In an effort to provide a guide for clinicians and a framework for future educational efforts, an international panel of healthcare stakeholders convened to arrive at consensus recommendations for the use of biosimilars to treat rheumatological diseases. The resulting recommendations were published in Annals of the Rheumatic Diseases.
The multidisciplinary task force—25 experts from Europe, Japan, and the United States (17 rheumatologists, 1 rheumatologist/regulator, 1 dermatologist, 1 gastroenterologist, 2 pharmacologists, 2 patients with rheumatic diseases, and 1 research fellow—convened in 2016 to develop an evidence-based, consensus-based statement on biosimilars after appraising evidence in the scientific literature. The task force members deliberated and revised statements on overarching principles and recommendations, which were later voted on and accepted if an 80% consensus was met.
The group agreed on 5 overarching principles:
- Treatment of rheumatic diseases is based on a shared decision-making process between patients and rheumatologists. Rheumatologists must educate patients about the disease process and appropriate treatments. Once informed, the patient can discuss preferences, goals, and the risks and benefits of specific treatments.
- Contextual aspects of the healthcare system should be considered when making treatment decisions. The structure of health systems varies by country, and in nations like the United States, where patients must pay a portion of the cost of their treatments, necessary treatment can be inaccessible to some patients. These factors must be considered when selecting an appropriate therapy option.
- A biosimilar approved in a highly regulated area is not better or worse than the originator product. A biosimilar that has satisfied requirements of a regulatory approval pathway can be expected to be the same as its reference in terms of efficacy, and will not have inferior safety to various batches of the reference. Efficacy and safety of a biosimilar can be expected to remain highly comparable with its reference product over time.
- Patients and providers should be informed about the nature of the approval process, safety, and efficacy of biosimilars. The misconception that biosimilars may be of lesser quality because of their lower price point can be addressed through education about biosimilarity.
- Harmonized methods should be established to obtain reliable pharmacovigilance data (including traceability) on both biosimilars and reference products. Regardless of the methods used to distinguish among biosimilars and reference products, batch numbers are essential to tracing problems, and should be carefully recorded.
The group also arrived at 8 consensus recommendations:
- Availability of biosimilars must lower the cost of treatment and increase access to therapy. Approved biosimilars should provide patients with equivalent biologics at lower costs than the originator product, and should allow patients access to drugs that may have been previously restricted because of cost considerations.
- Approved biosimilars can be used to treat patients in the same ways as their reference products. Once a biosimilar has demonstrated structural similarity and clinical equivalence in a sensitive population and has been approved for marketing, it can be considered “essentially the same biologic” as new batch of the originator.
- Because no clinically significant differences in immunogenicity between biosimilars and references have been detected, antidrug antibodies to biosimilars do not need to be measured in clinical practice. Immunogenicity of a biosimilar is compared with that of the originator in a clinical trial, and need not be measured in clinical practice (though assessment can be used for pharmacovigilance).
- Relevant preclinical and phase 1 data on a biosimilar should be available when phase 3 data are published. Availability of such information facilitates the assessment of biosimilarity based on a totality-of-the-evidence approach.
- Confirmation of efficacy and safety data is sufficient to extrapolate to other diseases for which an originator drug is approved. Biosimilars have demonstrated efficacy and safety when used in clinical practice to treat approved indications in which they have not been studied in comparison with their references.
- Evidence indicates that a single switch from reference to biosimilar is safe, so there is no reason to expect that switching among biosimilars of the same reference would result in a different clinical outcome; however, patient viewpoints must be considered. No studies have yet evaluated efficacy or safety of switching among different biosimilars, so patients’ perspectives on treatment options must be taken into account when determining an appropriate therapy.
- Multiple switches between biosimilars and originators (or among biosimilars) should be assessed in registries. Pertinent data must be collected in order to address lingering uncertainty regarding safety.
- No switching should be initiated without the prior awareness of both the patient and the treating healthcare provider. Transparency is of critical importance in the patient/provider relationship, and joint decisions are esssential.
The group concluded that the rapidly growing body of evidence has begun to reduce uncertainty about the use of biosimilars in treating rheumatic diseases. However, a treating physician should be the only one to decide whether to prescribe a biosimilar in place of a reference product, on a case-by-case basis, with the full awareness of the patient. While there is sufficient evidence about the safety and efficacy of biosimilars to allow for extrapolation of indications, there are not yet enough data to allay all concerns about switching among biosimilars or switching repeatedly between the reference and a biosimilar. To facilitate informed decision-making, providers are encouraged to gather pharmacovigilance data about the outcome of such switches.