PANLAR consensus statement on biosimilars

Clinical Rheumatology https://doi.org/10.1007/s10067-019-04496-3 ORIGINAL ARTICLE PANLAR consensus statement on biosimilars S. C. Kowalski 1 & J. A. Benavides 2 & P. A. B. Roa 2 & C. Galarza-Maldonado 3,4 & C. V. Caballero-Uribe 3,5 & E. R. Soriano 3 & C. Pineda 3 & V. F. Azevedo 3 & G. Avila-Pedretti 6 & A. M. Babini 7 & A. Cachafeiro-Vilar 8 & M. Cifuentes-Alvarado 9 & S. B. Cohen 10 & P. E. Díaz 11 & L. Diaz Soto 12 & C. Encalada 13 & B. Garro 14 & I. A. G. Sariego 15 & M. Guibert-Toledano 16 & V. J. K. Rodriguez 17 & M. E. L. Lopez 17 & A. P. Ortega 18 & A. S. Russell 19 & P. Santos-Moreno 20 & I. S. Terán 21 & A. Vargas 22 & G. Vásquez 20 & R. M. Xavier 23 & D. X. Xibillé Firedman 24 & E. Mysler 7 & J. Kay 10 Received: 17 January 2019 / Revised: 19 February 2019 / Accepted: 24 February 2019 # The Author(s) 2019 Abstract Introduction Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. Objective The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). Methods Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. Results Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Conclusion The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. Key Points • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology Keywords Biosimilars . Consensus . PANLAR . Rheumatic diseases Sergio C. Kowalski and Eduardo Mysler contributed equally to this work. * S. C. Kowalski Extended author information available on the last page of the article Introduction Biologics have improved the treatment of rheumatic and musculoskeletal diseases (RMDs), preventing joint damage and resulting in better outcomes. In several previous publications, the Pan American League of Associations of Rheumatology Clin Rheumatol (PANLAR) has discussed the advances in the use of biological therapies to treat RMDs in Latin America (LA) [1–3]. LA has a heterogeneous population estimated at 577 million people, with diverse healthcare systems and different levels of access, ranging from those that provide broad coverage to those in which individuals have to pay out-of-pocket for medical expenditures [4–6]. Following patent expiration for biologicals, biosimilars, which typically are less expensive due to lower development costs, have the potential to increase patient access to these very effective medications, and thereby may provide additional treatment options for patients with rheumatic diseases [7–10]. A biosimilar is a biological product that is “highly similar” to an existing approved reference product and has “no clinically meaningful differences” [11]. Biosimilars are equivalent in efficacy and comparable in safety to their reference biologics. However, unlike small-molecule generic drugs for which the active chemical substance is synthesized to be identical to that of the reference small molecule drug, biosimilars usually are not identical to their reference products because these complex molecules are manufactured in living cells by a process that is more complex than that for small-molecule drugs [12, 13]. Another drug category, the biomimics, also known as “intended copies,” are replicas of approved biologic drugs that had received marketing approval without adhering to the international standards for evaluation and approval of biosimilars. Biomimics of etanercept and rituximab are currently available in some Asian and Latin American countries [14]. Considering the evolving state of biologics, biosimilars, and biomimics in the Americas and the inconsistency of regulations regarding biosimilars among LA countries, PANLAR has created a consensus statement on biosimilars in rheumatology. Methods This consensus statement was intended for a target audience of rheumatologists and other healthcare providers, regulators, legislators, and patients. The consensus process was developed by four groups: the PANLAR steering committee, the scientific committee, panel members, and an external review panel. The steering committee was comprised of three representatives of PANLAR (the PANLAR president, a PANLAR education and scientific committee officer, and a rheumatologist). PANLAR selected members of the scientific committee to develop the consensus, based on professional experience in rheumatology, expertise in pharmacologic therapies for rheumatic diseases and in biosimilars, and disclosure of conflicts of interest (COI) supported by the conflict of interest form of the Health and Care Excellence, NICE, on which the members declared the absence of COI. This scientific committee consisted of two rheumatologists (one with expertise in clinical epidemiology and guidelines development), and one epidemiologist. The scientific committee had complete independence to develop the consensus statement, since PANLAR was the sole supporter of this project with no funding from or participation by the pharmaceutical industry. The consensus process development was guided by the GIN-McMaster Guideline Development Checklist [15]. This checklist contains 18 topics and 146 ite (...truncated)