Crohns Colitis. 2016 May 25.
Histological outcomes and predictive value of faecal markers in moderately to severely active ulcerative colitis patients receiving infliximab.
Magro F, Lopes SI, Lopes J, et al.
BACKGROUND AND AIMS: Histological healing has emerged as a promising therapeutic goal in ulcerative colitis. This is especially important in the context of biological therapies. The objectives of the present study were to investigate the ability of infliximab to induce histological remission in ulcerative colitis [UC] patients and to explore the utility of faecalcalprotectin and lactoferrin in predicting histological activity.
METHODS: Multi-centre, single-cohort, open-label, 52-week trial including moderately to severely biological-naïve UC patients receiving intravenous infliximab [5mg/kg]. The primary outcome was the proportion of patients with histological remission [Geboes index ≤3.0] after 8 weeks of treatment, scored by two independent pathologists.
RESULTS: Twenty patients were included. The rate of histological remission increased from 5% at baseline to 15% and 35% at Week 8 and Week 52, respectively. At Week 8, 40% of patients were in clinical remission [Mayo ≤2] and 45% achieved mucosal healing [Mayo endoscopy subscore 0-1]. At Week 52, 25% of patients had clinical, endoscopic and histological remission. Faecalcalprotectin and lactoferrin showed the highest correlation with histological activity at Week 8 (area under the curve [AUC] 94%, p = 0.017; and 96%, p = 0.013, respectively) and both markers revealed an excellent positive predictive value for this outcome at this time point [100%, p = 0.017; and 94%, p = 0.013, respectively].
CONCLUSIONS: Infliximab was able to induce histological remission. There was a good agreement between histology and faecal biomarkers. Faecalcalprotectin and lactoferrin were good predictors of histological remission. Our data support inclusion of histology as a treatment target complementary to endoscopy in clinical trials when evaluating therapeutic response in UC.
Aliment PharmacolTher. 2016 Jul;44(2):170-80.
The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-α naïve Crohn's disease.
Narula N1, Kainz S2, Petritsch W3, et al.
BACKGROUND: TNFα antagonists, including infliximab (IFX) and adalimumab (ADA), have revolutionised treatment for Crohn's disease. Studies comparing efficacy in patients with Crohn's disease naïve to TNFα antagonists are lacking.METHODS: Consecutive TNFα antagonist-naïve patients with luminal or perianal Crohn's disease from four tertiary centres in Austria were assessed prospectively for induction and maintenance efficacy, and safety, of either IFX or ADA.
RESULTS: In a total of 362 patients, 251 (69.3%) started IFX and 111 (30.7%) started ADA. At baseline, the median Harvey-Bradshaw Index (HBI) score was 8 (range 5-29) and 8 (5-36), and the median C-reactive protein (CRP) was 1.07 (interquartile range (IQR) 1.36) mg/dL and 1.16 (IQR 1.23) mg/dL for IFX and ADA, respectively. At week 12, there was no difference between IFX and ADA among patients with luminal Crohn's disease in clinical remission (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, P = 0.47), clinical response (IFX 154/204; 75.5% vs. ADA 82/107; 76.6%, P = 0.82) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57%, P = 0.60). At 12 months, there were similar numbers of patients treated with IFX and ADA who maintained clinical remission (IFX 77/154; 50.4% vs. ADA 47/82; 57.3%, P = 0.48) and steroid-free remission (IFX 68/154; 44.3% vs. ADA 44/82; 53.7%, P = 0.16). Baseline CRP >0.7 mg/dL (OR 0.24; 95% CI 0.07-0.77, P = 0.01) was the only predictor of clinical remission at 12 months in patients who did not have escalation of anti-TNFα therapy.
CONCLUSION: IFX and ADA appear comparable in clinical outcomes for patients with Crohn's disease who are naïve to TNFα antagonists.
J Gastrointest Surg. 2016 May 26.
Postoperative medical management of Crohn's disease: Prevention and surveillance strategies.
Regueiro M, Strong SA, Ferrari L, et al.
No abstract available.
BMJ Open Gastroenterol. 2016 May 3;3(1):e000093.
Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis.
Yokomizo L, Limketkai B, Park KT.
BACKGROUND: There are no head-to-head randomised controlled trials (RCTs) comparing the effectiveness of biologics in ulcerative colitis (UC). We aimed to assess the cost-effectiveness of adalimumab, infliximab and vedolizumab as first-line agents to induce clinical remission and mucosal healing (MH) in UC.
METHODS: We constructed a decision tree based on a payer's perspective in the USA to estimate the first year costs of adalimumab, infliximab or vedolizumab to achieve clinical remission and MH in patients with moderate-to-severe UC. Transition probabilities were derived from ACT, ULTRAand GEMINI RCT data. Costs were derived from Medicare reimbursement rates and wholesale drug prices.
RESULTS: Assuming a biological-naïve cohort, infliximab 5 mg/kg every 8 weeks was more cost-effective ($99 171 per MH achieved) than adalimumab 40 mg every other week ($316 378 per MH achieved) and vedolizumab every 8 weeks ($301 969 per MH achieved) at 1 year. Non-drug administration cost of infliximab exceeding $1974 per infusion would make adalimumab more cost-effective. First-line UC therapy with vedolizumab would be cost-effective if the drug acquisition price was <$2537 for each 300 mg administration during the 1-year time horizon.
CONCLUSIONS: If non-drug costs of infliximab administration are not excessive (<$2000), infliximab is the most cost-effective first-line biologic for moderate-to-severe UC. Exceeding this threshold infusion-related cost would make adalimumab the more cost-effective therapy. Considering its drug costs in the USA, vedolizumab appears to be appropriately used as a second-line biologic after antitumour necrosis factor failure.
World J Gastroenterol. 2016 Jun 7;22(21):5079-87.
Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse.
Nakarai A, Kato J, Hiraoka S, et al.
AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.
METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.
RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).
CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.
J Crohns Colitis.2016 Jun 9.
Predicting outcomes to optimize disease management in inflammatory bowel diseases.
Torres J, Caprioli F, Katsanos KH, et al.
BACKGROUND AND AIMS: Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higherrisk for complications. It is therefore essential to identify high-risk patients - both at diagnosis and throughout disease course.
METHODS: As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014.
RESULTS: Patients with Crohn's disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosingbehaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use.
CONCLUSIONS: Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient.