scholarly journals Clinical and Immunological Factors Associated with Recommended Trough Levels of Adalimumab and Infliximab in Patients with Crohn’s Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Beatriz Orts ◽  
Ana Gutierrez ◽  
Lucía Madero ◽  
Laura Sempere ◽  
Ruben Frances ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Negative Relationship ◽  
Serum Levels ◽  
Interferon Γ ◽  
Drug Dose ◽  
Clinical Evolution ◽  
Drug Concentrations ◽  
Serum Trough ◽  
Trough Levels

Introduction: Up to 40% of patients with Crohn’s disease do not respond to treatment with anti-TNF or lose response after the initial benefit. Low drug concentrations have been proposed as the main predictor of treatment failure. Our aim was to study the immunological profile and clinical evolution of patients with Crohn’s disease according to the anti-TNF dose and serum trough levels.Methods: Crohn’s disease patients in remission treated with infliximab or adalimumab at stable doses for at least for 3 months were included. Serum levels of anti-TNF, TNF-α, interferon-γ, and interleukin IL-12, IL-10, and IL-26 were determined in blood samples taken just before drug administration. Patients were classified according to anti-TNF levels below, within, or above the target level range and the use of intensified doses. Clinical evolution at 6 months was analyzed.Results: A total of 62 patients treated with infliximab (8 on intensified schedule) and 49 treated with adalimumab (7 on intensified schedule) were included. All infliximab-treated patients showed levels within the recommended range, but half of adalimumab-treated patients were below the recommended range. A significant negative relationship between body weight and adalimumab levels was observed, especially in patients treated with intensified doses. Patients with infliximab levels over 8 µg/ml presented higher median IL-10 than patients with in-range levels (84.0 pg/ml, interquartile range [IQR] 77.0–84.8 vs. 26.2 pg/mL, IQR 22.6–38.0; p < 0.001), along with lower values of interferon-γ (312.9 pg/ml, IQR 282.7–350.4 vs. 405.6 pg/ml, IQR 352.2–526.6; p = 0.005). Patients receiving intensified versus non-intensified doses of infliximab showed significantly higher IL-26 levels (91.8 pg/ml, IQR 75.6–109.5 vs. 20.5 pg/ml, IQR 16.2–32.2; p = 0.012), irrespective of serum drug levels. Patients with in-range levels of adalimumab showed higher values of IL-10 than patients with below-range levels (43.3 pg/ml, IQR 35.3–54.0 vs. 26.3 pg/ml, IQR 21.6–33.2; p = 0.001). Patients treated with intensified vs regular doses of adalimumab had increased levels of IL-12 (612.3 pg/ml, IQR 570.2–1353.7 vs. 516.4 pg/mL, IQR 474.5–591.2; p = 0.023). Four patients with low adalimumab levels (19%) and four treated with intensified doses were admitted to a hospital during a follow-up compared to none of the patients with levels within the range.Conclusion: Patients with Crohn’s disease treated with infliximab and adalimumab exhibit differences in serum levels of cytokines depending on the drug, dose intensification, and steady state trough serum levels.

scholarly journals Higher Postinduction Infliximab Serum Trough Levels Are Associated With Healing of Fistulizing Perianal Crohn’s Disease in Children

2018 ◽  
Vol 25 (1) ◽  
pp. 150-155 ◽  
Author(s):  
Wael El-Matary ◽  
Thomas D Walters ◽  
Hien Q Huynh ◽  
Jennifer deBruyn ◽  
David R Mack ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Crohn’S Disease ◽  
Serum Trough ◽  
Trough Levels ◽  
Serum Trough Levels ◽  
Perianal Crohn's Disease

Ustekinumab Serum Trough Levels May Identify Suboptimal Responders to Ustekinumab in Crohn’s Disease

2019 ◽  
Vol 65 (5) ◽  
pp. 1445-1452 ◽  
Author(s):  
Claire Painchart ◽  
Séverine Brabant ◽  
Nicolas Duveau ◽  
Maria Nachury ◽  
Pierre Desreumaux ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Serum Trough ◽  
Trough Levels ◽  
Serum Trough Levels

Su2020 - Higher Post-Induction Infliximab Serum Trough Levels are Associated with Healing of Fistulizing Peri-Anal Crohn's Disease in Children

2018 ◽  
Vol 154 (6) ◽  
pp. S-668
Author(s):  
Wael El-Matary ◽  
Thomas D. Walters ◽  
Hien Q. Huynh ◽  
Jennifer deBruyn ◽  
David R. Mack ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Post Induction ◽  
Serum Trough ◽  
Trough Levels ◽  
Serum Trough Levels

Utility of proactive infliximab levels in paediatric Crohn’s disease

2018 ◽  
Vol 104 (3) ◽  
pp. 251-255 ◽  
Author(s):  
Christopher J Burgess ◽  
Claire Reilly ◽  
Lana Steward-Harrison ◽  
Fariha Balouch ◽  
Peter J Lewindon
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Retrospective Chart Review ◽  
Sustained Remission ◽  
Duration Of Therapy ◽  
Serum Trough ◽  
Antidrug Antibodies ◽  
Established Role ◽  
Trough Levels

ObjectiveInfliximab (IFX) has an established role in Crohn’s disease (CD), with serum trough levels of IFX (TLI) increasingly used to optimise dosing. We report the utility of routine, proactive TLI in children on combination therapy with immunosuppression (IS) from a single paediatric centre.MethodsThis is a retrospective chart review of all children with CD receiving IFX therapy conducted betweenJanuary 2014–May 2017. Clinical phenotype, duration of therapy, TLI (µg/mL), drug antibodies, type of IS, biomarkers and changes in management were recorded.Results60 children (8–17 years; median 14.1 years) had 206 TLIs recorded. 56/60 (93%) were on IS, with 5/60 (8%) developing antidrug antibodies (ADAs). 63/206 TLIs were recorded duringan episode of relapse (median 3.0 µg/mL) vs 143/206 TLIs recorded in remission (median 5.2 µg/mL). For children with TLI <3 µg/mL, 31/63 (49%) were in relapse vs 30/143 (21%) in remission. For children with TLI >7 µg/mL, 7/63 (11%) were in relapse vs 46/143 (32%) in remission. Change in management resulted from 43/206 (21%) TLIs in 31/60 (52%) children: 21 dose escalations, 12 de-escalations and 10 changed to adalimumab. Of 31 postinduction TLIs, 15/17 (88%) children with TLI >7 µg/mL achieved clinical and biochemical remission for the duration of therapy (median 14 months), while 4/5 (80%) children with TLI <3 µg/mL required early dose escalation. Combination therapy with thiopurines (TP) (median TLI 4.9 µg/mL) versus methotrexate (MTX) (median TLI 5.2 µg/mL) achieved comparable levels with no difference in relapse frequency.ConclusionsRoutine, proactive TLIs guide optimal management in children with CD. Postinduction and during maintenance, levels <3 µg/mL were associated with relapse and levels >7 µg/mL with sustained remission. Combination IS with TP and MTX appears to offer comparable TLI and ADA rates.

Low serum trough levels are associated with post-surgical recurrence in Crohn's disease patients undergoing prophylaxis with adalimumab

2014 ◽  
Vol 46 (11) ◽  
pp. 1043-1046 ◽  
Author(s):  
Giorgia Bodini ◽  
Vincenzo Savarino ◽  
Laurent Peyrin-Biroulet ◽  
Chiara de Cassan ◽  
Pietro Dulbecco ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Surgical Recurrence ◽  
Serum Trough ◽  
Trough Levels ◽  
Serum Trough Levels ◽  
Low Serum

scholarly journals P519 Higher anti-TNF α trough levels are not associated with increased radiological response in perianal fistulising Crohn’s disease: A multicentre study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S449-S449
Author(s):  
T LEE ◽  
L Gilbert ◽  
A Srinivasan ◽  
A Lee ◽  
D van Langenberg ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Trough Level ◽  
Response Relationship ◽  
Drug Levels ◽  
Exposure Response ◽  
Serum Trough ◽  
Radiological Response ◽  
The Relationship ◽  
Trough Levels

Abstract Background Perianal fistulas remain a debilitating and clinically challenging manifestation of Crohn’s disease (CD), given their prevalence and relative treatment resistance. Since the advent of biologic therapy, particularly the anti-TNFα agents infliximab and adalimumab, patient outcomes have improved. Serum trough levels have been associated with mucosal healing in luminal CD. However, the relationship between trough drug levels and healing of perianal fistulas remains less clear, with few studies assessing this cohort, and clinical healing typically defined as the primary endpoint. The aim of this study was to assess the relationship between radiological healing of perianal fistulising Crohn’s Disease (pfCD) on MRI, and serum trough drug levels, in patients treated with anti-TNFα therapy. Methods In this multi-centre, retrospective cross-sectional study, patients with pfCD who had trough levels measured within 6 months of a pelvic MRI were included. We collected patient demographics, infliximab and adalimumab trough levels, the presence or absence of anti-drug antibodies, concomitant steroid or antibiotic therapy, and Van Assche scores on MRI. The primary outcome, radiological response, was defined as a Van Assche score of 7 or less, while no response was defined as a score of greater than 7. Results A total of 99 patients were included (65 on infliximab, 34 on adalimumab). For patients receiving infliximab, the median drug levels for responders (n = 22) compared with non-responders (n = 43) were 5.5 mg/ml vs. 3.9 mg/ml respectively (p = 0.16). For patients receiving adalimumab, the median drug levels for responders (n = 14) compared with non-responders (n = 20) were 6.3 mg/ml vs. 3.1 mg/ml respectively (p = 0.09). On ROC curve analysis, the AUC for the association between radiological response and infliximab levels was 0.61, while for adalimumab it was 0.67. On quartile analysis, there appeared to be an increased response for increase in infliximab trough level quartile, with the exception of the highest quartile, however this association was not statistically significant (OR 1.36, 95% CI 0.85–2.16, p = 0.20). In comparison, the quartile analysis of adalimumab trough level and response demonstrated an exposure-response relationship (OR 2.24, 95% CI 1.11–4.52, p = 0.02). Conclusion Trough infliximab and adalimumab levels in patients who achieved radiological response were not significantly higher compared with those who did not, however quartiles analyses demonstrated trends toward an exposure-response relationship, in particular for adalimumab. The association between trough levels and radiological response could be further characterised with a larger, and ideally longitudinal, study.

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