Highlights From the 2020 Virtual Advances in Inflammatory Bowel Diseases Conference
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January 2021 Volume 17, Issue 1, Supplement 2
A SPECIAL MEETING REVIEW EDITION
Highlights From the 2020 Virtual
Advances in Inflammatory Bowel
Diseases Conference
A Review of Selected Presentations From the 2020
Virtual AIBD Conference • December 9-12, 2020
Special Reporting on:
•P
ositioning Biologics and Small Molecules in the Management of
Moderate to Severe IBD
• Approach to Mild to Moderate IBD
• Disease Activity Assessment: What Should We Do in Clinical Practice?
• Precision Medicine in IBD
• Applying IBD Guidelines in the Real World
PLUS Meeting Abstract Summaries
With Expert Commentary by:
Gary R. Lichtenstein, MD
Professor of Medicine
Director, Center for Inflammatory Bowel Disease
University of Pennsylvania Health System
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
ON THE WEB:
gastroenterologyandhepatology.net
Indexed through the National Library of Medicine
(PubMed/Medline), PubMed Central (PMC), and EMBASE
TAKE CHARGE OF UC+CD
STELARA FOR
®
*In both the UC and CD studies, many patients achieved clinical
RAPID RESPONSE LASTING REMISSION
Many patients achieved clinical Many patients achieved clinical remission
response as early as Week 8 in UC at 1 year in the UC and CD clinical trials1,2‡
and Week 6 in CD in clinical trials1†
Clinical Response at Week 8 in UC (Major Secondary Endpoint): Clinical Response at Week 6 (Predominantly TNF Blocker Naïve)
• STELARA®: 58% (n=186/322); Placebo: 31% (n=99/319); P
Choose STELARA® as
your first-line biologic
Learn more at
www.ChooseSTELARA.com
FOR YOUR BIO-NAÏVE PATIENTS
LASTING REMISSION
*
remission at 1 Year with STELARA®. Please see supporting data below.
HISTO-ENDOSCOPIC MUCOSAL SAFETY PROFILE
IMPROVEMENT (HEMI) IN UC The overall safety profile in UC and CD studies
The first and only FDA-approved UC was consistent with that seen in other
treatment to achieve HEMI1§ approved indications1
INDICATIONS †
In UC, clinical response was defined as a decrease from baseline in the modified Mayo
score by ≥30% and ≥2 points, with either a decrease from baseline in the rectal bleeding
STELARA® (ustekinumab) is indicated for the treatment of adult subscore of ≥1 or a rectal bleeding subscore of 0 or 1. In CD, clinical response was
patients with moderately to severely active Crohn’s disease. defined as reduction in CDAI score of ≥100 points or CDAI score of
IMPORTANT SAFETY INFORMATION
STELARA® (ustekinumab) is contraindicated in patients with clinically significant contacts of STELARA® patients, as shedding and subsequent transmission to
hypersensitivity to ustekinumab or to any of the excipients. STELARA® patients may occur. Non-live vaccinations received during a course of
Infections STELARA® may not elicit an immune response sufficient to prevent disease.
STELARA® may increase the risk of infections and reactivation of latent Concomitant Therapies
infections. Serious bacterial, mycobacterial, fungal, and viral infections requiring The safety of STELARA® in combination with other biologic immunosuppressive
hospitalization or otherwise clinically significant infections were reported. In agents or phototherapy was not evaluated in clinical studies of psoriasis.
patients with psoriasis, these included diverticulitis, cellulitis, pneumonia, Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In
appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, psoriasis studies, the relevance of findings in mouse models for malignancy risk in
and urinary tract infections. In patients with psoriatic arthritis, this included humans is unknown. In psoriatic arthritis studies, concomitant methotrexate use
cholecystitis. In patients with Crohn’s disease, these included anal abscess, did not appear to influence the safety or efficacy of STELARA®. In Crohn’s disease
gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In and ulcerative colitis induction studies, concomitant use of 6-mercaptopurine,
patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes azathioprine, methotrexate, and corticosteroids did not appear to influence the
zoster, pneumonia, and listeriosis. overall safety or efficacy of STELARA®.
Treatment with STELARA® should not be initiated in patients with a clinically Noninfectious Pneumonia
important active infection until the infection resolves or is adequately treated. Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing
Consider the risks and benefits of treatment prior to initiating use of STELARA® in pneumonia have been reported during post-approval use of STELARA®. Clinical
patients with a chronic infection or a history of recurrent infection. Instruct patients presentations included cough, dyspnea, and interstitial infiltrates following one
to seek medical advice if signs or symptoms suggestive of an infection occur while to three doses. Serious outcomes have included respiratory failure and prolonged
on treatment with STELARA® and consider discontinuing STELARA® for serious or hospitalization. Patients improved with discontinuation of therapy and, in certain
clinically significant infections until the infection resolves or is adequately treated. cases, administration of corticosteroids. If diagnosis is confirmed, discontinue
Theoretical Risk for Vulnerability to Particular Infections STELARA® and institute appropriate treatment.
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to Allergen Immunotherapy
disseminated infections from mycobacteria, Salmonella, and Bacillus Calmette- STELARA® may decrease the protective effect of allergen immunotherapy (decrease
Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been tolerance) which may increase the risk of an allergic reaction to a dose of allergen
reported in such patients. It is not known whether patients with pharmacologic immunotherapy. Therefore, caution should be exercised in patients receiving or who
blockade of IL-12/IL-23 from treatment with STELARA® may be susceptible to these have received allergen immunotherapy, particularly for anaphylaxis.
types of infections. Appropriate diagnostic testing should be considered (eg, tissue
culture, stool culture) as dictated by clinical circumstances. Most Common Adverse Reactions
The most common adverse reactions (≥3% and higher than that with placebo) in
Pre-Treatment Evaluation of Tuberculosis (TB) adults from psoriasis clinical studies for STELARA® 45 mg, STELARA® 90 mg, or
Evaluate patients for TB prior to initiating treatment with STELARA®. Do not placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection
administer STELARA® to patients with active tuberculosis infection. Initiate (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively.
treatment of latent TB before administering STELARA®. Closely monitor patients The safety profile in pediatric patients with plaque psoriasis was similar to that
receiving STELARA® for signs and symptoms of active TB during and after treatment. of adults with plaque psoriasis. In psoriatic arthritis (PsA) studies, a higher
Malignancies incidence of arthralgia and nausea was observed in patients treated with
STELARA® is an immunosuppressant and may increase the risk of malignancy. STELARA® when compared with placebo (3% vs 1% for both). In Crohn’s disease
Malignancies were reported among patients who received STELARA® in clinical induction studies, common adverse reactions (3% or more of patients treated with
studies. The safety of STELARA® has not been evaluated in patients who have a STELARA® and higher than placebo) reported through Week 8 for STELARA®
history of malignancy or who have a known malignancy. There have been reports of 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In
the rapid appearance of multiple cutaneous squamous cell carcinomas in patients the Crohn’s disease maintenance study, common adverse reactions (3% or more of
receiving STELARA® who had risk factors for developing non-melanoma skin cancer patients treated with STELARA® and higher than placebo) reported through
(NMSC). All patients receiving STELARA®, especially those >60 years or those with Week 44 for STELARA® 90 mg subcutaneous injection or placebo were:
a history of PUVA or prolonged immunosuppressant treatment, should be monitored nasopharyngitis (11% vs 8%), injection site erythema (5% vs 0%), vulvovaginal
for the appearance of NMSC. candidiasis/mycotic infection (5% vs 1%), bronchitis (5% vs 3%), pruritus (4% vs
2%), urinary tract infection (4% vs 2%) and sinusitis (3% vs 2%). In the ulcerative
Hypersensitivity Reactions colitis induction study, common adverse reactions (3% or more of patients treated
Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA® and higher than placebo) reported through Week 8 for STELARA®
with STELARA®. If an anaphylactic or other clinically significant hypersensitivity 6 mg/kg intravenous single infusion or placebo included: nasopharyngitis
reaction occurs, institute appropriate therapy and discontinue STELARA®. (7% vs 4%). In the ulcerative colitis maintenance study, common adverse reactions
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) (3% or more of patients treated with STELARA® and higher than placebo) reported
One case of reversible posterior leukoencephalopathy syndrome (RPLS) was through Week 44 for STELARA® 90 mg subcutaneous injection or placebo included:
observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS nasopharyngitis (24% vs 20%), headache (10% vs 4%), abdominal pain
were observed in clinical studies of Crohn’s disease or ulcerative colitis. If RPLS is (7% vs 3%), influenza (6% vs 5%), fever (5% vs 4%), diarrhea (4% vs 1%),
suspected, administer appropriate treatment and discontinue STELARA®. RPLS is sinusitis (4% vs 1%), fatigue (4% vs 2%), and nausea (3% vs 2%).
a neurological disorder, which is not caused by an infection or demyelination. RPLS Please see Brief Summary on adjacent pages. Please see full
can present with headache, seizures, confusion, and visual disturbances. RPLS has Prescribing Information and Medication Guide for STELARA®
been associated with fatal outcomes. at STELARAhcp.com. Provide the
Immunizations Medication Guide to your patients
Prior to initiating therapy with STELARA®, patients should receive all age- and encourage discussion.
appropriate immunizations recommended by current guidelines. Patients being cp-124933v2
treated with STELARA® should not receive live vaccines. BCG vaccines should
not be given during treatment or within one year of initiating or discontinuing
STELARA®. Exercise caution when administering live vaccines to household
Brief Summary of Prescribing Information for STELARA® (ustekinumab) STELARA® (ustekinumab)
STELARA® Injection, for subcutaneous use suspected, administer appropriate treatment and discontinue STELARA®.
See package insert for Full Prescribing Information Immunizations: Prior to initiating therapy with STELARA®, patients should
INDICATIONS AND USAGE: Psoriasis (Ps): STELARA® is indicated for the receive all age-appropriate immunizations as recommended by current
treatment of patients 6 years or older with moderate to severe plaque immunization guidelines. Patients being treated with STELARA® should not
psoriasis who are candidates for phototherapy or systemic therapy. receive live vaccines. BCG vaccines should not be given during treatment
Psoriatic Arthritis (PsA): STELARA® is indicated for the treatment of adult with STELARA® or for one year prior to initiating treatment or one year
patients with active psoriatic arthritis. STELARA® can be used alone or in following discontinuation of treatment. Caution is advised when
combination with methotrexate (MTX). Crohn’s Disease (CD): STELARA® is administering live vaccines to household contacts of patients receiving
indicated for the treatment of adult patients with moderately to severely STELARA® because of the potential risk for shedding from the household
active Crohn’s disease. Ulcerative Colitis: STELARA® is indicated for the contact and transmission to patient. Non-live vaccinations received during
treatment of adult patients with moderately to severely active ulcerative a course of STELARA® may not elicit an immune response sufficient to
colitis. CONTRAINDICATIONS: STELARA® is contraindicated in patients prevent disease. Concomitant Therapies: In clinical studies of psoriasis the
with clinically significant hypersensitivity to ustekinumab or to any of safety of STELARA® in combination with other biologic immunosuppressive
the excipients [see Warnings and Precautions]. WARNINGS AND agents or phototherapy was not evaluated. Ultraviolet-induced skin cancers
PRECAUTIONS: Infections: STELARA® may increase the risk of infections developed earlier and more frequently in mice genetically manipulated to be
and reactivation of latent infections. Serious bacterial, mycobacterial, deficient in both IL-12 and IL-23 or IL-12 alone [see Concomitant Therapies,
fungal, and viral infections were observed in patients receiving STELARA® Nonclinical Toxicology (13.1) in Full Prescribing Information]. Noninfectious
[see Adverse Reactions]. Serious infections requiring hospitalization, or Pneumonia: Cases of interstitial pneumonia, eosinophilic pneumonia and
otherwise clinically significant infections, reported in clinical studies cryptogenic organizing pneumonia have been reported during post-approval
included the following: • Psoriasis: diverticulitis, cellulitis, pneumonia, use of STELARA®. Clinical presentations included cough, dyspnea, and
appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, interstitial infiltrates following one to three doses. Serious outcomes have
gastroenteritis and urinary tract infections. • Psoriatic arthritis: cholecystitis. included respiratory failure and prolonged hospitalization. Patients improved
• Crohn’s disease: anal abscess, gastroenteritis, ophthalmic herpes zoster, with discontinuation of therapy and in certain cases administration of
pneumonia, and listeria meningitis. • Ulcerative colitis: gastroenteritis, corticosteroids. If diagnosis is confirmed, discontinue STELARA® and
ophthalmic herpes zoster, pneumonia, and listeriosis. Treatment with institute appropriate treatment [see Postmarketing Experience]. ADVERSE
STELARA® should not be initiated in patients with any clinically important REACTIONS: The following serious adverse reactions are discussed
active infection until the infection resolves or is adequately treated. Consider elsewhere in the label: • Infections [see Warnings and Precautions]
the risks and benefits of treatment prior to initiating use of STELARA® in • Malignancies [see Warnings and Precautions] • Hypersensitivity
patients with a chronic infection or a history of recurrent infection. Instruct Reactions [see Warnings and Precautions] • Reversible Posterior
patients to seek medical advice if signs or symptoms suggestive of an Leukoencephalopathy Syndrome [see Warnings and Precautions] Clinical
infection occur while on treatment with STELARA® and consider Trials Experience: Because clinical trials are conducted under widely
discontinuing STELARA® for serious or clinically significant infections until varying conditions, adverse reaction rates observed in the clinical trials of
the infection resolves or is adequately treated. Theoretical Risk for a drug cannot be directly compared to rates in the clinical trials of another
Vulnerability to Particular Infections: Individuals genetically deficient in drug and may not reflect the rates observed in practice. Adult Subjects with
IL-12/IL-23 are particularly vulnerable to disseminated infections from Plaque Psoriasis: The safety data reflect exposure to STELARA® in 3117
mycobacteria (including nontuberculous, environmental mycobacteria), adult psoriasis subjects, including 2414 exposed for at least 6 months, 1855
salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) exposed for at least one year, 1653 exposed for at least two years, 1569
vaccinations. Serious infections and fatal outcomes have been reported in exposed for at least three years, 1482 exposed for at least four years and
such patients. It is not known whether patients with pharmacologic 838 exposed for at least five years. Table 1 summarizes the adverse
B:11.125"
T:10.875"
S:9.875"
blockade of IL-12/IL-23 from treatment with STELARA® may be susceptible reactions that occurred at a rate of at least 1% and at a higher rate in the
to these types of infections. Appropriate diagnostic testing should be STELARA® groups than the placebo group during the placebo-controlled
considered, e.g., tissue culture, stool culture, as dictated by clinical
period of Ps STUDY 1 and Ps STUDY 2 [see Clinical Studies (14) in Full
circumstances. Pre-treatment Evaluation for Tuberculosis: Evaluate
Prescribing Information].
patients for tuberculosis infection prior to initiating treatment with
STELARA®. Do not administer STELARA® to patients with active tuberculosis Table 1: Adverse Reactions Reported by ≥1% of Subjects through Week 12
infection. Initiate treatment of latent tuberculosis prior to administering in Ps STUDY 1 and Ps STUDY 2
STELARA®. Consider anti-tuberculosis therapy prior to initiation of STELARA®
STELARA® in patients with a past history of latent or active tuberculosis in
whom an adequate course of treatment cannot be confirmed. Closely Placebo 45 mg 90 mg
monitor patients receiving STELARA® for signs and symptoms of active Subjects treated 665 664 666
tuberculosis during and after treatment. Malignancies: STELARA® is an Nasopharyngitis 51 (8%) 56 (8%) 49 (7%)
immunosuppressant and may increase the risk of malignancy. Malignancies Upper respiratory tract infection 30 (5%) 36 (5%) 28 (4%)
were reported among subjects who received STELARA® in clinical studies
[see Adverse Reactions]. In rodent models, inhibition of IL-12/IL-23p40 Headache 23 (3%) 33 (5%) 32 (5%)
increased the risk of malignancy [see Nonclinical Toxicology (13) in Full Fatigue 14 (2%) 18 (3%) 17 (3%)
Prescribing Information]. The safety of STELARA® has not been evaluated in Diarrhea 12 (2%) 13 (2%) 13 (2%)
patients who have a history of malignancy or who have a known malignancy. Back pain 8 (1%) 9 (1%) 14 (2%)
There have been post-marketing reports of the rapid appearance of multiple Dizziness 8 (1%) 8 (1%) 14 (2%)
cutaneous squamous cell carcinomas in patients receiving STELARA® who
Pharyngolaryngeal pain 7 (1%) 9 (1%) 12 (2%)
had pre-existing risk factors for developing non-melanoma skin cancer. All
patients receiving STELARA® should be monitored for the appearance of Pruritus 9 (1%) 10 (2%) 9 (1%)
non-melanoma skin cancer. Patients greater than 60 years of age, those Injection site erythema 3 (STELARA® (ustekinumab) STELARA® (ustekinumab)
years of follow-up). Serious infections were reported in 2.8% of subjects Infections: In patients with Crohn’s disease, serious or other clinically
(0.01 per subject-years of follow-up). Malignancies: In the controlled and significant infections included anal abscess, gastroenteritis, and
non-controlled portions of psoriasis clinical studies (median follow-up of pneumonia. In addition, listeria meningitis and ophthalmic herpes zoster
3.2 years, representing 8998 subject-years of exposure), 1.7% of STELARA®- were reported in one patient each [see Warnings and Precautions].
treated subjects reported malignancies excluding non-melanoma skin Malignancies: With up to one year of treatment in the Crohn’s disease
cancers (0.60 per hundred subject-years of follow-up). Non-melanoma clinical studies, 0.2% of STELARA®-treated subjects (0.36 events per
skin cancer was reported in 1.5% of STELARA®-treated subjects (0.52 per hundred patient-years) and 0.2% of placebo-treated subjects (0.58 events
hundred subject-years of follow-up) [see Warnings and Precautions]. The per hundred patient-years) developed non-melanoma skin cancer.
most frequently observed malignancies other than non-melanoma skin Malignancies other than non-melanoma skin cancers occurred in 0.2% of
cancer during the clinical studies were: prostate, melanoma, colorectal STELARA®-treated subjects (0.27 events per hundred patient-years) and in
and breast. Malignancies other than non-melanoma skin cancer in none of the placebo-treated subjects. Hypersensitivity Reactions Including
STELARA®-treated patients during the controlled and uncontrolled portions Anaphylaxis: In CD studies, two patients reported hypersensitivity reactions
of studies were similar in type and number to what would be expected in following STELARA® administration. One patient experienced signs and
the general U.S. population according to the SEER database (adjusted symptoms consistent with anaphylaxis (tightness of the throat, shortness of
for age, gender and race).1 Pediatric Subjects with Plaque Psoriasis: The
breath, and flushing) after a single subcutaneous administration (0.1% of
safety of STELARA® was assessed in two studies of pediatric subjects with
moderate to severe plaque psoriasis. Ps STUDY 3 evaluated safety for up patients receiving subcutaneous STELARA®). In addition, one patient
to 60 weeks in 110 adolescents (12 to 17 years old). Ps STUDY 4 evaluated experienced signs and symptoms consistent with or related to a
safety for up to 56 weeks in 44 children (6 to 11 years old). The safety hypersensitivity reaction (chest discomfort, flushing, urticaria, and
profile in pediatric subjects was similar to the safety profile from studies increased body temperature) after the initial intravenous STELARA® dose
in adults with plaque psoriasis. Psoriatic Arthritis: The safety of STELARA® (0.08% of patients receiving intravenous STELARA®). These patients were
was assessed in 927 subjects in two randomized, double-blind, placebo- treated with oral antihistamines or corticosteroids and in both cases
controlled studies in adults with active psoriatic arthritis (PsA). The overall symptoms resolved within an hour. Ulcerative Colitis: The safety of
safety profile of STELARA® in subjects with PsA was consistent with the STELARA® was evaluated in two randomized, double-blind, placebo-
safety profile seen in adult psoriasis clinical studies. A higher incidence controlled clinical studies (UC-1 [IV induction] and UC-2 [SC maintenance])
of arthralgia, nausea, and dental infections was observed in STELARA®- in 960 adult subjects with moderately to severely active ulcerative colitis
treated subjects when compared with placebo-treated subjects (3% vs. 1% [see Clinical Studies (14.5) in Full Prescribing Information]. The overall
for arthralgia and 3% vs. 1% for nausea; 1% vs. 0.6% for dental infections) safety profile of STELARA® in patients with ulcerative colitis was consistent
in the placebo-controlled portions of the PsA clinical studies. Crohn’s with the safety profile seen across all approved indications. Adverse
Disease: The safety of STELARA® was assessed in 1407 subjects with reactions reported in at least 3% of STELARA®-treated subjects and at a
moderately to severely active Crohn’s disease (Crohn’s Disease Activity higher rate than placebo were: • Induction (UC-1): nasopharyngitis (7% vs
Index [CDAI] greater than or equal to 220 and less than or equal to 450) 4%). • Maintenance (UC-2): nasopharyngitis (24% vs 20%), headache (10%
in three randomized, double-blind, placebo-controlled, parallel-group, vs 4%), abdominal pain (7% vs 3%), influenza (6% vs 5%), fever (5% vs. 4%),
multicenter studies. These 1407 subjects included 40 subjects who received diarrhea (4% vs 1%), sinusitis (4% vs 1%), fatigue (4% vs 2%), and nausea
a prior investigational intravenous ustekinumab formulation but were not (3% vs 2%). Infections: In patients with ulcerative colitis, serious or other
included in the efficacy analyses. In Studies CD-1 and CD-2 there were clinically significant infections included gastroenteritis and pneumonia. In
470 subjects who received STELARA® 6 mg/kg as a weight-based single addition, listeriosis and ophthalmic herpes zoster were reported in one
intravenous induction dose and 466 who received placebo [see Dosage patient each [see Warnings and Precautions]. Malignancies: With up to one
and Administration (2.3) in Full Prescribing Information]. Subjects who year of treatment in the ulcerative colitis clinical studies, 0.4% of STELARA®-
were responders in either Study CD-1 or CD-2 were randomized to receive treated subjects (0.48 events per hundred patient-years) and 0.0% of
a subcutaneous maintenance regimen of either 90 mg STELARA® every placebo-treated subjects (0.00 events per hundred patient-years) developed
8 weeks, or placebo for 44 weeks in Study CD-3. Subjects in these 3 studies non-melanoma skin cancer. Malignancies other than non-melanoma skin
may have received other concomitant therapies including aminosalicylates, cancers occurred in 0.5% of STELARA®-treated subjects (0.64 events per
immunomodulatory agents [azathioprine (AZA), 6-mercaptopurine (6-MP),
hundred patient-years) and 0.2% of placebo-treated subjects (0.40 events
MTX], oral corticosteroids (prednisone or budesonide), and/or antibiotics
per hundred patient-years). Immunogenicity: As with all therapeutic
for their Crohn’s disease [see Clinical Studies (14.4) in Full Prescribing
Information]. The overall safety profile of STELARA® was consistent with proteins, there is potential for immunogenicity. The detection of antibody
the safety profile seen in the adult psoriasis and psoriatic arthritis clinical formation is highly dependent on the sensitivity and specificity of the assay.
studies. Common adverse reactions in Studies CD-1 and CD-2 and in Study Additionally, the observed incidence of antibody (including neutralizing
CD-3 are listed in Tables 2 and 3, respectively. antibody) positivity in an assay may be influenced by several factors,
including assay methodology, sample handling, timing of sample collection,
Table 2: Common adverse reactions through Week 8 in Studies CD-1 and
concomitant medications and underlying disease. For these reasons,
CD-2 occurring in ≥3% of STELARA®-treated subjects and higher
than placebo comparison of the incidence of antibodies to ustekinumab in the studies
described below with the incidence of antibodies to other products may be
STELARA® misleading.Approximately 6 to 12.4% of subjects treated with STELARA® in
6 mg/kg single intravenous psoriasis and psoriatic arthritis clinical studies developed antibodies to
Placebo induction dose ustekinumab, which were generally low-titer. In psoriasis clinical studies,
N=466 N=470 antibodies to ustekinumab were associated with reduced or undetectable
Vomiting 3% 4% serum ustekinumab concentrations and reduced efficacy. In psoriasis
studies, the majority of subjects who were positive for antibodies to
Other less common adverse reactions reported in subjects in Studies CD-1 ustekinumab had neutralizing antibodies. In Crohn’s disease and ulcerative
and CD-2 included asthenia (1% vs 0.4%), acne (1% vs 0.4%), and pruritus colitis clinical studies, 2.9% and 4.6% of subjects, respectively, developed
(2% vs 0.4%). antibodies to ustekinumab when treated with STELARA® for approximately
Table 3: Common adverse reactions through Week 44 in Study CD-3 one year. No apparent association between the development of antibodies
occurring in ≥3% of STELARA®-treated subjects and higher than to ustekinumab and the development of injection site reactions was seen.
placebo Postmarketing Experience: The following adverse reactions have been
reported during post-approval of STELARA®. Because these reactions are
STELARA® reported voluntarily from a population of uncertain size, it is not always
90 mg subcutaneous possible to reliably estimate their frequency or establish a causal
maintenance dose every
relationship to STELARA® exposure. Immune system disorders: Serious
Placebo 8 weeks
hypersensitivity reactions (including anaphylaxis and angioedema), other
N=133 N=131 hypersensitivity reactions (including rash and urticaria) [see Warnings and
Nasopharyngitis 8% 11% Precautions]. Infections and infestations: Lower respiratory tract infection
Injection site erythema 0 5% (including opportunistic fungal infections and tuberculosis) [see Warnings
Vulvovaginal candidiasis/mycotic 1% 5% and Precautions]. Respiratory, thoracic and mediastinal disorders:
infection Interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing
Bronchitis 3% 5% pneumonia [see Warnings and Precautions]. Skin reactions: Pustular
Pruritus 2% 4% psoriasis, erythrodermic psoriasis. DRUG INTERACTIONS: Concomitant
Urinary tract infection 2% 4% Therapies: In psoriasis studies the safety of STELARA® in combination with
Sinusitis 2% 3% immunosuppressive agents or phototherapy has not been evaluated [seeSTELARA® (ustekinumab) STELARA® (ustekinumab)
Warnings and Precautions]. In psoriatic arthritis studies, concomitant MTX safety and effectiveness of STELARA® for pediatric patients less than
use did not appear to influence the safety or efficacy of STELARA®. In 6 years of age with psoriasis have not been established. The safety and
Crohn’s disease and ulcerative colitis induction studies, immunomodulators effectiveness of STELARA® have not been established in pediatric patients
(6-MP, AZA, MTX) were used concomitantly in approximately 30% of with psoriatic arthritis, Crohn’s disease or ulcerative colitis. Geriatric Use:
subjects and corticosteroids were used concomitantly in approximately Of the 6709 patients exposed to STELARA®, a total of 340 were 65 years or
40% and 50% of Crohn’s disease and ulcerative colitis subjects, respectively. older (183 patients with psoriasis, 65 patients with psoriatic arthritis,
Use of these concomitant therapies did not appear to influence the overall 58 patients with Crohn’s disease and 34 patients with ulcerative colitis), and
safety or efficacy of STELARA®. CYP450 Substrates: The formation of 40 patients were 75 years or older. Although no overall differences in safety
CYP450 enzymes can be altered by increased levels of certain cytokines or efficacy were observed between older and younger patients, the number
(e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Thus, of patients aged 65 and over is not sufficient to determine whether they
STELARA®, an antagonist of IL-12 and IL-23, could normalize the formation respond differently from younger patients. OVERDOSAGE: Single doses up
of CYP450 enzymes. Upon initiation of STELARA® in patients who are to 6 mg/kg intravenously have been administered in clinical studies without
receiving concomitant CYP450 substrates, particularly those with a narrow dose-limiting toxicity. In case of overdosage, it is recommended that the
therapeutic index, monitoring for therapeutic effect (e.g., for warfarin) or patient be monitored for any signs or symptoms of adverse reactions or
drug concentration (e.g., for cyclosporine) should be considered and the effects and appropriate symptomatic treatment be instituted immediately.
individual dose of the drug adjusted as needed [see Clinical Pharmacology PATIENT COUNSELING INFORMATION: Advise the patient and/or caregiver
(12.3) in Full Prescribing Information]. Allergen Immunotherapy: STELARA® to read the FDA-approved patient labeling (Medication Guide and
has not been evaluated in patients who have undergone allergy Instructions for Use). Infections: Inform patients that STELARA® may lower
immunotherapy. STELARA® may decrease the protective effect of allergen the ability of their immune system to fight infections and to contact their
immunotherapy (decrease tolerance) which may increase the risk of an healthcare provider immediately if they develop any signs or symptoms of
allergic reaction to a dose of allergen immunotherapy. Therefore, caution infection [see Warnings and Precautions]. Malignancies: Inform patients of
should be exercised in patients receiving or who have received allergen the risk of developing malignancies while receiving STELARA® [see
immunotherapy, particularly for anaphylaxis. USE IN SPECIFIC Warnings and Precautions]. Hypersensitivity Reactions: • Advise patients to
POPULATIONS: Pregnancy: Risk Summary: Limited data on the use of seek immediate medical attention if they experience any signs or symptoms
STELARA® in pregnant women are insufficient to inform a drug associated of serious hypersensitivity reactions and discontinue STELARA® [see
risk [see Data]. In animal reproductive and developmental toxicity studies, Warnings and Precautions]. • Inform patients the needle cover on the
no adverse developmental effects were observed after administration of prefilled syringe contains dry natural rubber (a derivative of latex), which
ustekinumab to pregnant monkeys at exposures greater than 100 times the may cause allergic reactions in individuals sensitive to latex [see Dosage
human exposure at the maximum recommended human subcutaneous and Administration (2.4) in Full Prescribing Information] Immunizations:
dose (MRHD). The background risk of major birth defects and miscarriage Inform patients that STELARA® can interfere with the usual response to
for the indicated population(s) are unknown. All pregnancies have a immunizations and that they should avoid live vaccines [see Warnings and
background risk of birth defect, loss, or other adverse outcomes. In the U.S. Precautions]. Administration: Instruct patients to follow sharps disposal
general population, the estimated background risk of major birth defects recommendations, as described in the Instructions for Use.
and miscarriage of clinically recognized pregnancies is 2% to 4% and 15% REFERENCES: 1Surveillance, Epidemiology, and End Results (SEER)
to 20%, respectively. Data: Human Data: Limited data on use of STELARA® Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER
in pregnant women from observational studies, published case reports, and 6.6.2 Regs Research Data, Nov 2009 Sub (1973-2007) - Linked To County
postmarketing surveillance are insufficient to inform a drug associated risk. Attributes - Total U.S., 1969-2007 Counties, National Cancer Institute,
Animal Data: Ustekinumab was tested in two embryo-fetal development DCCPS, Surveillance Research Program, Surveillance Systems Branch,
toxicity studies in cynomolgus monkeys. No teratogenic or other adverse released April 2010, based on the November 2009 submission.
developmental effects were observed in fetuses from pregnant monkeys
Prefilled Syringe Manufactured by: Janssen Biotech, Inc., Horsham,
that were administered ustekinumab subcutaneously twice weekly or
PA 19044, US License No. 1864 at Baxter Pharmaceutical Solutions,
intravenously weekly during the period of organogenesis. Serum
Bloomington, IN 47403 and at Cilag AG, Schaffhausen, Switzerland
concentrations of ustekinumab in pregnant monkeys were greater than
100 times the serum concentration in patients treated subcutaneously with Vial Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044, US
90 mg of ustekinumab weekly for 4 weeks. In a combined embryo-fetal License No. 1864 at Cilag AG, Schaffhausen, Switzerland
development and pre- and post-natal development toxicity study, pregnant © 2012, 2016, 2019 Janssen Pharmaceutical Companies
cynomolgus monkeys were administered subcutaneous doses of
ustekinumab twice weekly at exposures greater than 100 times the human cp-125602v3
subcutaneous exposure from the beginning of organogenesis to Day 33
after delivery. Neonatal deaths occurred in the offspring of one monkey
administered ustekinumab at 22.5 mg/kg and one monkey dosed at 45 mg/
kg. No ustekinumab-related effects on functional, morphological, or
immunological development were observed in the neonates from birth
through six months of age. Lactation: Risk Summary: There are no data on
the presence of ustekinumab in human milk, the effects on the breastfed
infant, or the effects on milk production. Ustekinumab was present in the
milk of lactating monkeys administered ustekinumab. Due to species-
specific differences in lactation physiology, animal data may not reliably
predict drug levels in human milk. Maternal IgG is known to be present in
human milk. Published data suggest that the systemic exposure to a
breastfed infant is expected to be low because ustekinumab is a large
molecule and is degraded in the gastrointestinal tract. However, if
ustekinumab is transferred into human milk the effects of local exposure in
the gastrointestinal tract are unknown. The developmental and health
benefits of breastfeeding should be considered along with the mother’s
clinical need for STELARA® and any potential adverse effects on the
breastfed child from STELARA® or from the underlying maternal condition.
Pediatric Use: The safety and effectiveness of STELARA® have been
established in pediatric patients 6 to 17 years old with moderate to severe
plaque psoriasis. Use of STELARA® in adolescents is supported by evidence
from a multicenter, randomized, 60-week trial (Ps STUDY 3) that included a
12-week, double-blind, placebo-controlled, parallel-group portion, in 110
pediatric subjects 12 years and older [see Adverse Reactions, Clinical
Studies (14.2) in Full Prescribing Information]. Use of STELARA® in children
6 to 11 years with moderate to severe plaque psoriasis is supported by
evidence from an open-label, single-arm, efficacy, safety and
pharmacokinetics study (Ps STUDY 4) in 44 subjects [see Adverse
Reactions, Pharmacokinetics (12.3) in Full Prescribing Information]. TheSPECIAL MEETING REVIEW EDITION
Positioning Biologics and Small Molecules in the Management of
Moderate to Severe IBD
D
r William J. Sandborn umab and ustekinumab do not cause In a study presented at United
discussed how the roles of these complications. European Gastroenterology Week Vir-
biologics and small molecules Dr Sandborn proposed an algo- tual 2020, clinical remission (Crohn’s
are evolving in the management of rithm for treating moderate to severely Disease Activity Index score 2 years), have
embolism, deep vein thrombosis, and vedolizumab and ustekinumab have never received an anti-TNF agent,
hyperlipidemia. Importantly, vedoliz proved safer than TNF blockers. had moderate as opposed to severe
baseline endoscopy findings, and have
normal albumin levels are most likely
Table 1. Safety Considerations
to respond to anti-integrin therapy
Inflix- Adalim- Vedoliz Ustekin- Tofaci- with vedolizumab.6 In the case of CD,
imab umab umab umab tinib response and remission rates are better
in patients without previous surgi-
Granulomatous
infection + + − − − cal resection, anti-TNF treatment,
or fistulizing disease, with normal
Serious infection + + − − + albumin levels, and with relatively low
C-reactive protein levels.7
Herpes zoster − − − − +
Non-Hodgkin
+ + − − ? References
lymphoma 1. Sandborn WJ. Positioning biologics and small mol-
ecules in the management of moderate to severe IBD.
Demyelination + + − − − Presented at: 2020 Virtual Advances in Inflammatory
Bowel Diseases Conference; December 9-12, 2020.
DVT/PE − − − − + 2. Singh S, Murad MH, Fumery M, Dulai PS, Sand-
born WJ. First- and second-line pharmacotherapies
Hyperlipidemia − − − − + for patients with moderate to severely active ulcerative
colitis: an updated network meta-analysis. Clin Gastro-
DVT, deep vein thrombosis; PE, pulmonary embolism. Adapted from Sandborn WJ. Positioning biologics and small enterol Hepatol. 2020;18(10):2179-2191.e6.
molecules in the management of moderate to severe IBD. Presented at: 2020 Virtual Advances in Inflammatory 3. Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al;
Bowel Diseases Conference; December 9-12, 2020.1
8 Gastroenterology & Hepatology Volume 17, Issue 1, Supplement 2 January 2021HIGHLIGHTS FROM THE 2020 VIRTUAL ADVANCES IN IBD CONFERENCE
Severe disease Risk-averse
High structural damage Risk of Risk of Prior serious infections
disease-related treatment-related
High inflammatory burden complications Prior malignancy
complications
(disease (comorbidities)
Significant impact on severity) Advanced age, multiple
quality of life comorbidities
Patients’ values and
preferences (lifestyle/
First-line therapy: logistics, speed
Infliximab or adalimumab (for most of onset, cost)
patients), in combination with thiopurines
or methotrexate
• Higher inflammatory burden, higher Moderate disease severity Higher disease severity
disease severity, perianal disease, severe
extraintestinal manifestations, obese:
– Infliximab > adalimumab First-line therapy: First-line therapy:
– Combination therapy >> monotherapy Vedolizumab monotherapy Ustekinumab monotherapy
• Significant comorbidities or contraindications
to TNFa antagonists:
– Ustekinumab monotherapy Second-line therapy: Second-line therapy:
Ustekinumab monotherapy Infliximab or adalimumab
monotherapy
Second-line therapy (in patients with prior (or)
exposure to infliximab or adalimumab):
Vedolizumab in combination
Ustekinumab (for most patients), with thiopurines or
in combination with thiopurines or methotrexate
methotrexate
• Second TNFa antagonist (may consider for
patients with loss of response due
to immunogenicity to first TNFa
antagonist, or intolerance)
Figure 1. Proposed algorithm for positioning therapies for patients with high-risk Crohn’s disease. TNF, tumor necrosis factor. Adapted from
Nguyen NH et al. Clin Gastroenterol Hepatol. 2020;18(6):1268-12795 and Sandborn WJ. Positioning biologics and small molecules in the
management of moderate to severe IBD. Presented at: 2020 Virtual Advances in Inflammatory Bowel Diseases Conference; December 9-12, 2020.1
VARSITY Study Group. Vedolizumab versus adalim- UEG Week abstract OP089. Presented at: UEG Week outcomes of treatment with vedolizumab in patients
umab for moderate-to-severe ulcerative colitis. N Engl J Virtual 2020; October 11-13, 2020. with ulcerative colitis. Clin Gastroenterol Hepatol.
Med. 2019;381(13):1215-1226. 5. Nguyen NH, Singh S, Sandborn WJ. Positioning 2020;18(13):2952-2961.e8.
4. Sandborn W, Chan D, Johanns J, et al. The efficacy therapies in the management of Crohn’s disease. Clin 7. Dulai PS, Boland BS, Singh S, et al. Development
and safety of guselkumab induction therapy in patients Gastroenterol Hepatol. 2020;18(6):1268-1279. and validation of a scoring system to predict outcomes
with moderately to severely active Crohn’s disease: week 6. Dulai PS, Singh S, Casteele NV, et al. Develop- of vedolizumab treatment in patients with Crohn’s dis-
12 interim analyses from the phase 2 GALAXI 1 study. ment and validation of clinical scoring tool to predict ease. Gastroenterology. 2018;155(3):687-695.e10.
Approach to Mild to Moderate IBD
D
r Sunanda Kane reviewed The diagnosis of UC should and prevents the need for hospitaliza-
the treatment of mild to include both an assessment of the tion as well as surgery. Maintenance
moderate IBD.1 In 2019, the extent of disease and a biopsy, which therapy should be established for each
American College of Gastroenterology will determine histologic severity; a patient according to the response to
issued new clinical guidelines for the current goal in IBD care is to distin- induction therapy and the prognosis.
treatment of adults with UC, in which guish between activity and severity. An Screening and treatment for anxiety
urgency, measured as none, mild/ additional goal is to induce a clinical and depressive disorders should also be
occasional, or frequent, was added as response or remission. Mucosal healing part of management. The prevention
a consideration.2 The fecal calprotectin is crucial because it is associated with of complications, such as cancer and
level was also added. sustained, corticosteroid-free remission infections, is another important goal.
Gastroenterology & Hepatology Volume 17, Issue 1, Supplement 2 January 2021 9SPECIAL MEETING REVIEW EDITION
Table 2. Treatment for Mild to Moderate UC with mild to moderate disease, rather
Induction: than prednisone.
Budesonide MMX is also impor-
• Mild proctitis rectal 5-ASA recommended (1 g/day)1-5 tant in the treatment of CD, in which
• L eft-sided mild UC rectal 5-ASA (≥1 g/day) in combination with oral it has proved almost as effective as
5-ASA (≥2.0 g/day)1-6
prednisolone and superior to placebo
• Mild extensive UC oral 5-ASA (≥2.0 g/day)1,5 and mesalamine for patients with
• Mild UC (any extent) use a low dose (2.0-2.4 g) of 5-ASA,2 in comparison active ileal and right-sided colonic
with a higher dose (4.8 g)1
disease. In addition, it may be effective
• Mild to moderate UC not responding to oral 5-ASA + budesonide MMX for maintaining remission in mild to
9 mg/day1-3,5
moderate CD. Sulfasalazine may also
Maintenance: be effective when disease is limited to
the colon. Patients must be advised to
• Mildly active proctitis rectal 5-ASA (1 g/day)1,2,6 stop smoking and should be screened
• Mildly active left-sided or extensive UC oral 5-ASA therapy (≥2 g/day)1-4 for depression and anxiety, both of
• Recommend against systemic corticosteroids1,3,6 which will impede improvement.
5-ASA drugs, budesonide, aza-
UC, ulcerative colitis; 5-ASA, 5-aminosalicylic acid. 1Rubin DT et al. Am J Gastroenterol. 2019;114(3):384-413. thioprine, 6-mercaptopurine, and
2
Hardbord M et al. J Crohns Colitis. 2017;11(7):769-784. 3Bressler B et al. Gastroenterology. 2015;148(5):1035-1058.e3.
4
Coi CH et al. IntestRes. 2017;15(1):7-37. 5Ko CW et al. Gastroenterology. 2019;156(3):748-764. 6Wei CS et al.
methotrexate are all potential options
IntestRes. 2017;15(3):266-284. Adapted from Kane S. Approach to mild to moderate IBD. Presented at: 2020 Virtual for treating mild to moderate CD.
Advances in Inflammatory Bowel Diseases Conference; December 9-12, 2020.1 Lack of efficacy may be due to inad-
equate dosing, lack of adherence, or
Dr Kane also reviewed induction ASCEND III trial, additional treat- preferential metabolism via the thio-
and maintenance therapy for mild ment did not necessarily lead to better purine methyltransferase pathway.
to moderate UC (Table 2). Rectal outcomes.3 Clinicians must consider
administration of a 5-aminosalicylic whether a patient’s disease activity References
acid (5-ASA) drug at a dose of 1 g/ is mild or moderate when a 5-ASA 1. Kane S. Approach to mild to moderate IBD. Pre-
sented at: 2020 Virtual Advances in Inflammatory
day is recommended for patients with drug is prescribed. For patients with Bowel Diseases Conference; December 9-12, 2020.
mild proctitis, although many patients distal UC, research has shown that a 2. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer
may be fine with a dose taken every combination of oral and rectal mesa- BG, Long MD. ACG Clinical Guideline: ulcerative coli-
tis in adults. Am J Gastroenterol. 2019;114(3):384-413.
other day, or even every third day, once lamine therapy is better than either 3. Sandborn WJ, Regula J, Feagan BG, et al. Delayed-
remission has been attained. During agent alone, even if given for only 1 release oral mesalamine 4.8 g/day (800-mg tablet) is
maintenance, topical therapy can be to 2 weeks.4 If the combination can be effective for patients with moderately active ulcerative
colitis. Gastroenterology. 2009;137(6):1934-1943.e1-3.
discontinued for patients with mildly continued for 6 weeks, then the chance 4. Safdi M, DeMicco M, Sninsky C, et al. A double-
active left-sided or extensive UC, and of a successful outcome is even greater. blind comparison of oral versus rectal mesalamine versus
just oral 5-ASA therapy can be used (≥2 Budesonide MMX appears to be combination therapy in the treatment of distal ulcerative
colitis. Am J Gastroenterol. 1997;92(10):1867-1871.
g/day). Systemic corticosteroids should an effective agent for patients with UC 5. Sandborn WJ, Travis S, Moro L, et al. Once-daily
be restricted to induction treatment. who have failed 5-ASA treatment.5,6 budesonide MMX extended-release tablets induce
Successful treatment is defined as Dr Kane presented a treatment algo- remission in patients with mild to moderate ulcerative
colitis: results from the CORE I study. Gastroenterology.
overall improvement at week 6 accord- rithm for maximizing remission and 2012;143(5):1218-1226.e2.
ing to a clinical assessment of rectal minimizing corticosteroid dependence 6. Travis SP, Danese S, Kupcinskas L, et al. Once-daily
bleeding and stool frequency and in UC, noting that budesonide MMX budesonide MMX in active, mild-to-moderate ulcer-
ative colitis: results from the randomised CORE II
the results of sigmoidoscopy. In the may be the best option for patients study. Gut. 2014;63(3):433-441.
Disease Activity Assessment: What Should We Do in Clinical
Practice?
D
r Bruce E. Sands began his aiming for deep remission. symptoms, signs, endoscopy, histology,
presentation by emphasizing Dr Sands noted the importance of and biomarkers. It asks how the patient
how the goals of therapy have distinguishing between disease activity is today. In contrast, disease severity is
changed over time.1 Clinical response and disease severity. Disease activ- a measure of longitudinal and histori-
was once the target outcome, and then ity reflects cross-sectional evaluation cal factors. An assessment of disease
it was remission; today, clinicians are of biologic inflammatory impact on severity provides a more complete
10 Gastroenterology & Hepatology Volume 17, Issue 1, Supplement 2 January 2021HIGHLIGHTS FROM THE 2020 VIRTUAL ADVANCES IN IBD CONFERENCE
picture of a patient’s prognosis and
overall burden of disease. This assess- Stratify according to risk of relapse
ment asks about the course of disease
since the diagnosis.2
To assess disease severity, physi-
cians must consider the effect of the Low risk High risk
disease on the patient, the course of the
• Remission >1 year • Flare within 1 year
disease, the presence of any complica-
tions, and the inflammatory burden. • Stable maintenance therapy • R
ecent change in maintenance
therapy
Because CD and UC are progressive • Endoscopic healing
• Persistent endoscopic lesions
disorders, both disease severity and • Histologic healing
disease activity must be factored into • P
ersistent neutrophil
• Smoking habit
infiltration in biopsy
clinical decisions. • Good adherence to therapy
• Recent smoking cessation
An assessment of disease severity • Age >50 years
in CD considers whether mucosal • Low adherence to therapy
lesions, fistulae, abscesses, and stric- • AgeSPECIAL MEETING REVIEW EDITION
CD is more complicated. Dr Sands the treat-to-target approach, which Advances in Inflammatory Bowel Diseases Conference;
December 9-12, 2020.
pointed out that endoscopic software included biomarker monitoring, were 2. Peyrin-Biroulet L, Panés J, Sandborn WJ, et al.
enables clinicians to score various greatly superior to the outcomes of Defining disease severity in inflammatory bowel dis-
criteria automatically as part of the those who received clinical manage- eases: current and future directions. Clin Gastroenterol
Hepatol. 2016;14(3):348-354.e17.
colonoscopy report. Cross-sectional ment.6 3. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Select-
imaging is also important for evaluat- Patients with UC can be catego- ing Therapeutic Targets in Inflammatory Bowel Disease
ing CD activity. Clinicians should rized as low risk or high risk and moni- (STRIDE): determining therapeutic goals for treat-to-
target. Am J Gastroenterol. 2015;110(9):1324-1338.
look at thickening, hyperenhancement, tored accordingly. Low-risk patients 4. Christensen B, Hanauer SB, Erlich J, et al. Histologic
and the severity of edema and ulcers. can be seen every 6 to 12 months, for normalization occurs in ulcerative colitis and is associ-
Patients with transmural healing on example. High-risk patients should ated with improved clinical outcomes. Clin Gastroenterol
Hepatol. 2017;15(10):1557-1564.e1.
cross-sectional imaging are likely to be seen every 3 to 4 months, with the 5. Fernandes SR, Rodrigues RV, Bernardo S, et al. Trans-
have better outcomes and a reduced calprotectin level checked every 2 to 3 mural healing is associated with improved long-term
need for surgery and hospitalization.5 months. An endoscopic examination outcomes of patients with Crohn’s disease. Inflamm
Bowel Dis. 2017;23(8):1403-1409.
Finally, Dr Sands discussed the should be performed if a patient is 6. Colombel JF, Panaccione R, Bossuyt P, et al. Effect of
role of biomarkers in monitoring experiencing symptoms or has abnor- tight control management on Crohn’s disease (CALM):
disease activity. The fecal calprotectin mal biomarker findings (Figure 2).7 a multicentre, randomised, controlled phase 3 trial.
Lancet. 2018;390(10114):2779-2789.
level is widely used in CD; the higher 7. Panes J, Jairath V, Levesque BG. Advances in use
the score, the greater the endoscopic References of endoscopy, radiology, and biomarkers to moni-
activity. In the CALM study, the 1. Sands BE. Disease activity assessment: what should tor inflammatory bowel diseases. Gastroenterology.
we do in clinical practice? Presented at: 2020 Virtual 2017;152(2):362-373.e3.
outcomes of patients managed with
Precision Medicine in IBD
D
r Maria T. Abreu explored adapted as needed as care proceeds. genetic features have so far not been
several reasons for pursuing With regard to genetics, children tightly tied to responses to specific
precision medicine in IBD.1 who have mutations in IL-10 and the treatment approaches in adults. Dr
Because no single cause exists, no sin- IL-10 receptor pathway overproduce Abreu noted that in the management
gle cure exists. The range of treatments IL-1 and can often be treated effec- of IBD, clinicians often move from
is expanding, with many different tively with anti–IL-1 strategies, as one treatment approach to another
targets. The emergence of biomarkers well as hematopoietic bone marrow without allowing sufficient time for
is increasing the feasibility of tailoring transplant. However, although more a response, and without stratifying
treatment, and data are accruing on than 240 confirmed loci are associated patients according to phenotype,
combination therapies. Each patient with IBD, and more than 50 genes are genotype, or meta-type.
requires a unique approach that can be associated with very early–onset IBD, Biomarkers are emerging as an
important feature that can be applied
in precision medicine in IBD. Data
from a pediatric study showed that the
Outcomes of Standard and Intensified Dosing of Ustekinumab biological signature correlating per-
for Chronic Pouch Disorders foration and fibrotic complications is
Dr Rahul S. Dalal and colleagues used clinical data obtained from electronic present in pediatric patients with IBD
health records to assess the outcomes of both standard and intensified dos- before treatment.2 In addition, investi-
ing of ustekinumab (abstract P028). Of 13 patients, 4 discontinued antibiotics gators have found distinct changes in
within a year after treatment initiation, and 10 of the 19 patients using cortico- DNA methylation and transcription
steroids at the start of treatment discontinued them within 16 weeks. A total patterns in the colon epithelium of
of 18 of 42 patients required hospitalization within a year after starting treat- patients with CD and patients with
ment, and 23 of 46 patients received dose intensification. Of the 46 patients UC, compared with controls.3
whose records were obtained, a clinical response was achieved in 37 within 16 The HLA-DQ polymorphism is
weeks. The researchers concluded that dose intensification is effective for most likely to become important for patient
patients. Patients who were female and those who had a pouch fistula were stratification. Over 30% of patients
more likely to respond after treatment initiation, whereas those using cannabis with IBD have this polymorphism,
were less likely to respond. The patients who required dose intensification the and data show that anti-TNF agents
soonest tended to be younger at the time of IBD diagnosis. are most effective in this population
when combined with immunomodu-
lators. Antidrug antibodies almost
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