In inflammatory bowel diseases (IBD), biosimilars have been available for roughly 5 years, but more evidence may be necessary to persuade medical community to increase usage, according to a study.
Inflammatory bowel diseases (IBD), which include Crohn disease (CD) and ulcerative colitis (UC), are increasing in prevalence, and although biosimilars are available for treatment of these diseases and represent huge potential savings, there is lingering unwillingness to switch to these medications, according to a recent study.
“As the era of biosimilars is presently unavoidable, gaining a better understanding of biosimilars, especially for near future applications, is a crucial requirement in the field of therapeutics,” the authors said.
The authors noted safety and efficacy studies and pharmacokinetic studies that have demonstrated equivalency of biosimilar infliximab CT-P13 (Inflectra, Remsima) to the originator, Remicade.
They said more studies are underway that could help to confirm the long-term efficacy and safety of biosimilars and help to “clarify ongoing debates regarding several unresolved or partially resolved extrapolations, switching, and the immunogenicity of biosimilars.”
Prospective studies assessing CT-P13 alone in patients with CD and UC have shown strongly positive outcomes. A study noted by the authors (N = 78) demonstrated clinical remission in 79% of patients with CD and 56% in patience with UC after 14 weeks.
In a separate study of the efficacy of CT-P13 induction therapy on mucosal healing in patients with UC (N = 63), cumulative clinical response and steroid-free remission at week 14 were achieved in 82.5% and 47.4% of patients, respectively; mucosal healing was detected in 47.6% of patients, and complete mucosal healing was found in 27% of patients.
In the NOR-SWITCH study (N = 482) of switching from the originator to the biosimilar CT-P13, patients with CD, UC, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis. Disease worsening across all indications was observed in 26% of patients on originator infliximab and 30% of patients in the CT-P13 group. The frequency of adverse events was 10% in the reference group and 9% in the CT-P13 group. These findings led investigators to conclude that switching from the originator drug to CT-P13 was not inferior to continued treatment with the originator.
Despite such findings, there was a divergence in international consensus. The European Crohn’s disease and Colitis Organization recommended the use of biosimilars and confirmed that switching from the originals to biosimilars is acceptable, but only after discussion with stakeholders, including patients, nurses and pharmacists. The American Gastroenterological Association recommended that prescribing physicians should avoid nonmedical switching from originals to biosimilars.
With respect to immunogenicity studies, the authors cited an in vitro study that demonstrated that the antibodies that developed against originator infliximab during previous exposure to the drug were cross-reactive with CT-P13. “This important finding suggests that similar immunogenicity and immunodominant epitopes are shared between these infliximab agents [originator and biosimilar],” the authors wrote.
Especially for IBD, biosimilars have the potential to reduce costs. In Norway, CT-P13 achieved savings of 51% to 65% compared with originator infliximab; in France, the discount is 45%, and in Japan, the current price of CTP13 is 67% lower than that of originator infliximab, the authors wrote. “Thus, the magnitude of price reduction may be important for switching prescriptions to biosimilars.”
Another survey suggested that 83% of physicians in the United States would prescribe biosimilars if they were 25% cheaper. It also found a bias against switching among US providers.
Acceptance by physicians has increased as biosimilars are more widely used to treat IBD and more research has been published, according to the authors. They cite surveys of European physicians: In 2013, only 6% of physicians viewed biosimilars as interchangeable with their reference products. By 2015 that had increased to 44%. In 2013, 76% of physicians were opposed to extrapolation from other indications, which decreased to 33% in 2015. In 2013, 63% had little or no little or no confidence in biosimilars, which decreased to 20% in 2015.
There remain areas that need further investigation. The authors note there is a lack of scientific and clinical evidence when it comes to reverse switching, multiple switching, and cross-switching between biosimilars in patients with IBD.
The authors recommend long-term safety monitoring of biosimilars in IBD with post-marketing observational studies.
Looking to the future, the authors anticipate new evidence for IBD biosimilars. Besides CT-P13, additional infliximab biosimilars have been approved by FDA or EMA, and additional infliximab and adalimumab biosimilars are in preclinical testing and clinical trials. Cost reductions from biosimilars, the authors argue, will allow for the treatment of more patients with IBD and provide funds to educate patients and health care professionals on biosimilars, leading to increased adoption of biosimilars for further cost reductions. To achieve this, a better understanding of biosimilars from more research is necessary to address physician and patient concerns about extrapolations, switching, and immunogenicity concerns.
Park SH, Park JC, Lukas M, Kolar M, Loftus EV. Biosimilars: Concept, current status, and future perspectives in inflammatory bowel diseases. Intest Res. 2020;18(1):34-44. doi: 10.5217/ir.2019.09147.