Biosimilars as effective as originator drugs in rheumatoid arthritis treatment
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Key Takeaways:
- Monoclonal antibodies decrease inflammation in the immune system by binding to specific molecules.
- Biosimilars are a cost-effective version of brand name monoclonal antibody drugs.
Biosimilars have shown to be just as effective as original brand name medications in treating rheumatoid arthritis, and the former may be more cost-effective for patients.
Monoclonal antibodies are lab-created proteins engineered to target the immune system’s inflammatory response that have been shown to be effective in treating RA. Common targets include inflammatory cytokines as well as the immune system’s B cells and T cells to suppress some of the amplified autoimmune response experienced by patients with RA, with many studies showing their efficacy and safety.
In addition to the original brand name biologics, newer biosimilar monoclonal antibodies provide additional treatment options in rheumatoid arthritis.
Healio spoke with Emily Carroll, MD, attending physician and assistant professor of medicine in the division of rheumatology at the Icahn School of Medicine at Mount Sinai, about the use of biosimilars in treatment of RA.
Monoclonal antibodies in RA
Although monoclonal antibodies are manmade, they still target a specific antigen like naturally occurring antibodies.
“They’re produced in a lab from some sort of living source,” Carroll said. “So often, it’ll be a cell line obtained from a lab animal like a mouse that will be exposed to a target protein, and in response it will create antibodies to that protein. And we’re able to purify and amplify these antibodies to that target protein, and then humanize them in a way where we can safely give them to human beings.”
The most common class of monoclonal antibodies used in RA is the TNF alpha class of drugs. These all target the same molecule (TNF alpha), but they may differ in structure or means of administration. Infliximab (Remicade, Janssen) is administered IV, golimumab (Simponi/Simponi Aria, Janssen) has the option to be administered IV or via subcutaneous injection, and adalimumab (Humira, Abbvie), certolizumab (Cimzia, UCB), and etanercept (Enbrel, Amgen) are typically only administered as subcutaneous injections with slightly different timing of injection schedules. While these all achieve the same result of blocking the TNF alpha signaling pathway, they do so in slightly different ways.
Other monoclonal antibodies used in RA include tocilizumab (Actemra, Genentech), which targets IL-6 and can be administered by IV or by subcutaneous injection; abatacept (Orencia, Bristol Myers Squibb), which targets T cells, and can be administered as weekly subcutaneous injection or monthly infusion; and rituximab (Rituxan, Genentech) which targets B cells and is administered as an IV infusion administered every 6 months.
“IL1 inhibitors like anakinra are technically FDA approved for rheumatoid arthritis, but honestly, we really don't use them all that much, because they're a daily subcutaneous injection that no one really likes to do. And we have, I think, just much easier medications for patients to take, so that's an option, but not one that we really prescribe all that much,” Carroll said.
Choosing the right treatment for individuals
When choosing which treatment is right for a patient, Carroll said many factors are considered such as a patient’s insurance formulary, their reactions to previous or current therapies and how advanced in their disease course the patient is presenting. Patients with RA are often initially treated with methotrexate, a conventional synthetic disease-modifying antirheumatic drug, but if that treatment fails, clinicians may begin escalating the patient to a monoclonal antibody. Often the first monoclonal antibody a patient might be treated with is a TNF inhibitor.
“Often we would start on some sort of tumor necrosis factor inhibitor, because of the biologics those have been around the longest, so we certainly have the most long-term safety and efficacy data, and they tend to be I think, very quickly effective,” Carroll said. “Not that insurances rule everything when it comes to drug selection, but on most insurance formularies it's methotrexate first, then adalimumab unless there's a specific reason that we cannot give that drug. That's when we might start to think about other types of biologics.”
Keeping in mind a patient’s insurance, a clinician may administer MTX while waiting for monoclonal antibodies to be covered, but if a patient is presenting with advanced erosion or deformed joints, Carroll said it may be necessary to start a patient on monoclonal antibody treatment immediately.
Infection risk is heavily considered when prescribing treatment, and clinicians should be aware of opportunistic infections, Carroll said. While fungal infections and pneumocystis pneumonia are rare adverse effects, clinicians should be aware of these possibilities as well as the risk of a reactivation of prior infections like hepatitis B, tuberculosis or shingles. Patients with heart failure are not often put on TNF inhibitors as some studies show it can worsen heart failure. Another adverse event to monitor for is a drug-induced lupus syndrome, with rashes, joint pains and fevers, although it is uncommon. Lymphoma has been a concern for patients with RA, but Carroll raised concern about the lack of data showing that RA treatments conclusively raise the risk of lymphoma.
“There's always a lot of confounding in terms of the fact that patients with rheumatoid arthritis, especially highly active RA, are already at higher baseline risk. So, I think there is definitely a theoretical concern,” she said. “If someone has an active malignancy or a recent malignancy, especially a liquid one, it's always something that we consider, but I wouldn't say it's as cut and dry as these drugs cause malignancy.”
Efficacy of monoclonal antibodies
Carroll discussed many of the trials done on these drugs, like the ATTRACT trial, which compared infliximab with placebo in patients who were already on MTX; the RAPID 1 trial, which showed certolizumab’s effectiveness compared with placebo; the rituximab REFLEX, IMAGE and DANCER trials; and the tocilizumab CHARISMA and AMBITION trials. She noted that while the drugs are being compared with placebo, the patients in that group are often on a basic DMARD like MTX. The abatacept APIPPRA trial was essential in leading to its use in RA treatment, she said.
“All of [the trials] essentially will show that these drugs are superior compared to the sort of baseline standard of care. There's not much in terms of head-to-head trials, showing this one is definitely better than that one. So often, it'll be coming down more to specific patient factors, why we would pick one versus another,” she said.
Carroll said she doesn’t typically combine targeted DMARDs like JAK inhibitors with monoclonal antibodies because the drugs are already so immunosuppressive on their own. Conventional synthetic DMARDs, however, especially MTX, are commonly combined with monoclonal antibodies. By combining these conventional synthetic DMARDs with monoclonal antibodies, the immune system may be less likely to react and form anti-drug antibodies that neutralize the effect of the biologic. Carroll explained that it is possible for a patient’s immune system to “outsmart” a monoclonal antibody when it is administered because the body detects a protein that is not fully human and can begin to make blocking antibodies. The addition of methotrexate to biologics like infliximab could help prevent anti-drug antibodies from forming.
Biosimilars represent a relatively newer option that can be more cost-effective for patients, and Carroll noted that while they are not technically generics or the exact same medication, they behave almost identically to their reference brand name biologic drug.
“There are studies showing that the biosimilars for the various monoclonal antibodies, such as Hyrmioz compared to Humira, are equally efficacious and safe,” she said. “So that’s not to say for every individual patient they will have the same experience, but if we were to look at broad swaths of patients, people on these biosimilars are performing equally to those on the original drug.”
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