Serum Infliximab Trough Research Articles

Subcutaneous Infliximab in Refractory Crohn's Disease Patients: A Possible Biobetter?

A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 μg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (P = .0341), fecal calprotectin (P = .0002), and Harvey-Bradshaw index (P = .0029) since W0. Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Validation Study of a New Random-Access Chemiluminescence Immunoassay Analyzer i-TRACK10® to Monitor Infliximab and Adalimumab Serum trough Levels and Anti-Drug Antibodies.

Background. Monitoring of biological TNF inhibitors is a very important tool to guide clinical decisions using specialized algorithms, especially in gastroenterology. A new chemiluminescent instrument (i-TRACK10® from Theradiag) could replace ELISA techniques to calculate the dosage of drugs and anti-drug antibodies. In this bi-centric study, we explored the analytical performances of i-TRACK10® using manual or automated (DS2®) ELISA Lisa-Tracker® assays, and compared the results. Patients and methods. Intra- and inter-run performances were evaluated with i-TRACK10® in two different laboratories and for two different ranges of values for infliximab, adalimumab, and their respective antibodies. Patients’ samples were used in the labs to compare the results obtained between the new instrument and either the manual Lisa-Tracker® or the automated DS2. Results. Intra- and inter-run performances were satisfactory, with values between 1.8% and 16.1% (for inter-run imprecision at low/medium values of infliximab). Results were generally comparable between assays. with the lowest value of correlation at 0.59 (anti-adalimumab dosage between i-TRACK10® and manual ELISA). Most often, values of drugs and anti-drug antibodies were higher with i-TRACK10® than with manual ELISA assay, and correlation values were better with automated ELISA. Agreements were globally acceptable, and the lowest coefficients of 0.7 was obtained for adalimumab values between i-TRACK10® and the two ELISA methods, and for anti-adalimumab values between i-TRACK10® and manual ELISA. The type of assay can potentially induce a change in the class of patients and lead to divergent therapeutic decisions. Conclusions. The new random-access instrument i-TRACK10® presents many advantages in a routine laboratory: rapidity, the possibility of standardization, usability, and expansion of the measurement range. Despite the relatively good agreement of results, it is preferable to use the same assay in longitudinal follow-up of a patient, because quantitative results were not completely equivalent especially for anti-drug antibodies.

Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn's disease.

BACKGROUNDTumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn’s disease (CD), but not all patients achieve fistula healing.AIMTo determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels.METHODSIn this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test, t test or Mann-Whitney U test.RESULTSOne hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5) vs 3.0 (0.3-6.2) mg/L, P = 0.003; adalimumab: 9.2 (6.5-12.0) vs 5.4 (2.5-8.3) mg/L, P = 0.004]. For patients on infliximab, fistula healing was associated with lower rates of detectable anti-infliximab antibodies and younger age. For patients on adalimumab, fistula healing was associated with higher rates of combination therapy with an immunomodulator. Serum trough levels for patients with and without fistula closure were not significantly different for infliximab [6.9 (4.3-10.2) vs 5.5 (2.5-8.3) mg/L, P = 0.105] or adalimumab [10.0 (6.6-12.0) vs 7.8 (4.2-10.0) mg/L, P = 0.083].CONCLUSIONHigher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.

Point-of-care metoda měření hladiny infliximabu a adalimumabu u pacientů s idiopatickými střevními záněty na biologické léčbě

Aim of the study: To verify whether the results of infliximab and adalimumab concentration measurements by the point-of-care method ProciseDx correspond with the concentrations determined by enzyme-linked immunosorbent assay (ELISA). Methods: Twenty-three infliximab (IFX) and twenty-two adalimumab (ADL) concentrations were compared. IFX and ADL trough levels were measured by the ProciseDx point-of-care (POCT) system based on the Förster resonance energy transfer (FRET) principle, and by standard immunoassay (ELISA) in a clinical laboratory. Results: Spearman‘s correlation coefficient for IFX R = 0.9400 (P = 0.0001) and the weighted Cohen‘s kappa of 0.93 indicate a good correlation between data measured by two different measurement systems. The same excellent correlation of values was achieved for ADL, where R = 0.9098 (P = 0.0001) and the weighted Cohen‘s kappa is 0.834. Conclusion: The ProciseDx POCT system is a highly reliable method for measuring serum trough IFX and ADL levels in IBD patients. It is easy to operate and fast, it brings more effectiveness to the IBD biological treatment and reduces financial and time burden of this therapy. Keywords inflammatory bowel disease, infliximab, adalimumab, biologic therapy, proaktivní terapeutické monitorování léčiv, reaktivní terapeutické monitorování léčiv, point-of-care monitoring

Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis

Objective To evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA). Methods Longitudinal observational study involving 81 patients with axSpA monitored during infliximab therapy. Serum ITL were measured before starting infliximab treatment and at weeks 2 (W2), W6 and W12 of treatment. Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W52, and every 6 months thereafter until treatment discontinuation, regardless of the reason. Non-clinically important improvement was defined by ΔASDAS<1.1. The association between serum levels during the early stages and clinical outcomes (non-clinically important improvement at W52, drug survival and drop-out due to secondary inefficacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL. Results Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/mL vs 7.1 (4.3–11.3) µg/mL, respectively;p = 0.007). ITL<6.7 µg/mL at W12 was significantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3–3.9); ii) shorter drug survival (5.0 years (95% CI 3.8–6.2) vs 7.0 years (95% CI 4.8–6.9; p = 0.04), and iii) higher drop-out rates due to secondary inefficacy (OR: 3.5; 95% CI: 1.2–10.2). Conclusion Low serum ITL at W12 were associated with long-term clinical failure in patients with axSpA, due to secondary inefficacy.

Quality Improvement Methodology Optimizes Infliximab Levels in Pediatric Patients with Inflammatory Bowel Disease.

We participated in Intermediate Improvement Science Series, a course at Cincinnati Children's Hospital Medical Center designed to catalyze change using quality improvement methodology. We implemented interventions through plan-do-study-act cycles. Our outcome measure was balanced by 2 process measures to determine what actions impacted improvement. These measures included the percentage of infusion plans revised in response to a drug level <5 μg/mL and the proportion of plans for which a follow-up drug level was ordered. We increased the percentage of infusion plans revised before the next infusion from 63% to 87% and the percentage of plans that had an appropriate drug level recheck from 61% to 83% from July 2017 to January 2018. We increased the percentage of patients with an infliximab level >5 μg/mL, and results checked in the last 12 months, from 73% to 80%. Quality improvement methodology was effective in improving provider adherence to infliximab therapeutic drug monitoring guidelines. Improvement in adherence to guidelines directly improved the percentage of patients achieving target infliximab levels at any time during infliximab therapy.

Intermittent Appearance of Antibodies to Infliximab Is Not Associated With Reduced Efficacy in Patients With Inflammatory Bowel Diseases.

To assess the clinical significance of antibodies to infliximab (ATI) formation in patients with inflammatory bowel disease (IBD). Infliximab therapy in patients with IBD is highly effective though up to 50% of patients lose response to infliximab. ATI formation occurs in 6% to 60% of patients on scheduled infliximab maintenance therapy. Infliximab trough levels and ATI at trough were prospectively determined in patients with IBD on maintenance infliximab therapy. Patients on infliximab maintenance therapy with at least 3 ATI measurements were included. Patients were divided into 2 groups: sustained negative (<1 µg/mL) ATI levels, and fluctuating ATI levels (at least 1 sample with ATI <1 and at least one >1 µg/mL). Forty-eight patients with IBD with available clinical data and serum samples were included. 25 patients had sustained low ATI levels and 23 patients had fluctuating ATI levels. Both groups were similar in IBD subtype distribution (Crohn's disease in 73.9% and 60%), mean serum albumin levels (4.2 vs. 3.9 g/dL), and mean trough serum infliximab levels (3.3 vs. 4.6 µg/mL) in fluctuating ATI and low ATI groups, respectively. There were no significant differences in the rate of clinical response (64% vs. 76%) and mean serum C-reactive protein levels (9.4 vs. 8.5 mg/dL, ULN=5) in the fluctuating ATI and low ATI groups. Similar rates of clinical response in the fluctuating ATI and low ATI groups were observed in ulcerative colitis (33% vs. 40%) and Crohn's disease (76% vs. 100%). The fluctuating pattern of appearance of ATI in patients with IBD was not associated with loss of clinical response or a rise in C-reactive protein. The authors suggest that in clinical decision making, only sustained appearance of ATI should be considered as an adverse therapeutic factor.

Early serum infliximab trough level and mucosal healing could be predictors for one-year outcome after initiating therapy in Crohn’s disease

Background and aims Serum infliximab trough level(S-IFX) and antibody were documented to correlate with clinical response. The aim of this study was to identify the relationship between early S-IFX, early mucosal healing (MH) and one-year outcome in a cohort on maintenance IFX therapy in Crohn’s disease (CD). Methods The study group comprised of retrospectively enrolled patients diagnosed for Crohn’s disease (n = 108). Patients received scheduled maintenance therapy after response to IFX induction, and had undergone the early S-IFX test and endoscopic examination at week 14. Clinical outcomes were evaluated during maintenance therapy until week 52. Results Early S-IFX was 4.78 ± 6.16 ug/ml in all the patients and 19% (21/108) of them developed antibodies, and 52 patients reached early MH. During 52 weeks’ follow-up. Twenty-eight percent (30/108) of patients showed loss of response to IFX. Patients who lost response had lower early S-IFX than those who had sustained response (3.01 ± 3.66 vs. 5.47 ± 6.79 ug/ml, p = .02; 48 vs. 23%, p = .02). At week 52, 73 patients had repeated endoscopy and 42% of them reached MH. Early S-IFX had a predictive value on MH at week 52. When early S-IFX > 2.5 ug/ml, the sensitivity for predicting MH at week 52 was 87%, and the specificity were 61% (AUC = 0.73, p < .01). The combined predictive value of early S-IFX and early MH became stronger. Only 6% (1/18) of those patients who had low early S-IFX and had not reached early MH could reach MH at week 52. Conclusions Early S-IFX and early MH could predict one-year response after initiating IFX therapy in Crohn’s disease.

Pharmacogenetics of trough serum anti-TNF levels in paediatric inflammatory bowel disease.

Identifying DNA variants associated with trough serum anti-tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti-TNF levels and whether these variants are differential markers for infliximab and adalimumab. We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty-one polymorphisms were genotyped using real-time PCR. Trough serum anti-TNF levels were measured using enzyme-linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti-TNF drugs was analysed by Fisher exact test, student's t-test and logistic regression. The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05). Genotyping of these DNA variants before starting treatment may help to select the best anti-TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti-TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti-TNF levels.

A 3-year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease.

Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep-TDM) programme for dose adjustment. A 3-year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep-TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD-related surgery and IBD-related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis. In the mep-TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27-0.92; P = .037), IBD-related surgery (HR: 0.14; 95% CI: 0.03-0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17-0.87; P = .022). SIRs were lower in the mep-TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999). This study found that compared to empirical dosing, mep-TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD-related hospitalization and surgery and incidence of SIRs, and increasing long-term durability of treatment effects.

P683 Infliximab, adalimumab and vedolizumab levels are not altered by pregnancy progression in IBD patients and neonatal vedolizumab levels are lower than in mothers: Results from the PICCOLO study

Abstract Background Optimal timing for the last intrapartum dose of biologic agents is controversial. We established that cord blood levels of anti-TNF agents in exposed infants are greater than maternal levels,1 and another study with limited observations suggested maternal infliximab (IFX) levels increased in pregnancy but adalimumab (ADA) levels did not.2 The effect of pregnancy on vedolizumab (VDZ) levels, and placental transfer and time to clearance of VDZ in exposed infants remain undefined. Methods We performed a prospective observational study of maternal anti-TNF and VDZ levels pre-conception, in each trimester of pregnancy, at delivery and post-partum where possible. Women with IBD on IFX, ADA or VDZ who were pregnant or planning pregnancy were recruited. Serum trough IFX and ADA levels were measured by ELISA (Q-INFLIXI and Q-ADA (Matriks Biotek, Turkey) or Promonitor (Grifols, Spain)) and VDZ levels by ELISA (Theradiag, France). Infant VDZ levels were measured from the umbilical cord at delivery and at around 6–8 weeks and 3 months to assess time to clearance. Results Forty-nine patients (24 IFX, 14 ADA, 11 VDZ) with at least two observations on stable dosing were included. The median number of levels per patient was 3 (range 2–5). Infliximab cohort (n = 24): Median IFX levels were stable (Figure 1). IFX was administered 6–8 weekly at doses of 5 mg/kg (n = 21) or 10 mg/kg (n = 2) except for one patient on 4-weekly dosing. The last dose was given at a median 32 weeks; 3 remain pregnant. Adalimumab cohort (n = 14): Median ADA levels were stable (Figure 1). Twelve were on ADA fortnightly and 2 on weekly. Eleven continued ADA throughout pregnancy and 3 stopped at 30–33 weeks; 2 remain pregnant. Three patients were induced in pregnancy at least 12 weeks before the earliest ADA level. Vedolizumab cohort (n = 11): Trough VDZ levels were stable (Figure 2). Eight patients were on 8-weekly dosing and three were on 4-weekly. The last dose was given at a median 30 weeks; 4 remain pregnant (Patients H-K). Vedolizumab in infants (n = 8): The median VDZ cord blood level was 4.95 (1–19) μg/ml with a median infant:maternal ratio of 0.6 (0.4–0.9). VDZ was cleared at 8 weeks of age in three infants and by 15 weeks in two infants. Conclusion The stability of maternal levels of IFX, ADA and VDZ during pregnancy indicate that intrapartum dosing adjustment and routine therapeutic drug monitoring for patients in remission are not needed. Unlike anti-TNF, infant VDZ levels were lower in cord blood than in mothers and were cleared by 15 weeks. References

Monitoring of infliximab trough levels and anti-infliximab antibodies in inflammatory bowel diseases: A comparison of three commercially available ELISA kits

BackgroundThere are many studies presenting data of biologics and several ELISA kits commercially available for monitoring infliximab serum trough levels (s-IFXt) and anti-drug antibodies (ADAb). We propose to compare technical characteristics and results of three different assays on a cohort of 35 patients under infliximab (IFX) and suffering from inflammatory bowel disease (IBD). Patients and methodss-IFXt and ADAb were systematically measured with three ELISA kits: Lisa-Tracker® Duo infliximab (Theradiag®), Ridascreen® IFX Monitoring (R-Biopharm AG®) and Promonitor® IFX (Progenika Biopharma SA®). ResultsThe main technical features that differed between kits for measuring s-IFXt were: (i) TNF coating, (ii) immune complexes revelation strategy and/or (iii) interference with other anti-TNFα agents. For kits measuring ADAb, they were revelation steps and unit of results. There was an excellent mathematical correlation of s-IFXt between assays however Bland-Altman analysis denoted (i) s-IFXt were on average 48 to 69% higher in Ridascreen® than in the other two assays, and (ii) elevated s-IFXt were higher with Promonitor® compared to Lisa-Tracker®. As a consequence, there were some substantial discrepancies between assays for classification of s-IFXt into concentration ranges. Despite unstandardized units, pairwise qualitative comparison showed a perfect agreement between the three pairs of ADAb assays. ConclusionOur data show that the evaluated assays are not quantitatively interchangeable due to substantial variations in some results that could lead, for some patients, to divergent therapeutic decisions. We remind to be cautious when comparing study results issued from different kits and recommend using the same assay for the longitudinal follow-up of IBD patients.

Infliximab for pediatric patients with ulcerative colitis: a phase 3, open-label, uncontrolled, multicenter trial in Japan

BackgroundPediatric ulcerative colitis (UC) is typically more extensive and has a more active disease course than adult UC, and requires early treatment augmentation to achieve and maintain disease remission. The present study aimed to investigate the efficacy, safety, and pharmacokinetic profile of infliximab (IFX) in pediatric patients with moderate-to-severe UC and inadequate response to existing treatment.MethodsThis open-label, uncontrolled, multicenter, Phase 3 trial was conducted at 17 centers in Japan between April 2012 and September 2014. Pediatric patients (aged 6–17 years) diagnosed with moderate-to-severe UC received a treatment protocol comprising 5 mg/kg IFX at Weeks 0, 2, and 6, and Clinical Activity Index (CAI)-based responders at Week 8 also received treatment at 8-week intervals at Weeks 14 and 22, with a final evaluation at Week 30.ResultsA total of 21 patients were treated in this study. IFX therapy rapidly improved clinical symptoms, and this effect was maintained for up to 30 weeks. Overall CAI-based remission rate was 42.9% and overall Pediatric Ulcerative Colitis Activity Index (PUCAI)-based remission rate was 19.0%. Median partial Mayo score was 6.0 at baseline and 4.0 at Week 30 (overall). Among the eight patients who underwent sigmoidoscopy, Mayo response was achieved at Week 30 (overall) in three patients (37.5%). Trough serum IFX concentrations in Week 8 CAI-based responders were maintained throughout the study period. Adverse events and serious adverse events were observed in 95.2 and 14.3% of patients, respectively.ConclusionsThese results support the use of IFX in the treatment of pediatric patients with UC with inadequate response to existing treatment.Trial registrationClinicalTrials.gov, registration number: NCT01585155.

Anti-drug antibodies and low serum trough infliximab levels correlate with disease activity measures in spondyloarthritis patients on an as-needed infliximab treatment.

In India, many centers use infliximab at lower doses of 3-5mg/kg without the loading dose for spondyloarthritis (SpA) patients. It is then continued on an as-required basis, rather than a fixed schedule. Our study was undertaken to see if the trough drug levels and anti-drug antibodies in patients with SpA treated with as-needed infliximab dosing correlated with the disease activity measures. Thirty-five adult SpA patients in the age group 18-70years were recruited. They had received three or more infusions of infliximab at 3-5mg/kg over the past 6 to 12months. Patient's serum tumor necrosis factor-α, trough infliximab levels and anti-drug antibodies were measured by enzyme-linked immunosorbent assay technique. The disease activity was quantified by Ankylosing Spondylitis Disease Activity Score - erythrocyte sedimentation rate/ C-reactive protein (ASDAS-ESR/CRP) scores. Correlation between quantitative variables was analyzed by the Spearman's correlation assay. The difference in mean trough infliximab and ASDAS between the drug antibody positive and negative patients was assessed using the Mann-Whitney U test. There was a significant negative correlation between the trough infliximab levels and the ASDAS-ESR (rs = -0.57, P<0.01) and ASDAS-CRP scores (rs=-0.53, P<0.01). Anti-drug antibodies were positive in 68.7% of the patients and in comparison to the antibody negative patients, had significantly higher ASDAS-ESR and ASDAS-CRP scores. Spondyloarthritis patients on low-dose, as-needed infliximab therapy, have both the trough infliximab and anti-drug antibodies correlate significantly with the measures of disease activity. We hypothesize that trough infliximab levels and anti-drug antibodies may be used to predict a suboptimal response due to secondary resistance in SpA patients.

Association of Infliximab Levels With Mucosal Healing Is Time-Dependent in Crohn's Disease: Higher Drug Exposure Is Required Postinduction Than During Maintenance Treatment.

Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn's disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.

Minimum Infliximab Dosage for Keeping Serum Infliximab Levels Greater than 1 µg/mL among Patients with Rheumatoid Arthritis.

Infliximab shows drastic efficacy for controlling inflammation in rheumatoid arthritis (RA), though the ideal dose of infliximab to keep suppressing inflammation has not yet been identified. Recently, it has been evidenced that the minimum trough serum infliximab levels required for suppressing inflammation are greater than 1 µg/mL. This cross-sectional study was designed to identify the minimum dosage of infliximab for maintaining serum infliximab levels greater than 1 µg/mL. Thirty seven RA patients were enrolled in this study and they were divided into two groups (high-infliximab vs. low-infliximab) in reference to Remi-check Q®, a kit for examining serum infliximab levels above/below 1 µg/mL by LC. Infliximab dosage (p=0.06) and dosage interval (p=0.05) had trends to have differences between groups. A formula calculated by infliximab dosage divided by dosage interval and body weight (mg/weeks/kg) was shown to have significantly higher levels among high-infliximab group (p=0.04). Based on whether serum infliximab levels above/below 1 µg/mL and values led by the equation, infliximab dosage/infliximab interval/body weight (mg/weeks/kg), a receiver operating characteristic curve (ROC) was depicted with area under the ROC curve 0.750 and the cut-off point for the serum infliximab levels greater than 1 µg/mL was identified as infliximab dosage/infliximab interval/body weight ≧0.750 with the sensitivity 0.393 and the specificity 1.000. In conclusion, we identified that the minimum infliximab dosage to maintain serum infliximab levels greater than 1 µg/mL was infliximab dose/dosage interval/body weight (mg/weeks/kg)≥0.750.

Infliximab Trough Levels Are Associated With Mucosal Healing During Maintenance Treatment With Infliximab in Paediatric Crohn's Disease.

Mucosal healing is an important treatment goal in Crohn's disease. We investigated the association between serum infliximab trough levels and mucosal healing, and the infliximab cut-off levels required for mucosal healing in paediatric patients. In this multicentre, retrospective, cross-sectional study, medical records and electronic data of paediatric patients with luminal Crohn's disease, who had received infliximab for ≥1 year, were examined. Ileocolonoscopy was performed on the same day as the infliximab infusion, and serum samples for trough levels were collected immediately before infusion. Mucosal healing was defined as a Simple Endoscopic Score for Crohn's Disease of 0. Univariate, multivariate logistic regression, and receiver operating characteristic curve analyses were performed. Overall, 105 patients [median age 14.8 years] were included, with mucosal healing observed in 48.6%. Median serum infliximab trough levels were higher in patients with mucosal healing [4.5 µg/mL] than without [3.3 µg/mL, p = 0.002]. In the final multivariate model, infliximab trough level ≥4.2 µg/mL [p = 0.002] and ≥1-year duration from diagnosis to infliximab treatment [p = 0.003] were positively and negatively associated with mucosal healing, respectively. The infliximab trough level for achieving mucosal healing with a specificity of 80% was ≥5 µg/mL. Associations between serum infliximab trough concentrations and mucosal healing were observed in paediatric patients. Identification of the infliximab trough level that positively associates with mucosal healing in most paediatric patients with Crohn's disease [≥5 µg/mL] may guide treatment decisions to optimise therapeutic response in the era of treat-to-target.

Higher Postinduction Infliximab Serum Trough Levels Are Associated With Healing of Fistulizing Perianal Crohn's Disease in Children.

There is some evidence in adults that higher serum infliximab (IFX) levels are needed to adequately treat fistulizing perianal Crohn's disease (CD). However, data in children are lacking. We aimed to determine postinduction serum trough IFX levels that are associated with healing of fistulizing perianal CD (PCD) at week 24. In a multicenter inception cohort study, consecutive children younger than age 17 years with fistulizing perianal CD treated with IFX between April 2014 and June 2017 who had serum trough IFX titers measured before the fourth infusion were included. Area under the receiver operating characteristic curve (AUROC) was calculated to determine the best cutoff to predict fistula healing. A total of 667 children with Crohn's disease were recruited, with 85 (12.7%) patients diagnosed with fistulizing PCD. There were 27 of 52 (52%) children in whom pre-fourth infusion IFX levels were measured (mean age, 12.57 ± 5.12 years). At week 24, 14 of 27 (52%) patients responded with healing/healed PCD, whereas the rest had ongoing active fistulizing disease. The median IFX pre-fourth dose level in the responders was 12.7 ug/mL, compared with 5.4 ug/mL in the active disease group (P = 0.02). There was a strong correlation between IFX levels and healing of fistulizing PCD at week 24 (r = 0.65; P < 0.001). The AUROC was 0.80 (95% confidence interval, 0.64-0.97; P = 0.007) for pre-fourth IFX level to predict response of fistulizing PCD at week 24, and a level of 12.7 ug/mL best predicted fistula healing. Higher trough IFX levels are associated with healing of fistulizing perianal CD.

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

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