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Clin Res Hepatol Gastroenterol. 2015 Jun 29. [Epub ahead of print]
Therapeutic drug monitoring is predictive of loss of response after de-escalation of infliximab therapy in patients with inflammatory bowel disease in clinical remission.
Amiot A, Hulin A, Belhassan M, et al.

BACKGROUND: There is no evidence that therapeutic drug monitoring is helpful in patients with inflammatory bowel disease patients in clinical remission with infliximab therapy.

METHODS: Eighty consecutive inflammatory bowel disease patients in clinical remission on infliximab maintenance therapy were included and followed-up for at least one year. Infliximab trough level and antibody to infliximab concentration were measured prior to enrollment. At the time of enrollment, physicians in charge were free to alleviate infliximab therapy. Discrepancies between blind and therapeutic drug monitoring-based adjustments were assessed at the end of the follow-up period. Relapse-free survival was analyzed using univariate and multivariate analyses.

RESULTS: The mean infliximab trough level was 3.1μg/mL. Antibody to infliximab was found in 15 (19%) patients. At the end of the follow-up period, 18 (22.5%) patients experienced a relapse. The 3, 6, 9 and 12-month relapse-free rates were 98%, 87%, 86% and 80%, respectively. In our multivariate analysis, relapse-free survival was negatively associated with discrepancies between therapeutic drug monitoring-based and blind adjustments of infliximab therapy, absence of concomitant immunomodulator, the absence of mucosal healing, prior use of infliximab, infliximab therapy duration>2years and C-reactive protein levels>5mg/L at the time of enrollment.

CONCLUSION: In patients with inflammatory bowel disease in clinical remission on infliximab therapy, de-escalation of infliximab therapy should be considered based on therapeutic drug monitoring rather than according to symptoms and CRP


Aliment Pharmacol Ther. 2015 Jun 26. [Epub ahead of print]
Population pharmacokinetics of infliximab in patients with inflammatory bowel disease: potential implications for dosing in clinical practice.
Buurman DJ, Maurer JM, Keizer RJ, et al.

BACKGROUND: Infliximab (IFX) is effective in the treatment of inflammatory bowel diseases (IBD). Currently, IFX is administered at fixed doses and intervals; however, costs are high and optimisation is necessary. Several publications indicate that IFX should be dosed on trough levels ≥3.0 mg/L. For optimising IFX dosing, the use of a pharmacokinetic model is important. Population pharmacokinetics of IFX have been described earlier; however, these models were not used for dose optimising.

AIMS: To develop a pharmacokinetic model for IFX in IBD patients that can be used for dose-optimisation of IFX and to predict serum trough levels in this population.

METHODS: An observational retrospective study was performed in 42 IFX-treated IBD patients. Serum samples were drawn before infusion at T = 0, 2, 6, 14, 22 and 54 weeks and analysed for IFX and antibodies against IFX (ATI). Relevant covariates were recorded and a population pharmacokinetic model was developed.

RESULTS: Individual plots created using the final model showed good correspondence between observed and model predicted values. Serum levels were influenced by ATI, disease activity, sex and albumin. Our results show that in patients without ATI target trough levels ≥3.0 mg/L can be achieved by increasing dosing intervals from 8 to 12 weeks combined with a dose increase. This results in a reduction of 33% in concomitant costs.

CONCLUSIONS: In IBD patients without ATI, trough level dosing based on longer intervals can reduce IFX therapy-related visits to the hospital with one-third. Trough level based dose intensification should always be justified by disease activity parameters.


J Crohns Colitis. 2015 Jun 26. [Epub ahead of print]
Serum concentration of anti-TNF antibodies, adverse effects and quality of life in patients with inflammatory bowel disease in remission on maintenance treatment.
Brandse JF, Vos LM, Jansen J, et al.

BACKGROUND AND AIMS: High serum concentrations of Infliximab (IFX) and Adalimumab (ADA) may be associated with adverse effects in patients with inflammatory bowel disease (IBD). We aimed to investigate whether high anti-TNF trough levels (TLs) were associated with toxicity and impaired quality of life (QoL).

METHODS: We conducted a prospective cohort study in IBD patients in clinical and biochemical remission on IFX or ADA maintenance therapy. Trough serum concentrations and antidrug antibodies were measured in addition to biochemical markers of inflammation in serum and stool to confirm quiescent disease. QoL was assessed using IBDQ and SF-36. Side effects such as fatigue and arthralgia were measured with a visual analogue score. Skin toxicity was reported with an EORTC derived score.

RESULTS: 252 IBD patients on maintenance anti-TNF therapy were screened, of whom 95 (73 CD, 22 UC; 72 IFX, 23 ADA) were in clinical and biochemical remission and included. Median TLs were 5.5ug/ml and 6.6 ug/ml for IFX and ADA, respectively. Patients with anti-TNF TLs above median had lower IBDQ scores than patients with lower TLs (IBDQ 176 vs. 187, P=0.02), particularly regarding systemic symptoms and emotional status. A trend towards lower SF-36 and higher fatigue scores was observed in the higher anti-TNF TL group. Skin and arthralgia scores were not significantly different between both groups.

CONCLUSIONS: IBD patients with higher anti-TNF serum concentrations had significantly lower disease-specific QoL. Fatigue, arthralgia and skin lesions do not occur more often in these patients. This data is reassuring that high serum concentrations of anti-TNF antibodies are not toxic.


Aliment Pharmacol Ther. 2015 Jun 24. [Epub ahead of print]
Efficacy and safety of anti-TNF therapy in elderly patients with inflammatory bowel disease.
Lobatón T, Ferrante M, Rutgeerts P, et al.

BACKGROUND: The general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti-tumour necrosis factor (TNF) therapy in elderly is scarce and conflicting.

AIM: To assess the efficacy and safety of anti-TNF therapy in elderly patients taking into account eventual comorbidity.

METHODS: Observational and retrospective single-centred study where 66 IBD patients initiating anti-TNF treatment at age >= 65 years (cases: >= 65 anti-TNF) were compared with 112 IBD patients initiating anti-TNF < 65 years (controls < 65 anti-TNF) and 61 anti-TNF naïve IBD patients treated with immunosuppressants (IMS) and/or corticosteroids (CS) >= 65 years (controls >= 65 IMS/CS). Controls were matched to cases for IBD type, follow-up, disease duration and anti-TNF type. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Both efficacy and safety of treatment were adjusted for comorbidity.

RESULTS: The short-term clinical response to anti-TNF at 10 weeks was significantly lower in cases: >= 65 anti-TNF (68% vs. 89%; P < 0.001), whereas at >= 6 months, differences were not significant (79.5% vs. 82.8%; P = 0.639). The risk for any severe adverse events was higher in cases: >= 65 anti-TNF than in controls < 65 anti-TNF (RR = 4.7; P < 0.001) or controls >= 65 IMS/CS (RR = 3.09; P = 0.0008). Age older than 65 and CCI > 0 were independent risk factors for malignancy and mortality regardless of the medication.

CONCLUSION: Elderly patients treated with anti-TNF have a lower rate of short-term clinical response and a higher rate of severe adverse events than the younger patients under the same treatment.


Dermatol Clin. 2015 Jul;33(3):417-31.
Cutaneous manifestations of Crohn disease.
Hagen JW, Swoger JM, Grandinetti LM.

Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed.


Clin Gastroenterol Hepatol. 2015 Jun 30. [Epub ahead of print]
Effects of concomitant immunomodulator therapy on efficacy and safety of anti-TNF therapy for Crohn's disease: a meta-analysis of placebo-controlled trials.
Jones JL, Kaplan GG, Peyrin-Biroulet L, et al.

BACKGROUND & AIMS: There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy.

METHODS: We performed a systematic review of literature published from 1980 through 2008, and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naïve to anti-TNF and immunomodulator therapy. The primary endpoints were clinical response at weeks 4-14 and 24-30, and remission at weeks 24-30. Secondary endpoints included infusion- or injection-site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents.

RESULTS: Overall, combination therapy was no more effective than monotherapy in inducing 6 months remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI 0.79-1.48), maintaining a response (OR, 1.53; 95% CI 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68-1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.)

CONCLUSIONS: Based on a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated.


Therap Adv Gastroenterol. 2015 Jul;8(4):168-75.
Specialized enteral nutrition therapy in Crohn's disease patients on maintenance infliximab therapy: a meta-analysis.
Nguyen DL, Palmer LB, Nguyen ET, et al.

OBJECTIVES: Many patients with Crohn's disease on infliximab maintenance therapy have recurrent symptoms despite an initial clinical response. Therefore, concomitant therapies have been studied. We conducted a meta-analysis to assess the effect of specialized enteral nutrition therapy with infliximab versus infliximab monotherapy in patients with Crohn's disease.

METHODS: A comprehensive search of multiple databases was performed. All studies of adult patients with Crohn's disease comparing specialized enteral nutrition therapy (elemental or polymeric diet with low-fat or regular diet) with infliximab versus infliximab monotherapy without dietary restrictions were included. Meta-analysis was performed using the Mantel-Haenszel (fixed effect) model with odds ratio (OR) to assess for clinical remission.

RESULTS: Four studies (n = 342) met inclusion criteria. Specialized enteral nutrition therapy with infliximab resulted in 109 of 157 (69.4%) patients reaching clinical remission compared with 84 of 185 (45.4%) with infliximab monotherapy [OR 2.73; 95% confidence interval (CI): 1.73-4.31, p < 0.01]. Similarly, 79 of 106 (74.5%) patients receiving enteral nutrition therapy and infliximab remained in clinical remission after one year compared with 62 of 126 (49.2%) patients receiving infliximab monotherapy (OR 2.93; 95% CI: 1.66-5.17, p < 0.01). No publication bias or heterogeneity was noted for either outcome.

CONCLUSIONS: The use of specialized enteral nutrition therapy in combination with infliximab appears to be more effective at inducing and maintaining clinical remission among patients with Crohn's disease than infliximab monotherapy.


Intest Res. 2015 Jul;13(3):259-65.
Conventional versus biological therapy for prevention of postoperative endoscopic recurrence in patients with Crohn's disease: an international, multicenter, and observational study.
Kotze PG, Spinelli A, da Silva RN, et al.

BACKGROUND/AIMS: Postoperative endoscopic recurrence (PER) occurs in nearly 80% of patients 1 year after ileocecal resection in patients with Crohn's disease (CD). Biological agents were more effective in reducing the rates of PER in comparison with conventional therapy, in prospective trials. The aim of this study was to compare the PER rates of biological versus conventional therapy after ileocecal resections in patients with CD in real-world practice.

METHODS: The MULTIPER (Multicenter International Postoperative Endoscopic Recurrence) database is a retrospective analysis of PER rates in CD patients after ileocecal resection, from 7 referral centers in 3 different countries. All consecutive patients who underwent ileocecal resections between 2008 and 2012 and in whom colonoscopies had been performed up to 12 months after surgery, were included. Recurrence was defined as Rutgeerts' score ≥i2. The patients were allocated to either biological or conventional therapy after surgery, and PER rates were compared between the groups.

RESULTS: Initially, 231 patients were evaluated, and 63 were excluded. Of the 168 patients in the database, 96 received anti-tumor necrosis factor agents and 72 were treated with conventional therapy after resection. The groups were comparable regarding age, gender, and perianal disease. There was longer disease duration, more previous resections, and more open surgical procedures in patients on biologicals postoperatively. PER was identified in 25/96 (26%) patients on biological therapy and in 24/72 (33.3%) patients on conventional therapy (P=0.310).

CONCLUSIONS: In this retrospective observational analysis from an international database, no difference was observed between biological and conventional therapy in preventing PER after ileocecal resections in CD patients.


J Crohns Colitis. 2015 Jun 26. [Epub ahead of print]
Higher rates of dose optimization for infliximab responders in ulcerative colitis than in Crohn's disease.
O'Donnell S, Stempak JM, Steinhart HA, et al.

BACKGROUND: Studies have demonstrated the benefit of dose optimization in the setting of secondary loss of response to infliximab in inflammatory bowel disease.

AIM: The aim of our study was to retrospectively investigate the rates of dose optimization in an inflammatory bowel disease cohort receiving maintenance infliximab therapy to determine if there are different rates of dose optimization between CD and UC cases and what impact this has on the durability of treatment effect.

METHODS: Cases receiving infliximab for treatment of IBD between January 2008 and February 2014 were identified from an infusion center database. Cases receiving ≥ 4 infusions were included in the study. Details of infusion dosing and timing were obtained. A dose increase from 5 mg/kg to 10 mg/kg or a reduction in the dosing interval were considered a dose optimization.

RESULTS: 412 cases were included in the study. 52.7% required at least one dose optimization. Dose optimization was more common in UC than in CD cases (67.2% vs 46.3%, p=0.00006). The median time to dose optimization was 7 months (95% CI 4.8-9.2) for UC cases and 27 months (95% CI 7.3-46.7) for CD cases, p=0.00003.

CONCLUSION: Here we have shown that dose optimization is required more frequently in UC than in CD with a significantly shorter time to dose optimization for UC cases than CD cases. While the majority of cases responding to induction therapy with infliximab will have a sustained response to therapy, over 50% will require a dose optimization during their treatment.

 


J Crohns Colitis. 2015 Jun 26. [Epub ahead of print]
The Modified Mayo Endoscopic Score (MMES): a new index for the assessment of extension and severity of endoscopic activity in ulcerative colitis patients.
Lobatón T, Bessissow T, De Hertogh G, et al.

INTRODUCTION: Current endoscopic activity scores for ulcerative colitis (UC) do not take into account the extent of mucosal inflammation. We have developed a simple endoscopic index for UC that takes into account the severity and the distribution of mucosal inflammation.

METHODS: In this multicenter trial, UC patients undergoing colonoscopy were prospectively enrolled. For the Modified Score (MS), the sum of the Mayo endoscopic subscore (MES) for five colon segments (ascending, transverse, descending, sigmoid and rectum) was calculated. The Extended Modified Score (EMS) was obtained by multiplying the MS by the maximal extent of inflammation. The Modified Mayo Endoscopic Score (MMES) was obtained by dividing the EMS with the number of segments with active inflammation. Colon biopsies were standardly obtained from rectum and sigmoid, as well as from all inflamed segments. Clinical activity was scored according to the Partial Mayo score (PMS). Biological activity was scored according to C-reactive protein (CRP) and fecal calprotectin (FC) levels. Histological activity was scored according to the Geboes' score (GS).

RESULTS: 171 UC patients (38% female, median age 47 years, median disease duration 13 years) were included. The MMES correlated significantly with the PMS (r=0.535), CRP (r=0.238), FC (r=0.730) and GS (r=0.615) (all P<0.001). Median MMES scores were significantly higher in patients with clinical, biological or histological activity (all P ≤0.001)

CONCLUSIONS: The MMES is an easy to use endoscopic index for UC that combines the severity analysis of the MES with the disease extent, and correlates very well with clinical, biological and histological disease activity.


Scand J Gastroenterol. 2015 Jul 3:1-7.
Risk matrix model for prediction of colectomy in a population-based study of ulcerative colitis patients (the IBSEN study).
Solberg IC, Høivik ML, Cvancarova M, et al.

OBJECTIVES: Identifying ulcerative colitis (UC) patients with increased risk of colectomy is essential for appropriate treatment. We aimed to develop a prediction model assessing the risk of having colectomy within the first 10 years after diagnosis.

MATERIAL AND METHODS: A population-based inception cohort of UC patients diagnosed in south-eastern Norway between 1990 and 1994 has been followed for 10 years. Altogether 519 patients were recruited including 49 patients who were colectomized. Based on the best-fitted multivariate model, the probabilities of colectomy were computed for selected levels of baseline covariates, and the results arranged in a prediction matrix. The following risk factors at diagnosis were analyzed: age, smoking, sex, disease extent, weight loss and fever and need for systemic steroids. Biochemical markers included C-reactive protein (CRP, < 30 or >=30 mg/l); erythrocyte sedimentation rate (ESR, <30 or >=30 mm/h) and hemoglobin (Hgb, <10.5 or >=10.5 g/dL).

RESULTS: Extent of disease, age (<40 years, >=40 years), need for systemic steroids and CRP or ESR (< 30 or > 30) at diagnosis were independently associated with colectomy and were combined in a prediction matrix. The probabilities of colectomy during the follow-up period ranged from 2.6% to 40.1% depending on the combination of predictors at diagnosis.

CONCLUSIONS: Our prediction model revealed significant differences in the probability of undergoing colectomy during a 10-years course of disease, which supports an early individualized treatment approach in UC.


J Rheumatol. 2015 Jul;42(7):1105-11.
Incidence and management of infusion reactions to infliximab in a prospective real-world community registry.
Choquette D, Faraawi R, Chow A, et al.

OBJECTIVE: Infliximab (IFX) is a therapeutic monoclonal antibody targeting tumor necrosis factor-α indicated in the treatment of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with different types of infusion reactions.

METHODS: RemiTRAC Infusion (NCT00723905) is a Canadian observational registry in which patients receiving IFX are followed prospectively to document premedication use, adverse events, infusion reactions, and the management of infusion reactions. The primary endpoint was to assess factors associated with infusion reactions.

RESULTS: There were 1632 patients enrolled and 24,852 infusions recorded. Most patients (63.1%) were treated for rheumatologic conditions such as rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. Of the 1632 patients, 201 (12.3%) reported at least 1 infusion reaction. Three hundred twenty-two infusions were associated with an infusion reaction (1.3%), and most were mild to moderate in severity (95%). The most common infusion reactions were pruritus (19.9%), flushing (9.9%), or dyspnea (6.2%). Multivariate analysis showed that antihistamines premedication, number of previous infusion reactions, and female sex were significantly associated with an increased incidence of infusion reactions (p < 0.0011). The use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of infusion reactions. Antihistamine premedication was associated with an increased incidence of infusion reactions (OR 1.58, p = 0.0007).

CONCLUSION: This registry shows that in community-based infusion clinics, infusion reactions to IFX are uncommon and mild to moderate in nature. Antihistamines, intravenous steroids, and acetaminophen are widely used as preventative premedication, although this study showed an absence of benefit with their use.


Expert Opin Biol Ther. 2015 Jul 20:1-3. [Epub ahead of print]
Could therapeutic drug monitoring of anti-TNF-α be useful to consider a de-escalation of treatment?
Flamant M, Roblin X.

In recent years, many retrospective studies have demonstrated the interest of therapeutic anti-TNF drug monitoring in inflammatory bowel disease. This could be especially helpful in two different situations: a secondary loss of anti-TNF response where a re-elevation of drug levels by treatment optimization is predictive of better clinical outcome; a therapeutic de-escalation or discontinuation for Crohn's disease patients in long-standing remission where an undetectable anti-TNF drug level could be predictive of clinical remission.


Gastroenterology. 2015 Jul 10. [Epub ahead of print]
Proteolytic cleavage and loss of function of biologic agents that neutralize tumor necrosis factor in the mucosa of patients with inflammatory bowel disease.
Biancheri P, Brezski RJ, Di Sabatino A, et al.

BACKGROUND & AIMS: Many patients with inflammatory bowel disease (IBD) fail to respond to anti-tumor necrosis factor (TNF) agents such as infliximab and adalimumab, and etanercept is not effective in treatment of Crohn's disease. Activated matrix metalloproteinase 3 (MMP3) and MMP12, which are increased in inflamed mucosa of patients with IBD, have a wide range of substrates, including immunoglobulin (Ig)G1. TNF neutralizing agents act in inflamed tissues; we investigated the effects of MMP3, MMP12, and mucosal proteins from IBD patients on these drugs.

METHODS: Biopsies from inflamed colon of 8 patients with Crohn's disease and 8 with ulcerative colitis, and from normal colon of 8 healthy individuals (controls), were analyzed histologically, or homogenized and proteins were extracted. We also analyzed sera from 29 patients with active Crohn's disease and 33 with active ulcerative colitis who were candidates to receive infliximab treatment. Infliximab, adalimumab, and etanercept were incubated with mucosal homogenates from patients with IBD or activated recombinant human MMP3 or MMP12 and analyzed on immunoblots or in luciferase reporter assays designed to measure TNF activity. IgG cleaved by MMP3 or MMP12 and anti-hinge autoantibodies against neo-epitopes on cleaved IgG were measured in sera from IBD patients who subsequently responded (clinical remission and complete mucosal healing) or did not respond to infliximab. RESULTS: MMP3 and MMP12 cleaved infliximab, adalimumab, and etanercept, releasing a 32 kDa Fc monomer. After MMP degradation, infliximab and adalimumab functioned as F(ab')2 fragments, whereas cleaved etanercept lost its ability to neutralize TNF. Proteins from the mucosa of patients with IBD reduced the integrity and function of infliximab, adalimumab, and etanercept. TNF-neutralizing function was restored following incubation of the drugs with MMP inhibitors. Serum levels of endogenous IgG cleaved by MMP3 and MMP12, and anti-hinge autoantibodies against neo-epitopes of cleaved IgG, were higher in patients that did not respond to treatment vs responders.

CONCLUSIONS: Proteolytic degradation may contribute to non-responsiveness of patients with IBD to anti-TNF agents.


Crohns Colitis. 2015 Jul 17. [Epub ahead of print]
Disease outcome of ulcerative colitis in an era of changing treatment strategies - Results from the Dutch population-based IBDSL cohort.
Jeuring SF, Bours PH, Zeegers MP, et al.

BACKGROUND AND AIMS: In the last decades, treatment options and strategies for ulcerative colitis (UC) have radically changed. Whether these developments have altered the disease outcome at population level is yet unknown. Therefore, we evaluated the disease outcome of UC over the last two decades in the South-Limburg area of the Netherlands.

METHODS: In the Dutch population-based IBDSL cohort, three time cohorts were defined: cohort 1991-1997 (cohort A), cohort 1998-2005 (cohort B), and cohort 2006-2010 (cohort C). The colectomy and hospitalisation rates were compared between cohorts by Kaplan-Meier survival analyses. Hazard ratios (HR) for early colectomy (within six months after diagnosis), late colectomy (beyond six months after diagnosis), and hospitalisation were calculated using Cox regression models.

RESULTS: In total, 476 UC patients were included in cohort A, 587 patients in cohort B, and 598 patients in cohort C. Over time, an increase in the use of immunomodulators (8.1% to 22.8% to 21.7%, p<0.01) and biological agents (0% to 4.3% to 10.6%, p<0.01) was observed. The early colectomy rate decreased from 1.5% in cohort A to 0.5% in cohort B (HR 0.14; 95%CI 0.04-0.47), with no further decrease in cohort C (0.3%, HR 0.98; 95%CI 0.20-4.85). Late colectomy rate remained unchanged over time: 4.0% vs. 5.2% vs. 3.6% (p=0.54), respectively. Hospitalisation rate was also similar among cohorts (22.3% vs. 19.5% vs. 18.3%, p=0.10).

CONCLUSION: Over the last two decades, a reduction in early colectomy rate was observed, with no further reduction in the most recent era. Late colectomy rate and hospitalisation rate remained unchanged over time.


J Gastroenterol. 2015 Jul 11. [Epub ahead of print]
First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis-results from a multicenter prospective randomized controlled trial and its post hoc analysis.
Kobayashi T, Suzuki Y, Motoya S, et al.

BACKGROUND: Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response.

METHODS: Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes.

RESULTS: Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (p = 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95 % confidence interval 2.84-27.07, p < 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing.

CONCLUSIONS: IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options.

 

 

 

 

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