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

2020 ◽  
Vol 179 (12) ◽  
pp. 1935-1944 ◽  
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).

scholarly journals P408 Long-term impact of the decrease of infliximab trough levels on the disease course in Inflammatory Bowel Disease patients under maintenance treatment with infliximab

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S375-S376
Author(s):  
E Orfanoudaki ◽  
M Gazouli ◽  
K Foteinogiannopoulou ◽  
E Theodoraki ◽  
E Legaki ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Maintenance Treatment ◽  
Biologic Agent ◽  
Therapeutic Drug ◽  
Asymptomatic Patients ◽  
Treatment Optimisation ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background The measurement of infliximab trough levels (IFX-TLs) has been suggested as an important biomarker for the optimisation of treatment in patients with inflammatory bowel disease (IBD). We have previously reported that IFX-TLs of patients under maintenance treatment with IFX show decreasing patterns associated with an increasing pattern of CRP levels1. We aimed to study the clinical impact of this observation by recording the treatment changes that became necessary during a three year follow-up. Methods Consecutive asymptomatic patients on maintenance treatment with IFX were included. Two different measurements of IFX-TLs were made (ELISA, Eagle BioSciences) with a ten-month interval using serum samples drained before IFX infusion. After the second measurement patients were followed up for three years and all treatment modifications including IFX intensification, change of biologic agent or IBD-related surgical intervention were assessed. Results Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 CD, 15 UC, 42 men, mean age 44.2 ± 15.2 years, 41 in combination therapy with immunomodulator, 6 in intensified dose], with 2 available measurements of IFX-TLs (A and B) were included in the study. Median levels of IF-TLs were 5.07 (IQR 1.60–12.73) μg/ml in measurement A and 4.68 (1.19–7.83) μg/ml in measurement B (p &lt; 0.0001). Treatment was intensified in 8 patients after measurement A. Patients with stable IFX dose showed a significant reduction in median IFX-TLs from 5.65 to 3.8 μg/ml (p &lt; 0.0001). Moreover, CRP levels were significantly increased in measurement B compared with measurement A [0.33 (03–4.4) mg/dl vs. 0.31 (0.3–3.8) mg/dl, p = 0.02]. During a 3 year follow-up, 22 (34%) patients needed treatment optimisation (6 IFX intensification, 7 change of agent, 6 surgery, 3 change of agent plus surgery). In three patients IFX was stopped for safety reasons. Fifty-eight hospitalisations in 19 patients were also recorded. The decrease of IFX-TLs between the two measurements was significantly more in patients with treatment optimisation compared with patients without treatment optimisation (p = 0.03). Conclusion IBD patients who are on maintenance treatment with infliximab showing decreasing patterns of IFX-TLs often need treatment optimisation during the follow-up due to clinical or endoscopic activity. These results probably suggest the importance of the proactive therapeutic drug monitoring and early treatment optimisation in these patients References

Sa1890 DECREASING PATTERNS OF INFLIXIMAB TROUGH LEVELS IN ASYMPTOMATIC INFLAMMATORY BOWEL DISEASE PATIENTS UNDER MAINTENANCE TREATMENT WITH INFLIXIMAB; DOES IT MATTER?

2020 ◽  
Vol 158 (6) ◽  
pp. S-467
Author(s):  
Eleni Orfanoudaki ◽  
Maria Gazouli ◽  
Kalliopi Foteinogiannopoulou ◽  
Eirini Theodoraki ◽  
Evangelia Legaki ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Maintenance Treatment ◽  
Inflammatory Bowel ◽  
Trough Levels

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

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ana Martínez-Feito ◽  
Luz Yadira Bravo-Gallego ◽  
Borja Hernández-Breijo ◽  
Jesús Diez ◽  
Laura García-Ramirez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Outcomes ◽  
Bowel Disease ◽  
Infliximab Treatment ◽  
Drug Levels ◽  
Antidrug Antibody ◽  
Inflammatory Bowel ◽  
Post Hoc ◽  
Antibody Levels ◽  
Trough Levels

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.

scholarly journals Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients

2020 ◽  
pp. 1-10
Author(s):  
Ilana Reinhold ◽  
Sena Blümel ◽  
Jens Schreiner ◽  
Onur Boyman ◽  
Jan Bögeholz ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Clinical Disease ◽  
Therapeutic Drug ◽  
Real World Data ◽  
Significant Treatment ◽  
Infusion Reactions ◽  
Inflammatory Bowel ◽  
Trough Levels

<b><i>Background and Aims:</i></b> The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care. <b><i>Methods:</i></b> We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included. <b><i>Results:</i></b> The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (<i>p</i> = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (<i>p</i> = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9–38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients. <b><i>Conclusions:</i></b> TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

scholarly journals Serum trough levels of infliximab are not associated with peripheral arthralgia activity in patients with inflammatory bowel disease

2021 ◽  
Vol 8 (1) ◽  
pp. e000788
Author(s):  
Shaina Sekhri ◽  
Bharat Rao ◽  
Akanksha Mohananey ◽  
Poonam Beniwal-Patel ◽  
Alexandra Bruss ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Drug ◽  
Extraintestinal Manifestation ◽  
Cross Sectional ◽  
Patient Reported ◽  
Serum Trough ◽  
Inflammatory Bowel ◽  
Trough Levels ◽  
Serum Trough Levels

BackgroundInfliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined.ObjectiveWe aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease.DesignIn this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia.ResultsOut of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively).ConclusionsThis study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn’s disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease.

P329 Comparative Assessment of Adalimumab Trough Levels between Point-of-Care Testing and current Standard of Care (enzyme linked immunosorbent assay) in patients with Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S353-S353
Author(s):  
I Marsilio ◽  
D Maniero ◽  
G Lorenzon ◽  
A Rigo ◽  
R Cardin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Whole Blood ◽  
Point Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Point Of Care Testing ◽  
Deming Regression ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Adalimumab (ADL) is a therapeutic monoclonal antibody that targets the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) and has been shown to effectively induce and maintain disease remission in patients with Inflammatory Bowel Disease (IBD). However, some patients fail to respond to this treatment, experiencing primary failure (no response to induction therapy), while others initially respond but lose efficacy over time (secondary failure). Therapeutic Drug Monitoring (TDM), in clinical practice, may lead to maintain therapeutic drug concentration thereby optimizing individual dosage regimen and improving treatment response. Recently, a point of care testing (POCT) has been developed to rapidly measure trough levels in patients taking ADL. Comparative data with current gold standard are lacking. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) ADL assay which analyze capillary whole blood and the comparative enzyme linked immunosorbent assays (ELISA) from serum samples. Methods From December 2020 to February 2021, consecutive patients (aged ≥ 18 years) taking ADA (Humira, Amgevita, Imraldi) were recruited at Gastroenterology Unit, Padua University Hospital, during outpatient visits. In each patient, ADL levels from capillary whole blood collected by finger stick were performed using the ProciseDx ADL assay with reportable range between 1.3 µg/mL - 51.5 µg/mL; at the same time, a serum sample from venous blood was collected to carry out Grifols’ Promonitor ELISA test (range ≤ 0.024 – 12 µg/mL). A Deming regression test was used to identify the correlation between the two methods. Results Sixty patients were enrolled (67% males with mean age of 3±14), with 80% of them having CD, 17% UC and 3% an undetermined-Inflammatory Bowel Disease (IBD-U). The assessment with ProciseDx POCT was feasible and required a turnaround time of 3±0.2 minutes while serum ELISA analysis required the collection of at least 40 samples (around three weeks at our centre) and 3 hours to be performed. Thirty patients (63% males with mean age of 41±14) had therapeutic levels as assessed by ProciseDx ADL assay lower than 1.3 or greater than 12 µg/mL, in accordance with ELISA assessment. Among the remaining 30 patients (70% males with mean age of 43±15), the correlation between the two tests was high (r of 0.858 (95% CI 0.720 – 0.930)). Conclusion The ProciseDx POCT has similar accuracy but was more rapid and easy to be performed in providing the results of TDM in outpatients taking ADL. This could lead to a more rapid and effective optimization of the biological drug, thus avoiding treatment failure.

Infliximab trough levels are decreasing over time in patients with inflammatory bowel disease on maintenance treatment with infliximab

2019 ◽  
Vol 31 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Eleni Orfanoudaki ◽  
Maria Gazouli ◽  
Kalliopi Foteinogiannopoulou ◽  
Eirini Theodoraki ◽  
Evangelia Legaki ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Maintenance Treatment ◽  
Inflammatory Bowel ◽  
Trough Levels ◽  
Over Time

scholarly journals Serum-Infliximab Trough Levels in 45 Children with Inflammatory Bowel Disease on  Maintenance Treatment

2017 ◽  
Vol 18 (3) ◽  
pp. 575 ◽  
Author(s):  
Helena Rolandsdotter ◽  
Per Marits ◽  
Ulf Sundin ◽  
Ann-Charlotte Wikström ◽  
Ulrika Fagerberg ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Maintenance Treatment ◽  
Inflammatory Bowel ◽  
Trough Levels

scholarly journals P642 Serum adalimumab levels measured between days 9 and 13 from drug injection can be interpreted clinically in a similar way to trough levels in patients with inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S532-S532
Author(s):  
J Guardiola Capón ◽  
K Serra ◽  
L Rodríguez-Alonso ◽  
E Santacana ◽  
N Padullés ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Trough Level ◽  
Therapeutic Drug ◽  
Drug Injection ◽  
Time Points ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background AntiTNF therapeutic drug monitoring is currently performed at trough, immediately before drug administration. However, in clinical practice when subcutaneous medications are used, blood extractions often do not coincide with that moment. The aim of this study was to know if adalimumab levels measured between injections are sufficiently similar to trough levels to be used in clinical practice in a similar way. Methods 295 adalimumab level determinations performed at different time points of 99 injection cycles in 55 patients with inflammatory bowel disease (IBD) were included in the study. 51 patients received 40mg every 2 weeks and 4 patients received 80mg every 2 weeks. Results Median adalimumab levels (IQR) at trough, between days 1–4, 5–8 and 9–13 were 10.6 (6–12), 12.3 (7–18), 13 (7–19) and 10.8 (8–12), respectively. The median differences between trough level and days 1–4, 5–8 and 9–13 were 1.7 (IC 95% 1–2.3) (p &lt; 0.001), 2.3 (IC 95% 1.5–3.1) (p &lt; 0.001), 0.6 (IC 95% –0.2–1.3) (p = 0.13), respectively. Conclusion Adalimumab levels between days 9 and 13 from drug injection are very similar to trough level and could be interpreted clinically at the same way. Adalimumab levels between days 1 and 8 are significantly higher, although, differences are small.

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