695 Insufficient Infliximab Exposure Predisposes to Immunogenicity and Enhanced Clearance of Infliximab in IBD

Brandse, Johannan F.; Strik, Anne S.; Mould, Diane R.; Ashruf, Yaël; Smeekes, Oscar S.; Kuin, Sabine; Brink, Gijs van den; D’Haens, Geert R.

doi:10.1016/s0016-5085(16)30586-8

Cited by 8 publications

(11 citation statements)

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“…Absence of anti‐drug antibodies is associated with restoration of therapeutic drug levels on dose escalation . Dose escalating patients in remission with sub‐therapeutic levels and no anti‐drug antibodies, may prevent future anti‐drug antibody formation and loss‐of‐response as previously discussed . The addition of an immunomodulator also increases anti‐TNF drug levels, and this may be effective in patients with undetectable or low‐titre anti‐drug antibodies …”

Section: Resultsmentioning

confidence: 97%

“…Sub‐therapeutic adalimumab and infliximab drug levels are associated with increased future risk of developing anti‐drug antibodies and increased disease activity . The risk of ATI increased with the duration of the sub‐therapeutic drug levels . TDM shortly following successful induction therapy may identify patients with sub‐therapeutic drug levels.…”

Section: Resultsmentioning

confidence: 99%

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Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

245

207

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Summary Background Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti‐tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence‐based consensus statements for TDM‐guided anti‐TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti‐TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3‐8 and 5‐12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision‐making. In stable clinical response, TDM‐guided dosing may avoid future relapse. Data indicate drug‐tolerant anti‐drug antibody assays do not offer an advantage over drug‐sensitive assays. Further data are required prior to recommending TDM for non‐anti‐TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti‐TNF agents to treat IBD, especially in situations of treatment failure.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

245

207

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“…The potential effects of ATI formation on PK and clinical disease activity are schematically represented in Figure 1B. On the contrary, achieving higher IFX-TLs by increasing IFX dose or dosing interval can potentially prevent ATI formation (Table 2), because in adults both prolonged low IFX-TLs and low IFX-TLs at week 14 may precede ATI formation (68,69). Similarly to adult data, Rosenthal et al (21) reported an inverse association between IFX-TL at week 14 and ATIs at week 54 (P ¼ 0.003) in pediatric patients with IBD.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease

Winter

Joosse

Taminiau

et al. 2020

J. pediatr. gastroenterol. nutr.

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Objectives: Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which is often not adequate. While clinical trials have focused on safety and efficacy, there is limited data on pharmacokinetic characteristics and immunogenicity of IFX in children. The objective was to provide a systematic overview of current literature on pharmacokinetic and immunogenicity of IFX in children with IBD, to assess the validity of current adult to pediatric dosing extrapolation. Methods: A literature search identified publications up to October 2018. Eligibility criteria were study population consisting of children and/or adolescents with IBD, report of IFX trough levels and/or antibodies-to IFX, full text article or abstract, article in English, and original data. Results: Initial electronic search yielded 2360 potentially relevant articles, with 1831 remaining after removal of duplicates. An additional search yielded another 202 potentially relevant articles. Of the 2033 retrieved articles, 2000 articles were excluded based on title, abstract, or eligibility criteria. Clearance of IFX was increased in young children and children with extensive disease, leading to lower trough levels after extrapolated dosing of 5 mg/kg, antibodies-to IFX emergence, and subsequent reduced efficacy. Conclusions: Adult to pediatric weight-based dosing extrapolation is often inadequate. We provide several considerations for optimal dosing of IFX in children and adolescents with IBD.

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“…Esta estrategia de control terapéutico permite mantener las concentraciones del fármaco dentro de los márgenes terapéuticos donde la probabilidad de eficacia sea mayor, y la probabilidad de toxicidad y de desarrollo de inmunogenicidad sea mínima. Así, se han propuesto márgenes terapéuticos de referencia para los principales medicamentos biológicos utilizados en el tratamiento de la EII 84,[86][87][88][89][90] . Los márgenes terapéuticos para concentraciones mínimas de infliximab y adalimumab, que son los más utilizados, se han fijado en 3-10 μg/mL y 8 -14 μg/mL, respectivamente.…”

Section: Farmacocinética De Los Medicamentos Biológicos Anti-tnfunclassified

“…Los márgenes terapéuticos para concentraciones mínimas de infliximab y adalimumab, que son los más utilizados, se han fijado en 3-10 μg/mL y 8 -14 μg/mL, respectivamente. De hecho, se ha demostrado que la presencia de concentraciones en la zona superior del margen terapéutico se asocia con una menor inmunogenicidad y con una mayor probabilidad de remisión endoscópica 86,91 . La evidencia disponible para golimumab y certolizumab pegol, no permite caracterizar sus márgenes terapéuticos con fiabilidad.…”

Section: Farmacocinética De Los Medicamentos Biológicos Anti-tnfunclassified

Monitorización farmacocinética de anti-TNF para la personalización de la terapia en enfermedad inflamatoria intestina

Hernández¹,

Germán²

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695 Insufficient Infliximab Exposure Predisposes to Immunogenicity and Enhanced Clearance of Infliximab in IBD

Cited by 8 publications

References 0 publications

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease

Monitorización farmacocinética de anti-TNF para la personalización de la terapia en enfermedad inflamatoria intestina

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