World J Gastroenterol. 2015 May 21;21(19):6044-51.
Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis.
Mei WQ, Hu HZ, Liu Y, et al.

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC).

METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators.

RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety.

CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.


Inflamm Bowel Dis. 2015 Jun 19. [Epub ahead of print]
Extent of early clinical response to infliximab predicts long-term treatment success in active ulcerative colitis.
Murthy SK, Greenberg GR, Croitoru K, et al.


BACKGROUND: The long-term effectiveness of infliximab (IFX) in ulcerative colitis (UC) and predictors of treatment response remain poorly characterized.

METHODS: A retrospective cohort study was conducted in 213 consecutive patients with active steroid-refractory or steroid-dependent UC treated with induction and scheduled maintenance IFX at an inflammatory bowel disease referral center. Outcomes included annual steroid-free remission (SFR), IFX failure with discontinuation, colectomy, and serious adverse events.

RESULTS: The 1- and 5-year cumulative probabilities for SFR were 39% and 14%, for IFX failure were 31.7% and 55.6%, and for colectomy were 19.2% and 37.4%, respectively. A sensitivity analysis considering the last clinical observation in patients with incomplete follow-up demonstrated a long-term SFR rate of 36%. Among responders to IFX induction therapy, achieving clinical remission before maintenance IFX therapy predicted SFR at 1 year (adjusted odds ratio = 4.50; 95% CI, 1.75-11.53), whereas the need for IFX dose intensification during the first year of therapy predicted a lower odds of SFR at 1 year (adjusted odds ratio = 0.28; 95% CI, 0.11-0.67) and a greater hazard of IFX failure beyond 1 year (adjusted hazard ratio = 2.57; 95% CI, 1.14-5.81). Older age and shorter UC duration at IFX initiation predicted poorer long-term outcomes.

CONCLUSIONS: In patients with moderate-to-severe UC treated with scheduled IFX at an inflammatory bowel disease center, close to half of the patients are still on IFX at 5 years, although a smaller proportion of patients achieve long-term SFR. The magnitude and stability of early response to IFX is associated with long-term therapeutic benefit to this agent.


ClinGastroenterolHepatol. 2015 Jun 10.pii: S1542-3565(15)00787-9.
Defining disease severity in inflammatory bowel diseases: current and future directions.
Peyrin-Biroulet L, Panés J, Sandborn WJ, et al.


No abstract available.


Systematic review: factors associated with relapse of inflammatory bowel disease after discontinuation of anti-TNF therapy.
Gisbert JP, Marín AC, Chaparro M.


BACKGROUND: The discontinuation of anti-tumour necrosis factor (anti-TNF) treatment in inflammatory bowel disease (IBD) patients in remission could be considered.

AIM: To evaluate the factors associated with relapse of IBD after discontinuation of anti-TNF therapy.

METHODS: Electronic (PubMed/Embase) and manual search up to January 2015.

RESULTS: The overall risk of relapse after discontinuation of anti-TNFs (27 studies) was 44% for Crohn's disease (CD; follow-up range: 6-125 months) and 38% for ulcerative colitis (follow-up range: 6-24 months). Several factors were investigated to identify patients who are more likely to achieve long-lasting remission after anti-TNF discontinuation. The factors associated with a higher risk of relapse are younger age, smoking, longer disease duration, and fistulising perianal CD. Laboratory markers such as low haemoglobin levels, high C-reactive protein levels and high faecalcalprotectin seem to increase the risk of relapse. On the other hand, low serum anti-TNF levels seem to be associated with a lower risk of flare-up. Mucosal healing seems to decrease the risk of relapse after anti-TNF discontinuation (overall, this risk is 26% at 1 year with mucosal healing and 42% without), although this observation has not been confirmed by some authors. In patients receiving escalated anti-TNF doses or receiving anti-TNFs for the prevention of post-operative CD recurrence, the risk of relapse after discontinuation is high (>75%). Re-administration of the drug in those who relapsed after stopping treatment is effective and safe.

CONCLUSIONS: A high proportion of patients with IBD relapse after discontinuation of anti-TNF treatment. As available data are insufficient to make strong recommendations on when anti-TNF therapy could be stopped, decisions should be taken on an individual basis.


J Rheumatol.2015 Jun 15.pii: jrheum.140538. [Epub ahead of print]
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.


J Crohns Colitis.2015 Jun 7.pii: jjv099. [Epub ahead of print]
Treatment steps, surgery and hospitalization rates during the first year of follow-up in patients with inflammatory bowel diseases from the 2011 ECCO-EpiCom inception cohort.
Vegh Z, Burisch J, Pedersen N, et al.


BACKGROUND AND AIMS: The ECCO-EpiCom study investigates the differences in the incidence and therapeutic management of inflammatory bowel diseases (IBD) between Eastern and Western Europe. The aim of this study was to analyze the differences in the disease phenotype, medical therapy, surgery and hospitalization rates in the ECCO-EpiCom 2011 inception cohort during the first year after diagnosis.

METHODS: Nine Western, five Eastern European centers and one Australian center with 258 Crohn's disease (CD), 380 ulcerative colitis (UC) and 71 IBD unclassified (IBDU) patients (female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years) participated. Patients' data were registered and entered in the web-based ECCO-EpiCom database (

RESULTS: In CD, 36 (19%) Western Europe/Australian and 6 (9%) Eastern European patients received biological therapy (p=0.04), but the immunosuppressive (IS) use was equal and high in these regions (Eastern Europe vs. Western Europe/Australia: 53% vs. 45%; p=0.27). Surgery was performed in 17 (24%) CD patients in Eastern Europe and 13 (7%) in Western Europe/Australia (p<0.001, pLogRank=0.001). Twenty-four (34%) CD patients from Eastern Europe and 39 (21%) from Western Europe/Australia were hospitalized (p=0.02, pLogRank=0.01). In UC, exposure to biologics and colectomy rates were low and hospitalization rates did not differ between these regions during the one-year follow-up period (16% vs. 16%; p=0.93).

CONCLUSIONS: During the first year after diagnosis, surgery and hospitalization rates were significantly higher in CD patients in Eastern Europe compared to Western Europe/Australia, while significantly more CD patients were treated with biologicals in the Western Europe/Australian centers.


Dig Dis Sci. 2015 Jun 5. [Epub ahead of print]
Infliximab dose escalation as an effective strategy for managing secondary loss of response in ulcerative colitis.
Taxonera C, Barreiro-de Acosta M, Calvo M, et al.


BACKGROUND: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated.

AIMS: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC.

METHODS: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis.

RESULTS: Seventy-nine patients were included. Fifty-four patients (68.4 %) achieved short-term clinical response and 41 patients (51.9 %) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8 %) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95 % confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4 %) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95 % CI 0.03-0.69; p < 0.007).

CONCLUSIONS: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70 % of patients. In the long term, 58 % of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86 % reduction in the relative risk of colectomy.


J GastroenterolHepatol.2015 Jun 5. [Epub ahead of print]
Magnetic resonance enterography findings as predictors of clinical outcome following antitumor necrosis factor treatment in small bowel Crohn's disease.
Gibson DJ, Murphy DJ, Smyth AE, et al.


AIMS: To determine whether specific magnetic resonance enterography (MRE) findings can predict outcome following commencement of antitumor necrosis factor (aTNF) in small bowel Crohn's disease (CD).

PATIENTS AND METHODS: This was a single-centre retrospective study of patients with CD who commenced aTNF (infliximab or adalimumab) between 2007 and 2013. Patients who had an MRE within 6 months before commencing aTNF were included. The primary end-point was the need for CD-related surgery. The secondary end-points were time to surgery and time to treatment failure. The relationship between these end-points, clinical variables and specific MRE findings were studied.

RESULTS: Four hundred and eighteen patients commenced aTNF for CD during the study period. Seventy-five patients had an MRE within 6 months before commencing aTNF (30 infliximab; 45 adalimumab). The median time from MRE to commencing aTNF was 43 days (IQR 19.5-87 days). Eighteen of 75 (24%) had surgery during a median follow-up of 16.7 months (IQR 9.0-30.1 months). Patients with small bowel stenosis (SBS) on MRE were at a significantly higher risk of requiring surgery: 12/18 (66.7%) versus 6/57 (10.5%) (P<0.001). Time to surgery was significantly shorter in patients with SBS on MRE (P<0.001). In a multivariate analysis, SBS (P<0.0001, hazard ratio 26.45, 95% confidence interval 5.45-128.49) and presence of penetrating complications (P=0.003, hazard ratio 36.53, 95% confidence interval 3.40-393.19) were associated independently with time to surgery.

CONCLUSION: SBS and penetrating complications on MRE are associated independently with a need for early surgery and treatment failure in patients commencing aTNF.


BMJ. 2015 Jun 5;350:h2809.
Association between tumour necrosis factor-α inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study.
Nyboe Andersen N, Pasternak B, Friis-Møller N, et al.


OBJECTIVE: To investigate whether people with inflammatory bowel disease treated with tumour necrosis factor-α (TNF-α) inhibitors are at increased risk of serious infections.

DESIGN: Nationwide register based propensity score matched cohort study.

SETTING: Denmark, 2002-12.

PARTICIPANTS: The background cohort eligible for matching comprised 52 392 people with inflammatory bowel disease, aged 15 to 75 years, of whom 4300 were treated with TNF-α inhibitors.To limit confounding, a two stage matching method was applied; firstly matching on age, sex, disease duration, and inflammatory bowel disease subtype, and secondly matching on propensity scores (1:1 ratio); this yielded 1543 people treated with TNF-α inhibitors and 1543 untreated to be included in the analyses. MAIN OUTCOME MEASURES: The main outcome was any serious infection, defined as a diagnosis of infection associated with hospital admission. Cox regression was used to estimate hazard ratios for two risk periods (90 and 365 days after the start of TNF-α inhibitor treatment). Hazard ratios of site specific serious infections were obtained solely for the 365 days risk period.

RESULTS: Within the 90 days risk period, 51 cases of infection were observed in users of TNF-α inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1.75). In analyses of site specific infections, the hazard ratio was above 2 for several of the subgroups but only reached statistical significance for skin and soft tissue infections (2.51, 1.23 to 5.12).

CONCLUSIONS: This nationwide propensity score matched cohort study suggests an increased risk of serious infections associated with use of TNF-α inhibitors within the first 90 days of starting treatment and a subsequent decline in risk. This calls for increased clinical awareness of potential infectious complications among people with inflammatory bowel disease using these drugs, especially early in the course of treatment.


ArqGastroenterol. 2015 Jan-Mar;52(1):76-80.
Biosimilars in inflammatory bowel diseases: an important moment for Brazilian gastroenterologists.
Teixeira FV, Kotze PG, Damião AO, et al.


Biosimilars are not generic drugs. These are more complex medications than small molecules, with identical chemical structures of monoclonal antibodies that lost their patency over time. Besides identical to the original product at the end, the process of achieving its final forms differs from the one used in the reference products. These differences in the formulation process can alter final outcomes such as safety and efficacy of the drugs. Recently, a biosimilar of Infliximab was approved in some countries, even to the management of inflammatory bowel diseases. However, this decision was based on studies performed in rheumatologic conditions such as rheumatoid arthritis and ankylosing spondylitis. Extrapolation of the indications from rheumatologic conditions was done for Crohn's disease and ulcerative colitis based on these studies. In this article, the authors explain possible different mechanisms in the pathogenesis between rheumatologic conditions and inflammatory bowel diseases, that can lead to different actions of the medications in different diseases. The authors also alert the gastroenterological community for the problem of extrapolation of indications, and explain in full details the reasons for being care with the use of biosimilars in inflammatory bowel diseases without specific data from trials performed in this scenario.


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