Therapeutic Drug Monitoring Guides the Management of Crohn's Patients with Secondary Loss of Response to Adalimumab

Background: Managing loss of response (LOR) in Crohn's disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Methods: Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed. Primary outcomes were composite remission at 3, 6, and 12 months in those with empiric adjustments versus TDM-guided optimization. Results: There were 104 patients (54.8% men) who were included in the study. Of this group, 81 patients (77.9%) had serum level (SL) >= 5 mu g/ml at index TDM with a median value of 12 mu g/ml (IQR 6.1-16.5). There were 10 patients (9.6%) who had undetectable SL with high anti-ADA antibodies and 48 (46.2%) received empiric escalation. TDM led to change in treatment in 58 patients (55.8%). Among them, 28 (48.3%) had discontinued ADA, 12 (21.7%) had addition of immunomodulator or steroid, and 18 (31%) had ADA dose escalation. Empiric dose escalation before TDM-based optimization was not associated with improved outcomes at 3, 6, and 12 months, irrespective of SL levels. Clear SL cutoff associated with composite remission was not identified. Conclusions: Our data do not support empiric dose adjustment beyond that based on the result of the TDM in patients with LOR to ADA. TDM limits unnecessary dose escalation and provides appropriate treatment strategy without compromising clinical outcomes

Effectiveness of third-class biologic treatment in crohn’s disease : A multi-center retrospective cohort study

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.Peer reviewe

Effectiveness of third-class biologic treatment in Crohn's disease : a multi-center retrospective cohort study

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Risk factors for lymphoma in patients with inflammatory bowel disease: a case-control study

Background: Subgroups of patients with inflammatory bowel disease (IBD) may have an increased risk of developing lymphoma. We sought to identify factors that were associated with lymphoma in IBD patients. Methods: Cases and controls were identified though a centralized diagnostic index. We identified 80 adult IBD patients who subsequently developed biopsy-proven lymphoma between 1980 and 2009. For each case, two controls were matched for subtype of IBD, geographic location, and length of IBD follow-up at our institution prior to lymphoma diagnosis. Medical records were abstracted for demographic and clinical information. Conditional logistical regression was used to assess associations between risk factors and the development of lymphoma. Results: Sixty cases were males (75%) vs. 77 controls (48%). Median age at index date was 59 years for cases and 42 years for controls. Twenty cases (25%) and 23 controls (14%) were receiving immunosuppressive medications at the index date. Four cases (5%) and six controls (4%) were receiving anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents at the index date. In multivariate analysis, age per decade (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.37-2.43), male gender (OR, 4.05; 95% CI, 1.82-9.02) and immunosuppressive exposure at the index date (OR, 4.20; 95% CI, 1.35-13.11) were significantly associated with increased odds of developing lymphoma. Disease severity and use of anti-TNF-alpha agents were not independently associated with developing lymphoma. Conclusions: In this case-control study, increasing age, male gender and use of immunosuppressive medications were associated with an increased risk of lymphoma in patients with IBD, whereas disease severity and anti-TNF-alpha use were not associated with increased odds.Cadre de l'étude: Certains sous-groupes de patients atteints de maladies inflammatoires de l'intestin (MII) peuvent courir un risque accru de développer un lymphome. Nous avons chercher à identifier les facteurs associés avec le lymphome chez les patients avec des MII. Méthodologie: Les cas et les témoins ont été identifiés à partir d'un répertoire de diagnostics centralisé. Nous avons identifié 80 patients adultes atteints de MII et qui ont dévelopé un lymphome confirmé par biopsie entre les années 1980-2009. Deux témoins étaient appariés pour chaque cas sur le sous-type de MII, la localisation géographique et la durée du suivi pour les MII dans notre centre jusqu'au diagnostic de lymphome. Les dossiers médicaux ont été consultés afin d'obtenir les données démographiques et cliniques. Un modèle de régression logistique conditionel a été utilisé pour évaluer les associations entre les facteurs de risque et le développement d'un lymphome. Résultats: Parmi les cas retenus, 60 étaient des hommes (75%) vs 77 dans le groupe de témoins (48%). L'âge médian à la date index était de 59 ans pour les cas et de 42 ans pour les témoins. Vingt cas (25%) et 23 témoins (14%) recevaient des médicaments immunosuppresseurs à la date index. Quatre cas (5%) et six témoins (4%) recevaient des anticorps antagonistes du TNF-alpha à la date index. Lors d'une analyse multivariée, l'age par décennie (rapport de cotes [RC]:1,83, intervalle de confiance à 95%[IC]: 1,37-2,43), le sexe masculin (RC:4,05, IC 95%:1,82-9,02) et l'exposition aux médicaments immunosuppresseurs à la date index (RC:4,20, IC 95%: 1,35-13,11) ont été associés, de façon significative, à un risque accru de developper un lymphome. La sévérité de la maladie et l'utilisation d'anticorps antagonistes du TNF-alpha n'ont pas été associés de manière indépendante au developpement d'un lymphome. Conclusion: Dans cette étude de cas-témoin, l'age avancé, le sexe masculin et l'tilisation de médicaments immunosuppresseurs ont été associés à un risque supérieur de lymphome chez les patients atteints de MII. Par contre, la sévérité de la maladie et l'utilisation des anticorps antagonistes du TNF-alpha n'ont pas été associés à un risque plus élevé

Update on TDM (Therapeutic Drug Monitoring) with Ustekinumab, Vedolizumab and Tofacitinib in Inflammatory Bowel Disease

The goal of therapeutic drug monitoring (TDM) is to optimize anti-TNF (tumor necrosis factor) biologic treatment in patients with inflammatory bowel disease (IBD). Although commercial assays are readily available for both ustekinumab and vedolizumab, the use of TDM with these newer biologic medications is at its infancy. The clinical utility of TDM with non-anti-TNF mechanisms of action is not clear. This review summarizes the latest available data on the pharmacokinetics of newer biologic and oral small molecules and highlights the threshold concentrations that have been associated with improved outcomes in IBD patients

Thiopurines in the Management of Crohn’s Disease: Safety and Efficacy Profile in Patients with Normal TPMT Activity—A Retrospective Study

Background and Aims. Thiopurines are used in the treatment of Crohn’s disease (CD) and thiopurine S-methyltransferase (TPMT) activity can guide thiopurine dosing to avoid adverse events. This retrospective study evaluated the safety and efficacy of starting thiopurines at low dose versus full dose in patients with CD and normal TPMT. Methods. This was a single center retrospective study including adult CD patients with normal TPMT levels (≥25 nmol/hr/g Hgb) who were followed for 1 year. Patients started at full dose of azathioprine (2–2.5 mg/kg) or 6-mercaptopurine (1–1.5 mg/kg) were compared to patients started at low dose. Harvey-Bradshaw index, treatment failure, and drug-related adverse events were recorded. Results. Our study included 134 patients. Both groups had similar incidences of drug-related adverse events and discontinuation of therapy due to side effects. Fifty-six percent of all adverse events occurred within 31 days and 92% occurred within 3 months of therapy. Clinical response favored the full-dose group at 6 months (69% versus 27%, p=0.0542). Conclusions. Our study indicates that it is safe to start patients on full-dose thiopurine when they have a normal TPMT given its very similar toxicity profile to patients started on low dose. This may also positively impact efficacy