Su1206 Association Between Crohn's Disease Activity and Therapeutic Drug Monitoring of Thiopurines and Infliximab Comparing Free and Total Antidrug Antibody Measurement

2015 ◽  
Vol 148 (4) ◽  
pp. S-437 ◽  
Author(s):  
Mark G. Ward ◽  
Benjamin D. Warner ◽  
Nick Unsworth ◽  
Jeremy D. Sanderson ◽  
Zehra Arkir ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Antidrug Antibody ◽  
Crohn’S Disease Activity

scholarly journals P441 Clinical efficacy, drug sustainability and results from therapeutic drug monitoring in Crohn’s disease patients treated with ustekinumab – 1-year follow-up of a prospective, nationwide, multicenter cohort from Hungary

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S441-S441
Author(s):  
L Gonczi ◽  
K Szanto ◽  
K Farkas ◽  
T Molnar ◽  
T Szamosi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Clinical Efficacy ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Disease Phenotype ◽  
Dose Intensification

Abstract Background Although efficacy and safety of ustekinumab (UST) in the treatment of inflammatory bowel disease have been demonstrated through randomized trials, data from real-life prospective cohorts are still of great interest. Our aim was to evaluate the clinical efficacy, drug sustainability, frequency of dose intensification, and results from therapeutic drug monitoring in UST treated Crohn’s disease (CD) patients using a prospective, nationwide, multicenter cohort from Hungary. Methods Patients were consecutively enrolled in this cohort between 2019 January and 2020 May from 5 academic centers and 5 county hospitals. Data from patient demographics, disease phenotype, treatment history (surgical history, prior and present medical therapies), clinical disease activity (using the Crohn’s Disease Activity Index (CDAI), Harvey Bradshaw Index (HBI)), biomarkers (C-reactive protein – CRP), and therapeutic drug monitoring were captured. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. Results N=142 CD patients were included with a median follow-up time of 60 weeks (IQR:47.5–79.5w) [57.4% female; age 38.4±13.0 years]. Based on the Montreal classification, complicated disease behavior (B2orB3) was 48.2%, whereas ileocolonic disease location(L3) 55.7%. Perianal manifestation was present in 46.8% of the patients. Previous anti-TNF exposition was 97.2%, while previous vedolizumab failure was 25.5%. 66.2%/ 66.9% of the patients had moderate-to-sever clinical disease activity at baseline (CDAI>220/HBI>7). Clinical response and remission rates were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores after induction treatment (w8). One year clinical remission rates were 58% / 57.3% (CDAI/HBI) Composite clinical and biomarker remission (CDAI<150 and CRP<10mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Parallel corticosteroid use was 34%/26.3%/16.5%/21%/16.9% at baseline and w8/w16-20/w32-36/w52-56. Drug sustainability was high with 81.9% (SD: 3.4) of patients remaining on treatment at one year.(Figure1) Probability of dose intensification was high and introduced early in the treatment, 42.2% (SD: 4.2) at ~w32 and 51.9% (SD: 4.4%) at 1y.(Figure2) Patients with complex disease phenotype (B2/B3) had higher probability for dose intensification (log-rank: p=0.042). Mean serum trough levels of UST were 4,28±3,35/ 1,35±1,42/ 0,82±0,65 and 1,13±0,74µg/mL measured at w8/w16-20/w32-36 and w52-56. ADAs were exceeding 1AU/mL in only 2 patients. Conclusion Ustekinumab showed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure, however frequent and early dose intensification was required.

scholarly journals P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S331-S333
Author(s):  
C Liefferinckx ◽  
M Fassin ◽  
D Thomas ◽  
C Minsart ◽  
A Cremer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Median Time ◽  
Real World ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

scholarly journals P465 Therapeutic drug monitoring in Crohn’s disease patients, a comparison between homogeneous mobility shift assay and point of care method

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S412-S412
Author(s):  
G Bodini ◽  
M G Demarzo ◽  
A Djahandideh ◽  
I Baldissarro ◽  
E Savarino ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Therapeutic Drug ◽  
Serum Drug Concentration ◽  
Disease Relapse

Abstract Background Therapeutic Drug Monitoring (TDM) is a useful tool to help physicians managing patients with Inflammatory Bowel Disease treated with anti-tumour necrosis factor (TNF) drugs. Different techniques are available to evaluate serum drug concentration (TL), However, these techniques are time-consuming. A point-of-care (POC) method has been proposed to evaluate drug TL and overcome the limitations inherent to other methodologies. Our aim was to evaluate the capability of POC to discriminate between IBD relapse and remission and to evaluate the concordance of drug TL measured with POC and HMSA Methods We analysed with Quantum BlueÒ (Buhlmann Laboratories AG, Schonenbuch, Switzerland) (POC) 200 Adalimumab (ADA) and 200 Infliximab serum samples of 46 Crohn’s disease (CD) patients previously assessed with HMSA. Blood samples were drawn at standardised time points during anti-TNF treatment (2, 6, and every 8 weeks), before anti-TNF administration. Disease activity was assessed by the Harvey–Bradshaw Index (HBI, remission defined by HBI<5). Results We evaluated 46 CD patients responders to anti-TNF induction with ADA (n = 25, 54.3%) and IFX (n = 21, 45.6%) with a median follow-up of 83 weeks (range 16–144 weeks). At week 16, median ADA TL of patients in remission were significantly higher as compared with patients in disease relapse using both HMSA [12.7 μg/ml (range, 8.9–23.6 μg/ml) vs. 6.6 μg/ml (range, 0.7–9.6 μg/ml), p = 0.0001] and POC [17.8 μg/ml (range 7.6–35.0 μg/ml) vs. 9.8 μg/ml (range 5.8–11.4 μg/ml), p = 0.0003]. The concordance between the two different techniques has been assessed as 0.76 by Choen Kappa. Considering IFX TL, patients in remission had higher serum drug concentration using both HMSA [7.0 μg/ml (range, 0.0–21.8 μg/ml)] and POC [6.2 μg/ml (range 0.4–14.3 μg/ml)] as compared with patients who experienced disease relapse [HMSA, 0.1 μg/ml (range, 0.0–4.1 μg/ml), p = 0.019; POC, 0.45 μg/ml (range 0.4–3.3 μg/ml), p = 0.0072]. The concordance between the two different test for IFX TL was 0.81. We obtained similar results at the end of follow-up: median ADA TL was higher in remission than in disease relapse patients using both HMSA and POC [p = 0.001 and p = 0.0012] with a concordance of 0.75. Median IFX TL was higher in remission than in disease relapse patients using both HMSA and POC (p = 0.13 and p = 0.25) with a concordance of 0.70. Conclusion Both POC and HMSA are TL tests able to differentiate relapse and remission in IBD patients. The association between anti-TNF TL and disease status (remission/relapse) was better in ADA-treated patients rather than patients treated with IFX. Finally, we demonstrated a good concordance between HMSA and POC. Anti-drug antibody concentrations while available on HMSA were not available on POC

Sign in / Sign up

Export Citation Format

Share Document