Biologics for Crohn’s Disease

Biologics for Crohn’s Disease have revolutionized the treatment of patients with severe symptoms who do not respond to the first and second line of treatments. 

Physicians tend to use biologics in patients with Crohn’s disease to:

• Induce remission of the disease
• Avoid flare-ups and hospitalization
• Avoid complications of the disease
• Avoid complications of steroids and other conventional therapies
• Heal intestinal mucosa and fistulas

The main objective of using Biologics for Crohn’s disease is to induce remission, relieve the symptoms, and stop inflammation.

When previous treatments have failed to provide relief for more severe Crohn’s symptoms, biological therapy is typically administered.

However, guidelines now advise that physicians also prescribe biologics as a first-line treatment for patients with severe illnesses.

How do Biologics for Crohn’s Disease Work?

Biologics are humanized monoclonal antibodies that target a specific pathway of inflammation. There are three different groups of biologics approved for the treatment of Crohn’s disease. These include:

• TNF Inhibitors:

  • Infliximab (Remicade)
  • Adalimumab (Humira)
  • Certolizumab Pegol (Cimzia)

• Interleukin Targeted Therapies

  • Ustekinumab (Stelara)

• Integrin Inhibitors:

  • Vedolizumab (Entyvio)
  • Natalizumab (Tysabri)

Because TNF (Tumor necrosis factor), Interleukins, and Integrins play a primary role in the inflammatory process, inhibiting these cytokines can markedly reduce inflammation.

In addition, since these biologics are very specific, they have minimal systemic side effects.

These drugs help a lot of people, and improvements can sometimes be seen right away or up to eight weeks later.

Benefits of Biologics for Crohn’s Disease:

Biologics are strong and specific anti-inflammatory drugs, these drugs can have significant benefits in the treatment of patients with Crohn’s disease [Ref].

• Biologics are used when other therapies fail to control the symptoms of the patients
• To avoid the relapse or recurrence of symptoms
• These drugs may be used for a prolonged duration via injections or intravenous infusions every 2 to 8 weeks.
• Apart from infections and allergic reactions, biologics for Crohn’s disease are not associated with systemic side effects as may occur with corticosteroids and other first-line therapies for Crohn’s disease.

TNF Inhibitors: Biologics for Crohn’s Disease:

TNF inhibitors are the most commonly used biologics for Crohn’s disease. Infliximab (Remicade) was the first approved biological treatment for Ulcerative Colitis and Crohn’s disease.

Remicade (Infliximab):

Among other names, Remicade is a brand name for the drug infliximab, a chimeric monoclonal antibody that is used to treat a variety of autoimmune diseases like Crohn’s disease.

Remicade may make it easier for patients to control flare-ups. It may also help sustain remission to prevent symptoms from returning.

Remicade is administered straight into the circulation, enabling it to begin reducing symptoms right away.

It is administered at a hospital. There will be skilled medical personnel on hand to keep an eye out for adverse effects both during and after treatment.

Remicade does not require daily administration. After the first three doses, the infusion frequency may be adjusted to the patient’s clinical response. As few as 6 doses per year may be required.

The drawback of Remicade is that it needs to be administered intravenously at a hospital for a two-hour period [Ref].

Adalimumab (Humira):

Humira is the brand name of Adalimumab, which is a potent TNF inhibitor. It inhibits the inflammatory cascade that occurs as a result of immune dysregulation in patients with Crohn’s disease.

It is an injectable medicine that is administered subcutaneously every two weeks until clinical remission is achieved.

By preventing inflammatory responses in your body, biological medications such as Humira can decrease inflammation and control the symptoms of Crohn’s disease. This can aid in the disease’s remission and reduce the symptoms of Crohn’s.

You could be given Humira as your first-choice medication to treat your moderate to severe Crohn’s disease. If other forms of therapy have failed for you, the medicine may also be taken into consideration.

The clinical response and remission rates with Adalimumab have been in the ranges of about 40% to 50% [Ref]

Humira has also resulted in meaningful remission rates in patients who are either intolerant to infliximab or have a poor response to Infliximab.

It has also been approved for the treatment of children with Crohn’s disease.

Certolizumab pegol (Cimzia):

Certolizumab pegol is sold under the trade name Cimzia. It is a biological medication that belongs to the anti-TNF class of drugs or simply is a TNF inhibitor.

In multiple clinical trials and meta-analyses, it has been proven to induce remission of moderate to severe Crohn’s colitis [Ref].

The clinical response of patients with moderate to severe Crohn’s disease with Certolizumab has been around 37% compared to 26% in patients treated with placebo medicine [Ref]

Cimzia is administered into the skin every 2 – 4 weeks initially and then every month. The injection can be administered at home or at your doctor’s office.

You have the possibility of choosing your therapy in powder form if you decide to receive it at your doctor’s office. The powder is injected after being diluted with sterile water.

The use of prefilled syringes is the alternate choice. Medicine that has previously been prepared in precise dosages is in the syringes. Prefilled syringes can be used both at home and at the doctor’s office.

If you decide to administer the treatments yourself, you’ll get a kit that includes two syringes and administration guidelines.

You can take Cimzia once every 4 weeks after the initial three doses, which are administered every 2 weeks.

Interleukin-targeted therapies for Crohn’s disease:

It has been observed that the intestinal lumen overexpresses certain cytokines in patients with Crohn’s disease. These cytokines are pro-inflammatory.

IL-12 is one such cytokine that can be inhibited by Ustekinumab.

Ustekinumab (Stelara):

Ustekinumab is a monoclonal antibody. It is available by the trade name Stelara. It is manufactured and marketed by Janssen Pharmaceuticals to treat Crohn’s disease.

It targets IL-12 and IL-23 which are overexpressed in the intestinal lumen of patients with Crohn’s disease.

For treating people with moderate to severe Crohn’s disease who have not responded enough to conventional therapy, Stelara is the only medication in this class that has received approval.

In clinical trials, it has achieved a good response rate of 50 – 60% in patients with moderate to severe Crohn’s disease compared to 25% in the placebo group of treated patients [Ref].

The medication specifically targets proteins involved in the process of inflammation.

Stelara is originally administered intravenously under a healthcare professional’s supervision.

Following the initial dose, it can be administered by a medical professional through an injection beneath the skin every 8 weeks or by yourself once you’ve received training.

Integrin Inhibitors: Novel Biologics for Crohn’s Disease:

Integrin-targeted therapies are among the most effective and safest biologics for Crohn’s disease. These drugs are effective even in patients who are non-responsive to other biologics for Crohn’s disease including TNF inhibitors.

The two integrin-targeted therapies approved for use in the United States are Vedolizumab and Natalizumab.

Vedolizumab (Entyvio):

Vedolizumab, sold under the brand name Entyvio, is a prescription drug. When previous treatments haven’t sufficiently helped a patient’s moderate-to-severe ulcerative colitis (UC) or Crohn’s disease, this drug is frequently utilized.

Entyvio has been used for the therapy of individuals with moderate to severe Crohn’s disease who haven’t reacted well to, are intolerant of, or can’t take a TNF blocker, immunomodulator, or corticosteroid for other reasons. [Ref]

It functions in a manner similar to Tysabri, working on certain white blood cells to stop them from creating the intestinal inflammation connected with Crohn’s disease.

Entyvio, on the other hand, targets the stomach and doesn’t seem to have the same risk of PML (Progressive multifocal leukoencephalopathy).

Entyvio is a highly specific integrin inhibitor compared to Natalizumab. It inhibits the binding of α₄β₇ integrin and MAdCAM-1.

It is indicated in patients with Crohn’s disease to induce clinical remission, reduce the dependency on corticosteroids, and achieve a clinical response.

As an intravenous infusion, Entyvio is administered under a doctor’s supervision. On the first day of therapy, more than 30 minutes are spent on it. Following that, it is done every eight weeks on weeks two and six.

Entyvio medication should be stopped if Crohn’s disease symptoms do not improve by week 14. Make sure your vaccinations are up to date before beginning Entyvio.

Natalizumab (Tysabri):

Tysabri, which contains Natalizumab, belongs to a group of drugs known as alpha-4 integrin inhibitors.

Tysabri is indicated for those patients who have moderate-to-severe Crohn’s disease that is not adequately responding to immunomodulatory or at least one anti-TNF drug.

By inhibiting a protein on the surface of these cells, Tysabri stops white blood cells that cause inflammation from penetrating tissues.

Tysabri is administered intravenously every four weeks over one hour. Patients are monitored for an hour or so after the infusion.

Natalizumab (Tysabri) is associated with progressive multifocal leukoencephalopathy (PML) which is a serious brain disease.

Because of its association with PML, it is a less preferred integrin inhibitor compared to Entyvio (Vedolizumab).

In Summary:

Biologics for Crohn’s disease are a breakthrough in the treatment of this serious long-lasting and debilitating disease.

TNF inhibitors, Stelara (Ustekinumab), and Entyvio (Vedolizumab) are the preferred biologics for Crohn’s disease.

The efficacy of the different biologics differ. Vedolizumab (Entyvio) is a more effective biologic for Crohn’s disease compared to TNF inhibitors.