scholarly journals Lengthening adalimumab dosing interval in quiescent Crohn’s disease patients: protocol for the pragmatic randomised non-inferiority LADI study

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e035326
Author(s):  
L J T Smits ◽  
R W M Pauwels ◽  
W Kievit ◽  
D J de Jong ◽  
A C de Vries ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Cost Effectiveness ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Disease Activity ◽  
Cumulative Incidence ◽  
Control Group ◽  
Physician Global Assessment ◽  
Dosing Interval

IntroductionAdalimumab is effective for maintenance of remission in patients with Crohn’s disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW).Methods and analysisThe Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10 mg/L, faecal calprotectin (FC) <150 µg/g, Harvey-Bradshaw Index (HBI) <5). Patients will be randomised 2:1 into the intervention (adalimumab interval lengthening) or control group (adalimumab EOW). The intervention group will lengthen the adalimumab administration interval to every 3 weeks, and after 24 weeks to every 4 weeks. Clinical and biochemical disease activity will be monitored every 12 weeks by physician global assessment, HBI, CRP and FC. In case of disease flare, dosing will be increased. A flare is defined as two of three of the following criteria; FC>250 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness.Ethics and disseminationThe study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences.Trial registration numbersEudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417).

Clinical Correlates of Urolithiasis in Ankylosing Spondylitis

2011 ◽  
Vol 38 (9) ◽  
pp. 1953-1956 ◽  
Author(s):  
NAI LEE LUI ◽  
ADELE CARTY ◽  
NIGIL HAROON ◽  
HUA SHEN ◽  
RICHARD J. COOK ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Ankylosing Spondylitis ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Functional Disability ◽  
Spinal Mobility ◽  
Joint Involvement ◽  
Control Group ◽  
Significant Difference ◽  
History Of

Objective.To determine the association between urolithiasis and syndesmophyte formation and the effect of urolithiasis on ankylosing spondylitis (AS) disease activity.Methods.In a longitudinal cohort of 504 patients with AS, we conducted an analysis of all patients with AS who have a history of urolithiasis. All patients met the modified New York criteria for AS. Demographics, clinical characteristics, extraarticular features, and comorbidities are systematically recorded in the database. We compared disease activity, functional indices, medical therapy and radiographic damage between AS patients with (Uro+) and without urolithiasis (Uro–) using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).Results.Thirty-eight patients with AS (7.5%) had a history of urolithiasis in our cohort. Seventy-six patients with AS who did not have urolithiasis, matched for age, sex, and ethnicity, were selected as controls. Patients who were Uro+ were more likely to have more functional disability, based on the Bath AS Functional Index (BASFI; mean 5.3 vs 3.6 in control group, p = 0.003). Trends were noted in the Uro+ group toward higher Bath AS Disease Activity Index (BASDAI; mean 4.9 vs 4.0, p = 0.09), more peripheral joint involvement (p = 0.075), and higher frequency of biologic therapy (p = 0.09). No significant difference was detected in mSASSS or the Bath AS Metrology Index (BASMI). Significant association with diabetes mellitus (DM; p = 0.016) and Crohn’s disease (p = 0.006) was noted in the Uro+ group.Conclusion.Although there is no acceleration of syndesmophyte formation or spinal mobility restriction, more functional disability was detected in the urolithiasis group. The higher risk with concomitant DM or Crohn’s disease should alert clinicians to these comorbidities in Uro+ patients with AS.

Mo1041 MRE Findings at Crohn's Disease Diagnosis: Disease Activity, Bowel Damage and Predictive Value for Long-Term Outcomes

2012 ◽  
Vol 142 (5) ◽  
pp. S-579-S-580 ◽  
Author(s):  
Gionata Fiorino ◽  
Laurent Biroulet ◽  
Patrizia Naccarato ◽  
Chiara De Cassan ◽  
Cristiana Bonifacio ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Predictive Value ◽  
Disease Diagnosis ◽  
Long Term Outcomes

scholarly journals P603 Persistence of vedolizumab maintenance therapy: Findings from a Belgian registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S503-S504
Author(s):  
E Louis ◽  
V Muls ◽  
P Bossuyt ◽  
A Colard ◽  
A Nakad ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Disease Activity ◽  
Real World ◽  
Clinical Remission ◽  
Disease Activity Score ◽  
Activity Score

Abstract Background Clinical trials and observational studies have demonstrated the clinical efficacy of vedolizumab (VDZ) as maintenance therapy for Crohn’s disease (CD) and ulcerative colitis (UC). This report presents long-term data on persistence of VDZ maintenance therapy in real-world clinical practice in Belgium. Methods The Belgian VDZ Registry (ENCePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres across Belgium. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months after enrolment with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as the Harvey–Bradshaw Index (HBI) &lt;5 or partial Mayo Score (pMS) &lt;2. Missing value imputation (last observation carried forward) was used to partially account for missing disease activity scores. If a 6-monthly disease activity score was missing, the disease activity score from the previous 6-monthly assessment was used. Results The mean duration of VDZ therapy, including use prior to enrolment, was 31 months, with 68% of CD patients and 75% of UC patients using VDZ therapy for 48 months. Clinical remission rate after 42 months of VDZ therapy was higher in UC (84%) than CD (67%), and higher for patients without prior anti-TNF therapy (87%) than those with prior anti-TNF therapy (70%). Fifty-seven (29.4%) patients discontinued VDZ during follow-up, due to loss of response (n = 40), adverse event (n = 7), clinical remission (n = 4), pregnancy planning (n = 3), and patient choice (n = 3). Conclusion These real-world long-term Belgian data demonstrate a high persistence of VDZ maintenance therapy among both CD and UC patients, with highest clinical remission rates seen in patients with UC and those with no prior anti-TNF therapy.

scholarly journals Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Cem Çekiç ◽  
Adnan Kırcı ◽  
Sezgin Vatansever ◽  
Fatih Aslan ◽  
Huriye Erbak Yılmaz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Normal Population ◽  
Disease Activity Index ◽  
Serum Levels ◽  
Control Group ◽  
Serum Samples ◽  
Reactive Protein

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn’s disease (CD).Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn’s disease activity index (CDAI).Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL)p=0.03. SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL)p<0.001. A significant positive correlation was found between SDC-1 and CRP (r=0.687,p<0.001) and between SDC-1 and CDAI (r=0.747,p<0.001).Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.

scholarly journals P352 A propensity score-matched, real-world comparison of ustekinumab vs vedolizumab as a second-line treatment for Crohn’s disease. The Cross Pennine study II

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S372-S373
Author(s):  
M V Lenti ◽  
V Dolby ◽  
T Clark ◽  
V Hall ◽  
S Tattersall ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Propensity Score ◽  
Adverse Events ◽  
Clinical Response ◽  
Real World ◽  
Propensity Score Analysis ◽  
Physician Global Assessment ◽  
Real World Data ◽  
The Difference

Abstract Background The best choice of biological agents after failure to an anti-tumour necrosis factor (TNF)α agent in patients with Crohn’s disease (CD) is yet to be defined. Real-world data dealing with this issue are still emerging. Methods This is a multicentre retrospective study including eight UK hospitals (August 2014-April 2020). We retrospectively collected data of patients treated with ustekinumab. Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Predictors of clinical response were examined, and a propensity score-matched analysis with a cohort of patients treated with vedolizumab was performed. Results Overall, 282 patients (mean age 40±15, F:M ratio 1.7:1) treated with ustekinumab were included. Clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and by 162/259 patients (62.5%) at 52 weeks. The most common reason for discontinuation was either primary failure or loss of response, followed by the occurrence of adverse events and by the need for surgery. The rate of non-adherence was rather low (1.4%). Current smoking (OR 2.48, 95% CI 1.13-5.44; p=0.02), baseline PGA (OR 2.4, 95% CI 1.55-3.69, p&lt;0.001), and use of steroids (OR 2.42, 95% CI 1.26-4.65, p=0.008) were associated with 52-week treatment failure. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person-year). After exclusion of patients without anti-TNFα exposure prior to starting ustekinumab or vedolizumab and exclusion of patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) from the ustekinumab cohort and 118/135 patients (87.4%) from the vedolizumab cohort. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25-50%; p&lt;0.001) more likely to achieve a clinical remission, while at 52 weeks, the difference of 9% (95% CI -15-33%; p=0.462) was not significant. Conclusion Ustekinumab was effective and well tolerated in this real-world cohort. While ustekinumab proved more effective at 14-week follow-up, we found no statistically significant differences in outcomes at 52 weeks.

The Impact of Cholecystectomy on Long-Term Disease Outcomes and Quality of Life in Patients with Crohn’s Disease

2020 ◽  
Author(s):  
Filippos Koutroumpakis ◽  
Maham Lodhi ◽  
Maaz Ahsan ◽  
Claudia Ramos Rivers ◽  
Marc Schwartz ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Hospital Admissions ◽  
Tertiary Center ◽  
Prospective Longitudinal ◽  
The Impact

Abstract Background Cholecystectomy (CCY) is one of the most frequently performed abdominal surgeries. However, the impact of CCY in clinical settings with altered gastrointestinal physiology and anatomy, such as Crohn’s disease (CD), has not been fully characterized. We sought to investigate clinical outcomes, disease severity, and quality of life of CD patients after CCY. Methods We utilized a prospective, longitudinal registry of consented CD patients followed at a tertiary center. Crohn’s disease patients that had or had not undergone CCY formed the 2 study groups. The absence or presence of gallbladder was confirmed with abdominal CT scans obtained during routine care. Multiyear clinical, biochemical, and histologic data were collected and analyzed. Results Among 834 CD patients, 151 (18%) had undergone CCY. History of CCY was associated with higher disease activity (median Harvey-Bradshaw index; P &lt; 0.001), more years with anemia (P = 0.048), lower albumin (P = 0.001), worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P &lt; 0.001), chronic abdominal pain (P &lt; 0.001), higher risk for incident colonic dysplasia (P = 0.011), higher rates of annual hospital admissions (P = 0.004), and opioid use (P &lt; 0.001). In multivariate analysis, CCY remained associated with higher disease activity (P &lt; 0.001), lower albumin (P = 0.008), lower quality of life (P &lt; 0.001), and more hospital admissions (P = 0.008), whereas CD patients with diseased ileum had higher risk for colonic dysplasia (P = 0.031). Conclusions CCY in CD patients was associated with multiple markers of disease activity and worse quality of life during multiyear follow up. This data suggests that CCY in CD patients may adversely impact the long-term clinical course.

scholarly journals P499 Objectively assessed disease activity during ustekinumab treatment in a nationwide real-life Crohn’s disease cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S434-S435
Author(s):  
C G af Björkesten ◽  
T Ilus ◽  
T Hallinen ◽  
E Soini ◽  
A Eberl ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Real Life ◽  
Patient Characteristics ◽  
Activity Data ◽  
Faecal Calprotectin ◽  
One Year

Abstract Background Real-life long-term evidence on ustekinumab treatment response in patients with Crohn’s disease (CD) is scarce. We performed a retrospective non-interventional nationwide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920). Methods FINUSTE2 involved 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous first dose of ustekinumab during 2017 or 2018. Disease activity data, such as C-reactive protein (CRP), faecal calprotectin (fCal), and the Simple Endoscopic Score for Crohn’s disease (SES-CD) were collected at baseline, 16 weeks, and one year from treatment initiation. A local gastroenterologist at each centre collected the data from health records in an electronic standardised health questionnaire. Results One hundred and fofty-five patients (48% female) with a mean age of 44 and disease duration of 14 years initiated ustekinumab treatment for CD. Table 1 summarises patient characteristics at baseline. After induction consisting of one intravenous dose and one to two subcutaneous doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with subcutaneous ustekinumab. Of 93 patients with a follow-up of at least one year, 77 were still on ustekinumab. During ustekinumab treatment, SES-CD (10 at baseline, 3 at 1 year, medians, p = 0.033) and CRP (7 mg/l at baseline, 5 mg/l at 1 year, medians, p &lt; 0.001) and fCal (776 μg/g at baseline, 305 μg/g at 1 year, medians, p &lt; 0.001) decreased significantly in those patients with data available. Figure 1 describes changes in fCal levels over time. Conclusion In this nationwide real-life long-term follow-up study, covering all major centres in Finland, ustekinumab treatment of patients with highly refractory and long-standing CD effectively reduced inflammatory activity, assessed by endoscopy, CRP, and fCal.

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