Preclinical discovery and development of adalimumab for the treatment of rheumatoid arthritis

Drosos, Alexandros A.

doi:10.1080/17460441.2021.1846516

Cited by 12 publications

(8 citation statements)

References 67 publications

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“…It is a fusion protein with a human TNFα receptor extracellular portion 75 kDa attached to the Fc portion of human IgG1 immunoglobulin (TNFR: FC) [11]. This protein is a large molecule with a molecular weight of 150 kDa that binds to TNFα and inhibits autoimmune diseases [12]. However, these treatments cause many problems and side effects for patients.…”

Section: Introductionmentioning

confidence: 99%

The effects of a truncated form of Staphylococcus aureus protein A (SpA) on the expression of cytokines of autoimmune patients and healthy individuals

Rigi

Kardar

Hajizade

et al. 2022

Preprint

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Background: The recombinant Staphylococcal protein A (SpA) is widely used in biotechnology to purify polyclonal and monoclonal IgG antibodies. At very low concentrations, the highly-purified form of the protein A can down-regulate the activation of human B-lymphocytes and macrophages which are the key cells in determining autoimmune diseases. Methods: In the present study, the efficiency of three different forms of protein A, including native SpA, the recombinant full-length SpA, and a truncated form of SpA on the reduction of 4 inflammatory cytokines, including IL-8, IL-1β, TNF-α, and IL-6 by peripheral blood mononuclear cell (PBMCs) were studied and compared to an anti-rheumatoid arthritis commercial drug, Enbrel. The recombinant proteins were expressed in E. coli expression vector and the native form of SpA was commercially provided. PBMCs were obtained from adult patients with active rheumatoid arthritis (RA) and healthy control donors. Then, the effect of different doses of the three pure forms of SpA in comparison with Enbrel was investigated by analyzing the expression of selected cytokines using ELISA. Results: The results showed that the recombinant truncated form of SpA significantly reduced the expression of the cytokines more effectively than other full-length formulations as well as the commercial drug Enbrel. In silico analysis suggests that in the truncated protein, by increasing the radius of gyration, the IgG-binding domains find a more open structure and are more exposed to IgG. Conclusion: In conclusion, our results showed that the truncated form of protein A is the most potent form of SpA that reduces the secretion of the evaluated cytokines from PBMCs in vitro.

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Section: Introductionmentioning

confidence: 99%

The effects of a truncated form of Staphylococcus aureus protein A (SpA) on the expression of cytokines of autoimmune patients and healthy individuals

Rigi

Kardar

Hajizade

et al. 2022

Preprint

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show abstract

“…The reason for this difference might be that although ETN was launched earlier than ADA in China, its prescription was limited by medical insurance, and most RA patients were not able to receive this treatment, leading to a longer disease duration and greater disease activity at baseline 29,30 . However, after ADA was placed in the market, medical insurance policy also started to improve; hence, many patients choose to use ADA after early diagnosis of RA, resulting in a shorter disease duration and lower disease activity at baseline 31 . In addition, these findings may provide an objective picture of Chinese physicians' prescribing habits.…”

Section: Discussionmentioning

confidence: 99%

Adalimumab exhibits superiority over etanercept in terms of a numerically higher response rate and equivalent adverse events: A real‐world finding

Yu,

Gao,

Zang

et al. 2024

Immunity Inflam & Disease

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IntroductionAdalimumab (ADA) and etanercept (ETN) are the most commonly applied biologics for rheumatoid arthritis (RA) management in China; however, the evidence regarding their superiority is controversial. In addition, in real‐world clinical settings, many factors may affect the application of these agents, such as dosage and administration period. Therefore, the present real‐world study aimed to compare the efficacy and safety of ADA and ETN treatment in RA patients via the propensity score matching method.MethodsIn total, 105 RA patients receiving ADA (n = 66) or ETN (n = 39) were reviewed in this retrospective study. The propensity score matching method was used to eliminate discrepancies in baseline features. Clinical response, low disease activity (LDA), and remission were evaluated based on the DAS28.ResultsBefore propensity score matching, compared with ETN, ADA yielded higher rates of clinical response at W24 (97.0% vs. 84.6%, p = .021), LDA at W12 (78.8% vs. 51.3%, p = .003), and remission at W24 (75.8% vs. 46.2%, p = .002). After propensity score matching, compared with ETN, ADA only achieved a higher rate of clinical response at W24 (96.3% vs. 77.8%, p = .043), whereas the rates of LDA and remission were not different between ADA and ETN treatments at any time point (all p > .05). In addition, the incidence of adverse events was not significantly different between the ADA and ETN treatments (all p > .05).ConclusionADA shows superiority over ETN in terms of a numerically greater response rate and equivalent adverse events.

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“…ADA was approved by the Food and Drug Administration (FDA) in 2002 as an anti-TNF-α drug made by producing a novel antibody protein by cloning “phage display” [ 35 , 36 ]. It is a fully recombinant human mAb that is structurally and functionally indistinguishable from naturally occurring human IgG1 [ 37 ].…”

Section: Adalimumabmentioning

confidence: 99%

Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis

Lim

Kim

Choi

2022

JPM

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Precision medicine refers to a highly individualized and personalized approach to patient care. Pharmacogenomics is the study of how an individual’s genomic profile affects their drug response, enabling stable and effective drug selection, minimizing side effects, and maximizing therapeutic efficacy. Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in the joints. It mainly starts in peripheral joints, such as the hands and feet, and progresses to large joints, which causes joint deformation and bone damage due to inflammation of the synovial membrane. Here, we review various pharmacogenetic studies investigating the association between clinical response to monoclonal antibody therapy and their target genetic polymorphisms. Numerous papers have reported that some single nucleotide polymorphisms (SNPs) are related to the therapeutic response of several monoclonal antibody drugs including adalimumab, infliximab, rituximab, and tocilizumab, which target tumor necrosis factor (TNF), CD20 of B-cells, and interleukin (IL)-6. Additionally, there are some pharmacogenomic studies reporting on the association between the clinical response of monoclonal antibodies having various mechanisms, such as IL-1, IL-17, IL-23, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the receptor activator of nuclear factor-kappa B (RANK) inhibition. Biological therapies are currently prescribed on a "trial and error" basis for RA patients. If appropriate drug treatment is not started early, joints may deform, and long-term treatment outcomes may worsen. Pharmacogenomic approaches that predict therapeutic responses for RA patients have the potential to significantly improve patient quality of life and reduce treatment costs.

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Preclinical discovery and development of adalimumab for the treatment of rheumatoid arthritis

Cited by 12 publications

References 67 publications

The effects of a truncated form of Staphylococcus aureus protein A (SpA) on the expression of cytokines of autoimmune patients and healthy individuals

The effects of a truncated form of Staphylococcus aureus protein A (SpA) on the expression of cytokines of autoimmune patients and healthy individuals

Adalimumab exhibits superiority over etanercept in terms of a numerically higher response rate and equivalent adverse events: A real‐world finding

Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis

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