Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis

Radstake, Timothy R D J; Svenson, Morten; Eijsbouts, A.M.M.; Hoogen, F.H.J. van den; Enevold, Christian; Riel, P.L.C.M. van; Bendtzen, Klaus

doi:10.1136/ard.2008.092833

Cited by 338 publications

(237 citation statements)

References 27 publications

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“…A study based on a genome-wide association scan suggests a complex multigenetic basis for response or resistance to therapy (34)(35)(36). Secondary nonresponsiveness after a successful initial response does appear, in part, to be related to the immunogenicity of the therapeutic Ab (37).…”

mentioning

confidence: 99%

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Feldmann

Maini

2010

The Journal of Immunology

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In the mid-1980s, new molecular tools enabled the biology of cytokine expression and regulation to be studied. Our group uncovered a TNF-dependent cascade in active rheumatoid synovium, suggesting that TNF might be a therapeutic target; this concept was supported in an animal model of the disease. The proof of concept was a series of clinical trials, which have led to marked changes in the therapy of human rheumatoid arthritis and subsequently of other diseases. The work with TNF clearly demonstrated the importance of cytokines in medicine as well as the capacity of mAbs (or receptor fusion proteins) to be used long-term in large populations, thus changing the therapeutic landscape.

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confidence: 99%

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Feldmann

Maini

2010

The Journal of Immunology

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“…The incidence of anti-drug antibodies appears to be higher in patients treated with infliximab (18,19). Dose escalation in some patients, perhaps those in whom anti-drug antibodies have developed, may increase drug levels and overcome associated loss of efficacy (20). The data in our study were not analyzed in relation to the presence of anti-CZP antibodies, although the impact of this factor on our results is likely to be minimal.…”

Section: Discussionmentioning

confidence: 68%

Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no additional efficacy in rheumatoid arthritis: An analysis of individual patient‐level data

Curtis¹,

Chen²,

Luijtens³

et al. 2011

Arthritis & Rheumatism

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Objective. To determine whether certolizumab pegol (CZP) dosage escalation from 200 mg to 400 mg every other week benefits some patients with rheumatoid arthritis (RA).Methods Results. In the group of patients who had completed the RAPID 1 study and had moderate or severe disease activity at entry into the open-label study, and in those who had been withdrawn early from the RAPID 1 study, the median DAS28 improvements 12 weeks after enrollment into the open-label study were similar in the dose-escalation and stable-dose groups. Individual patient-level data revealed no greater likelihood of response in the group of patients who received an increased dosage of CZP versus those in whom a stable dosage was maintained, whether they had completed the RAPID 1 study or had been withdrawn early.Conclusion. Although patient heterogeneity in clinical settings is acknowledged, the present results indicate that increasing the dose of CZP from 200 mg to 400 mg offers little additional benefit in RA, even for selected patients.

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“…Because each fully human therapeutic antibody has its own inherent immunogenicity caused by its particular sequence [369], this immunogenicity is to be determined in part by the sequence of its CDRs. Adalimumab, a fully human antibody, has been reported to induce an antibody production in a subset of patients (5-89) % that varies depending on the situation, and a reduction in therapeutic efficacy was observed in the antibody-positive patients [394][395][396][397]. This significant immunogenicity of adalimumab was supported by the presence of effector T-cell epitopes in regions containing a CDR sequence determined by an in vitro helper CD4+ T-cell assay.…”

Section: Fully Human Mabsmentioning

confidence: 77%

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

Klein

Templeton

Schwenk

2014

Pure and Applied Chemistry

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This report discusses the history and mechanisms of vaccination of humans as well as the engineering of therapeutic antibodies. Deeper understanding of the molecular interactions involved in both acquired and innate immunity is allowing sophistication in design of modified and even synthetic vaccines. Recombinant DNA technologies are facilitating development of DNA-based vaccines, for example, with the recognition that unmethylated CpG sequences in plasmid DNA will target Toll-like receptors on antigen-presenting cells. Formulations of DNA vaccines with increased immunogenicity include engineering into plasmids with "genetic adjuvant" capability, incorporation into polymeric or magnetic nanoparticles, and formulation with cationic polymers and other polymeric and non-polymeric coatings. Newer methods of delivery, such as particle bombardment, DNA tattooing, electroporation, and magnetic delivery, are also improving the effectiveness of DNA vaccines. RNA-based vaccines and reverse vaccinology based on gene sequencing and bioinformatic approaches are also considered. Structural vaccinology is an approach in which the detailed molecular structure of viral epitopes is used to design synthetic antigenic peptides. Virus-like particles are being designed for vaccine deliveries that are based on structures of viral capsid proteins and other synthetic lipopeptide building blocks. A new generation of adjuvants is being developed to further enhance immunogenicity, based on squalene and other oil-water emulsions, saponins, muramyl dipeptide, immunostimulatory oligonucleotides, Toll-like receptor ligands, and lymphotoxins. Finally, current trends in engineering of therapeutic antibodies including improvements of antigen-binding properties, pharmacokinetic and pharmaceutical properties, and reduction of immunogenicity are discussed. Taken together, understanding the chemistry of vaccine design, delivery and immunostimulation, and knowledge of the techniques of antibody design are allowing targeted development for the treatment of chronic disorders characterized by continuing activation of the immune system, such as autoimmune disorders, cancer, or allergies that have long been refractory to conventional approaches.

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Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis

Cited by 338 publications

References 27 publications

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no additional efficacy in rheumatoid arthritis: An analysis of individual patient‐level data

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

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