Janus kinase versus TNF inhibitors: where we stand today in rheumatoid arthritis

Venetsanopoulou, Aliki I.; Aa, Drosos

doi:10.1080/1744666x.2022.2064275

Cited by 15 publications

(4 citation statements)

References 93 publications

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“…Thus, the included literature analyses the miRNAs associated with response to csDMARDs [ 25 ], csDMARDs/bDMARDs combination [ 27 , 28 , 30 ] anti-TNFα [ 1 , 13 , 24 , 26 , 29 ], and rituximab [ 34 ]. It was not possible to include biomarkers for Jakus kinase inhibitor (JAKi), a promising new drug for RA treatment [ 39 ]. To date, no study identifying specific miRNAs as predictors of JAKi response has been published.…”

Section: Resultsmentioning

confidence: 99%

miRNA-Mediated Epigenetic Regulation of Treatment Response in RA Patients—A Systematic Review

Mucientes

Lisbona-Montañez

Mena-Vázquez

et al. 2022

IJMS

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This study aimed to evaluate the role of microRNAs (miRNA) as biomarkers of treatment response in rheumatoid arthritis (RA) patients through a systematic review of the literature. The MEDLINE and Embase databases were searched for studies including RA-diagnosed patients treated with disease-modifying antirheumatic drugs (DMARDs) that identify miRNAs as response predictors. Review inclusion criteria were met by 10 studies. The main outcome of the study was the response to treatment, defined according to EULAR criteria. A total of 839 RA patients and 67 healthy donors were included in the selected studies. RA patients presented seropositivity for the rheumatoid factor of 74.7% and anti-citrullinated C-peptide antibodies of 63.6%. After revision, 15 miRNAs were described as treatment response biomarkers for methotrexate, anti-tumour necrosis factor (TNF), and rituximab. Among treatments, methotrexate presented the highest number of predictor miRNAs: miR-16, miR-22, miR-132, miR-146a and miR-155. The most polyvalent miRNAs were miR-146a, predicting response to methotrexate and anti-TNF, and miR-125b, which predicts response to infliximab and rituximab. Our data support the role of miRNAs as biomarkers of treatment response in RA and point to DMARDs modifying the miRNAs expression. Nevertheless, further studies are needed since a meta-analysis that allows definitive conclusions is not possible due to the lack of studies in this field.

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Section: Resultsmentioning

confidence: 99%

miRNA-Mediated Epigenetic Regulation of Treatment Response in RA Patients—A Systematic Review

Mucientes

Lisbona-Montañez

Mena-Vázquez

et al. 2022

IJMS

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“…The PERFECTRA study addressed the question of where we stand with a tsDMARD first versus a TNFi first treatment strategy for patients with RA failing to achieve DAS28-CRP <2.6 on csDMARDs. 35 This real-world study in a T2T setting applying EULAR guidelines 13 showed that after failing csDMARDs baricitinib is non-inferior and superior as compared with TNFi strategy with respect to clinical effectiveness, PROMs and drug survival. This study was not powered to address neither comparative safety nor radiological damage between baricitinib and TNFi.…”

Section: Discussionmentioning

confidence: 96%

PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

van de Laar,

Oude Voshaar,

ten Klooster

et al. 2024

RMD Open

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ObjectiveTo compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting.MethodsPatients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression.ResultsA total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients.ConclusionUp to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.

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“…In bDMARD-IR severe RA patients, TOFA + MTX is cost-effective only when rituximab is contraindicated or not tolerated. ( Baricitinib for moderate to severe, 2017 ; Tofacitinib for moderate to severe, 2017 ; Ren et al, 2018 ; Uttley et al, 2018 ) Further, JAK-i is more frequently linked to serious adverse events, including malignancy and cardiovascular disease ( Venetsanopoulou et al, 2022 ). According to a recent study by Ytterberg et al (2022) , JAK-i is associated with a higher risk of serious infections, blood clots, cancer, and cardiovascular conditions than TNF inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies

et al. 2022

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Introduction: Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports.Methods: Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers’ cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger’s test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented.Results: We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1–46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598).Conclusion: Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541

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Janus kinase versus TNF inhibitors: where we stand today in rheumatoid arthritis

Cited by 15 publications

References 93 publications

miRNA-Mediated Epigenetic Regulation of Treatment Response in RA Patients—A Systematic Review

miRNA-Mediated Epigenetic Regulation of Treatment Response in RA Patients—A Systematic Review

PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies

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