The goal of Crohn’s disease treatment is to control inflammation in the gut and prevent symptoms from flaring up. These interventions involve a combination of medications, dietary changes, and possibly surgery.

Crohn’s disease is a form of inflammatory bowel disease (IBD) that causes inflammation and irritation in the digestive tract. It is a chronic condition, though symptoms may appear in a relapsing-remitting pattern.

Everyone with Crohn’s disease responds differently to treatment. What works for one person may not work well for another. Even if a treatment works at first, it may not work forever, as the disease changes and progresses.

This article explores how to determine whether a treatment change for Crohn’s disease is necessary, including signs that medications may have stopped working and options for next steps.

When treating Crohn’s disease, doctors often use a combination of medication and lifestyle changes. The goal of these treatments is to control and prevent inflammation in the digestive tract to help prevent symptoms from occurring.

Most medications to treat Crohn’s disease work by suppressing the activity of the immune system, which is responsible for the disease-causing inflammation. These medications do not cure the disease but can help prevent symptoms and further damage to the intestines.

There are several different types of medications to help manage Crohn’s disease, including:

  • corticosteroids, such as:
    • hydrocortisone
    • prednisone
    • budesonide
  • immunomodulatory, such as:
    • azathioprine (Azasan)
    • cyclosporine (Restasis)
    • methotrexate (Trexall)
  • biologics, such as:
    • adalimumab (Humira)
    • ustekinumab (Stelara)
    • natalizumab (Tysabri)
  • aminosalicylates (off-label use), such as:
    • balsalazide (Colazal)
    • mesalamine (Lialda)
    • olsalazine (Dipentum)

Off-label use

The Food and Drug Administration (FDA) approves drugs for certain health conditions. When a doctor prescribes a drug off-label, they are prescribing it for a different condition or at a different dosage than the FDA has approved.

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Within each group of medications, there are many different options healthcare professionals can choose from to help manage Crohn’s disease symptoms.

When deciding between medications, healthcare teams will consider various factors, including:

  • the severity of symptoms
  • possible side effects or safety concerns
  • how well a person has responded to previous medications

It is important to note that individual preference is also an important part of building a treatment plan. A person can work closely with their healthcare team to find the best treatment for them.

When Crohn’s disease treatments stop working, symptoms can flare up. This happens when the immune system stops responding to the medication or medications, allowing for a resurgence in active inflammation.

However, not all digestive symptoms occur due to a Crohn’s disease flare. To determine if a person is experiencing a Crohn’s disease relapse, the healthcare team will first assess for other possible causes of symptoms, such as infection or other sources of intestinal inflammation.

They will likely use an endoscopy to confirm that inflammation and symptoms are due to a Crohn’s disease flare.

Switching treatment

If treatment has stopped working, healthcare professionals may consider increasing the dose of medication, changing medications, or adding another to help provide better disease control.

People whose doctors initially prescribed an aminosalicylate may have the addition of a corticosteroid or immunomodulator to their treatment plan. Corticosteroids can help achieve quick remission but are generally only for short-term use due to safety concerns. Immunomodulators take longer to work but are useable more over the long term.

People with moderate to severe symptoms who stop responding to other treatments may switch to a biologic or undergo a new intervention along with their treatment plan. People who are already on a biologic may switch to a new one or have another medication.

Biologics that target a protein known as tumor necrosis factor (TNF) are some of the most common treatments for Crohn’s disease and include medications such as adalimumab (Humira) and infliximab (Remicade). Older studies have found that up to 45% of people for whom adalimumab stops working experience remission after switching to infliximab.

Some newer research suggests that if an anti-TNF medication does not work for someone with Crohn’s disease, they may benefit from switching to a different class of medication. These medications include the integrin receptor blocker vedolizumab (Entyvio) or the interleukin inhibitor ustekinumab (Stelara).

A newer class of medications, Janus kinase 2 inhibitors, such as upadacitinib (Rinvoq), also have approval to help treat moderate to severe Crohn’s disease.

Doctors may also prescribe an immunomodulator at the same time as a biologic to help prolong responses to these medications. People may start on a short-term corticosteroid simultaneously to help provide quick relief while these medications begin working.

Some people may never respond to treatments after they start taking them. This is known as primary nonresponse.

Others may initially respond to treatment but then begin experiencing symptoms again after some time — doctors call this secondary nonresponse. This term describes people for whom Crohn’s disease treatments stop working.

Immunomodulators may prevent relapse for longer periods than aminosalicylates. In an older study from 2014, 7% of people with Crohn’s disease who received immunomodulators early in the course of treatment had a relapse within 1 year, 22.3% relapsed within 2 years, and 60.9% relapsed within 3 years.

Secondary loss of response occurs in an estimated one-quarter to one-half of people who receive biologic therapies, but long-term remission is possible. One older study from 2013 found that at least 30% of people taking adalimumab were still in remission after 4 years of treatment.

In a long-term extension study of ustekinumab, 45–55% of people who received regular, ongoing treatment were still in remission after 5 years. Notably, though, the long-term extension phase of this study was optional and may have included a higher percentage of people who initially responded well to treatment.

Stopping treatment can increase the chance of relapse. However, for people taking a treatment combination of a biologic and immunomodulator, studies have found that stopping an immunomodulator after remission does not increase the likelihood of relapse.

If treatment stops working and relapse occurs, a healthcare professional may consider switching someone to a different treatment option. The choice to switch medications or continue on the one a person is using may depend on a variety of factors, including:

  • time to remission
  • time to relapse
  • severity of symptoms
  • current dosage
  • the use of other medications

Side effects

There are other reasons to consider switching treatment as well. Some people may need to switch treatment options if they are experiencing intolerable or severe side effects that are unmanageable with supportive treatments.

For instance, people who experience bothersome skin effects from anti-TNF biologics may benefit from switching to ustekinumab or an integrin receptor blocker if their symptoms become unmanageable.


Some people may want to switch medications for convenience. Certain biologics, such as vedolizumab, are available as both an intravenous (IV) infusion that healthcare professionals administer through a vein and an injectable. In some cases, people may prefer the convenience of an injection, which they can perform at home or at an outpatient clinic rather than an infusion center or hospital.

Recent studies have found that switching from IV to injectable vedolizumab is possible with low risk for relapse and may even help reduce the costs of treatment.


Doctors may also suggest switching medications if costs are a concern. Biosimilars are a group of biologic therapies that are structurally and functionally similar to already approved biologics, which are known as originators. These medications are typically available at a lower cost. Biosimilar options are available for adalimumab (Amjevita, Cyltezo, Hymiroz) and infliximab (Renflexis, Inflectra, IXIFI).

Switching from an originator to a biosimilar can provide substantial cost savings and provide a low risk of disease recurrence.

Whether a medication stops working or a change is necessary for other reasons, options are available for people with Crohn’s disease who need to switch treatments.

If a person has concerns about their current Crohn’s disease treatment plan, their healthcare team can help them understand what options are available. Before switching medications, they can try other steps, including dose adjustments and supportive therapies to manage side effects.