Infliximab concentrations in two non-switching cohorts of patients with inflammatory bowel disease: originator vs. biosimilar

Abstract Biosimilars are replacing originator compounds due to their similar effectiveness, safety and pharmacokinetics. Our objective was to compare the differences in pharmacokinetics and clinical outcomes between the originator infliximab (Ifx) and the biosimilar CT-P13 in a patient cohort with inflammatory bowel disease (IBD). Our cohort study included 86 patients from a historical and a prospective cohort from the start of infliximab treatment to 22 weeks later. Serum infliximab, antidrug antibody levels and other serum biomarkers were measured at weeks 0, 2, 6, 14 and 22. Remission outcomes were evaluated at weeks 14 and 22. Drug levels were measured prospectively and analysed using MANOVA. Of the 86 patients, 44 (51%) and 42 (49%) were administered the originator and CT-P13, respectively. Originator trough levels were higher than the biosimilar trough levels (35 vs. 21, 20.1 vs. 11, 6.6 vs. 2.9 and 4.3 vs. 1.7 μg/mL at weeks 2, 6, 14 and 22, respectively). A post-hoc analysis demonstrated changes in mean serum drug levels over time (p < 0.001) and according to the drug employed (p = 0.001). At week 22, 13 (81%) patients administered the originator achieved clinical remission compared with 5 (19%) patients with the biosimilar (p = 0.02). None of the patients administered the originator withdrew from the treatment compared with 7 for the biosimilar. During the study, there were significant differences in serum infliximab levels between the originator and the CT-P13 in the patients with IBD. The clinical outcomes were influenced by the type of compound administered.

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OC.12.5 VEDOLIZUMAB TROUGH LEVELS AND CLINICAL OUTCOMES IN INFLAMMATORY BOWEL DISEASE

Digestive and Liver Disease ◽

10.1016/s1590-8658(18)30337-2 ◽

2018 ◽

Vol 50 (2) ◽

pp. e99-e100

Author(s):

L. Guidi ◽

D. Pugliese ◽

T. Panici Tonucci ◽

B. Tolusso ◽

C. Felice ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Outcomes ◽

Bowel Disease ◽

Inflammatory Bowel ◽

Trough Levels

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P575 Vedolizumab trough levels predict clinical outcomes in inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx180.702 ◽

2018 ◽

Vol 12 (supplement_1) ◽

pp. S398-S398 ◽

Cited By ~ 6

Author(s):

L Guidi ◽

D Pugliese ◽

T Panici Tonucci ◽

B Tolusso ◽

C Felice ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Outcomes ◽

Bowel Disease ◽

Inflammatory Bowel ◽

Trough Levels

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Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus

Digestion ◽

10.1159/000501930 ◽

2019 ◽

Vol 101 (6) ◽

pp. 683-691 ◽

Cited By ~ 3

Author(s):

Thomas Greuter ◽

Michel H. Maillard ◽

Pascal Juillerat ◽

Pierre Michetti ◽

Frank Seibold ◽

...

Keyword(s):

Decision Making ◽

Inflammatory Bowel Disease ◽

Therapeutic Drug Monitoring ◽

Therapeutic Drug ◽

Drug Levels ◽

Loss Of Response ◽

Antidrug Antibody ◽

Antibody Titers ◽

Inflammatory Bowel ◽

Trough Levels

Background: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. Methods: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. Results: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn’s disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. Conclusion: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

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P483 Vedolizumab serum drug levels are not associated with clinical outcomes or markers of disease activity in inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.612 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S424-S426

Author(s):

S Shields ◽

J P Seenan ◽

E Nowell ◽

A Dunlop ◽

P Galloway ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Activity ◽

Clinical Outcomes ◽

Bowel Disease ◽

Clinical Decision Making ◽

Severe Disease ◽

Therapeutic Drug ◽

Published Data ◽

Drug Levels ◽

Inflammatory Bowel

Abstract Background Treatment options in Inflammatory Bowel Disease (IBD) include anti-TNFα and anti-integrin biologics. Therapeutic drug monitoring (TDM) is used to support clinical decision making and improve treatment outcomes with anti-TNFα drugs infliximab and adalimumab.1,2 It is unclear if TDM can offer similar benefits with vedolizumab (VDZ) and there are no clinical guidelines for using TDM with VDZ3. The aim of this study was to identify if drug levels (DL) are associated with clinical outcomes and markers of disease activity in patients treated with VDZ. Methods All VDZ DLs performed since introduction of testing at our unit in December 2018 were retrospectively identified. Target DLs of >30 μg/ml during induction (≤14 weeks since treatment initiation (TI)) and >10 μg/ml in maintenance (>14 weeks after TI) were agreed based on available published data. Dose information, timing of DL, lab results and disease activity scores were obtained from electronic patient records and paired with the DL dose. Calprotectin was included if recorded within 3 months of DL. Patients were classified as in remission or mild, moderate or severe active disease according to partial Mayo Score for ulcerative colitis and Harvey–Bradshaw Index for Crohn’s disease. Sub-analysis was undertaken according to timing of testing in relation to TI. Results Sixty pre-dose trough VDZ levels were identified from 41 patients. Median VDZ level was 25.7 μg/ml (<3.5–>70). Median time from TI to first VDL DL was 36 weeks (4.6–184). No relationship was identified between VDZ levels and biochemical markers of disease (Figure 1). Fourteen (23.3%) TDM were performed during induction. 6/14(42.8%) had subtherapeutic DLs; 3 in remission, 1 mild, 2 severe disease. The remaining 8/14(57.1%) had therapeutic DL; 3 mild, 3 moderate, 1 severe disease, 1 unknown. Forty-six (76.7%) TDM were performed during maintenance. Five out of 46(10.9%) had subtherapeutic DLs; 3 remission, 1 moderate disease, 1 unknown. The remaining 41/46(89.1%) had therapeutic DLs; 16 remission, 11 mild, 10 moderate, 3 severe disease, 1 unknown. For both sub-analysis groups, no relationship between disease state and drug level was observed. Conclusion The results from this small cohort do not suggest a relationship between serum VDZ levels and clinical outcomes. Further research in larger cohorts is needed to confirm or refute these findings. References

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Infliximab in young paediatric IBD patients: it is all about the dosing

European Journal of Pediatrics ◽

10.1007/s00431-020-03750-0 ◽

2020 ◽

Vol 179 (12) ◽

pp. 1935-1944 ◽

Cited By ~ 1

Author(s):

Maria M. E. Jongsma ◽

◽

Dwight A. Winter ◽

Hien Q. Huynh ◽

Lorenzo Norsa ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Treatment Regimen ◽

Bowel Disease ◽

Maintenance Treatment ◽

Young Patients ◽

Intensive Treatment ◽

Therapeutic Drug ◽

Infliximab Treatment ◽

Inflammatory Bowel ◽

Trough Levels

AbstractInfliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known? •Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year. What is New? •The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment.•Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment.•The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years).

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