCT protocols were rated as intermediate in the pragmaticexplanatory continuum. Future research may guide all stakeholders on how best to incorporate the level of pragmatism in the interpretation of the results so that the trials are more likely to be applicable in real-world settings.

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Section: Discussionmentioning

confidence: 64%

“…However, this finding should be interpreted cautiously since almost one‐fifth of the eligible papers failed to report information on the analysis plan. Lack of information on this domain was also reported in previous studies 31,32 …”

Section: Discussionmentioning

confidence: 64%

Generalizability of randomized controlled trials in primary health care: Applying the PRECIS‐2 tool on published protocols

Papagiannopoulou

Laiou

Tatsi³

et al. 2022

Evaluation Clinical Practice

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“…The association of rheumatoid arthritis (RA) with long-term health care costs are unclear and difficult to measure because of the unique treatment pathway of this complex chronic disease requiring long-term medication therapy [1,2]. Clinical trials of medications used in RA are highly selective with only 8% of patients seen in usual care meeting eligibility criteria [3][4][5]. Because of their design and short follow-up, clinical trials cannot capture the long-term costs of RA that accrue over many years or the additional costs of RA patients that may arise years before diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Health care costs of rheumatoid arthritis: A longitudinal population study

et al. 2021

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Quantifying the contribution of rheumatoid arthritis to the acquisition of subsequent health care costs is an emerging focus of the rheumatologic community and payers of health care. Our objective was to determine the healthcare costs before and after diagnosis of rheumatoid arthritis (RA) from the public payer’s perspective. The study design was a longitudinal observational administrative data-based cohort with RA cases from Ontario Canada (n = 104,933) and two control groups, matched 1:1 on year of cohort entry from 2001 to 2016. The first control group was matched on age, sex and calendar year of cohort entry (diagnosis year for those with RA); the second group added medical history to the match before RA diagnosis year. The main exposure was new onset RA. The secondary exposure was calendar year of RA diagnosis to compare attributable costs over the study observation window. Main outcomes were health care costs in 2015 Canadian dollars, overall and by cost category. We used attribution methods to classify costs into those associated with RA, those associated with comorbidities, and age/sex-related underlying costs. Health care costs associated with RA increased up to the year of diagnosis, where they reached $8,591: $4,142 in RA associated costs; $1,242 in RA comorbidity associated costs; and $3,207 in underlying costs. In the eighth-year post diagnosis, the RA costs declined to $2,567 while the RA comorbidity associated costs remained relatively constant at $1,142, and the underlying age/sex related cost increased to $4,426. RA patients had lower costs when diagnosed in later calendar years. Our results suggest a large proportion of disease related health care costs are a result of costs associated with RA comorbidities, which may appear many years before diagnosis.

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“…Several treatments have been proposed for RA including non-steroidal anti-inflammatory agents, disease-modifying medicines, and biological drugs to counteract the immune and inflammatory pathological cascade. All these therapeutic approaches have been shown to be effective in the management of rheumatoid arthritis, even if they are expensive and their chronic use in clinical practice is hampered by the occurrence of mild-to-moderate side effects [7,8,9,10].…”

Section: Introductionmentioning

confidence: 99%

β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

et al. 2019

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β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.

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Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rheumatoid Arthritis: A Systematic Review

Abstract: RCTs of biologic DMARD treatment in combination with methotrexate for RA were rated as predominantly explanatory, which may affect the generalizability of trial results to clinical practice. This article is protected by copyright. All rights reserved.

Cited by 14 publications

References 23 publications

Generalizability of randomized controlled trials in primary health care: Applying the PRECIS‐2 tool on published protocols

Generalizability of randomized controlled trials in primary health care: Applying the PRECIS‐2 tool on published protocols

Health care costs of rheumatoid arthritis: A longitudinal population study

β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

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