Infliximab Optimization for Crohn's Disease

Recruiting at 25 trial locations

Overseen By Vivian Cheng

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must be taking: Infliximab

Must not be taking: Adalimumab

Disqualifiers: Infections, Malignancy, Immunodeficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

124 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on oral corticosteroids, you may need to taper off by Week 14. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Infliximab for Crohn's disease?

Research shows that Infliximab, an anti-TNF-alpha antibody, is effective in treating severe Crohn's disease, especially when other treatments have failed. It helps reduce inflammation and maintain remission, improving the quality of life for patients. ^{1 2 3 4 5}

Is infliximab safe for humans?

Infliximab, used for Crohn's disease and other conditions, has been studied in many trials and is generally considered safe, though it can cause side effects like headaches, fever, and chills. It may increase the risk of infections, but not serious ones, and has a low risk of causing drug-induced lupus, which resolves after stopping the drug. ^{3 6 7 8 9}

How is the drug infliximab unique in treating Crohn's disease?

Infliximab is unique because it is a biologic drug that targets TNF (tumor necrosis factor), a protein involved in inflammation, making it effective for patients with moderate to severe Crohn's disease who do not respond to standard treatments. It can reduce the need for steroids and surgery, and is particularly useful for treating fistulas, which are abnormal connections between organs. ^{1 3 8 10 11}

What is the purpose of this trial?

This trial tests if using a computer program to decide infliximab doses is better and safer than standard dosing for patients with inflammatory bowel disease. The program helps doctors choose the best dose by looking at individual health details, aiming to keep the medication working well and prevent the disease from getting worse. Infliximab is commonly used to treat inflammatory bowel disease, and dose optimization has been shown to improve treatment outcomes.

Eligibility Criteria

The OPTIMIZE Trial is for males and females aged 16-80 with moderately to severely active Crohn's Disease. Participants must have certain disease markers like elevated CRP or fecal calprotectin, and no prior significant use of Infliximab. Exclusions include those with specific CD complications, infections like tuberculosis or hepatitis B/C, recent serious infections, cancer within the last 5 years (except some skin cancers), immunodeficiency disorders, high-dose steroid use without tapering plans, pregnancy or lactation.

Inclusion Criteria

Moderately to severely active CD, defined by a total Crohn's Disease Activity Index (CDAI) score between 220 and 450 points, and at least 1 of the following: Elevated CRP > upper limit of normal, Elevated fecal calprotectin (FC) (> 250 μg/g), SES-CD > 6, or SES-CD > 3 for isolated ileal disease, Physician intends to prescribe IFX as part of the usual care of the subject, No previous use of IFX prior to enrolment in the current study, unless the participant received 1 prior dose of IFX (within 2.5 weeks of enrolment) and met all eligibility criteria at the time of starting IFX and IFX was administered according to the requirements outlined in this protocol, Able to participate fully in all aspects of this clinical trial, Written informed consent must be obtained and documented

I am a male or a non-pregnant, non-breastfeeding female aged between 16 and 80.

I have been diagnosed with Crohn's disease based on tests.

Exclusion Criteria

I do not have complications or conditions that would interfere with the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either proactive infliximab optimization using a pharmacokinetic dashboard or standard of care infliximab dosing

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Infliximab

Trial Overview This trial tests if using an iDose dashboard-driven dosing method for Infliximab is more effective and safer than standard dosing in achieving and maintaining remission in Crohn's Disease patients. The study compares these two approaches to see which one better controls the symptoms of this digestive disorder.

Participant Groups

Group I: standard of care infliximab dosing Experimental Treatment 1 Intervention

standard of care infliximab dosing

Group II: proactive infliximab optimization Experimental Treatment 1 Intervention

proactive infliximab optimization using a pharmacokinetic dashboard

Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in United States as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Canada as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Japan as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Findings from Research

Infliximab therapy was effective in treating severe and refractory Crohn's disease, with 79% of patients showing an objective response and 72% achieving remission during an average follow-up of 8 months.

The treatment also had a steroid-sparing effect in 73% of patients, and those on immunosuppressive therapy experienced a significantly lower relapse rate (18% vs. 56%), indicating that combining therapies may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study]. Doubremelle, M., Bourreille, A., Zerbib, F., et al.[2015]

In a 52-week study involving 24 patients with Crohn's disease who previously lost response to infliximab, adalimumab demonstrated significant efficacy, with clinical remission rates increasing from 35% at baseline to 58% at week 52.

Adalimumab was well tolerated, with no patients experiencing intolerance and no serious toxicities reported, indicating it is a safe option for maintaining remission in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. Peyrin-Biroulet, L., Laclotte, C., Bigard, MA.[2015]

Remicade (Infliximab) has been shown to be effective in treating active Crohn's disease, maintaining remission, and managing fistulae, but it is not recommended as a first-line treatment.

Due to potential risks, including unknown malignancy rates, Remicade should be administered in a controlled setting with monitoring for adverse reactions, and further studies are needed to gather more data on its efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group. Lochs, H., Adler, G., Beglinger, C., et al.[2015]

In a study involving 6290 patients with Crohn's disease, infliximab treatment did not show a higher mortality rate compared to other therapies, indicating its long-term safety in this regard.

While there was an observed increased risk for serious infections in infliximab-treated patients, this risk was more closely linked to factors like disease severity and the use of prednisone rather than infliximab itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Lichtenstein, GR., Feagan, BG., Cohen, RD., et al.[2022]

Infliximab, an anti-TNF-alpha monoclonal antibody, was studied in 771 patients for Crohn's disease and rheumatoid arthritis, showing an acceptable safety profile with only 17% experiencing acute infusion reactions compared to 7% in the placebo group.

While infliximab was associated with a higher overall rate of infections (26% vs. 16% for placebo), there was no increased risk of serious infections or difference in mortality rates, indicating it is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. Schaible, TF.[2019]

In a study of 6,273 Crohn's disease patients with an average follow-up of 5.2 years, infliximab treatment did not increase mortality risk compared to other treatments, indicating its long-term safety in this regard.

However, infliximab was associated with a higher risk of serious infections, although this risk was also influenced by the severity of the disease and the use of medications like prednisone and narcotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Lichtenstein, GR., Feagan, BG., Cohen, RD., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study]. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Adalimumab for the treatment of Crohn's disease. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Infliximab use in Crohn's disease. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment of luminal and fistulizing Crohn's disease with infliximab. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Infliximab as disease-modifying therapy. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Clinical outcome of newly diagnosed Crohn's disease: a comparative, retrospective study before and after infliximab availability. [2019]