Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study

Gottenberg, Jacques-Éric; Morel, Jacques; Perrodeau, Élodie; Bardin, Thomas; Combe, Bernard; Dougados, Maxime; Flipo, René‐Marc; Saraux, Alain; Schaeverbeke, Thierry; Sibilia, Jean; Soubrier, Martin; Vittecoq, Olivier; Baron, Gabriel; Constantin, Arnaud; Ravaud, Philippe; Mariette, Xavier

doi:10.1136/bmj.l67

Cited by 96 publications

(78 citation statements)

References 30 publications

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“…In a meta-analysis of studies on RA, TCZ and MTX combination was identi ed as the best intervention [37]. TCZ showed higher retention rates than TNFi and ABA in other studies [38,39], which supports the results of this study. It is also reported that elderly patients with RA have higher disease activity at baseline and higher CRP level owing to age-related increases in in ammation; thus, IL-6 inhibitors may be suitable for elderly patients with RA [34,40,41].…”

Section: Discussionsupporting

confidence: 84%

Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry

Kawabe

Nakano

Kubo

et al. 2020

Preprint

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Background. The effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) by age group (<65, 65–74, and ≥75 years) are uncertain. We examined retention rates reflecting the effectiveness and safety of bDMARDs in actual clinical practice for clarifying optimal therapeutic strategies for rheumatoid arthritis (RA) by age groups.Methods. Data of patients who were treated with tumor necrosis factor inhibitors (TNFi), abatacept (ABA), and tocilizumab (TCZ) between February 2011 and April 2017 were collected from a prospective observational registry of RA patients. A total of 1,362 patients were enrolled, of which 695 were aged <65 years, 402 were aged 65–74 years, and 265 were aged ≥75 years. Primary outcome was the drug retention rate in adjusted data using inverse probability of treatment weighting based on generalized propensity scores.Results. In patients aged <65 years, three-year retention rates of TNFi, ABA, and TCZ were 43%, 47%, and 69%, respectively (ABA versus TCZ, p = 0.017; TNFi versus TCZ, p = 0.002). In patients aged 65–74 years, three-year retention rates of TNFi, ABA, and TCZ were 44%, 53%, and 60%, respectively (TCZ versus TNFi, p = 0.034). In patients aged ≥75 years, three-year retention rates for TNFi, ABA, and TCZ were 38%, 63%, and 58%, respectively (ABA versus TNFi, p = 0.017).Conclusions. We found that the effectiveness and safety of TCZ were maximal in patients aged <75 years and that patients aged ≥75 years might be suitable candidates for TCZ and ABA therapy. The use of therapeutic strategies appropriate to each age group might improve the outcomes of bDMARD therapy for RA.

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Section: Discussionsupporting

confidence: 84%

Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry

Kawabe

Nakano

Kubo

et al. 2020

Preprint

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“…[40][41][42][43][44][45] AIH is an immune-mediated liver disease, thus biological agents, such as infliximab (anti-tumour necrosis factor [TNF] therapy), rituximab (anti-B cell therapy) or even tocilizumab (anti-IL-6 therapy) may have a potential role as disease-modifying agents and salvage therapies. 17,46,47 Anti-TNF treatment (infliximab) has been applied successfully as a rescue therapy in AIH. 17 Adult patients with AIH who have not responded sufficiently or are intolerant to standard of care are currently being recruited for the first randomised placebo-controlled trial of the B cell-depleting anti-BAFF receptor antibody (VAY736) (NCT03217422).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group

et al. 2019

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Graphical abstract Highlights• Study of rituximab therapy in 22 patients with autoimmune hepatitis over a follow-up period of 24 months.• No serious adverse events were noted during followup in patients treated with rituximab.• Rituximab therapy improved liver enzymes significantly during the 2 years of follow-up.• Prednisolone dose reductions were seen in 62% of patients at 12-month follow-up.• A total of 71% of patients were free of AIH flares during the 24 months of follow-up. Lay summaryAutoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to firstor second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome.Background & Aims: Treatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH.Methods: Clinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period.Results: Twenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19-79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3-28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p <0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1-10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded. Conclusion:In patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated w...

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“…Evidence from observational studies have demonstrated no increased risk of adverse cardiovascular events or safe cardiovascular outcomes among RA patients treated with tocilizumab compared to patients treated with other biological disease-modifying antirheumatic drugs (bDMARDs) [37][38][39][40][41][42]. In 2017, a prospective community-based clinical study evaluated the association between tocilizumab and CAD in RA population, and showed that tocilizumab could improve endothelial function [43].…”

Section: Case-control Gene Expression Analysismentioning

confidence: 99%

“…In 2017, a prospective community-based clinical study evaluated the association between tocilizumab and CAD in RA population, and showed that tocilizumab could improve endothelial function [43]. In 2019, Gottenberg et al performed a population based prospective study of 3,162 RA adults, and found no difference in major adverse cardiovascular events (MACE) using rituximab, abatacept, and tocilizumab in the treatment of RA [37]. In 2019, Virone et al found that tocilizumab could improve cardiovascular riskassociated biomarkers lipoprotein (a) and the leptin/adiponectin ratio than tumor necrosis factor inhibitor (TNFi) [38].…”

Section: Case-control Gene Expression Analysismentioning

confidence: 99%

IL-6R protective variant rs7529229 reduces interleukin-6 signaling and contributes to decreased ischemic stroke risk

Zhang

Zhao

Liu

et al. 2020

Preprint

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BackgroundInterleukin-6 (IL-6) signaling is associated with the increased risk of coronary artery disease (CAD) and ischemic stroke (IS). Growing evidence shows that the minor allele of IL-6R rs7529229 variant could significantly increase the soluble IL-6 receptor levels and reduce CAD risk. However, it is largely unknown about the role of rs7529229 in IS, which promotes us to perform a comprehensive analysis. MethodsIn stage 1, we performed a meta-analysis of three GWAS datasets from MEGASTROKE, UK Biobank, and Million Veteran Program to evaluate the association of rs7529229 with IS. In stage 2, we conducted an expression quantitative trait loci analysis to examine the effects of rs7529229 on IL-6R expression in neuropathologically normal individuals from UK Brain Expression Consortium, GTEx project and eQTLGen Consortium. In stage 3, a tissue-specific gene expression analysis is used to evaluate the potential difference of IL-6R expression across the human tissues using gene expression data from GTEx. In stage 4, a case-control gene expression analysis is used to explore the potentially differential expression of IL-6R in IS and healthy controls in whole blood. ResultsOur results show that (1) rs7529229 minor allele could significantly reduce the risk of IS (OR=0.97, 95% CI 0.95-0.99, P=2.30E-03); (2) rs7529229 minor allele could significantly reduce IL-6R expression in relevant tissues especially in blood vessels and whole blood; (3) IL-6R is mainly expressed in skeletal muscle and whole blood; (4) expression of IL-6R is significantly reduced in healthy controls compared with IS cases in whole blood. Importantly, the biological senses in stage 1-4 are all convergent. ConclusionsCollectively, these findings indicate that rs7529229 minor allele may first reduce IL-6R expression in relevant tissues, further reduce IL-6 signaling, and eventually reduce the IS risk. Hence, IL-6R may be a potential therapeutic target, and blocking IL-6 signaling might be effective in treatment of IS.

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Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study

Cited by 96 publications

References 30 publications

Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry

Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry

Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group

IL-6R protective variant rs7529229 reduces interleukin-6 signaling and contributes to decreased ischemic stroke risk

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