The available evidence is sufficient to support switching appropriate patients with rheumatologic diseases from a bio-originator agent to an approved biosimilar agent, according to new consensus-based recommendations from an international multidisciplinary task force.

“Treatment with biological agents has dramatically improved the outcome for patients with inflammatory diseases. However, the high cost of these medications has limited access for many patients,” Jonathan Kay, MD, of UMass Memorial Medical Center and the University of Massachusetts, Worcester, and his colleagues wrote on behalf of the Task Force on the Use of Biosimilars to Treat Rheumatological Diseases. Biosimilars of agents no longer protected by patent allow for increased availability at lower costs, they noted. In the European Union, the United States, Japan, and other countries, biosimilars of adalimumab, etanercept, infliximab, and rituximab have been approved, and those for which the bio-originator is no longer protected by patent have been marketed.

However, there is a paucity of data to guide health care providers in “critically evaluating and differentiating the scientific data available for each of these molecules,” the task force wrote.

The task force, convened in 2016 to address the matter at an international level, included 25 experts from Europe, Japan, and the United States, including 17 rheumatologists, a rheumatologist/regulator, a dermatologist, a gastroenterologist, 2 pharmacologists, 2 patients, and a research fellow. The task force identified five overarching principles and made eight specific recommendations, based on expert opinion and an extensive literature review that yielded 29 relevant full-text papers and 20 relevant abstracts from the 2015 and 2016 American College of Rheumatology and European League Against Rheumatism annual meetings (Ann Rheum Dis. 2017 Sep 2. doi: 10.1136/annrheumdis-2017-211937).

“This statement was intended both to guide clinicians and to serve as a framework for future educational efforts,” they wrote.

The experts based all five overarching principles for the use of biosimilars on level 5, grade D evidence, indicating that they were derived mainly from expert opinion. They determined that:

Treatment of rheumatic diseases is based on a shared decision-making process between patients and their rheumatologists.
The contextual aspects of the health care system should be taken into consideration when treatment decisions are made.
A biosimilar, as approved by authorities in a highly regulated area, is neither better nor worse in efficacy and is not inferior in safety to its bio-originator.
Patients and health care providers should be informed about the nature of biosimilars, their approval process, and their safety and efficacy.
Harmonized methods should be established to obtain reliable pharmacovigilance data, including traceability, about both biosimilars and bio-originators.

These principles represent the key issues regarding biosimilars as identified by the task force. As for the specific recommendations, the task force agreed that:

1. The availability of biosimilars must significantly lower the cost of treating an individual patient and increase access to optimal therapy for all patients with rheumatic diseases (level 5, grade D evidence).

2. Approved biosimilars can be used to treat appropriate patients in the same way as their bio-originators (level 1b, grade A evidence, indicating that the recommendation is based on an individual randomized, controlled trial and that the level 1 evidence is consistent).

3. Antidrug antibodies to biosimilars need not be measured in clinical practice as no significant differences have been detected between biosimilars and their bio-originators (level 2b, grade B evidence, indicating that the recommendation is based on an individual cohort study/low-quality randomized, controlled trial and consistent level 2 or 3 evidence).

4. Relevant preclinical and phase 1 data on a biosimilar should be available when phase 3 data are published (level 5, grade D evidence).

5. Confirmation of efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the bio-originator has been approved because biosimilars are equivalent in physiochemical, functional, and pharmacokinetic properties to the bio-originator (level 5, grade D evidence).

6. Available evidence suggests that a single switch from a bio-originator to one of its biosimilars is safe and effective; there is no reason to expect a different clinical outcome. However, patient perspectives must be considered (level 1b, grade A evidence).

7. Multiple switching between biosimilars and their bio-originators or other biosimilars should be assessed in registries (level 5, grade D evidence).

8. No switch to or among biosimilars should be initiated without the prior awareness of the patient and the treating health care provider (level 5, grade D evidence).

Differing opinions about the use of biosimilars as published by various subspecialty organizations highlight a lack of confidence among many clinicians with respect to appropriate use of the products, but that is changing amid a rapidly growing body of evidence, the task force said. The group achieved a high level of agreement about both the evaluation of biosimilars and their use to treat rheumatologic diseases, reaching 100% consensus for six of the recommendations and 91% and 96% for the other two.

“Data available as of December 2016 support the use of biosimilars by rheumatologists to encourage a fair and competitive market for biologics. Biosimilars now provide an opportunity to expand access to effective but expensive medications, increasing the number of available treatment choices and helping to control rapidly increasing drug expenditures,” they concluded.

The task force’s work was funded by an unrestricted educational grant from Amgen. Dr. Kay and his coauthors reported financial relationships with multiple pharmaceutical companies, many of which are developing biosimilars.

sworcester@frontlinemedcom.com

New recommendations tout biosimilars for rheumatologic diseases