A retrospective, postmarketing study demonstrates higher incidence of joint and bone pain, neutropenia with certain filgrastim biosimilars, compared with Neupogen.
Editor's Note: Since publication of this article, the findings in the study by Rastogi S et al referenced below have been criticized as having been based on poor scientific methodology. Reliance upon data from the VigiBase adverse event database of the World Health Organisation, which is not intended for the testing of medical hypotheses, is one of the criticisms leveled against this study. The Center for Biosimilars® is preparing a follow-up article on this issue.
A new study has associated a higher incidence of certain adverse events with the filgrastim biosimilars, Zarzio, Grasin, Nivestim, and Tevagrastim compared with the reference product Neupogen.
These biosimilar products are marketed outside the United States under these brands and have US equivalents.
Filgrastim was originally approved in 1991 for the treatment of patients with cancer who are receiving myelosuppressive chemotherapy. It was subsequently approved for multiple oncology related indications and severe chronic neutropenia. Multiple filgrastim biosimilars have been approved in the United States, Europe, and elsewhere since 2008.
The retrospective, postmarketing study comprised data from 1991 to May 2018 from VigiBase, a World Health Organization database of adverse events information. VigiBase is often used to aid postmarket studies.
Distribution of Adverse Events
Investigators identified 11,183 adverse drug reaction reports, of which 51.5% (5764) were related to Neupogen, the originator. Leucostim had 680; Zarzio, 622; Grasin, 545; Nivestim, 359; and Tevagrastim, 152.
Grasin was associated with higher reporting of pyrexia, or fever, compared with neupogen (11.5% vs 7.9%, reporting odds ratio [ROR] 1.52); myalgia, or muscle pain, (37% vs 2.2%, ROR 25.94); and back pain (11.3% vs 4%, ROR 3.09).
Findings showed that Zarzio was associated with increased reporting of arthralgia, also known as joint pain (4.5% vs 2.9%, ROR 1.59). Zarzio also had higher reporting of neutropenia, or low white blood cell count (11.4% vs 4%, ROR 2.59).
Bone pain was reported more often for Nivestim than reference filgrastim (14.4% vs 8.3%, ROR 1.87).
Drug ineffectiveness was reported in cases with Zarzio (35.9%), Nivestim (19.4%), and Tevagrastim (42.2%).
Efficacy Differences Also Observed
The authors also observed significant differences between the originator and biosimilars in regard to efficacy, adverse events reported, and time to onset of occurrences.
They stressed that epidemiologic studies are needed to confirm these findings and provide additional insights.
Zarzio is owned by Sandoz and is marketed is as Zarxio in the United States. Grasin is owned by Teva Pharmaceuticals Japan and is marketed in Republic of Korea. Tevagrastim is marketed in Europe and is owned by Teva Generics GmbH, a Teva Pharmaceuticals company. Tevagrastim is marketed as Tbo-filgrastim in the United States. Nivestim is owned by Pfizer and is marketed as Nivestym in the United States.
Leucostim is marketed in Peru, the Republic of Korea, and Turkey.
In the United States, the FDA recently launched the FDA adverse Event Reporting system (FAERS). FAERS is a public search engine for drugs and biologics and contains adverse event reports submitted by healthcare providers, consumers, manufacturers of drugs and biologics, and other stakeholders.
AMCP Posters Tackle Interchangeability and Medicaid, Factors Driving Biosimilar Access
April 24th 2024Two posters from the Academy of Managed Care Pharmacy (AMCP) annual meeting explore how an interchangeable insulin glargine biosimilar plays into Medicaid budgets and the top factors driving access to biosimilars.
A New Chapter: How 2023 Will Shape the US Biosimilar Space for 2024 and Beyond
December 31st 2023On this episode of Not So Different, Cencora's Brian Biehn and Corey Ford take a look back at major policy and regulatory advancements in 2023 and how these changes will alter the space going forward.
What Clinicians Need to Know About Using Biosimilars to Treat IBD
April 13th 2024A review article, intended to act as a guide for clinicians, summarizes the available infliximab and adalimumab biosimilars for treating inflammatory bowel disease (IBD) as well as others that are coming down the pipeline.
Study: More Biosimilar Competition Is Not Lowering Patient OOP Costs
March 29th 2024Despite more biosimilars entering the market and generating significant savings for payers and health care systems, these savings are not resulting in lower out-of-pocket (OOP) costs for patients, according to a recent study.