Biosimilars, Originators Have Near Identical Stop Rates in Natural Experiment

Ted Bosworth

February 14, 2023

Real-world, population-based data suggest that the discontinuation rates for biosimilars prescribed to treat inflammatory rheumatic diseases are similar to those for their corresponding originator biologics, according to a study of patients in British Columbia who were required to switch to biosimilars.

"The decision to mandate use of biosimilars provided an ideal context for a natural experiment," Diane Lacaille, MD, chair in arthritis research at the University of British Columbia, Vancouver, explained in her presentation of the study at the annual meeting of the Canadian Rheumatology Association.

On the basis of the real-world data, which was collected before and after a province-wide requirement to use biosimilars in place of originator biologics, there was no major difference in discontinuation rates, an outcome that Dr. Lacaille characterized as "a surrogate for both efficacy and safety."

In the 2019 rheumatoid arthritis treatment guidelines from the European Alliance of Associations for Rheumatology, biosimilars are advocated for addressing the high cost of biologics based on evidence of efficacy and safety comparable with originator biologics. According to one of the coauthors of those guidelines, Tom W. J. Huizinga, MD, PhD, head of rheumatology at Leiden (Netherlands) University Medical Center, there is reasonable confidence in biosimilars as an adequate substitute for originator drugs, but real-world data are welcome.

"Real-world data provide different information than controlled trials and long-term data as well, so these [Canadian findings] are useful to support the data from [randomized controlled trials]," Dr. Huizinga said in an interview. He was not involved in the Canadian study.

Survivorship evaluated after switch to biosimilars

In British Columbia, biosimilars were mandated province-wide for new prescriptions of infliximab and etanercept in June 2017. In 2019, the mandate was extended to patients already taking originator infliximab (Remicade) and originator etanercept (Enbrel). Since that time, the mandate for biosimilars has also been applied to adalimumab (Humira). For the comparison of infliximab and etanercept originators with their biosimilars, Dr. Lacaille and associates compared survivorship for the 3 years after the policy change, when patients were on biosimilars, with the 3 years prior to the change, when patients were on the originators. They compared survivorship with originator adalimumab with its biosimilars for prior to and after the switch.

"People were followed from anti-TNF [tumor necrosis factor] initiation until discontinuation for any reason," reported Dr. Lacaille, who said data were censored for death and moving out of the province. In British Columbia, where there is universal health care, all dispensed medications can be tracked. The definition of anti-TNF discontinuation in this study was no prescription renewal for at least 6 months.

The follow-up was censored on March 2, 2020, to avoid the potential impact of COVID-19 on antirheumatic drug use. Discontinuation was standardized for the comparison of originator with biosimilar drugs as rates per 100 person-years. Statistical adjustments were made for potential confounders.

The researchers compared 1,312 patients on etanercept and 827 on a biosimilar of it, 230 patients on infliximab and 271 on a biosimilar of it, and 1,773 on adalimumab and 2,213 on a biosimilar of it. The indication was RA in approximately 60% of those on etanercept or a biosimilar and 50% of those on infliximab or adalimumab and their biosimilars. More than half of the remaining patients had indications for psoriatic arthritis, and the rest had ankylosing spondylitis.

No differences reach statistical significance

On the basis of discontinuation rates per 100 person-years, etanercept and its biosimilars performed almost identically (37.10 vs. 37.02, respectively). Although the discontinuation rate per 100 person-years was lower on infliximab than a biosimilar of it (29.97 vs. 37.96), the difference was not statistically significant (P = .076).

For adalimumab, the discontinuation rate was also lower on the originator drug than a biosimilar of it (32.92 vs. 36.36), but, again, this difference was also insignificant (P = .56).

When the discontinuation data were evaluated on the basis of a Cox model involving a propensity weight overlap, the univariate and the multivariable analyses found that the biosimilars had similar risks for discontinuation. Univariate analysis revealed hazard ratios for discontinuation of the biosimilar relative to the originator were 0.98 (P = .783) for etanercept, 1.17 (P = .242) for infliximab, and 1.08 (P = .09) for adalimumab. In the multivariable model, adjusted HRs for discontinuation were about the same for each of the biosimilars relative to the originator: 0.98 (P = .807) for etanercept, 1.19 (P = .183) for infliximab, and 1.08 (P = .089) for adalimumab.

Relative to previously published direct comparisons, this real-world analysis and its duration of follow-up address the limitations of formal trials. In a 2020 BMJ meta-analysis of published data from 45 trials comparing biosimilar with originator drugs in patients with RA who had failed methotrexate, the authors found only "minor differences in harms and benefits," but they cautioned that the analysis was "hampered by a lack of long-term direct comparisons."

In an interview, Dr. Huizinga noted that a systematic review of adalimumab biosimilars that he led 2 years ago showed that they perform comparably with the originator biologics. This and other published studies have consistently shown "that there is no difference between biologics and originators."

Dr. Lacaille disclosed financial relationships with Fresenius Kabi, Janssen, Organon, Pfizer, and Viatris. Dr. Huizinga disclosed financial relationships with Abbott, Ablynx, Biotest, Bioscience, Boehringer Ingelheim, Bristol-Myers Squibb, Crescendo Bioscience, Eli Lilly, Galapagos, Janssen, Merck, Novartis, MycoMed, Roche, Sanofi-Aventis, Takeda, and Zydus.

This article originally appeared on, part of the Medscape Professional Network.


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