The goal of Crohn’s disease treatment is to control inflammation in the gut and prevent symptoms from flaring up. This is done through 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. And 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 needed, 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 Crohn’s treatments is to control and prevent inflammation in the digestive tract to help prevent symptoms from happening.

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

There are several different types of medications used to treat Crohn’s disease, including:

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 doctors can choose from to help manage Crohn’s disease symptoms.

When deciding between medications, healthcare teams will consider a variety of factors, including the severity of symptoms, possible side effects or safety concerns, and how well a person has responded to other medications used before.

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

Not all digestive symptoms are caused by a Crohn’s disease flare, though. 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.

An endoscopy will likely be used to confirm that inflammation and symptoms are caused by a Crohn’s disease flare.

Switching treatment

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

People who were initially prescribed an aminosalicylate may have a corticosteroid and/or immunomodulator added to their treatment regimen. Corticosteroids are used to help achieve quick remission but are generally only used for short periods due to safety concerns. Immunomodulators take longer to work but can be used more long-term.

People with moderate to severe symptoms who stop responding to other treatments may be switched to a biologic or have one added to their treatment plan. People who are already on a biologic may be switched to a new one or have another added.

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

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

An immunomodulator may be prescribed at the same time as a biologic to help prolong responses to these medications as well. A short-term corticosteroid may also be started at the same time 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 having symptoms again after a period of time. This is called secondary nonresponse. This term is used to describe people for whom Crohn’s disease treatments stop working.

Immunomodulators may prevent relapse for longer periods than aminosalicylates. In one study, 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 study found that at least 30% of people treated with 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 who are treated with a combination of a biologic and immunomodulator, studies have found that stopping an immunomodulator after remission is achieved does not increase the likelihood of relapse.

If treatment stops working and relapse occurs, a gastroenterologist may consider switching to a different treatment option. The choice to switch medications or continue on the one being used may depend on a variety of factors, including:

  • time to remission
  • time to relapse
  • severity of symptoms
  • current dosage
  • other medications being used

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 cannot be managed 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 cannot be managed with other medications.

Convenience

Some people may want to switch medications for convenience. Certain biologics, such as vedolizumab, are available as both an intravenous (IV) infusion and a subcutaneous injectable. In some cases, people may prefer the convenience of a subcutaneous injectable, which can be done at home or at an outpatient clinic rather than an infusion center or hospital.

Recent studies have found that switching from IV to subcutaneous vedolizumab can be done with low risk for relapse and may even help reduce the costs of treatment. However, the subcutaneous injection is not available in the United States.

Cost

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 — known as originators — that 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 are low risk for disease recurrence.

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

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