A review article discussed the characteristics of the available adalimumab biosimilars to help clinicians navigate the various treatment options with their patients.
After Humira’s patent expired in 2018 in the European Union (EU) and earlier this year in the US, 10 adalimumab biosimilars entered the market in the EU and 8 entered the market in the US. A review article discussed the characteristics of the available biosimilars to help clinicians navigate the various options with their patients.
The European review looks at most but not all EMA-approved biosimilars, including:
It did not cover information on Cyltezo, an adalimumab biosimilar approved in the United States but not the European Union.
Adalimumab is a monoclonal antibody targeting tumor necrosis factor (TNF)- α, used to treat a variety of immune-mediated inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, Crohn disease, and ulcerative colitis. Since Humira was authorized in the US and EU in 2003, its sales have exceeded $20.7 billion.
By the end of 2019 in Europe, about 35% of patients receiving adalimumab therapy had been switched from Humira to a biosimilar. According to the authors, the increasing variety of available biosimilars has made treatment selection “a more complex task” for healthcare providers.
Amgen’s Amgevita (Amjevita in US), Samsung Bioepis’s Imraldi (Hadlima in US), Sandoz’s Hyrimoz, Biocon’s Hulio, Fresenius Kabi’s Idacio, Pfizer’s Amsparity, Celltrion’s Yuflyma/Lybmyris, Samsung Bioepis’ Imraldi, and Alvotech and STADA Arzneimittel’s Hukyndra are available in the EU. Amjevita, Hadlima, Hyrimoz, Hulio, Idacio, Cyltezo, Yusimry, and Yuflyma are available in the US.
Although all of the adalimumab biosimilars have demonstrated similarity to the reference product, there are some differences in excipients, preservatives, and injection devices that may influence safety for the individual patient, as well as adherence and satisfaction with treatment.
The original formulation of the reference product included a citrate-containing buffer, delivered a dose of 40 mg adalimumab in an injection volume of 0.8 mL, and used pre-filled syringes with 27-gauge needles. Aiming to reduce injection-site pain, a newer formulation of Humira was released in 2018, which is citrate-free, has a smaller injection volume (0.4 mL) delivering the same dose, and uses a smaller (29-gauge) needle. The reviewers cited trials that demonstrated reductions in injection-site pain with the revised formulation of Humira compared to the original. However, they said the relative contributions of the lack of citrate, the narrower needle gauge, and the injection volume to improved injection-site comfort is unclear.
Injection-site reactions, such as redness, bleeding, and pain have been frequently reported with the reference product, according to the authors, and for some patients, injection-site pain negatively affects their adherence to treatment and their overall satisfaction with treatment. One strategy for minimizing pain is to choose a biosimilar product that uses a narrower needle. Imraldi/Hadlima, Hulio, Idacio, Amsparity, Yuflyma, and Hukyndra use 29-gauge needles.The reviewers added that patients with a fear of needles may prefer an autoinjector pen device with a concealed needle rather than a pre-filled syringe.
Biosimilar adalimumab formulations available in a 0.4 mL compared to 0.8 mL volume will also likely reduce injection discomfort. Imraldi/Hadlima, Hyrimo, Yuflyma, and Hukyndra deliver 40 mg adalimumab in a total injection volume of 0.4 mL.
Finally, the authors said the presence of citrate “may increase the sensation of injection-site pain in some patients,” and for these patients, a citrate-free formulation is preferred. Most adalimumab biosimilars do not contain citrate: Amgevita/Amjevita, Hyrimoz, Hulio, Amsparity, Yuflyma, and Hukyndra. In the United States, Cyltezo is also citrate-free.
Other factors to consider include latex allergy, shelf-life, and dose availability
Whether the patient has a latex allergy is another factor in choosing an adalimumab biosimilar. The original formulation of the reference product and Amgevita/Amjevita contain latex, whereas the other currently available formulations do not.
Some patients, for example those who travel frequently, may require their biosimilar to have a longer duration of stability at room temperature. Amgevita/Amjevita, Hulio, and Hukyndra have a 14-day shelf-life at room temperature, whereas Hyrimoz (21 days), Idacio (28 days), Amsparity (30 days), Imraldi/Hadlima (31 days), and Yuflyma (31 days) may be stored at room temperature for a longer period of time. Notably, Cyltezo also has a 14-day shelf-life at room temperature.
For patients receiving adalimumab treatment for inflammatory bowel disease (Crohn disease or ulcerative colitis), a larger dose of 80 mg may be required. In addition to the citrate-free formulation of the reference product (pen device only), 80 mg of Yuflyma and Hukyndra (syringe only) can be delivered with a single injection.
The reviewers also discussed studies finding that individualized patient instructions are necessary for a successful switch to a biosimilar. They said providers must be familiar with any differences in the devices used by the reference product and the selected biosimilar to ensure that patients are comfortable operating the device.
The reviewers emphasized effective patient-physician communication, with a clear explanation of the switch to a suitable biosimilar and the reasons for it, to minimize the nocebo effect, as well as to discuss treatment-related issues such as injection-site pain. They recommended physicians carefully consider which adalimumab is most suitable for their individual patients on a case-by-case basis.
Abitbol V, Benkhalifa S, Habauzit C, Marotte H. Navigating adalimumab biosimilars: an expert opinion. J Comp Eff Res. 2023;12(11):e230117. doi:10.57264/cer-2023-0117