Infliximab Maintenance Treatment Research Articles

P983 Treatment of patients with moderate-to-severe Crohn’s disease with subcutaneous infliximab leads to an endoscopic response across all segments of the colon and terminal ileum: A post hoc analysis of the LIBERTY-CD study

Abstract Background Mucosal healing (MH) has been associated with positive long-term clinical and surgical outcomes in patients (pts) with Crohn’s disease (CD).1 Patterns of MH vary by therapeutic agent, with limited efficacy in the terminal ileum.2–4 This post hoc analysis aimed to investigate the pattern of endoscopic MH across intestinal segments in pts who received subcutaneous (SC) infliximab (IFX) maintenance treatment in the Phase 3 LIBERTY-CD study. Methods LIBERTY-CD demonstrated superior efficacy of SC CT-P13 120 mg every 2 weeks (Q2W) vs placebo (PBO) after IV IFX induction for clinical remission and endoscopic response at Week (W) 54.5 This post hoc analysis evaluated centrally read and batch analysed Simple Endoscopic Score for Crohn's Disease (SES-CD) values obtained at screening, W22 and W54 for 5 ileocolonic segments (rectum; left, transverse and right colon; and terminal ileum). Pts with missing data or who underwent dose escalation to SC IFX 240 mg Q2W upon loss of response from W22 were imputed as non-responders. Endoscopic complete MH (CMH; defined as SES-CD=0) or partial MH (PMH; defined as ≥50% decrease in the SES-CD from screening) were evaluated for segments that had endoscopic abnormalities at screening (segmental SES-CD ≥1 at screening). Results were analysed descriptively. Results Among all randomised pts (N=343; SC CT-P13: n=231, PBO: n=112), the most frequently affected segment at screening was the left colon (187/343; 54.5%), followed by the right colon (185/343; 53.9%), rectum (163/343; 47.5%), terminal ileum (156/343; 45.5%) and transverse colon (134/343; 39.1%). In an analysis of all affected segments, endoscopic CMH rates were higher with SC CT-P13 vs PBO (Figure 1A). Endoscopic CMH rates in the terminal ileum at W54 were 46.7% and 19.6% in the SC CT-P13 and PBO arm, respectively (p=0.0014). PMH rates were also significantly higher in the SC CT-P13 arm across all segments at W22 and W54 (Figure 1B), with rates in the terminal ileum of 64.8% and 33.3% in the SC CT-P13 and PBO arm, respectively (p=0.0003). Conclusion SC IFX 120 mg Q2W led to high and consistent endoscopic MH rates across all segments, including the terminal ileum. Early observation of endoscopic MH (at W22) underscores the potency of SC IFX treatment. Further studies are warranted to investigate the association between segmental MH and long-term outcomes. 1Otte ML et al. World J Gastroenterol 2023;29:1157–72. 2Danese S et al. Gastroenterology 2019;157:1007–18. 3Reinisch W et al. J Crohns Colitis 2017;11:425–34. 4Wu Y et al. Therap Adv Gastroenterol 2020;13:1756284820976923. 5Hanauer SB et al. Gastroenterology 2023;164(S6):S220–1.

P353 Optimal Interval for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Receiving Stable Infliximab Maintenance Treatment

Abstract Background Recent studies suggest that proactive therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) improves clinical outcomes. However, as proactive TDM may lead to increased medical costs, we aimed to determine the optimal interval for TDM during infliximab maintenance therapy in IBD patients. Methods We conducted a retrospective analysis of a prospective cohort comprising 103 patients with IBD on IFX maintenance therapy who went through proactive TDM between February 2020 and May 2023. Following dose optimization till achieving a therapeutic trough level (TL) of 3 to 10 ug/mL, we applied the Kaplan-Meier (KM) method to calculate the time to subtherapeutic IFX TL (two consecutive IFX TLs below 3 ug/mL). Results 90% of patients had a sustained therapeutic IFX TL for 10.3 months, whilst 80% had it for 14.3 months. In multivariable analysis, IFX TL at enrollment had a association with the risk of subtherapeutic IFX TL (P=0.025). Persistence rates for therapeutic IFX TL were significantly lower in patients with IFX TL from 3 to 5 µg/mL at recruitment than in those with IFX TL >5 µg/mL (P=0.017). For patients who had IFX TL between 3 to 5 µg/mL upon enrollment, the percentage of those who maintained therapeutic IFX TL was 80% after 12.0 months. The group with IFX TL greater than 5 µg/mL had a persistence rate of 90% after 12.3 months. Conclusion These results suggest that conducting annual measurement of IFX TL in patients with IBD who are on stable maintenance therapy with IFX, which may reduce the cost of proactive TDM.

Association between drug trough concentration and disease outcome before infliximab maintenance treatment in children with Crohn's disease

To study the association between infliximab trough level (IFX-TL) prior to maintenance treatment and disease outcome in children with Crohn's disease (CD). A retrospective analysis was performed on 35 children with CD who received induction therapy with infliximab (IFX) and the measurement of IFX-TL before maintenance treatment from August 2018 to November 2021. Clinical data and laboratory markers at baseline and before maintenance treatment were collected, and the association between outcome and IFX-TL was analyzed. The clinical remission group, endoscopic remission group, and combined remission group had a significantly higher IFX-TL level than the corresponding non-remission groups (P<0.05), and there was no significant difference in the IFX-TL level between the biological remission and non-biological remission groups (P>0.05). The receiver operating characteristic (ROC) curve showed that IFX-TL had an area under the ROC curve of 0.959 (95%CI: 0.894-1) in predicting clinical remission, with a sensitivity of 90% and a specificity of 100% at the optimal cutoff value of 2.3 µg/mL (P<0.001). Among children with CD receiving infliximab induction therapy, the children achieving clinical and endoscopic remission before maintenance treatment tend to have a higher level of IFX-TL. IFX-TL has a certain predictive value for clinical remission.

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn's disease under infliximab therapy.

BACKGROUNDInfliximab trough level (ITL) severely affects therapeutic outcomes of Crohn’s disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIMTo explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODSCD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn’s disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn’s disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTSAt week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 μg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 μg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 μg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 μg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 μg/mL (92.68% vs 30.77%).CONCLUSIONCombination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Population Pharmacokinetics of Infliximab in Children with Juvenile Idiopathic Arthritis.

The recommended infliximab (IFX) dose in (pediatric) rheumatology practice is 3-6 mg/kg every 4-8 weeks. Higher dosage regimens (>10 mg/kg) of IFX are effective and safe. To optimize IFX treatment in patients with juvenile idiopathic arthritis (JIA), therapeutic drug monitoring might be beneficial. To support routine therapeutic drug monitoring of IFX and regimen optimization for patients with JIA, in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. As soon as the optimal therapeutic drug ranges are known, PK model-based simulation can be used to individualize drug dosing recommendations. In this study, a population PK model for IFX is described for patients with JIA. Data including IFX trough concentrations and anti-IFX antibodies of 27 pediatric patients with JIA on IFX maintenance treatment were retrieved from electronic charts. Three population PK models from the literature were validated for the authors' data set using the nonlinear mixed-effects modeling program NONMEM. A novel population PK model was developed based on the study data. A total of 65 blood samples obtained after a median of 32 days after the last IFX infusion (interquartile range 28-42) were analyzed. The 3 published models underpredicted the observed trough concentrations. A newly developed one-compartment model best described the data corresponding to IFX serum concentration over time in patients with JIA. This study shows a novel PK model for IFX in patients with JIA. The data show that different PK models are needed for different age categories (children or adults) and different diseases.

Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial

Objectives Loss of response (LOR) to infliximab (IFX) remains a challenge in the management of inflammatory bowel diseases (IBD). Proactive dosing strategies to achieve and maintain predefined IFX trough levels (TL) may prevent LOR. We aimed to investigate the efficacy of dashboard driven IFX dosing compared to standard dosing in a prospective trial in IBD patients. Methods In this multicentre 1:1 ‘PRECISION’ trial, we randomized IBD patients in clinical remission (Harvey Bradshaw Index ≤4 for Crohn’s disease (CD) or a partial Mayo score ≤2 for ulcerative colitis (UC)) receiving IFX maintenance treatment. The precision group (PG) received IFX dosing guided by a Bayesian pharmacokinetic model, aiming to achieve and maintain a TL of 3 µg/ml by treatment (de)escalation as indicated by the dashboard. Patients in the control group (CG) continued treatment without dose adaptations. The primary endpoint was the proportion of patients in sustained clinical remission after 1 year. Results Eighty patients were enrolled (66 CD, 14 UC), and the median [interquartile range] age was 37 years [27–51]). After one year, 28/32 (88%) of patients in the PG were in sustained clinical remission versus 25/39 (64%) in the CG (p = .017). PG patients had lower median faecal calprotectin levels after 1 year (p = .031), whereas no significant differences in median CRP levels were found. Conclusion We demonstrated that the use of a Bayesian dashboard for IFX dosing in maintenance treatment for IBD reduced the incidence of LOR compared to standard dosing. Precision dosing also resulted in lower FCP levels. ClinicalTrials.gov number NCT02453776.

Infliximab in young paediatric IBD patients: it is all about the dosing

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years.What is Known?•Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year.What is New?•The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment.•Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment.•The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years).

Bayes‐based dosing of infliximab in inflammatory bowel diseases: Short‐term efficacy

Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a real-world dataset of patients suffering from inflammatory bowel disease. We performed a single-centre prospective study with one-group pre-test/post-test design in 108 adult inflammatory bowel disease patients treated with model-based dosing of infliximab maintenance treatment. We recorded clinical activity scores (Harvey-Bradshaw index and partial Mayo) and inflammatory biomarkers per patient. The initial infliximab regimen was maintained in 49 (45.4%) patients and was adjusted in 59 (54.6%) patients (34 treatment intensifications, 9 de-intensifications and 16 treatment discontinuations or therapy replacements). The median time from intervention to index measurement was 126 (103-160) days. The overall proportion of patients in clinical remission increased from 65.7% to 80.4% (P < .0001) and the median infliximab trough concentrations increased from 3.21 (0.99-5.45) to 5.13 mg/L (3.57-6.53) (P < .0001). In the intensified group, the remission rate increased from 35.3% to 61.8% (P = .001) and the percentage of patients in clinical remission or with mild symptoms increased from 76.5% to 94.1%. In the de-intensification cohort, no patients experienced an increase in the Harvey-Bradshaw index or partial Mayo scores, and all patients maintained an infliximab trough concentration of >5 mg/L. In our cohort of inflammatory bowel disease patients, Bayes-based optimized dosing improved the short-term efficacy of infliximab treatment.

Sustained clinical benefit, improved quality of life, and reduced intestinal surgery from maintenance infliximab treatment in inflammatory bowel disease

Objectives: Anti-TNF treatment is established for patients with severe inflammatory bowel disease (IBD) refractory to conventional medication. However, long-term real-life observations are limited. We have monitored 200 patients with primary response to infliximab (Remicade®).Methods: Patients with either Crohn’s disease (CD) or ulcerative colitis (UC) who started IFX and had clinical response at 1 year were prospectively followed. C-reactive protein (CRP), albumin, fecal calprotectin (FCP), Harvey Bradshaw index (HBI) in CD cases, and Quality of Life index were monitored. Concomitant medications, surgery and hospitalisation were assessed.Results: Out of the 200 patients, 164 suffered from CD. Median disease duration was 5.0 (0.2–44.0) years and the observation time was 3.4 (1.0–13.9) years. Steroid use was reduced from 51% to 10%. HBI in CD patients decreased from 8.0 ± 0.40 to 2.7 ± 0.26. Disease activity in UC patients was only assessed by biochemical markers. CRP decreased from 29.0 ± 6.2 to 8.0 ± 7.1 mg/L. FCP showed a decrease from 1918 (1837) to 191 (646) mg/kg. Hospitalization showed similar tendency and quality of life was improved. Twenty-seven percent had been operated before IFX introduction compared to 11% during the observation period. Loss of response was seen in 42 patients, of which 20 patients needed intestinal surgery.Conclusion: Two-thirds of the patients demonstrated stable clinical benefit from maintenance IFX. The results show steroid-sparing efficacy as well as improved quality of life and reduced need for surgery.

Tu1818 – Ultra-Proactive Therapeutic Drug Monitoring Incorporating Infliximab Point-Of-Care Testing with Ad Hoc Dose Adjustment Reduces C-Reactive Protein Levels in Patients with IBD During Infliximab Maintenance Treatment

Tu1818 – Ultra-Proactive Therapeutic Drug Monitoring Incorporating Infliximab Point-Of-Care Testing with Ad Hoc Dose Adjustment Reduces C-Reactive Protein Levels in Patients with IBD During Infliximab Maintenance Treatment

Application value of MRI examination in the efficacy evaluation of infliximab combined with seton placement for perianal fistulizing Crohn′s disease and influencing factors analysis of deep remission

Objective To investigate the application value of magnetic resonance imaging (MRI) examination in the efficacy evaluation of infliximab combined with seton placement for perianal fistulizing Crohn′s disease (PFCD) and influencing factors of deep remission. Methods The retrospective case-control study was conducted. The clinicopathological data of 57 patients with PFCD who were admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from August 2010 to October 2017 were collected. There were 39 males and 18 females, aged (24±9)years, with a range of 14-58 years. Patients underwent MRI examination preoperatively and postoperatively. Observation indicators: (1) follow-up situations; (2) influencing factors analysis of deep remission of PFCD. Follow-up using outpatient and inpatient reexamination was performed to detect clinical recovery of patients up to October 2017. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were described as M (range). Count data were represented as absolute number or percentage. The univariate analysis was performed using the chi-square test. The multivariate analysis was done using the logistic regression model, using P<0.15 as an inclusion criteria in the univariate analysis. Results (1) Follow-up situations: 57 patients with PFCD undergoing inflixmab combined with seton placement were followed up for (40±24)months. During the follow-up, 24 of 57 patients had clinical response, 33 had long-term clinical healing. The fistulas of 24 patients with clinical response presented as high signal on T2 weighted image (T2WI) of postoperative MRI. Of 33 patients with long-term clinical healing, the fistulas of 16 patients with deep remission presented loss of high signal and replacement of fibrosis tissue on T2WI of postoperative MRI, the fistulas of 17 patients without deep remission presented as high signal on T2WI of postoperative MRI. (2) Influencing factors analysis of deep remission of PFCD: results of univariate analysis showed that extent of fistula was related factors affecting deep remission of PFCD (χ2=4.312, P<0.05). Results of multivariate analysis showed that a single fistula complicated with branches and times of infliximab maintenance treatment ≤3 were independent risk factors affecting deep remission of PFCD (odds ratio=4.377, 4.296, 95% confidence interval: 1.124-17.043, 1.158-15.940, P<0.05) and fistula under levator ani muscle was an independent protective factor affecting deep remission of PFCD (odds ratio=0.182, 95% confidence interval: 0.041-0.815, P<0.05). Conclusions Partial patients with long-term clinical healing can achieve deep remission after Infliximab combined with seton placement for perianal fistulizing Crohn′s disease, requiring MRI examination to further evaluate recovery situations. A single fistula complicated with branches and times of infliximab maintenance treatment ≤3 are independent risk factors affecting deep remission of PFCD and fistula under levator ani muscle is an independent protective factor affecting deep remission of PFCD. Key words: Crohn′s disease; Anal fistula; Infliximab; Long-term clinical remission; Deep remission; Influencing factors

P530 Ultra-proactive therapeutic drug monitoring incorporating infliximab point-of-care testing with ad hoc dose adjustment reduces C-reactive protein levels in patients with IBD during infliximab maintenance treatment

P530 Ultra-proactive therapeutic drug monitoring incorporating infliximab point-of-care testing with ad hoc dose adjustment reduces C-reactive protein levels in patients with IBD during infliximab maintenance treatment

Success and safety of high infliximab trough levels in inflammatory bowel disease

Objective: A prospective trial suggests target infliximab trough levels of 3–7 μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce.Aim: To explore whether high infliximab trough levels (≥7 μg/mL) are more effective and still safe.Material and methods: In this cohort study of 183 patients (109 Crohn’s disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 μg/mL during 420 patient-years.Results: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg [30–257]; C-reactive protein 3 mg/L [3–3]) compared to trough levels below 7 μg/mL (fecal calprotectin 155 mg/kg [72–474]; C-reactive protein 3 mg/L [3–14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 μg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7 μg/mL (32/344 [9.3%]) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2–54%) increase of infliximab consumption.Conclusion: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

Outcome of continued infliximab therapy in Crohn’s disease patients with response but without remission after one year of infliximab – a retrospective cohort study

Background: Optimal management of Crohn’s disease patients having responded to infliximab but without achieving remission is not well defined. The present study examined if these patients benefit from continued long-term infliximab maintenance therapy.Method: Retrospective cohort study including all patients treated with infliximab for 1 year until the end of 2017 who have had a response but not reached remission on infliximab. Clinical outcomes were defined by the physicians’ global evaluation, supported by clinical indices and objective markers of disease activity.Results: In total, 376 Crohn’s disease patients received infliximab. Among these, 76 (20%) were classified as having response but non-remission (RNR) after 1 year of therapy. A great majority (n = 54; 71%) experienced no additional therapeutic benefit after a further year of infliximab maintenance therapy, thus still having RNR. Nineteen patients (25%) obtained remission during continued infliximab, whereas only 4% (n = 3) experienced treatment failure. Although infliximab therapy beyond 2 years (follow-up median 35 months, IQR: 23–55) was accompanied by a higher proportion attaining remission (40%), nearly half (46%) still failed to improve. Among patients who had discontinued infliximab while having RNR (n = 21), half (n = 11) experienced disease flare within five months (median 22 weeks, IQR: 12–31).Conclusion: Most patients (71%) had no additional therapeutic benefit after an additional year of infliximab therapy, and after a median maintenance infliximab treatment period of 3 years, half still failed to improve further. Considering the importance of achieving complete remission, these patients appear to have an unmet medical need.

A systematic review of cost-effectiveness studies comparing conventional, biological and surgical interventions for inflammatory bowel disease.

BackgroundInflammatory bowel disease (IBD) is a chronic disease placing a large health and economic burden on health systems worldwide. The treatment landscape is complex with multiple strategies to induce and maintain remission while avoiding long-term complications. The extent to which rising treatment costs, due to expensive biologic agents, are offset by improved outcomes and fewer hospitalisations and surgeries needs to be evaluated. This systematic review aimed to assess the cost-effectiveness of treatment strategies for IBD.Materials and methodsA systematic literature search was performed in March 2017 to identify economic evaluations of pharmacological and surgical interventions, for adults diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC). Costs and incremental cost-effectiveness ratios (ICERs) were adjusted to reflect 2015 purchasing power parity (PPP). Risk of bias assessments and a narrative synthesis of individual study findings are presented.ResultsForty-nine articles were included; 24 on CD and 25 on UC. Infliximab and adalimumab induction and maintenance treatments were cost-effective compared to standard care in patients with moderate or severe CD; however, in patients with conventional-drug refractory CD, fistulising CD and for maintenance of surgically-induced remission ICERs were above acceptable cost-effectiveness thresholds. In mild UC, induction of remission using high dose mesalazine was dominant compared to standard dose. In UC refractory to conventional treatments, infliximab and adalimumab induction and maintenance treatment were not cost-effective compared to standard care; however, ICERs for treatment with vedolizumab and surgery were favourable.ConclusionsWe found that, in general, while biologic agents helped improve outcomes, they incurred high costs and therefore were not cost-effective, particularly for use as maintenance therapy. The cost-effectiveness of biologic agents may improve as market prices fall and with the introduction of biosimilars. Future research should identify optimal treatment strategies reflecting routine clinical practice, incorporate indirect costs and evaluate lifetime costs and benefits.

Sa1961 - Low-Dose Azathioprine Improves Long-Term Efficacy of Infliximab Maintenance Treatment in Japanese Patients with Crohn's Disease

Sa1961 - Low-Dose Azathioprine Improves Long-Term Efficacy of Infliximab Maintenance Treatment in Japanese Patients with Crohn's Disease

P685 Switching from originator-infliximab to biosimilar-infliximab has no influence on health-related quality of life and clinical disease activity among patients with inflammatory bowel disease

Background: Biosimilar-infliximab (CT-P13) was approved for all indications as an originator-infliximab although the clinical efficacy was only demonstrated in rheumatoid arthritis and ankylosing spondylitis. The objective of this study was to evaluate the clinical efficacy and effectiveness of biosimilar-infliximab in the maintenance treatment of inflammatory bowel diseases (IBDs). Methods: We conducted an observational, prospective single-center study of the IBD patients receiving infliximab (IFX) maintenance treatment. All IBD patients on IFX maintenance treatment were systematically switched from originator-IFX to biosimilar-IFX. The health-related quality of life (HRQoL) measures used in this survey were a disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) and a generic 15D instrument. Patient reported outcomes were collected at three IFX administration visits at clinic: 8 weeks before the switching (the last originator-IFX infusion), at the time of switching (the first biosimilar-IFX infusion) and 16 weeks after the switching (the third biosimilar-IFX infusion). Clinical disease activity (Harvey-Bradshaw Index (HBI) or partial Mayo score) was collected from patients' records. The primary endpoints of the study were the changes in HRQoL and clinical disease activity before and after the switching. Results: In the study, 56 patients (30 male and 26 female) were included: 24 patients diagnosed with Crohn's disease, 29 with ulcerative colitis and 3 as IBD unclassified. The patients' ages varied from 20 to 74 (mean 35.82, SD 11.51). Seven patients were smoker, 13 patients were former smoker and 36 patients never smoked. The duration of the treatment with originator-IFX ranged from 3 months to 11 years (mean 3.3 years, SD 2.91). The median IBDQ score was 189 (SD 29.006) 8 weeks before the switching, 186 (SD 31.789) at the time of switching, and 192 (SD 29.340) 16 weeks after the switching. Respective median 15D scores were 0.915 (SD 0.067), 0.909 (SD 0.072), and 0.913 (SD 0.080). Before the last originator-IFX infusion the mean HBI was 1.80 (SD 3.34) and the mean partial Mayo score 0.95 (SD 1.69), whereas the mean HBI was 1.93 (SD 3.71) and the mean partial Mayo score 0.60 (SD 1.05) before the third biosimilar-IFX infusion. No statistically significant difference was observed between IBDQ (p=0.300), 15D (p=0.700), HBI (p=0.317), and the partial Mayo scores (p=0.481) before and after the switching. No serious adverse events were observed during the follow-up. Conclusions: These early data suggested that in maintenance treatment of IBDs biosimilar-IFX was, in light of IBDQ, 15D, HBI, and the partial Mayo scores, comparable to originator-IFX during the first 16 weeks after the switching.

P564 Low-dose azathioprine improves long-term efficacy of infliximab maintenance treatment in Japanese patients with Crohn's disease

P564 Low-dose azathioprine improves long-term efficacy of infliximab maintenance treatment in Japanese patients with Crohn's disease

Development and Internal Validation of a Model Using Fecal Calprotectin in Combination with Infliximab Trough Levels to Predict Clinical Relapse in Crohnʼs Disease

The best noninvasive method predicting clinical relapse remains undetermined in infliximab (IFX)-treated patients with Crohn's disease. All patients with CD on IFX maintenance treatment and in clinical remission for at least 16 weeks, between 2011 and 2014, were enrolled in a prospective single-center study. The Crohn's Disease Activity Index (CDAI), fecal calprotectin, C-reactive protein levels, antibodies (ATI), and trough level (TLI) of IFX were measured at every IFX infusion. The best thresholds of TLI (2 versus 3 μg/mL) and calprotectin (50 versus 250 μg/g stools) were identified across four logistic regression models. One hundred nineteen patients (mean age: 34 ± 12 yrs, mean disease duration: 7.8 yrs) were included. Mean follow-up was 20.4 months, and 17% of the patients were on IFX and azathioprine at inclusion. During follow-up, 37 patients (31.1%) relapsed, 78% within the first 6 months. The clinical characteristics of the relapsed and nonrelapsed patients were similar. After logistic regression, fecal calprotectin >250 μg/g stools (OR: 4.09; 95% CI, 1.01-16.21; P = 0.049) and TLI <2 μg/mL (OR: 14.85; 95% CI, 3.67-60; P < 0.0001) were associated with loss of response. A training cohort of 55 patients was isolated randomly to implement prediction rules for loss of response. The best predictive rules were the combination of a TLI <2 μg/mL and a fecal calprotectin level >250 μg/g stools (78.3%). These rules were validated on a test cohort of 64 patients with an accuracy of 87%, (sensitivity = 0.94, specificity = 0.84, positive predictive value = 0.73, and negative predictive value = 0.97). In IFX-treated patients with CD in clinical remission, a combination of TLI (<2 μg/mL) and fecal calprotectin (>250 μg/g of stools) is a good model for predicting loss of response. In contrast with previous data, low TLIs ranging from 2 to 3 μg/mL should neither systematically lead to the optimization of IFX use nor a switch in the treatment.

Prognostic factors for long-term infliximab treatment in Crohn's disease patients: a 20-year single centre experience.

The long-term efficacy of infliximab in patients with Crohn's disease is suboptimal. To study prognostic factors for real-life long-term effcacy of infliximab in Crohn's disease. All consecutive Crohn's disease patients treated with infliximab at a tertiary centre were retrospectively analysed. Only patients who received scheduled infliximab maintenance treatment were considered. Patient- and disease-related factors were used to identify independent predictors of infliximab failure-free survival using Cox proportional hazards regression. Of 1031 patients with Crohn's disease, 261 were eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4-4.7] years, and 65 (24.9%) patients experienced infliximab failure. Estimated 5-year infliximab failure-free survival was 65.9% (95% CI 58.3-73.5). Multivariate Cox regression identified disease duration ≥1 year (HR 2.5 (95% CI 1.2-5.2), P = 0.02), L1 disease location [HR 2.0 (1.1-3.5), P = 0.02], prior anti-TNF use [HR 2.3 (1.1-4.8), P = 0.03], haemoglobin <13.5 g/dL [HR 2.3 (1.2-4.4), P = 0.02], not using therapeutic drug monitoring [HR 8.0 (4.1-15.6), P = 1 × 10(-9) ], and first dose optimisation within first year [HR 3.7 (2.1-6.6), P = 5 × 10(-6) ] as independent predictors of infliximab failure-free survival. Stratifying patients into risk groups resulted in estimated 3-year infliximab failure-free survival rates ranging from 95.3% (94.2-96.4) to 26.3% (8.6-44.0) depending on the number of risk factors (P = 8 × 10(-13) ). This study identified several easy to obtain predictors of infliximab failure in patients with Crohn's disease, and these are in line with previous reports. Those with a high-risk profile for infliximab failure in whom infliximab initiation is considered, should be treated as early as possible making use of therapeutic drug monitoring.