There is much enthusiasm surrounding the use of biosimilars because of the potential for appreciable cost savings in the United States, acknowledging that the 70% discounted rates reported in Europe in the context of a single-payer system (eg, Norway) are unlikely to be realized here. However, there are some important caveats with biosimilars. Small differences in manufacturing processes could result in small—but potentially significant—molecular differences, and there is at least a theoretical risk of differential immunogenicity resulting from biosimilar use. The concern may be greatest when there are multiple biosimilar switches over time, as repeated switching could potentiate a greater risk of developing anti-drug antibodies. Although this may be a negligible or mainly theoretical concern, it is unclear who bears responsibility to ensure that this type of repeated nonmedical switching does not impede the biosimilar’s long-term effectiveness. Another logistic issue from a clinician and health care system perspective is that infusion centers likely will have to stock and manage all of the various versions of an infusion drug and its biosimilars because different insurance companies may dictate the use of different biosimilars, and those preferences may change over time, as preferred agents shift due to contracting considerations.

While payers are likely to experience cost savings with the use of biosimilars, the economic benefits to patients are less clear. Based on the findings of an analysis by Yazdany and colleagues in The Journal of the American Medical Association, there is also concern that patients with some types of insurance might actually have increased out-of-pocket expenses when they use biosimilars. This is because most of the RA drug companies currently have highly effective co-payment assistance programs that result in patients having minimal out-of-pocket costs (eg, $10/month or even less). Thus, the patient out-of-pocket costs of the originator product will be difficult to beat from the patient’s perspective, particularly if the biosimilar company does not offer patient support programs that are as equally robust as those of the originator biologic manufacturer.

Finally, patient acceptance of biosimilars bears additional consideration. While patients receiving infusion biosimilars (eg, a biosimilar version of infliximab) may not be particularly aware that they are not on the originator biologic, they may become less accepting of a self-administered injectable biosimilar, as visual differences in the packaging and auto-injector mechanism will be readily apparent. Unless patients have a clear understanding of the motivating factors behind biosimilars and why they may have been switched, there could be a backlash among patients. Some may be hesitant or may even refuse to use the drug until they get additional information from their health care provider, which may not occur for weeks or even a few months until their next office visit. I suspect that patients may draw on both their experience and expectations regarding generic small molecule drugs. These attitudes may be positive or negative, and they have the potential to greatly influence patient acceptance and undermine effective disease control.