LAUSR

We read with great interest the recently published “Systematic Review: non-medical switching of Infliximab to CT-P13 in inflammatory bowel disease” [1]. The review included three randomized controlled trials and about forty observational studies, in which stable patients with ulcerative colitis or Crohn’s disease were switched from originator infliximab to the CT-P13 biosimilar. The majority of these studies suggest that a non-medical switch is safe and effective. Scott, in the paired editorial [2], emphasizes the reassuring results of Bernard et al. about non-medical switching from infliximab to CT-P13, but argues that further prospective studies are required before non-medical switching can be widely adopted, and long-term observation is requisite when it does occur to ensure the safety and effectiveness of such strategies [2]. We wrote to remark on the concept of non-medical switching with a focus on its definition. Non-medical switching is generally defined as a change in a patient’s medication despite clinical remission—i.e., replacing an originator biologic with its interchangeable biosimilar—for reasons apart from lack of clinical effectiveness, tolerability, or adherence—usually to save money [3]. The regulations governing biosimilar replacement can vary in different parts of the world, in particular between the USA and Europe [3–5]. Replacement can be done both by switching (made by the physician) and by automatic substitution (made by the pharmacist, without consulting the prescriber) [4, 6]. The European regulations indicate that any decision on switching should involve the prescriber in consultation with the patient [4, 6]. The US regulations indicate that substitution of a biosimilar for a reference product is a matter of state pharmacy law. So, the laws of many states permit a pharmacist to replace a biologic with an interchangeable biosimilar without consulting the prescriber physician—a practice commonly called pharmacylevel substitution [5]. It has been hypothesized that most of the failures following a non-medical switch are due to a nocebo effect, which is the failure of therapy due to a patient’s negative expectation toward a change in therapy, for example forced switching to a biosimilar. Interestingly, the nocebo effect is higher following a mandated non-medical switch such as the automatic substitution by the pharmacist [7]. It has been estimated that a “forced switch” due to government policies without considering the patients’ perspectives is destined to fail, especially in those patients who started the biologic therapy for acute severe disease at presentation [8]. Interestingly, a recent study from the USA showed that implementation of a biosimilar switch program entered through a plan of actions that includes patient education could not compromise clinical efficacy [9]. In conclusion, the systematic review by Bernard et al. indicates that non-medical switching from the originator to a biosimilar is acceptable because it is safe and efficacious and leads to significant cost savings. It is noteworthy that non-medical switching could be considered a potential novel strategy of therapy in IBD. For better results, this strategy should be managed by physicians and should include patients’ education.