Diet as Adjuvant Therapeutics in the Era of Biologics in Pediatric-onset Crohn's Disease.
Phase: NA
Conditions: Crohn's Disease
Sponsor: Hospital Italiano de Buenos Aires

Diet as adjuvant therapeutics in the era of biologics in pediatric-onset
Crohn's disease
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Table of contents:
Introduction
page 3
Objectives
page 6
Material and methods
page 7
Statistical analysis
page 12
Ethical considerations
page 14
Bibliography
page 16
Annex 1
page 18
Annex 2
page 20
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Introduction:
Crohn's disease (CD) is part of the inflammatory bowel diseases( IBD) with
increasing incidence worldwide. It is postulated to be multifactorial in cause, but in
pediatrics, genetics and environmental exposure seem to be the main triggers.
Pediatric-onset IBD is often more extensive and is associated with a more
aggressive course requiring early immunomodulation. The cumulative risk of
progression to complicated CD is similar to that of adults, but by virtue of early
disease onset, children are more likely to require surgery upon reaching adulthood
for disease management.
The use of new medications such as biologics have changed the natural history of
the disease, inducing a rapid response and remission, but involve high costs and
additional
toxicity,
presenting
considerable
adverse effects such as severe
infections, malignant and autoimmune sequelae. (Ruemmele et al. 2014). Moreover
an increasing number of patients face loss of response to one or more of these
agents despite combination therapy with immune modulators, therapeutic drug
monitoring
and
dose
adjustments.Even
though
combination
with
immunomodulators is considered an effective option to increase the long-term
therapeutic effect of biologics such as infliximab, there are serious complications
associated with this approach, such as an increased risk of hepatosplenic T-cell
lymphoma (Mackey et al., 2009). Having alternative therapeutics that can potentiate
a remission in immunosuppressed patients are an unmet need, especially in the
pediatric population for whom new biologics will not be available in the near future.
(Sigall Boneh et al. 2017; Nguyen et al. 2015)
Thinking about the pathophysiology of the disease, anti-TNF (the most used
biologics currently used in the pediatric population) control only one inflammatory
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pathway leaving others active and thus there may be disease progression. In
addition,
with
this
treatment
we
are
not
treating
the
factor
that induces
inflammation: CD is probably caused by a sequence of events, in which the
Western diet (environmental factor) drives changes in the intestine and intestinal
lining such as decreased microbial diversity and dysbiosis, altered barrier function,
formation of bacterial biofilms and bacterial translocation and activation of the
immune system leading to a vicious cycle of inflammation. (Levine, Sigall Boneh,
and Wine 2018). So if diet is one of the triggers of inflammation and disease
progression, dietary treatment should improve outcomes over time, reducing the
need for immunosuppressive treatments and their sequelae in addition to nutritional
improvements(Triantafillidis et al. 2009).
Exclusive enteral nutrition (ENN) has been endorsed since 2014 by international
guidelines for induction of remission in patients with mild to moderate luminal CD
because of its excellent safety profile, with success rates between 60-80% that
further
favor
the
theory
of
diet
as
the
axis
of the pathogenesis of the
disease.(Ashton, Gavin, and Beattie 2019).(Levine, Sigall Boneh, and Wine 2018),
but its tolerance is difficult.(Levine et al. 2019). This is why multicenter studies have
been advanced to evaluate the efficacy of partial enteral nutrition (PEN) plus a
nutritionally adequate diet (among them Crohn`s Diet exclusion disease, CDED)
with very good results in terms of tolerance and inclusion of remission around 70%
as well as in patients with secondary loss of response to anti TNF( anti-tumor
necrosis factor) treatment (Levine et al. 2019) (Sigall-Boneh et al. 2014) (Limketkai
et al. 2019).
Patients often view diet as a vital component of their IBD management. Dietary
modification is a common practice in patients for a variety of reasons, including
relapse prevention.Studies have found that more than 50% of patients believe that
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food plays a role in the onset of symptoms, and nearly 70% of patients self-impose
dietary restrictions.(Gu and Feagins 2020).
There is a growing need to replace invasive procedures with noninvasive markers
to monitor the course of the disease. Several pediatric studies have shown that low
fecal calprotectin levels [below 150 to 250 μg/g] correspond well with endoscopic
remission and higher levels usually reflect ongoing intestinal inflammation. A recent
study evaluated that those patients with a calprotectin result <250 μg/g and the
absence of symptoms at 12 weeks ( end of biologic induction) had a higher
likelihood of sustained remission during the first year (van Rheenen et al. 2020).
The GROWTH CD study, a multicenter study of 222 untreated pediatric CD patients
followed for 52 weeks, demonstrated that patients with Pediatric Crohn's Disease
Activity Index [PCDAI] >5 [p = 0.012], C-reactive protein [CRP] >20 mg/L [p =
0.019] and fecal calprotectin > 400 µg/g [p = 0.001] at week 12 after starting
induction therapy had an increased risk of relapse and early surgery.
Another recent study in children with quiescent CD receiving maintenance therapy
with infliximab, a calprotectin level >250 μg/g before each infusion was a reliable
predictor of clinical relapse in the following 3 months. In contrast, a decrease in
fecal calprotectin to <250 μg/g [which is the upper limit of the target range] could be
considered a reliable indicator of treatment success. The closer the calprotectin
value is to 50 μg/g, the higher the probability of complete endoscopic cure(van
Rheenen et al. 2020).
Works such as that of (Strisciuglio et al. 2020) have found a significant association
between adherence to specific diets and a low fecal calprotectin level (p = 0.027).
Currently in our service, according to international guidelines, patients who present
severe inflammatory disease with severe activity or poor prognostic factors (deep
colonic ulcers, marked growth retardation) or who present severe persistent
disease after induction are started on biologic therapy. Once the induction with the
selected biologic medication is completed, they are clinically monitored with
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inflammatory markers and calprotectin in fecal matter, and according to the results,
the need and time to perform a new endoscopy is evaluated. If calprotectin is
elevated, generally higher than 300 ug/g, a new endoscopy is indicated.(Koninckx
et al. 2021) However, when the only elevated value in isolation is calprotectin and
clinically and endoscopically the patient presents favorable evolution, once the
biologic is optimized there are not many therapeutic tools to offer and the evolution
is usually observed, knowing that they will probably present relapses in the future. It
is in this group where we believe that the diet can collaborate to their total
remission and mucosal healing.
Due to the success of diet in achieving remission in mild-moderate forms of the
disease, and an increasing number of patients with loss of response to available
drugs despite increasing dosage and pathophysiology of the disease, the aim of
the present study is to evaluate whether there is response with the addition of diet
therapy in patients with moderate/severe CD who receive biologic therapy
(infliximab or adalimumab) and present active disease. (Sigall Boneh et al.
2017)(Triantafillidis et al. 2009; Hartman et al. 2008).
General objective:
To evaluate the response to the addition of dietary therapy in
CD patients with severe disease at debut or with poor
prognostic factors on treatment with biologics, who after
induction present at some point in their evolution calprotectin
values greater than limit value ( greater than 250 ug/g).
Specific objectives:
In CD patients on biologic treatment who after induction
present at some point in their evolution calprotectin values
greater than the limit value (>250 ug/g):
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Compare the proportion of patients with normalization in
calprotectin values (<250 ug/g) at 12 weeks with or without the
addition of dietary therapy.
Evaluate calprotectin level at 0 and 12 weeks in patients with
or without the addition of dietary therapy.
Assess tolerance to the diet in the treatment period: defined as
adherence/ability to continue the diet and not drop out during
at least the 12 weeks of the study.
To assess the number of relapses and treatment changes
(need for intensification of biological treatment, need for
steroids, immunosuppressants or surgery) during the first year
with and without the addition of diet therapy. To compare the
growth of patients by anthropometry with and without the
addition of diet therapy.
Material and Methods:
Study design:
Multicenter randomized controlled intervention study.
Setting:
Hospital Italiano de Buenos Aires is a reference university center in
Argentina, with an annual average of 10/15 patients diagnosed with pediatric
IBD per year . We currently have about 30 patients with CD treated with
anti-TNF therapy. Patients undergo periodic follow-up in the Pediatric
Gastroenterology Service, then transition to the Adult Service, to which they
are referred once the process is completed.
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Period
The study is scheduled to start in May 2021. Patients will be invited to
participate in the protocol for 12 weeks with pre-set consultations at weeks
0, 6 and 12. They will then continue their usual consultations with the
service and will be evaluated one year after the start of the protocol by EHR.
The total duration of the study is estimated to be 2 years.
Population
Patients under 18 years of age
With a diagnosis of CD
Who completed remission induction with biologic therapy
Who are on maintenance biologic therapy
and present calprotectin values greater than the laboratory established limits
(greater than 250 ug/g).
Exclusion criteria
Children who are unable to receive the diet by enteral route.
Comorbidities affecting nutritional status and/or bone metabolism, growth or
pubertal development.
Children already on special diets.
Proposed intervention:
All patients who meet the inclusion criteria and do not present exclusion
criteria will be offered to enter the protocol and after signing informed
consent, they will be informed about the possible interventions. They will
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then be randomized into a DIET group and a NO DIET group.
Patients in the NO DIET group will continue with their usual treatment with
biologics according to the usual practices and criteria of the treating
physician.
Patients in the DIET group will receive CDED (Crohn's Diet Exclusion
Disease) with NEP (partial enteral nutrition) 50% of the calculated calories,
according to the recommended diet for the first 6 weeks and CDED with
PEN (partial enteral nutrition) 25% for the following 6 weeks, they will also
continue with their usual treatment with biologics according to the usual
practices and criteria of the treating physician.
Patients will receive as NEP a polymeric formula made exclusively for
patients
with
inflammatory
diseases
at
1
kcal/ml
(Modulen,
Nestlé,
Switzerland). Patients will be able to contact the nutritionists by e-mail and
receive a collection of recommended recipes compatible with the CDED that
could be used to improve the palatability and variety of meals (Annex 1).
All patients in the DIET group will receive the same diet for 12 weeks.
Compliance will be assessed directly by questions from physicians and
nutritionists ( annex 1 ). Patients who cannot consume the full amount of the
recommended formula or alternative formulas could reduce the dose, as
long as they meet the nutritional requirements according to sex and age.
In all patients (DIET and NO DIET group) calprotectin levels will be
measured at 12 weeks according to usual practice and will be monitored at 6
and 12 weeks according to usual practice.
Outcome Variable:
Proportion of patients with calprotectin normalization at 12 weeks 1:
calprotectin normalization: less than 250ug/g , 0: calprotectin greater than
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250 ug/g.
Calprotectin values at 0 and 12 weeks. Numerical variable Continuous
Tolerance to the diet for 12 weeks 1: yes 0 : no. To be evaluated by
symptoms according to short PCDAI (annex 2).
Diet adherence: a 5-day feeding report will be requested prior to the
consultation at weeks 6 and 12. The report will be evaluated by a nutritionist
to verify food compliance, caloric/protein intake according to particular
needs.
Number of relapses at 12 weeks and one year after the intervention:
Numerical variable. Relapse is considered when the patient presents
worsening
of
intestinal/extraintestinal
symptomatology,
elevated
inflammatory parameters, endoscopy/pathological anatomy or imaging with
active disease.
Need for changes in the basic treatment at 12 weeks and one year after the
intervention 1: yes 0: no .
Growth assessment at 0, 12 weeks and 1 year after the intervention: weight,
height and score according to the Guidelines (Guide for physical growth
assessment, SAP 2013).
Our center does not have drug or antibody dosing for biological drug dosing.
Explanatory variables
Demographic characteristics
Date of diagnosis: according to EHR, the date of diagnosis will be the first
pathological endoscopy.
Age in years at the time of evaluation. Continuous variable.
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Sex: according to phenotypic sex. Dichotomous variable: 1: female 0: male.
Related to pathology
Location of the disease Categorical variable according to Montreal Classification:
1: ileal, 2: colonic, 3: ileocolonic or 4: combined with upper gastrointestinal
involvement.
Duration of the disease: number of months between diagnosis and admission to
the protocol. Numerical variable.
IBD treatment: at the time of protocol entry and at 12 weeks and 1 year.
Non-exclusive categorical variable: 1: 5 ASA, 2: corticosteroids, 3 biologics
(Infliximab, Adalimumab), 4 Nutrition, 5 surgery.
Disease activity: continuous variable according to pediatric Crohn's disease activity
index(short PCDAI(Turner et al. 2012), appendix 2) at protocol entry and at weeks
6 and 12 and at 1 year. 1: remission less than 10, 2: mild disease 10-25 3:
moderate 25-40 4: severe more than 40
Results of inflammatory markers at weeks 0, 12 and one year of protocol
(calprotectin, albumin, CRP, ESR and hematocrit). Continuous variable
Nutritional status: anthropometry and z score according to national guidelines
(Guide for the evaluation of physical growth, SAP 2013).
Data collection
Hospital Italiano has an Electronic Health Record (EHR) system, where clinical,
laboratory and imaging data are recorded. The data will be obtained from the visits
stipulated according to the protocol (0, 6 and 12 weeks) and will be entered in a
card (Appendix 1) that will be used as a template for the EHR evolution.
Patients will be evaluated at each visit by a gastroenterologist and a nutritionist.
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A database will be created in RedCap, coordinated by the researchers of the
Hospital Italiano, where the data of the patients included in the study will be
anonymized and coded (see ethical considerations section).
Sample size calculation
The sample size calculation is performed considering a calprotectin normalization
ratio in the diet group of 50% versus 10% in the control group (Sigall Boneh et al.
2017; Nguyen et al. 2015) for an alpha of 0.5 and a power of 80% a total of 40
patients are required( 20 per group).Considering a loss of 20% 24 patients per
group will be included. The sample calculation was performed using STATA 13
software for MAC.
Inclusion, evaluation and follow-up
Sampling will be consecutive. All patients who meet the inclusion and not exclusion
criteria will be invited to participate in the study and, after signing the informed
consent form, they will be randomly assigned to one of the two treatment arms.
This assignment will be made by generating a randomization table by blocks
associating the treatment assigned to each patient number included. This
assignment will be kept in sealed envelopes for each patient until the time of
patient inclusion.
Statistical analysis:
The analysis will be performed per protocol and by intention-to-treat. The unit of
analysis will be each patient within one of the two treatment branches.
In the descriptive analysis, quantitative variables are expressed as mean and
standard deviation or median and interquartile range according to the observed
distribution.
Categorical
variables
are expressed in proportion with relative
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frequency and absolute frequency.
The association between the outcome variables and the assigned treatment branch
will be evaluated with Chi-square test for dichotomous results and with t test or
Mann Whitney test for quantitative results. ORs with their 95% CI will be reported.
The confounding effect of the variables will be tested with logistic
regression or linear regression model as appropriate. A probability of less than 5%
will be considered statistically significant. The analysis will be performed with the
statistical software package STATA13 for MAC.
Adverse Events
Adverse events will be collected during each control and each time the patient
contacts the investigator. They will be classified according to their severity
according to the investigator's experience they will be classified as: Mild, Moderate
and Severe:
1. Mild are those that are transitory, do not require special treatment and do not
interfere with the patient's daily activities.
Moderate are those that cause a low level of inconvenience or concern to the
patient and may interfere with daily activities, but which respond to simple
therapeutic measures.
3. Severe are those that disrupt the patient's daily activity and require systemic
treatment with drugs or other treatment. Severe adverse events are all those that
lead to death, hospitalization or threat to life.
Clinical Management and Study Withdrawal
The patient may withdraw from the study at any time by informing the investigators.
If the team of treating physicians or the investigators consider, according to medical
criteria, that the patient presents any additional risk by participating in the
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study, the patient will be withdrawn and the reasons for this decision will be
explained.
In addition, patients will be withdrawn from the study if during the treatment they
present a nutritional deterioration that requires another type of intervention or if
during the protocol the enteral route is contraindicated for any reason.
Ethical considerations
The right not to participate in the study will be respected at all times, without this
implying
in
any
case
any
type
of
discrimination,
differential treatment or
mistreatment.
The proposed intervention only contemplates the addition of a specific diet to the
usual treatment. No invasive procedures or changes in pharmacological treatment
beyond the usual practice will be performed, so no complications related to the
protocol are expected.
The present study will be carried out respecting the considerations related to the
care of clinical research participants included in the Declaration of Helsinki and in
accordance with the Guidelines for Research in Human Health (Resolution
1480/11) of the National Ministry of Health. All the information will be obtained from
the EHR and will be used by the researchers with the strictest confidentiality, taking
into account the details of Law 25.326 on data protection. For this purpose, each
patient will be registered with a consecutive number in a database to which only the
principal investigator and the sub-investigators will have access.
To keep the information secure, the principal investigator and the sub-investigators
of the Hospital Italiano will have a codified list of the patients included in their
center, under security norms and only with access by them. This list will be used to
identify patients and complete the RedCap database. The same methodology will
be applied by the other participating centers.
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In the event of any doubts arising at the time of data verification or analysis, the
coordinating center will ask each participating center to review the data, using the
patient code entered in the database. With this code, the investigators of the
participating centers will be able to review what was requested by the coordinating
center without jeopardizing the identity of the research subjects.
The legal guardians of the patients will sign an informed consent form to participate
in the study and in those children over 14 years of age, their consent will also be
requested.
The protocol has been developed with advice from the Research Department.
Funding
The administrative expenses of the study will be financed by the pediatric
gastroenterology service.
The milk formula will be requested to the patient's coverage as part of his treatment
for his underlying pathology, which is routinely requested to the coverage in our
service, since according to the recommendations of the ESPEN guidelines,
polymeric enteral nutrition of moderate fat content can be used as primary
nutritional therapy and support in active IBD (recommendation 18) (Bischoff et al.
2020) and in published research such as that of Hartman (Hartman et al. 2008)
where Modulen IBD was used in addition to conventional treatment, showed an
improvement in the remission of the disease and in the body mass index of the
patients.
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Bibliography:
Ashton, James J., Joan Gavin, and R. Mark Beattie. 2019. “Exclusive Enteral
Nutrition in Crohn’s Disease: Evidence and Practicalities.” Clinical Nutrition 38
(1): 80–89.
Bischoff, Stephan C., Johanna Escher, Xavier Hébuterne, Stanisław Kłęk, Zeljko
Krznaric, Stéphane Schneider, Raanan Shamir, et al. 2020. “ESPEN Practical
Guideline: Clinical Nutrition in Inflammatory Bowel Disease.” Clinical Nutrition
39 (3): 632–53.
Gu, Phillip, and Linda A. Feagins. 2020. “Dining With Inflammatory Bowel Disease:
A Review of the Literature on Diet in the Pathogenesis and Management of
IBD.” Inflammatory Bowel Diseases 26 (2): 181–91.
Hartman, Corina, Drora Berkowitz, Batia Weiss, Ron Shaoul, Arie Levine, Orly
Eshach Adiv, Riki Shapira, et al. 2008. “Nutritional Supplementation with
Polymeric Diet Enriched with Transforming Growth Factor-Beta 2 for Children
with Crohn’s Disease.” The Israel Medical Association Journal: IMAJ 10 (7):
503–7.
Koninckx, Carmen Ribes, Ester Donat, Marc A. Benninga, Ilse J. Broekaert,
Frederic Gottrand, Kaija-Leena Kolho, Paolo Lionetti, et al. 2021. “The Use of
Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the
European
Society
for
Paediatric
Gastroenterology
and
Nutrition
Gastroenterology Committee.” Journal of Pediatric Gastroenterology and
Nutrition 72 (4): 617–40.
Levine, Arie, Rotem Sigall Boneh, and Eytan Wine. 2018. “Evolving Role of Diet in
the Pathogenesis and Treatment of Inflammatory Bowel Diseases.” Gut 67 (9):
1726–38.
Levine, Arie, Eytan Wine, Amit Assa, Rotem Sigall Boneh, Ron Shaoul, Michal
Kori, Shlomi Cohen, et al. 2019. “Crohn’s Disease Exclusion Diet Plus Partial
Enteral Nutrition Induces Sustained Remission in a Randomized Controlled
Trial.” Gastroenterology 157 (2): 440–50.e8.
VERSIÓN 2-17 de abril de 2021
18
Limketkai, Berkeley N., Zipporah Iheozor-Ejiofor, Teuta Gjuladin-Hellon, Alyssa
Parian, Laura E. Matarese, Kelly Bracewell, John K. MacDonald, Morris
Gordon, and Gerard E. Mullin. 2019. “Dietary Interventions for Induction and
Maintenance
of
Remission
in
Inflammatory
Bowel
Disease.”
Cochrane
Database of Systematic Reviews 2 (February): CD012839.
Document approved by  a human subjects protection review board 05/13/2021
16

Nguyen, Douglas L., Lena B. Palmer, Emily T. Nguyen, Stephen A. McClave,
Robert G. Martindale, and Matthew L. Bechtold. 2015. “Specialized Enteral
Nutrition Therapy in Crohn’s Disease Patients on Maintenance Infliximab
Therapy: A Meta-Analysis.” Therapeutic Advances in Gastroenterology 8 (4):
168–75.
Rheenen, Patrick F. van, Marina Aloi, Amit Assa, Jiri Bronsky, Johanna C. Escher,
Ulrika L. Fagerberg, Marco Gasparetto, et al. 2020. “The Medical Management
of Paediatric Crohn’s Disease: An ECCO-ESPGHAN Guideline Update.”
Journal of Crohn’s & Colitis, October. https://doi.org/10.1093/ecco-jcc/jjaa161.
Ruemmele, F. M., G. Veres, K. L. Kolho, A. Griffiths, A. Levine, J. C. Escher, J. Amil
Dias, et al. 2014. “Consensus Guidelines of ECCO/ESPGHAN on the Medical
Management of Pediatric Crohn’s Disease.” Journal of Crohn’s & Colitis 8 (10):
1179–1207.
Sigall-Boneh, Rotem, Tamar Pfeffer-Gik, Idit Segal, Tsili Zangen, Mona Boaz, and
Arie Levine. 2014. “Partial Enteral Nutrition with a Crohn’s Disease Exclusion
Diet Is Effective for Induction of Remission in Children and Young Adults with
Crohn's Disease.” Inflammatory Bowel Diseases 20 (8): 1353–60.
Sigall Boneh, Rotem, Chen Sarbagili Shabat, Henit Yanai, Irit Chermesh, Sivan
Ben Avraham, Mona Boaz, and Arie Levine. 2017. “Dietary Therapy With the
Crohn’s Disease Exclusion Diet Is a Successful Strategy for Induction of
Remission in Children and Adults Failing Biological Therapy.” Journal of
Crohn’s & Colitis 11 (10): 1205–12.
Strisciuglio, Caterina, Sabrina Cenni, Maria Rosaria Serra, Pasquale Dolce,
Massimo
Martinelli,
Annamaria
Staiano,
and
Erasmo
Miele.
2020.
“Effectiveness
of
Mediterranean
Diet’s
Adherence
in
Children
with
Inflammatory
Bowel
Diseases.”
Nutrients
12
(10).
https://doi.org/10.3390/nu12103206.
Triantafillidis, J. K., A. Stamataki, V. Karagianni, and G. Malgarinos. 2009. “P270
LONG-TERM EFFECT OF A POLYMERIC FEED, RICH IN TGF-β, ON ADULT
PATIENTS
WITH
CROHN’S
DISEASE:
COMPARISON
WITH
PEROS
ADMINISTRATION
OF
MESALAMINE.”
Clinical
Nutrition
Supplements.
https://doi.org/10.1016/s1744-1161(09)70320-5.
Turner, Dan, Anne M. Griffiths, Thomas D. Walters, Tong Seah, James Markowitz,
Marian Pfefferkorn, David Keljo, et al. 2012. “Mathematical Weighting of the
Pediatric Crohn’s Disease Activity Index (PCDAI) and Comparison with Its
VERSIÓN 2-17 de abril de 2021
19
Other Short Versions.” Inflammatory Bowel Diseases 18 (1): 55–62.
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Annex 1
Patient no:
Week: ⬀OR ⬀6 ⬀12 ⬀Year.
Group ⬀Diet plus biologic ⬀Biologic
Date of diagnosis
Age
Sex
Location of disease
⬀ileal ⬀colonic ⬀ileo colonic ⬀combined with upper gastrointestinal
involvement.
Relapses between this and previous evaluation ⬀Yes n°__ ⬀No. Current
treatment ⬀5 oral or topical ASA ⬀oral corticosteroids, topical or ev
⬀Infliximab ⬀Adalimumab)
Dose of infliximab/ adalimumab: ___ mg/kg.
Frequency of biologic administration: ⬀weekly ⬀every 2 weeks ⬀every 3
weeks ⬀every 4 weeks ⬀every 6 weeks ⬀other:___.
Short PCDAI : ⬀less than 10 ⬀10-25 ⬀25-40 ⬀more than 40
Laboratory
Hematocrit ____%
Calprotectin __ ug/g
Albumin ____ g/dl
CRP ____ mg/L
ERS ___ mm
Nutritional status: Weight:_____ kg z score:____ Height____ z score: ___
BMI: ____ growth rate:____
For the Diet plus biological group:
Amount of modulen per day: _____ ml
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Bring report ⬀Yes ⬀No
How difficult was it to perform the diet?
Score from 1( minimum)-10( maximum) ____
How similar is it to your usual diet?
Score from 1( minimum)-10( maximum): ___
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Annex 2- short PCDAI:
In the week prior to consultation you presented with:
Abdominal pain
⬀No
⬀Mild (short, does not interfere with activities)
⬀Moderate/severe( all day, lasted a long time, affected usual activity,
nocturnal).
General well-being.
⬀No activity limitation.
⬀Occasional difficulty in maintaining age-appropriate activities.
⬀Frequent activity limitations.
Daily catharsis
⬀0-1, liquid, bloodless
⬀up to 2 semiformed with little blood or 2-5 liquid.
⬀Significant bleeding or greater than or equal to 6 liquids or nocturnal
diarrhea.
Physical examination
Age---
Current weight and 1 year ago ---/----
Current height and 1 year ago ---/---/---
Abdomen
⬀- No mass or tenderness
⬀Local mass or tenderness
⬀Sensitivity, defensiveness, well-defined mass.
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Perianal disease
⬀No, skin tags
⬀1-2 asymptomatic fistulas
⬀Active fistula, draining or abscess.
Extraintestinal manifestations
⬀Fever
⬀Arthritis
⬀Uveitis
⬀Erythema nodosum
⬀Pioderma Gangrenosum
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