Humira (adalimumab) is a reference biological drug that has been a cornerstone in treating various autoimmune diseases for decades, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. It is a Tumor Necrosis Factor (TNF) blocker, meaning it works by inhibiting the inflammatory protein TNF-alpha, which plays a major role in these conditions. When Humira's patent expired, it paved the way for the development of biosimilars, which are the closest possible biologic substitutes.
What are biosimilars?
Unlike conventional drugs, which can be replicated as identical generics, biologics are complex molecules derived from living organisms, making an exact replica impossible. A biosimilar is a biological product that is 'highly similar' to a reference biologic, with no clinically meaningful differences in terms of safety, purity, and potency. The U.S. Food and Drug Administration (FDA) requires extensive data to approve a biosimilar, often extrapolating efficacy and safety from trials conducted in one or two conditions to others for which the reference product is approved.
Interchangeability: The next level of similarity
Some biosimilars receive an additional FDA designation of 'interchangeable'. This means that the FDA has determined that the product can be substituted for the reference product at the pharmacy without the prescriber's specific approval, much like a generic is substituted for a brand-name drug. State laws govern pharmacy-level substitution, but the interchangeable designation is a crucial factor. The FDA requires additional clinical testing, including 'switching studies,' to prove that alternating between the reference product and the interchangeable biosimilar has no negative impact on safety or efficacy.
Key adalimumab biosimilars
As of 2025, a number of adalimumab biosimilars have been approved by the FDA and are available in the U.S. market. These products are all considered highly similar and offer comparable clinical benefits to Humira. They primarily differ in factors like their interchangeable status, formulation (e.g., citrate-free to reduce injection site pain), and concentration (high vs. low).
Notable adalimumab biosimilars available in the U.S.
- Cyltezo (adalimumab-adbm): One of the first interchangeable biosimilars approved for Humira. It is available in a citrate-free formulation.
- Simlandi (adalimumab-ryvk): This was the first high-concentration, citrate-free interchangeable biosimilar to Humira.
- Yuflyma (adalimumab-aaty): A high-concentration, citrate-free formulation that has also received an interchangeable designation for some presentations.
- Abrilada (adalimumab-afzb): Another biosimilar with interchangeable status.
- Hadlima (adalimumab-bwwd): Approved with an interchangeable designation and available in both low and high-concentration formulations.
- Amjevita (adalimumab-atto): The very first adalimumab biosimilar to be approved by the FDA, though not initially interchangeable.
Comparison of Humira and its biosimilars
This table summarizes key characteristics of Humira and some of its most notable biosimilars based on regulatory status and formulation features.
| Feature | Humira (adalimumab) [Reference Product] | Cyltezo (adalimumab-adbm) | Simlandi (adalimumab-ryvk) | Yuflyma (adalimumab-aaty) | Hadlima (adalimumab-bwwd) |
|---|---|---|---|---|---|
| Interchangeable | N/A | Yes | Yes | Yes (for specific presentations) | Yes |
| Concentration | Low & High | Low | High | High | Low & High |
| Citrate-Free | Yes (newer formulations) | Yes | Yes | Yes | Yes (High-conc.), No (Low-conc.) |
| Manufacturer | AbbVie | Boehringer Ingelheim | Alvotech/Teva | Celltrion | Samsung Bioepis/Organon |
Other biologic alternatives to Humira
While adalimumab biosimilars are the most similar options, other biologics that function as TNF-alpha inhibitors or have different mechanisms of action are also viable alternatives, depending on the patient's specific condition and response to treatment. These medications can be explored if a patient does not respond adequately to adalimumab or experiences side effects.
- Other TNF-alpha Inhibitors:
- Enbrel (etanercept): A fusion protein that inhibits TNF-alpha, administered via subcutaneous injection.
- Remicade (infliximab): A chimeric monoclonal antibody, often requiring intravenous infusion in a clinical setting.
- Cimzia (certolizumab pegol): Another TNF-alpha inhibitor that is administered via subcutaneous injection.
- Simponi (golimumab): A human monoclonal antibody that is given via subcutaneous injection or intravenous infusion.
- Biologics with Different Mechanisms:
- Orencia (abatacept): Works by modulating T-cell activation, a different pathway in the immune system.
- Stelara (ustekinumab): Targets different inflammatory proteins (IL-12 and IL-23), used for conditions like Crohn's and psoriasis.
- Entyvio (vedolizumab): Specifically targets the gut, making it a common choice for inflammatory bowel diseases.
Considerations for switching medications
Deciding to switch from Humira to a biosimilar or another biologic should be a shared decision between a patient and their healthcare provider. Key factors to discuss include cost, insurance coverage, and the potential for a 'nocebo effect,' where a patient experiences negative outcomes simply due to the psychological effect of switching, even if the medication is clinically equivalent. Citrate-free and high-concentration formulations can offer greater injection comfort, which is another consideration for patient preference.
Conclusion
For those asking what is the closest biologic to Humira, the most accurate answer is one of the many adalimumab biosimilars now available, such as Cyltezo, Simlandi, or Yuflyma. These products are highly similar, offering comparable effectiveness and safety, and often at a lower cost. While other TNF-alpha inhibitors and biologics with different mechanisms exist as alternatives, the adalimumab biosimilars provide the most direct therapeutic equivalence. Ultimately, the best choice for an individual will depend on their specific medical needs, insurance coverage, and a careful discussion with their healthcare provider.
Resources
- National Institutes of Health (NIH): Navigating adalimumab biosimilars: an expert opinion
