Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure

Ungar, Bella; Haj-Natour, Ola; Kopylov, Uri; Yavzori, Miri; Fudim, Ella; Picard, Orit; Loebstein, Ronen; Lahat, Adi; Maor, Yasmin; Avidan, Benjamin; Lang, Alon; Weiss, Batia; Chowers, Yehuda; Eliakim, Rami; Ben‐Horin, Shomron

doi:10.1097/md.0000000000000673

Cited by 16 publications

(7 citation statements)

References 36 publications

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“…Immunogenicity is a multifactorial phenomenon, influenced by patient (genetic background, ethnicity), disease (type, activity), treatment (episodic vs. scheduled, co‐administration of immunosuppressive agents) and/or drug‐related factors (dosing, route of administration, product aggregation and denaturation), that can have a significant impact both on the efficacy and safety of biological therapies …”

Section: Resultsmentioning

confidence: 99%

Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases

Papamichael

Stappen

Jairath

et al. 2015

Aliment Pharmacol Ther

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Summary Background Anti‐tumour necrosis factor (anti‐TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT‐P13; however, some uncertainty exists regarding their pharmacology in IBD. Aim To review the literature on anti‐TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. Methods A PubMed literature search was performed using the following terms individually or in combination: ‘biosimilars,’ ‘CT‐P13,’ ‘Crohn's disease,’ ‘inflammatory bowel disease,’ ‘ulcerative colitis,’ ‘anti‐TNFα therapy,’ ‘infliximab,’ ‘adalimumab,’ ‘pharmacokinetics,’ ‘immunogenicity.’ Results Bioequivalence of CT‐P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT‐P13 in IBD come from small post‐marketing registries and case series with a relatively short‐term follow‐up period and suggest comparable efficacy and safety to infliximab. Inter‐ and intra‐individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross‐reactivity of anti‐drug antibodies and whether similar exposure–response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. Conclusions It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post‐marketing studies and pharmacovigilance are warranted in the coming years.

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Section: Resultsmentioning

confidence: 99%

Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases

Papamichael

Stappen

Jairath

et al. 2015

Aliment Pharmacol Ther

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“…Patients receiving MTX were significantly less likely to develop ADAs and 83% of ADA-positive patients developed loss of response compared with 6% of ADA-negative patients. Genetic susceptibility to risk of ADA formation has been suggested in recent studies that found that an Ashkenazi Jewish ancestry was protective of ADA formation, with a relative risk reduction on par with concomitant DMARD therapy [48]. Together these studies highlight the potential importance of therapeutic drug level and ADA monitoring in patients receiving anti-TNF-α therapy and is evidenced by their routine monitoring in many patient care settings.…”

Section: Immunogenicity and Therapeutic Drug Monitoring With Biologicmentioning

confidence: 91%

Disease modifying anti-rheumatic drugs in juvenile idiopathic arthritis: striving for individualized therapy

Funk

Becker

2016

Expert Review of Precision Medicine and Drug Development

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Disease-Modifying Anti-Rheumatic Drug (DMARD) use in the treatment of juvenile idiopathic arthritis (JIA) has experienced a dramatic evolution since the early introduction of methotrexate in the 1970's. This renaissance has been primarily driven by innovation in drug discovery and development that has resulted in the approval of a number of protein-based therapeutics targeting disease-specific pathways. Despite the expansion in the number of drugs available in the treatment of JIA, interindividual variation in therapeutic response and drug-associated toxicities continue to be a major concern and has driven efforts towards individualized therapy. Recent advances in pediatric drug development and innovative approaches to identifying a priori predictors of drug response hold the promise for an individualized approach to therapy that will yield the highest efficacy and safety potential for each JIA patient.

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“…Smoking has often been associated with significantly lower rates of response to anti-TNF for CD [Arnott et al 2003; Cohen et al 2012; Juillerat et al 2015; Ungar et al 2015a]. Other reports did not observe this association [Fefferman et al 2004; Orlando et al 2005].…”

Section: Response To Previous Therapies Disease Phenotype and Locationmentioning

confidence: 99%

“…In an Israeli study, Ashkenazi Jewish origin was associated with a less frequent formation of anti-TNF antibody formation compared with the prevalence in Jews of Sephardic origin, in both UC and CD. However, genetic analysis was not performed [Ungar et al 2015a].…”

Section: Antidrug Antibodiesmentioning

confidence: 99%

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

Kopylov

Seidman

2016

Therap Adv Gastroenterol

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Monoclonal antibodies to tumor necrosis factor (TNF) have become a mainstay of the therapeutic armamentarium in inflammatory bowel disease (IBD) over the last 15 years. Although highly effective, primary and secondary nonresponse are common and associated with poor clinical outcomes and significant costs. Multiple clinical, genetic and immunopharmacological factors may impact the response to anti-TNFs. Early stratification of IBD patients by the expected risk of therapeutic failure during the induction and maintenance phases of treatment may allow for treatment optimization and potentially optimal short-and long-term outcomes. The aim of this review is to summarize the current data concerning the potential predictors of therapeutic success and failure of anti-TNFs in IBD.

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Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure

Abstract: Supplemental Digital Content is available in the text

Cited by 16 publications

References 36 publications

Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases

Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases

Disease modifying anti-rheumatic drugs in juvenile idiopathic arthritis: striving for individualized therapy

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

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