Biologic therapies for Crohn’s disease (CD) do more than reduce the common symptoms of diarrhea, abdominal cramping, and pain. These drugs can also help the “other” symptoms of CD, known as extraintestinal manifestations.

CD and ulcerative colitis (UC) are the two primary conditions that make up inflammatory bowel disease (IBD). This is an umbrella term for several manifestations of chronic inflammation affecting the gastrointestinal (GI) tract.

CD is traditionally treated with a variety of medications to help manage inflammation and unusual immune activity, but exactly which medications a doctor prescribes depends on a person’s symptoms, the severity of CD, the extent of their disease, prior medications tried, and personal choice.

In severe cases of CD or when traditional medications are not effectively managing symptoms, doctors may prescribe biologic therapies, which are medications created from components of living organisms. While these therapies usually alleviate GI symptoms in CD, they may also help symptoms that do not occur in the GI tract, known as extraintestinal manifestations (EIMs).

This article explores how biologics help with the other symptoms of CD, how they work, and what side effects to be aware of.

Biologic therapies for CD can be effective for managing GI symptoms like diarrhea and abdominal pain, but they can also help reduce non-GI symptoms or EIMs.

Common EIMs in CD include:

  • arthritis
  • skin irritation, rashes, or sores
  • decrease in bone strength or density
  • eye inflammation
  • kidney and liver complications
  • low red blood cell count

A 2019 review notes that the targeted actions of biologics allow doctors to customize CD treatment for each individual and their symptoms. Each class of biologics targets certain elements of inflammation, and depending on how they do that, they may also be effective for specific EIMs.

Some biologics for CD, for example, also have Food and Drug Administration (FDA) approval for the treatment of musculoskeletal conditions that frequently coexist with IBD. For someone experiencing the EIM of arthralgias (joint pain), these biologics may become a preferred option over others.

Current biologic therapies in CD and their inflammation targets include:

  • Anti-TNF agents: These target the inflammatory cytokine tumor necrosis factor (TNF).
  • Anti-integrin agents: These block the ability of immune cells to travel to inflamed areas in the intestines.
  • Interleukin inhibitors: These block interleukin cytokines that stimulate an inflammatory response.

How well a biologic works for the non-GI symptoms in CD depends on the medication’s mode of action. A doctor may prescribe a less effective biologic for EIMs if it has superior effects for severe GI symptoms, negatively affecting quality of life.

It is helpful to understand why symptoms develop in the first place and how biologics can help with GI symptoms and EIMs in CD.

Why symptoms develop

CD is considered an inflammatory condition of the entire GI tract, but it primarily affects the end of the small intestine and the large intestine. Inflammation and irregular immune activity in these areas create classic uncomfortable symptoms like diarrhea and abdominal cramping.

However, the effects of CD can become body-wide. Over time, persistent inflammation in the intestines affects the permeability of the intestinal lining, making it more porous to inflammatory substances.

As these substances cross through the lining of the intestines into the bloodstream, they can also trigger immune reactions throughout the body, resulting in various non-GI symptoms — EIMs.

Although the exact cause of EIM in Crohn’s is still unknown, researchers believe EIMs result from either a targeted immune response from the intestine that travels to an extraintestinal location or an independent immune response triggered by a combination of genetic susceptibility and environmental risk factors.

Research suggests that inflammation in the gut disrupts the gut microbiome and may lead to alterations in the immune response. This causes an increase in gut permeability, which leads to the traveling of bacteria, toxins, and inflammatory markers outside the GI tract, where they trigger the immune response.

How biologics can help

Biologics for CD work by interrupting these inflammatory processes. Their method of action, or where and how they break the inflammation cycle, can affect both GI symptoms and EIMs.

Some biologics, for example, are “gut-selective,” meaning they target inflammation pathways specifically in the GI tract. Other biologics are “non-gut selective.” They work throughout the body to suppress inflammation.

One multicenter study from 2022, which compared non-gut-selective biologics to the gut-selective biologic vedolizumab (VDZ), found that non-gut-selective biologics appeared to be more successful in managing EIMs than VDZ.

Experts believe this is because EIMs represent body-wide inflammatory processes. Therefore, they’re more likely to respond to non-gut selective biologics.

That does not mean gut-selective biologics will not work for EIMs. Ultimately, reducing inflammation in CD may help reduce related inflammation elsewhere in the body.

Which biologics are most effective for EIMs in Crohn’s?

While EIMs in CD can be very individual, a 2022 practical guide on the selection of biologics suggests infliximab and adalimumab are the most effective for managing EIMs.

Infliximab and adalimumab are both anti-TNF agents.

Was this helpful?

As with most medications, biologics in CD can cause side effects, also known as adverse drug reactions (ADRs).

Common ADRs in biologic use for CD include:

  • injection site swelling, discoloration, or lump formation
  • skin flushes
  • coughing
  • blood pressure spikes
  • nausea
  • headaches
  • rash
  • dizziness
  • fever
  • difficulty breathing
  • sense of chest constriction
  • increased susceptibility to infection
  • drug-induced lupus
  • reactivation of hepatitis B
  • tuberculosis

In rare cases, biologic use may lead to leukopenia, which is decreased levels of white blood cells in the bloodstream.

Biologic therapies for CD are still an emerging and evolving area of therapy. Though typically reserved for moderate/severe CD or CD that is unresponsive to first-line treatments, these medications are increasingly making their way into standard practice for IBD as a part of combination therapy.

CD does not have to be significantly affecting a person’s quality of life before biologics become a topic of conversation. Discussing available biologic options with a doctor can help provide insight into why they may or may not support current treatment strategies.

To help make the most of this conversation, a person can consider:

  • learning more about current biologic therapies in CD
  • writing a list of questions about biologic use
  • noting personal experiences that may warrant adding biologics to current therapies
  • bringing a loved one to help take notes

When adding biologics to a treatment plan, doctors factor in more than just EIMs. They will consider a person’s age, medical history, symptoms, disease severity, and quality of life.

Biologics are a relatively new and promising area of therapy for treating both GI and non-GI symptoms of Crohn’s disease. These medications work by disrupting the inflammatory cycle responsible for the symptoms.

Biologics are mainly used to help treat moderate to severe Crohn’s. A person can talk with their doctor to determine whether biologics may be right for them.