Switching between reference adalimumab (Humira) and its approved biosimilars results in no differences in efficacy, safety, and immunogenicity, investigators in Spain have concluded following a systematic review of available studies that was published in British Journal of Clinical Pharmacology.
The authors conducted a systematic review of the 21 studies that met their inclusion criteria. These included 2802 adult patients treated with 8 adalimumab biosimilars for chronic immune-mediated inflammatory diseases. Investigators reviewed 8 studies on rheumatoid arthritis, 6 on psoriasis, 6 on inflammatory bowel diseases, and 1 on multiple diseases.
Adalimumab, a monoclonal antibody to tumor necrosis factor alpha, was first approved by the FDA in 2002 and European Commission in 2003. By 2017, the authors said, “it was the best-selling drug worldwide, with global sales of $18 billion.”
In the European Union, Humira’s key patent expired in 2018, and adalimumab biosimilars have long been available there for patient treatment. In the United States, Humira’s compound patent expired in 2016; however, due to other patents and settlements between AbbVie and biosimilar manufacturers, biosimilars will not enter the US market until 2023.
The systematic review encompassed studies on adalimumab biosimilars approved in the United States and European Union:
- ABP501 (Amjevita; Amgen; 7 studies)
- SB5 (Hadlima; Samsung Bioepis; 5 studies)
- FKB327 (Hulio; Mylan with Fujifilm Kyowa Kirin Biologics; 2 studies)
- BI695501 (Cyltezo; Boehringer Ingelheim; 1 study)
- MSB11022 (Idacio; Fresenius Kabi; 1 study)
- GP2017 (Hyrimoz; Sandoz; 3 studies)
- PF-061410293 (Amsparity/Abrilada; Pfizer; 1 study)
- CT-P17 (Yuflyma; Celltrion; 1 study).
Of the 21 studies, 19 assessed clinical efficacy and 10 of these were double-blind, randomized, placebo-controlled trials. According to the authors, no significant differences in efficacy (or effectiveness) were demonstrated between switch and no-switch groups in these trials.
Nocebo Effect and Pain
Safety was investigated in 18 studies. The authors found that infection was the most frequently reported treatment-emergent adverse event, and rates of adverse events were similar between switch and no-switch groups in these studies. Notably, the authors wrote, their finding “contradicts the information from some systematic reviews where there appears to be a greater number of treatment cessations following the switching due to the possible nocebo effect.”
Greater pain at the injection site was reported in switch groups than no-switch groups in 2 studies reviewed by the authors, which they noted were nonrandomized studies, indicating a possible nocebo effect. They suggested “careful communication among all the implicated health professionals—doctors, nurses and pharmacists—and a clear explanation of the treatment schedule to the patient could help to minimize this nocebo effect.”
Fifteen studies evaluated immunogenicity, which was indicated by the percentage of patients who developed neutralizing antidrug antibodies (ADAs). Rates of development of ADAs were comparable, with no significant differences between reference adalimumab, biosimilar, and switching groups in these studies, according to the authors.
The authors concluded their systematic review suggests switching between adalimumab and its biosimilars has “no impact on efficacy, safety, and immunogenicity in patients with chronic immune-mediated inflammatory diseases.” They said this finding was consistent across the different adalimumab biosimilars they studied.
The authors contended their review is significant because “both health care professionals and patients, as well as health administrations, need this information to conduct safe switching of these medicines and gain confidence in their management.”
They wrote their review was limited by the relatively small number of studies, which did not allow them to conduct a meta-analysis, and the quality of the studies, some of which were not blinded and randomized. Also, just 1 study investigated multiple switches, and none investigated switching between different biosimilars.
Pego Reigosa JM, García Beloso N, Altabás González I, et al. Switching between reference adalimumab and biosimilars in chronic immune-mediated inflammatory diseases: a systematic literature review. Br J Clin Pharmacol. Published online October 8, 2021. doi:10.1111/bcp.15101