Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Romão, Vasco C; Vital, Edward M; Fonseca, João Eurico; Buch, Maya H

doi:10.1186/s13075-017-1445-3

Cited by 43 publications

(31 citation statements)

References 153 publications

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“…Furthermore, experimental investigations have not yet validated this concept 22. Within the elegantly described biological paradigm23 underpinned by clinical observation of a cytokine network that is host to key druggable nodes (such as TNF, IL-6 and GM-CSF), the inter-relationship of such cytokine nodes (does response to TNFi implicitly indicate TNF-driven disease not amenable to IL-6 targeting?…”

Section: Mechanisms Underlying Refractory Ra Diseasementioning

confidence: 99%

Defining refractory rheumatoid arthritis

2018

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While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.

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Section: Mechanisms Underlying Refractory Ra Diseasementioning

confidence: 99%

Defining refractory rheumatoid arthritis

2018

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“…Of the currently available treatments, conventional disease modifying antirheumatic drugs (DMARDs) and biological DMARDs, also known as biologics or biological immunotherapies, are the most effective for long-term management of RA. However, the effectiveness of these treatments at managing disease progression varies among patients [1], and can be influenced by genetic factors [2,3] and the duration of symptoms prior to the first treatment [4][5][6]. For example, these factors play a role in why nearly one third of patients do not respond to methotrexate, one of the most common first lines of defense against RA [2,5].…”

Section: Introductionmentioning

confidence: 99%

“…Multiple meta-analyses have used pharmacogenetic studies to summarize how the efficacy, toxicity, and other adverse reactions of conventional DMARDs, such as methotrexate [2,7,8], and biologics [3] such as adalimumab and etanercept can be influenced by genetics. These studies point to polymorphisms in a variety of genes associated with a particular medication's metabolism, transport, target, and/or mechanism of action as a reason to why response to medication varies among patients.…”

Section: Introductionmentioning

confidence: 99%

Berberine delays onset of collagen induced arthritis through T cell suppression

Vita¹,

Lyons²,

Aljobaily³

et al. 2019

Preprint

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RUNNING TITLE (less than 50 characters): Berberine delays onset of collagen arthritis model KEY WORDS (5 words not in the title): CIA, berberine, RA, autoimmune, T cell ABSTRACT (250 words or less): Previous evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role from in vitro studies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4 + T cells, CXCR5 + T fh cells, and an increased proportion of T reg at both day 14 and day 28 endpoints, as well as decreased CD28 + and CD154 + CD4 + T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19 + B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity. and PBS controls ( Fig. 2B). When comparing anti-CII IgG levels between arthritic and nonarthritic mice within the BBR group specifically, however, anti-CI IgG1, IgG2a and total IgG were all significantly reduced in the non-arthritic mice compared to those who developed arthritis (Fig. 2C). Additionally, there appeared to be a vehicle-specific effect on circulating anti-CII IgG in which the administration of PBS with 0.01% DMSO elicited elevated levels of anti-CII IgG1 and total IgG in vehicle control mice ( Fig. 2A-B).Key CD4 + T cell population characteristics in response to berberine treatment-On day 14, we observed a significant reduction in populations of both CD4 + T cells and CXCR5 + T fh cells in the LNs and spleen of BBR-treated mice (Fig. 3A-B), as well as a reduction in the percentage of CD28 + and CD154 + CD4 + T cells in the spleen and LNs of BBR-treated mice (Fig. 3A-B). By the day 28 experimental endpoint we continued to observe a significant reduction in CD4 + T cells and CXCR5 + T fh cells in the spleen and LNs of BBR-treated mice ( Fig. 3C-D), however, there was no significant difference in the percentage of CD28 + and CD154 + CD4 + T cells between treatment groups (Fig 3C-D). Berberine treatment leads to increased proportion of FOXP3 + CD25 + CD4 + T cells-To examineBBRs effect on ...

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“…New treatment modalities by the initiation of targeted biologic therapies are recommended to for disease control, damage prevention, persevering affected joint function, increase in patients' quality of life, and increase the possibilities to achieve complete remission of the disease [4]. The biologic disease-modifying antirheumatic drugs (bDMARDs) or known as the monoclonal antibody (mAb) therapies, which target directly to the specific cytokines cells and molecules of the disease pathophysiology, can be initiated either alone as monotherapy or as combination therapy with the conventional synthetic DMARDs (csDMARDs) therapy within the first 3 months of early RA diagnosis [5][6][7]. This review will provide an overview of the RA disease, the use of new mAb therapies in addition to the csDMARDs used in the management of RA, as well as suggestive prescreening test based on disease history or concurrent condition on selection of biologic treatment initiation in RA patient.…”

Section: Introductionmentioning

confidence: 99%

Management of Rheumatoid Arthritis: Special Consideration for Biologic Disease-Modifying Antirheumatic Drugs

Razak

Makmor-Bakry

Redzuan

2018

Asian J Pharm Clin Res

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Rheumatoid arthritis (RA) is a progressive chronic inflammatory disease affecting 0.5–1.0% of the adult population worldwide. Due to the damages caused by this autoimmune disease, new biologic therapies, particularly the biologic disease-modifying antirheumatic drugs (bDMARDs), are now being the treatment of choice in the management of RA. However, special precaution and prescreening before the usage of bDMARDs are needed to ensure better clinical response and avoiding risk of adverse event during treatment with the selected bDMARDs. In this review paper, we will provide overview on the incidence and pathogenesis of the disease, available pharmacological treatment and emphasizing special consideration in need on initiation of bDMARDs among RA patients. A literature review was performed by searching for relevant articles in Medline database through PubMed using medical subject headings terms and keywords: RA, bDMARDs, special consideration, tumor necrosis factor inhibitor, and non-tumor necrosis factor inhibitor. All papers reviewed were from 1999 to 2017 and were written in English. In this article, use of conventional synthetic DMARDs (csDMARDs), bDMARDs and special consideration to be taken upon initiation of biologic therapies in RA will be reviewed.

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Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Cited by 43 publications

References 153 publications

Defining refractory rheumatoid arthritis

Defining refractory rheumatoid arthritis

Berberine delays onset of collagen induced arthritis through T cell suppression

Management of Rheumatoid Arthritis: Special Consideration for Biologic Disease-Modifying Antirheumatic Drugs

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