BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.

• MeSH
• adalimumab aplikace a dávkování   škodlivé účinky   MeSH
• antiflogistika aplikace a dávkování   škodlivé účinky   MeSH
• azathioprin aplikace a dávkování   škodlivé účinky   MeSH
• časové faktory MeSH
• Crohnova nemoc diagnóza   farmakoterapie   imunologie   patologie   MeSH
• dospělí MeSH
• hospitalizace statistika a číselné údaje   MeSH
• indukce remise metody   MeSH
• kombinovaná farmakoterapie škodlivé účinky   metody   MeSH
• lidé MeSH
• mladý dospělý MeSH
• následné studie MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH

Background: The etiology of celiac disease (CD) is related to undigested fragments of gluten and gliadin which damage the small bowel. Mucosal enzyme deficiency is an important factor in CD pathology. A clinical trial has shown that the effects of a gluten challenge to patients with CD could be ameliorated by the use of an enzyme supplement. Objective: Enzyme therapy using enterically coated tablets containing caricain (Gluteguard) was investigated as a means of protecting patients with CD against wheat gluten. Methods: A randomized placebo-controlled trial was carried out on 20 CD patients in clinical remission. The patients were divided into a group of 14 given Gluteguard and a group of 6 given a placebo daily. Both groups were given a challenge of 1g of gluten daily. Symptoms were graded and recorded over a period of 42 days. Duodenal tissue was taken at the beginning and end of this period, together with blood for assay of tissue transglutaminase (tTG-IgA) antibodies. Results: The results showed that oral enzyme therapy based on caricain, was effective in ameliorating the symptoms of CD giving a statistically significant difference between treatment and placebo (P<0.01) after 14 days challenge. General well-being was also improved from 6.1 to 8.4 (P< 0.01) by the enzyme therapy. Four of the six placebo group patients (67%) and one of the 14 treatment patients (7%) to withdraw from gluten challenge after 14 days due to development of serious symptoms. The difference between the groups was significant (p < 0.001). For the per protocol patients on Gluteguard therapy, there were no significant changes in markers of histological damage or biopsy results after 42 days of gluten challenge. Conclusions: This study demonstrated that oral anti-gluten enzyme therapy using Gluteguard was able to significantly protect celiac patients from adverse symptoms being induced by gluten challenge. Furthermore, mucosal damage was not exacerbated in patients taking Gluteguard along with their daily gluten challenge, suggesting that the enzyme tablets may also help with the recovery of epithelium in the longer term. Availability of a preventative enzyme treatment like Gluteguard will likely add to the quality of life and well-being of coeliac patients, especially those who have difficulty in strictly adhering to a gluten-free diet.

• Klíčová slova
• caricain, Gluteguard,
• MeSH
• celiakie * farmakoterapie   patologie   patofyziologie   MeSH
• cysteinové endopeptidasy terapeutické užití   MeSH
• dospělí MeSH
• duodenum patologie   MeSH
• enzymová substituční terapie * MeSH
• gluteny aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• protilátky krev   MeSH
• rostlinné proteiny terapeutické užití   MeSH
• senioři MeSH
• spokojenost pacientů MeSH
• statistika jako téma MeSH
• transglutaminasy metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH

BACKGROUND AND AIMS: Toll-like receptors [TLRs] are potential drug targets for immunomodulation. We determined the safety and efficacy of the TLR-9 agonist DNA-based immunomodulatory sequence 0150 [DIMS0150] in ulcerative colitis [UC] patients refractory to standard therapy. METHODS: In this randomized, double-blind, placebo-controlled trial, 131 patients with moderate-to-severe active UC were randomized to receive two single doses of the oligonucleotide DIMS0150 [30 mg] or placebo administered topically during lower GI endoscopy at baseline and Week 4. The primary endpoint was clinical remission, defined as Clinical Activity Index [CAI] ≤4, at Week 12. Secondary endpoints included mucosal healing and symptomatic remission of key patient-reported outcomes [absence of blood in stool and weekly stool frequency <35]. RESULTS: There was no statistical significant difference between the groups in the induction of clinical remission at Week 12, with 44.4% in the DIMS0150 group vs. 46.5% in the placebo group. However, the proportion of patients who achieved symptomatic remission was 32.1% in the DIMS0150 group vs. 14.0% in the placebo group at Week 4 [p = 0.020], and 44.4% vs. 27.9% at Week 8 [p = 0.061]. More patients on DIMS0150 compared with those on placebo had mucosal healing [34.6% vs. 18.6%; p = 0.09] and histological improvement regarding the Geboes score [30.9% vs. 9.3%; p = 0.0073] at Week 4. Significantly more patients on DIMS0150 were in clinical remission with mucosal healing at Week 4: 21% vs. 4.7% in the placebo group [p = 0.02]. DIMS0150 was well tolerated, and no safety signals compared with placebo were evident. CONCLUSIONS: Therapy with the topically applied TLR-9 agonist DIMS0150 is a promising and well-tolerated novel therapeutic option for treatment-refractory, chronic active UC patients, warranting further clinical trials.

• MeSH
• aplikace lokální MeSH
• DNA aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• endoskopie metody   MeSH
• imunologické faktory aplikace a dávkování   terapeutické užití   MeSH
• kolon účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• toll-like receptor 9 agonisté   MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH