Biologics for Ulcerative Colitis

Biologics for Ulcerative Colitis include drugs that target Interleukins, TNFs, Integrins, and JAK receptors.

Entyvio and Stelara are being increasingly used because of their exceptional efficacy in the treatment of severe ulcerative colitis.

In addition, oral Biologics for ulcerative colitis include Tofacitinib (Xeljanz)

Biological treatment is an effective treatment for most pathological diseases. It is used frequently because it has minimum side effects as compared to other steroidal or pharmaceutical drugs.

The commonly used conventional drugs prescribed for ulcerative colitis are:

• Aminosalicylates (Pentasa and Asacol)
• Corticosteroids (Budesonide and prednisolone)
• Immunosuppressive drugs (Azathioprine and Cyclosporine)

The above-mentioned drugs are not biologics for Ulcerative Colitis but these are common in use because they are very cheap compared to biologics therapy.

What are Biologics?

Biologics are man-made drugs that are produced in the laboratory. They are typically derived from biological sources which include viruses, proteins, blood, etc.

The main difference between a drug and a biological one is that these are large complex molecules that are produced by recombinant DNA technology.

The use of biologics is important and very vast because these are very specific in action and their side effects are not as usual and dangerous as other pharmaceutical drugs.

Biologics for Ulcerative Colitis:

There are four types of biologics that are usually given to patients suffering from ulcerative colitis. These are as follows:

• Interleukin inhibitors.
• Anti-tumor necrosis factors.
• Integrin receptor antagonists.
• JAK Inhibitors

These types of biologics have different mechanisms of action as well as efficacy and potency. These are described below.

Anti-tumor necrosis factors or TNF Inhibitors:

The main goal of using TNF Inhibitors is to reduce the inflammation in the body. They bind with the TNF-alpha receptors and inhibit the inflammatory cascade.

In patients with UC, tumor necrosis factors are the culprit for the inflammation. Anti-TNF drugs are potent inhibitors of intestinal inflammation.

Different types of anti-TNF are available but some of them which are used for UC are discussed below:

• Infliximab (Remicade) for Ulcerative Colitis:

It is a monoclonal antibody that can be given to patients with UC because they bind with TNF-alpha and blocks its action of causing inflammation in the body.

It is mostly prescribed when the other remedies have not been fruitful to the patient. It is given by infusion through a vein and the time period to get the results can be reached up to 6 weeks. It comes under the trade name Remicade.

Three doses are given in the first weeks which is followed by one dose after eight weeks. It is effective for patients with moderate to severe UC.

Infliximab has been studied in patients with moderate to severe ulcerative colitis in comparison to placebo. Infliximab was administered at two doses (5 and 10 mg/kg) at 1, 2, and 6 weeks. The results of the two large clinical trials are given in the table below [Ref]:

• Adalimumab (Humira) for Ulcerative Colitis:

Adalimumab is a fully human monoclonal antibody and hence is not associated with injection site reactions and antibody formation.

It is a prescription drug for moderate to severe UC and is given with the help of an injection. The injections are admitted into the abdomen or thigh after every two weeks.

The success rate of adalimumab is between 16.5 to 18.5 % and it comes under the brand name Humira.

It is contraindicated in children below 5. It is more effective than a placebo and the one using this can achieve remission after 8 weeks.

Ultra 1 and Ultra 2 were two clinical trials that evaluated the efficacy of Adalimumab in the treatment of ulcerative colitis.

Adalimumab was given in two different dosing regimens as:

• 160/80/40 dose: 160 mg at week 0, 80 mg at week 2, and 40 mg every other week thereafter
• 80/40/40 dose: 80 mg at week 0, 40 mg at week 2, and 40 mg every other week thereafter

The clinical remission rates at 8 weeks in the two studies were significantly greater in the Adalimumab group compared to patients in the placebo group:

In addition, the incidence of hospitalization was reduced by about 50% in patients treated with Adalimumab compared to those treated with placebo.

• Golimumab (Simponi) for Ulcerative Colitis:

Golimumab (Simponi) has been approved for the treatment of other autoimmune rheumatic diseases like severe Rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

This biologic is used when the patients who were taking steroids have stopped using them and they are facing some issues like nausea, fatigue, headache, etc.

Usually, two injections are administered on the first day of treatment and then 1 injection after two weeks. After two weeks the dose becomes one injection every 4 weeks.

In patients with moderate to severe ulcerative colitis who were treated with Simponi, the clinical remission rates are around 30% compared to 15% in the placebo group.

The mucosal healing rate as determined by endoscopy is about 40% compared to 25% in the placebo group.

Its brand name is Simponi which was approved in 2013 by FDA for UC.

Integrin receptor antagonists (IRAs) for Ulcerative Colitis:

These are the biologics that have the same role of reducing inflammation just like anti-TNF but they work differently.

These are also antibodies just like the anti-TNF but they are against the integrin molecules. They bind to the alpha 4 subunit of the integrin molecule resulting in halting of the movement of lymphocytes or cytokines.

The two adhesion molecules that are overexpressed in patients with inflammatory bowel diseases including ulcerative colitis are ICAM-1 and MAdCAM-1.

These two molecules are targets for the commonly used drug, Vedolizumab (Entyvio), and the new drug, Ertolizumab.

The effect is reduced inflammation due to a lack of movement of cells responsible for inflammation and thus the symptoms of UC are relieved.

• Vedolizumab (Entyvio) for Ulcerative Colitis:

It comes with the trade name Entyvio and it is an IV medication. They are given to patients who are avoiding taking steroids or are tolerant of other medications.

Vedolizumab inhibits the binding of MAdCAM-1 and α4β7 integrin. This inhibits leukocyte movements to the intestinal mucosa.

In clinical trials, Entyvio was found more effective than placebo as induction and maintenance therapy in patients with active ulcerative colitis [Ref].

The clinical response, clinical remission, and mucosal healing rates with Vedolizumab treatment in patients with Ulcerative colitis are around 50%, 17%, and 40% respectively.

Entyvio can also be given to patients who have been previously treated with a TNF inhibitor.

Normally 3 doses are given with every single dose at the interval of two weeks and after that single dose, every 8 weeks is administered.

• Ertolizumab:

Ertolizumab is another novel integrin inhibitor that targets the ß7 subunit of α4β7 and αEβ7 molecules.

The clinical response to Ertolizumab has been evaluated in patients non-responsive to other therapies.

In clinical trials, two dosing regimens 100 mg and 300 mg were administered at weeks 2, 4, and 8 after a loading dose of 240 mg subcutaneously.

The clinical remission rates ranged from 25% to 40% in patients not treated with a TNF inhibitor. In patients previously treated with a TNF inhibitor, the clinical remission rates were in the range of 5% [Ref].

Interleukin inhibitors for Ulcerative Colitis:

Interleukin inhibitors are the biologics used to suppress the immune system. Interleukins of different types are responsible for the proper functioning of the immune system as well as the movement of immune cells.  In the case of UC, they target the proteins that direct inflammation.

It is considered one of the most effective treatments with the infusion of a single dose which is followed by another dose after 8 weeks.

• Ustekinumab (Stelara) for Ulcerative Colitis:

The recent biologic that is approved by FDA in 2019 is ustekinumab which comes under the brand name Stelara. It works by inhibiting the two interleukins specifically. These are IL-12 and IL-23.

It is also an antibody obtained from a single clone of an animal source. It is a slow-acting drug as it can take up to three years for the upheld symptomatic remission.

It has been one of the potent biologics for Ulcerative Colitis in the induction and maintenance treatment of moderate to severe ulcerative colitis [Ref].

JAK Inhibitors for Ulcerative Colitis:

JAK inhibitors are orally available biologics for the treatment of ulcerative colitis. Among the biologics for ulcerative colitis, JAK inhibitors are potent, the cheapest, and orally available biologics.

Tofacitinib (Xeljanz) for Ulcerative Colitis:

Tofacitinib (Xeljanz) is a novel class of potent JAK inhibitors that inhibits JAK 1, 2, and 3. It inhibits the six cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 that are primarily responsible for lymphocyte activation and proliferation.

The clinical response rate in patients with ulcerative colitis was:

• Placebo: 42%
• Xeljanz 0.5 mg twice daily: 32%
• Xeljanz 3 mg twice daily: 48%
• Xeljanz 10 mg twice daily: 61%
• Xeljanz 15 mg twice daily: 78%

Tofacitinib is also available as a generic medication at a much cheaper price. In addition, because it is taken orally twice daily, it may be one of the few first-line biologics for Ulcerative Colitis.

Side effects of using biologics for Ulcerative Colitis:

As we all know that everything that has merits contains demerits as well.

Some of the demerits or adverse effects are mentioned below:

• Headache
• Fever
• Chills
• Allergic reactions can also occur sometimes.
• Injection site reactions.

Apart from the above-listed effects, some serious hazards that can occur are as follows:

• Lymphoma
• Liver complications.
• Heart abnormalities.
• Pain in the joints.

Advantages of using biologics over other drugs in UC

The best advantage of using biologics over other drugs is that they do not interfere with the whole immune system rather they just affect the inflammatory areas in the body.

The use of biologics has decreased the need for surgery and other treatments in the case of UC so it may be considered a rescue therapy for patients with severe ulcerative colitis.

Disadvantages of Biologics in Ulcerative Colitis:

Disadvantages of using biologics primarily include immunosuppression resulting in opportunistic infections and higher costs.

In fact, the biggest disadvantage of it is that they are quite an expensive treatment. Not all patients have got access to these expensive medications.

Furthermore, most biologics, with the exception of Tofacitinib, are administered as injections.