Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

Hofmekler, Tatyana; Bertha, Madeline; McCracken, Courtney; Martineau, B.; McKinnon, E.; Schoen, Bess T.; McElhanon, Barbara O.; Tenjarla, Gayathri; Kugathasan, Subra; Sauer, Cary G.

doi:10.1097/mpg.0000000000001302

Cited by 30 publications

(18 citation statements)

References 43 publications

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“…Some experts experienced that altering IFX injection to 5 mg/kg with 4-week intervals was sometimes effective in patients initially administered 10 mg/kg IFX at 8-week intervals. Shortening of the interval can be more effective than increasing the dose because the serum concentration of TNF-α inhibitors is maintained at stably high levels [12-14]. Although dose optimization based on the serum trough level is ideal, it is not covered by Japanese national health insurance and can only be measured in limited institutions.…”

Section: Summary Of the Meetingmentioning

confidence: 99%

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

et al. 2020

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Induction therapy with tumor necrosis factor-α (TNF-α) inhibitors is highly effective for the treatment of Crohn’s disease. However, there are primary nonresponders (PNR) of TNF-α inhibitors without clinical response during the induction period. In addition, there are partial responders (PR), who show some efficacy, but clinical remission is not achieved by induction therapy. To date, the definition and clinical management of PNR and PR have not been established. This report summarizes the opinions of 36 Japanese experts attending the Japan Round Table Discussion on IBD Meeting regarding how to determine PNR and PR of TNF-α inhibitors and how to manage these patients in clinical practice. PNR, who do not show any initial improvement of clinical symptoms and serum C-reactive protein (CRP) levels, require re-assessment of intestinal complications. PR can be determined either by clinical symptoms, serum CRP levels, or imaging results. PR need intensification of the treatment with TNF-α inhibitors either with or without optimization of immunomodulators. Optimization of initial TNF-α inhibitor therapy may improve long-term outcomes, but more evidence is required to improve the use of TNF-α inhibitors for the prevention and management of PNR and PR.

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Section: Summary Of the Meetingmentioning

confidence: 99%

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

et al. 2020

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“…Several pediatric studies, however, reported TLs below the therapeutic range with a standard 5 mg/kg dose at an 8-week interval (25,27). Four studies comparing different age groups showed TLs to be lower in younger children with IBD compared to adolescents (25,29,37,43).…”

Section: Discussionmentioning

confidence: 99%

“…Two studies reported that week 14 TLs may have predictive value for clinical remission without dose intensification during maintenance or deep remission (clinical remission with normal CRP) (21,46). Hofmekler et al (37) defined clinical outcome as the need for dose optimization and reported that 37% of children who required dose optimization had low TLs during maintenance (<3 mg/mL). Stein et al (49) reported that children who were still on IFX treatment after 12 months had higher 10-week median TLs compared to patients who had stopped IFX treatment.…”

Section: Clinical Outcome: Pharmacodynamicsmentioning

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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“…In children with moderate-to-severe UC, week 8 levels of serum IFX concentrations (≥41.1 μg/ml) were associated with greater proportions of patients achieving efficacy endpoints (clinical response: 92.9%; mucosal healing: 92.9%; and clinical remission: 64.3%) versus those with lower serum concentrations (<18.1 μg/ml; 53.9%, 53.9%, and 30.8%, respectively) 87 . A retrospective study from a tertiary care center demonstrated that interval shortening rather than dose escalation results in higher IFX levels, and the authors recommended a dose of every 6 weeks for optimizing levels 88 .…”

Section: Anti-tnfsmentioning

confidence: 99%

Recent advances in understanding and managing pediatric inflammatory bowel disease

Gurram¹,

Patel²

2019

F1000Res

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The landscape of pediatric inflammatory bowel disease is rapidly evolving. The therapeutic advances seen in the adult arena are rapidly being adopted by pediatric gastroenterologists and evaluated in both controlled trials and real-world experience. Though anti-tumor necrosis factor agents have been the primary therapy over the last decade, recently there has been an expansion of therapeutic targets and alternative mechanism of action drugs with a focus on individualized and personalized therapy. By reviewing epidemiology, pathophysiology, and goals of treatment, we hope to frame the discussion of current and novel therapeutics for the pediatric gastroenterologist. As scientific discovery continues to push the envelope in defining our understanding of pediatric inflammatory bowel disease, the current era of therapeutics gives us hope that a cure may be realized soon.

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Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

Cited by 30 publications

References 43 publications

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

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

Recent advances in understanding and managing pediatric inflammatory bowel disease

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