Why consider an alternative to Humira?
Humira (adalimumab) is a potent and widely used biologic medication for treating moderate to severe Crohn's disease. However, treatment with Humira may not be effective for everyone, or it may lose its effectiveness over time. This can be due to the development of anti-drug antibodies or a natural progression of the disease. When this happens, healthcare providers will often consider alternative therapies to help patients regain control of their symptoms and maintain remission.
Humira biosimilars: The direct alternative
A biosimilar is a biologic medical product that is highly similar to an existing FDA-approved reference product, like Humira. The safety and effectiveness of a biosimilar are considered to have no clinically meaningful differences from the original biologic. This provides a more cost-effective option while maintaining a similar treatment approach.
Several biosimilars to Humira are available and approved for Crohn's disease, with some designated as 'interchangeable.' An interchangeable biosimilar means a pharmacist can substitute it for the reference product without needing the prescriber's approval, depending on state laws.
Approved Humira biosimilars for Crohn's disease include:
- Cyltezo (adalimumab-adbm): An interchangeable biosimilar that is also citrate-free, potentially reducing injection site pain.
- Simlandi (adalimumab-ryvk): Another interchangeable option for Crohn's disease.
- Yuflyma (adalimumab-aaty): A high-concentration, citrate-free formulation that is also interchangeable.
- Amjevita (adalimumab-atto): A biosimilar copy of Humira.
- Hadlima (adalimumab-bwwd): Available in both high and low-concentration formulations.
Other biologic alternatives
When a patient fails to respond to a TNF-alpha inhibitor like Humira, switching to a biologic with a different mechanism of action is often the next step. These alternatives target different inflammatory pathways to reduce the immune response causing inflammation in the gut.
Biologics with different mechanisms for Crohn's disease:
- Entyvio (vedolizumab): This is an integrin receptor blocker that specifically targets the gut, reducing inflammation in the gastrointestinal tract with a potentially lower risk of systemic side effects. It is administered via intravenous (IV) infusion or as an at-home subcutaneous (under-the-skin) injection.
- Stelara (ustekinumab): An interleukin-12 and interleukin-23 blocker, Stelara targets different inflammatory proteins than Humira. After an initial IV dose, maintenance doses are given every 8 weeks via self-administered injection.
- Skyrizi (risankizumab): This medication is a selective interleukin-23 (IL-23) blocker. It begins with IV induction doses, followed by at-home subcutaneous injections every 8 weeks.
- Remicade (infliximab): A biologic that is also a TNF-alpha inhibitor, similar in mechanism to Humira, but administered as an IV infusion in a clinical setting. It can be an option if Humira loses effectiveness, though patients may develop antibodies to it over time.
Non-biologic alternatives
For some patients, especially those with less severe disease or those who have exhausted biologic options, other classes of medication may be considered.
Conventional drug options for Crohn's disease:
- JAK Inhibitors (e.g., Rinvoq/upadacitinib): These are oral medications that target specific enzymes involved in inflammation. Rinvoq is approved for moderate to severe Crohn's disease in adults who have not responded to a TNF blocker.
- Immunomodulators (e.g., azathioprine, 6-mercaptopurine): These drugs suppress the immune system to reduce inflammation. They can take several months to become effective and are sometimes used alongside biologics.
- Corticosteroids (e.g., prednisone, budesonide): Used for short-term control of flare-ups, corticosteroids reduce inflammation quickly. Long-term use is not recommended due to significant side effects.
- Aminosalicylates (e.g., mesalamine): These are used for mild-to-moderate Crohn's disease, particularly for inflammation in the colon.
Comparison of Humira and key alternatives
| Feature | Humira (adalimumab) | Cyltezo (adalimumab-adbm) | Stelara (ustekinumab) | Entyvio (vedolizumab) |
|---|---|---|---|---|
| Drug Class | TNF-alpha Inhibitor | TNF-alpha Inhibitor (Biosimilar) | IL-12/23 Blocker | Integrin Blocker |
| Target | Systemic TNF-alpha | Systemic TNF-alpha | IL-12 and IL-23 proteins | Gut-specific integrin receptors |
| Administration | Subcutaneous injection, every two weeks | Subcutaneous injection, every two weeks | Initial IV infusion, then subcutaneous every 8 weeks | IV infusion, then subcutaneous or IV every 8 weeks |
| Availability | Available as the reference product | Available as a biosimilar, including interchangeable versions | Available as a reference product | Available as a reference product |
| Cost | Typically higher than biosimilars | Lower cost alternative | Varies, potentially lower than older biologics | Varies, often covered by insurance |
| Mechanism of Action | Blocks a key inflammatory protein throughout the body | Highly similar mechanism to Humira, blocking the same protein | Blocks different inflammatory proteins involved in Crohn's | Targets immune cells specifically in the gut |
Making an informed decision
Choosing the right alternative to Humira for Crohn's disease depends on several factors, including the specific reasons for switching, disease severity and location, and patient preferences. A discussion with your gastroenterologist is crucial to weigh the options. They can consider the reason for the initial treatment failure (primary non-response, secondary loss of response, or side effects), along with your personal medical history, to select the most suitable next-step therapy.
Furthermore, financial and insurance considerations are important, especially with the introduction of biosimilars offering cost savings. Clinical trials are also continuously exploring new and combination therapies, presenting more options for patients in the future.
Conclusion
For patients with Crohn's disease, the availability of numerous treatment options beyond Humira is a significant advancement in managing this chronic condition. These alternatives include direct, cost-effective biosimilars and other biologics that act through different mechanisms, offering new avenues for effective symptom control. Non-biologic oral medications and immunomodulators also play a role in certain situations. The decision to switch treatments should always be made in close consultation with a healthcare professional to ensure the chosen therapy aligns with the patient's specific needs and circumstances. Patients are encouraged to engage with their medical team to navigate these choices and find a path toward sustained remission and improved quality of life. For more resources on managing Crohn's, the Crohn's & Colitis Foundation offers valuable information and support.
