To grow up with Crohn’s disease

2011 ◽  
Vol 152 (14) ◽  
pp. 546-554 ◽  
Author(s):  
Judit B. Kovács ◽  
Anikó Nagy ◽  
András Szabó ◽  
Margit Lőrincz
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Growth Failure ◽  
Granuloma Formation ◽  
Male Dominance ◽  
Childhood Onset ◽  
Biologic Treatment ◽  
Course Of Illness ◽  
The Mean

Objective: To assess the characteristics and course of childhood-onset Crohn’s disease among Hungarian patients. Methods: Records of 81 patients admitted between 1984 and 2006 and treated at least for one year until the 18th year of age were reviewed. Results: There was a 62% male dominance and a rate of 12.5% of familial cases. The diagnostic lag was 11.36 (1–96) months. The mean age was 13.6 years (4–17), the activity index was 37.88 (5–80) at diagnosis and the initial frequencies were as follows: ileal affection 87%, stricturing and penetrating forms 27%, perianal manifestation 26%, giant cells or granuloma formation 47%, malnutrition 23,5%, growth failure 11%. Steroid therapy and azathioprin treatment were given in 84% and 62% of the patients, respectively. Biologic treatment was not possible during the study period. 31% of the patients underwent surgery (abdominal surgery 20%, perianal surgery 11%). When patients reached the 18th year of age the mean activity index decreased to 6.63 (0–35), the rate of malnutrition to 9.9% and that of growth failure to 2.5%. All these changes were statistically significant. Conclusions: Characteristics of childhood-onset Crohn’s disease in Hungary are similar to those obtained in other European countries. The prolonged diagnostic lag, the high initial activity index, the granuloma formation and the stricturing/penetrating behavior may predict subsequent complications and need for surgery, and, therefore, justify intense initial therapy. The early introduction of immunomodulatory therapy affects favorably the course of illness. Orv. Hetil., 2011, 152, 546–554.

scholarly journals OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S026-S027
Author(s):  
S W Schreiber ◽  
M Ferrante ◽  
R Panaccione ◽  
J F Colombel ◽  
T Hisamatsu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Unmet Need ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind

Abstract Background Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies. Results A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment. References

B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn’s Disease and Its Relation with Disease Severity

2018 ◽  
Vol 36 (3) ◽  
pp. 194-201 ◽  
Author(s):  
Rafael Gil-Borras ◽  
Carlos García-Ballesteros ◽  
Carmen Benet-Campos ◽  
Ignacio Catalán-Serra ◽  
Francisca López-Chuliá ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Severity ◽  
Peripheral Blood ◽  
Activity Index ◽  
Innate Immune ◽  
B1a Cells ◽  
Endoscopic Score ◽  
The Mean ◽  
Severity Of The Disease

Background/Aims: B1a cells (CD19+CD5+) are considered elements of the innate immune system. The aim of this study was to evaluate the frequency of B1a cells in the peripheral blood of patients with Crohn’s disease (CD) and its relation with disease severity. Methods: In this prospective study, a total of 128 subjects (64 CD patients and 64 healthy controls) were studied. B1a cells in peripheral blood, CD Activity Index, and Simple Endoscopic Score of B1a cells were studied. Results: A significant decrease of B1a cells in peripheral blood was observed in patients with CD versus controls (p = 0.002), especially in perforating or penetrating patterns (p = 0.017). A lower frequency of B1a cells is related to increased endoscopic severity (Spearman’s Rho: –0.559, p = 0.004). The mean frequency of B1a cells in patients with pre- and post-study surgery was significantly lower than that in patients who did not undergo surgery (p = 0.050 and p = 0.026, respectively). Conclusions: The B1a cell count in peripheral blood is lower in CD patients. This decrease is directly related to the severity of the disease (penetrating or perforating, Simple Endoscopy Score and surgery complication). These results pointed to the fact that B1a cells play an important role in immune protection in CD.

scholarly journals Expression of Cyr61 is associated with Clinical Course in Patients with Crohn’s Disease

2020 ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Jin Ook Chung ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wound Repair ◽  
Clinical Course ◽  
Activity Index ◽  
Recurrence Rates ◽  
Clinical Recurrence ◽  
Important Regulator ◽  
The Mean

Abstract Backgrounds: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).Methods: Endoscopic samples were identified from 83 CD patients with and 372 controls without any pathologic findings by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. Results: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P<0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P=0.01). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend=0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95%CI 0.20~0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P=0.03). Conclusions: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. In the future, the possible therapeutic role of Cyr61 should be considered.

scholarly journals OP36 Risankizumab therapy induces improvements in endoscopic endpoints in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S033-S034
Author(s):  
P Bossuyt ◽  
M Ferrante ◽  
F Baert ◽  
S Danese ◽  
B G Feagan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Activity Index ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind ◽  
Clinical Endpoints ◽  
Endoscopic Remission

Abstract Background Endoscopic healing has become a critical treatment target in Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin 23, is being investigated as a treatment for moderate-to-severe CD. This analysis assessed different endoscopic endpoints in patients treated with RZB induction therapy in two double-blind, randomised, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had demonstrated prior inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE) or to biologic treatment (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous (IV) RZB 600 mg, RZB 1200 mg, or PBO at weeks 0, 4, and 8. This analysis evaluated the proportion of patients who achieved endoscopic remission ulcer-free endoscopy (ie, absence of ulcers), and composite endpoints of CDAI clinical response and endoscopic response, and enhanced clinical response and endoscopic response at week 12 (endpoints defined in Figure 1 footnotes). All endoscopies were centrally read by a blinded reviewer. Safety was assessed throughout the studies. Results In ADVANCE and MOTIVATE, 850 and 569 patients, respectively, were randomised and included in the intent-to-treat population for this analysis. At week 12 greater proportions of RZB- vs PBO-treated patients in both studies achieved endoscopic remission (P ≤ .001), ulcer-free endoscopy (P ≤ .01), CDAI clinical response and endoscopic response (P ≤ .001), and enhanced clinical response and endoscopic response (P ≤ .001; Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with IV RZB 600 mg or 1200 mg resulted in improved outcomes at week 12 compared with PBO as assessed by endoscopy and by composite endoscopic-clinical endpoints in patients with moderate-to-severe CD. References

scholarly journals Expression of Cyr61 is associated with Clinical Course in Patients with Crohn’s Disease

2020 ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Jin Ook Chung ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wound Repair ◽  
Clinical Course ◽  
Activity Index ◽  
Recurrence Rates ◽  
Clinical Recurrence ◽  
Important Regulator ◽  
The Mean

Abstract Backgrounds: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).Methods: Endoscopic samples were identified from 83 CD patients with and 372 controls without any pathologic findings by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. Results: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P<0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P=0.01). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend=0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95%CI 0.20~0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P=0.03). Conclusions: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. In the future, the possible therapeutic role of Cyr61 should be considered.

scholarly journals Expression of Cyr61 is associated with Clinical Course in Patients with Crohn’s Disease

2021 ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Jin Ook Chung ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wound Repair ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Activity Index ◽  
Mrna Levels ◽  
Recurrence Rates ◽  
Clinical Recurrence ◽  
The Mean

Abstract Backgrounds: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).Methods: Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients.Results: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P<0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P=0.01). Cyr61 mRNA levels in inflamed mucosa were 2-fold higher than those in non-inflamed lesion (P>0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P<0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend=0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95%CI 0.20~0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P=0.03).Conclusions: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.

scholarly journals Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia-yin Yao ◽  
Min Zhang ◽  
Wei Wang ◽  
Xiang Peng ◽  
Jun-zhang Zhao ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Trough Concentration ◽  
Activity Index ◽  
Therapeutic Drug ◽  
Antibody Concentration ◽  
Baseline Characteristic ◽  
Endoscopic Remission ◽  
The Mean

Abstract Background Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure–response relationship in CD treatment in the real-world setting. Methods We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn’s disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn’s disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. Results Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). Conclusions UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).

scholarly journals Expression of Cyr61 is associated with clinical course in patients with Crohn’s disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Dong Hyun Kim ◽  
Jin Ook Chung ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wound Repair ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Activity Index ◽  
Mrna Levels ◽  
Recurrence Rates ◽  
Clinical Recurrence ◽  
The Mean

Abstract Backgrounds Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD). Methods Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients. Results The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20–0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03). Conclusions Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.

Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

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