Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels

2021 ◽  
Author(s):  
Xavier Roblin ◽  
Capucine Genin ◽  
Stéphane Nancey ◽  
Nicolas Williet ◽  
Pauline Veyrard ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Group Treatment ◽  
Treatment Discontinuation ◽  
Dose Optimization ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Trough Levels

Abstract Background In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma—either ADA dose optimization or switching to vedolizumab or ustekinumab. Methods Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels > 4.9 μg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. Results Adalimumab was optimized (n = 61 patients, 42 Crohn’s disease, 19 ulcerative colitis) or swapped for vedolizumab (n = 40, 20 ulcerative colitis) or ustekinumab (n = 30, 30 Crohn’s disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (P < 0.001). The median time without therapeutic discontinuation was significantly longer in the swap group (>24 months) than in the optimization group (13.3 months, P < 0.001). In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 μg/g (HR, 3.53; 95% CI, 1.16–10.72; P = 0.026) and inversely associated with variation of trough levels of adalimumab (>2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13–0.82; P = 0.03). In the swap group, no factor was associated with treatment discontinuation. Conclusion In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.

scholarly journals DOP88 Visceral fat area correlates well with anti-TNFα drug levels and secondary loss of response in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S126-S127
Author(s):  
Z Lim ◽  
C Welman ◽  
W Raymond ◽  
L Thin
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Body Mass ◽  
Visceral Fat ◽  
Trough Level ◽  
Secondary Outcome ◽  
Visceral Fat Area ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Trough Levels

Abstract Background A high body mass index (BMI) is known to adversely affect anti-TNFα trough levels and secondary loss of response (SLOR); however, the literature is scarce in defining what aspect of body mass determine these outcomes. We hypothesise that a large visceral fat area is associated with a lower anti-TNFα level and a higher rate of SLOR. Our aim was to determine the impact of fat and muscle compartment areas on these outcomes. Methods Crohn’s disease (CD) patients who were prescribed standard doses of an anti-TNFα agent [5 mg/kg, 8 weekly infliximab (IFX) or 40 mg EOW of adalimumab (ADA)] from 1 February 2015 to 30 June 2018 were examined retrospectively. Primary responders with a minimum therapy duration of 12 weeks, at least 12 months of follow-up and a trough level within 6 months of a CT or MRI, were eligible for inclusion. The primary outcome was the trough level and the secondary outcome was time to SLOR, defined as a need to dose escalate, change out of class, requiring ≥3 courses of corticosteroids in a 12-month period, or surgery. Patients were followed until they met a SLOR or the census date of 30 June 2019. Visceral fat area (VFA), subcutaneous fat area (SFA) and skeletal muscle area (SMA) were measured on the CT/MRI at the L3 vertebral level in cm2 by a radiologist blinded to the clinical outcome and corrected for patient height (cm2/m2). Results Of 813 patients prescribed an anti-TNFα agent in the study period, data from 69 eligible CD patients were included for analysis. The median age was 43.5 ± 16.2 years, and 42 (60.9%) were males. Forty-four (63.8%) and 25 (36.2%) patients were treated with IFX and ADA respectively. The mean BMI was 26.9 ± 5.2. Univariate analysis of infliximab trough levels found that total fat area, VFA, visceral fat index [VFI (VFA/height in m2)] and VFA/SMA ratio were inversely correlated with anti-TNFα trough level (p < 0.05). No association was found between ADA trough level and muscle/fat areas. After multivariate adjustment for CRP, albumin, presence of antibodies, concurrent immunomodulator use and gender, IFX levels were inversely associated with VFA [-0.021 (−0.038, −0.003) p = 0.025], VFI [−0.066 (−0.119, −0.013) p = 0.016] and VFA/SMA [−3.805 (−7.132, −0.477) p = 0.026] but not BMI [−0.232 (−0.520, 0.055) p = 0.11). No association was found for ADA trough levels. Kaplan–Meir analyses showed a trend towards a shorter time to SLOR with an increasing tertile of VFI in both IFX and ADA treated patients. Conclusion Visceral fat area corrected for height (VFI) is a better determinant of anti-TNFα trough levels and SLOR than BMI.

S1140 Infliximab Maintenance Therapy Decreases Productivity Loss and Direct Resource Use in Patients with Crohn's Disease or Ulcerative Colitis

2009 ◽  
Vol 136 (5) ◽  
pp. A-198
Author(s):  
Isabel Vera ◽  
Carlos Taxonera ◽  
Beatriz Alvarez ◽  
Raquel Garcia Sanchez ◽  
Juan De la Revilla ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Resource Use ◽  
Productivity Loss

Higher Vedolizumab Levels are Associated with Deep Remission in Patients with Crohn's Disease and Ulcerative Colitis on Maintenance Therapy with Vedolizumab

2017 ◽  
Vol 152 (5) ◽  
pp. S389 ◽  
Author(s):  
Andres J. Yarur ◽  
Alexandra Bruss ◽  
Anjali Jain ◽  
Venkateswarlu Kondragunta ◽  
Theresa L. Luna ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy

Serum Adalimumab Trough Levels Required for Endoscopic Mucosal Healing during Maintenance Therapy of Crohn's Disease

2017 ◽  
Vol 152 (5) ◽  
pp. S393 ◽  
Author(s):  
Hirotsugu Imaeda ◽  
Kyohei Nishino ◽  
Masashi Ohno ◽  
Atsushi Nishida ◽  
Mitsushige Sugimoto ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Mucosal Healing ◽  
Trough Levels ◽  
Therapy Of Crohn's Disease

scholarly journals Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn’s Disease and Ulcerative Colitis—A Prospective Polish Population Study

2021 ◽  
Vol 10 (22) ◽  
pp. 5311
Author(s):  
Anna Pękala ◽  
Rafał Filip
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Therapeutic Drug ◽  
Induction Phase ◽  
Drug Levels ◽  
Trough Levels

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.

scholarly journals Anti-TNFα-terápiában részesülő gyulladásos bélbetegek hosszú távú utánkövetése

2020 ◽  
Vol 161 (47) ◽  
pp. 1989-1994
Author(s):  
Péter Bacsur ◽  
Soma Skribanek ◽  
Ágnes Milassin ◽  
Klaudia Farkas ◽  
Renáta Bor ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Treatment Period ◽  
Efficacy And Safety ◽  
Loss Of Response ◽  
Term Efficacy ◽  
Steroid Dependent ◽  
Inflammatory Bowel

Összefoglaló. Bevezetés: A gyulladásos bélbetegségek kezelésében a tumornekrózisfaktor-alfa-ellenes (anti-TNFα) antitestek elsődleges választási lehetőséget jelentenek a kortikoszteroid- és immunmoduláns kezelésre refrakter páciensek kezelési stratégiájában. Ezek a hatóanyagok hatékonyak, ám hosszú távú hatásosságukkal kapcsolatban sok az ellentmondás. Célkitűzés: Vizsgálatunk célja megvizsgálni az anti-TNFα-terápia (infliximab [IFX], adalimumab [ADA]) hosszú távú hatékonyságát gyulladásos bélbetegek körében. Módszerek: Retrospektív, adatgyűjtéses vizsgálatunkba a Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinikáján gondozott, 18–65 év közötti gyulladásos bélbetegeket vontunk be. Az adatgyűjtést a Klinika informatikai rendszeréből végeztük a betegek ambuláns megjelenéseinek kezelőlapjaiból, illetve a zárójelentésekből. Eredmények: 102 beteg adatait elemeztük (Crohn-beteg: 67 fő, colitis ulcerosás: 35 fő). A Crohn-betegség diagnózisát követően átlagosan 7,84 év, a colitis ulcerosa diagnózisát követően átlagosan 9,86 év telt el az első anti-TNFα-terápia elkezdéséig. Az első kezelési ciklus átlagosan 2,64 évig tartott, a ciklus végén az IFX-t kapó betegek 50%-ánál, az ADA-t kapó betegek 46%-ánál volt remisszióban a betegség. A második kezelési ciklus átlagosan 4,67 évig tartott, a ciklus végén az IFX-t kapó betegek 36%-a, az ADA-t kapó betegek 40%-a volt remisszióban. Az első, illetve a második kezelési ciklus alatt az allergiás reakciók gyakorisága IFX esetében 13% és 18%, ADA esetében 4% és 3% volt. A primer hatástalanság és a másodlagos hatásvesztés az első ciklusban IFX esetében 4% és 10,5%, ADA esetében 11,5% és 19% volt. A második kezelési ciklusban IFX esetében 9%-ban és 18%-ban, ADA esetében 23%-ban és 10%-ban jelentették a ciklus végét. Következtetés: Az anti-TNFα-terápiák eredményeink alapján hosszú távon is hatékonynak és biztonságosnak bizonyultak. Másodlagos hatásvesztés kisebb arányban fordult elő a vizsgált populációban az irodalmi adatokhoz képest. Orv Hetil. 2020; 161(47): 1989–1994. Summary. Introduction: Anti-tumor necrosis factor-alpha (anti-TNFα) treatment is reserved for steroid-dependent or steroid/immunomodulator-refractory inflammatory bowel diseases patients. These agents are effective, however, their long-term safety is still questionable. Objective: We aimed to assess the long-term efficacy and safety of two anti-TNFα therapies. Methods: In our retrospective study, we reviewed medical records via the administration system of the First Department of Medicine, University of Szeged. Female and male patients, aged between 18–65 years who received anti-TNFα therapy between 2010–2019 were enrolled. Results: 102 patients with inflammatory bowel disease were enrolled (Crohn’s disease: 67, ulcerative colitis: 35). The first anti-TNFα therapy was introduced after an average 7.84 and 9.86 years from diagnosis of Crohn’s disease and ulcerative colitis. The first treatment period lasted for 2.64 years; 50% of patients receiving IFX and 46% of patients receiving ADA were in remission at the end of the period. The second treatment period lasted for 4.67 years, 36% of IFX-treated patients and 40% of ADA-treated patients were in remission at the end of the period. 13% and 18% of patients treated by IFX and 4% and 3% of patients treated by ADA experienced infusion reaction during the first and the second treatment period. Primary non-response and loss of response rates were 4% and 10.5% (IFX) and 11.5% and 19% (ADA) during the first treatment period. These rates were 9% and 18% (IFX) and 23% and 10% (ADA) during the second treatment period. Conclusion: Our study confirmed the long-term efficacy and safety of the anti-TNFα therapies. Loss of response rate is lower in our population compared to the literature. Orv Hetil. 2020; 161(47): 1989–1994.

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