Zenas Z.N. Yiu, MBChB, PhD

Credit: University of Manchester

There are no clinically or statistically significant differences in safety or effectiveness for psoriasis treatment between biosimilars and originators of etanercept, adalimumab, infliximab, and ustekinumab, according to recent findings.¹

These findings resulted from a systematic review of the available literature on evidence for the use of biosimilars in treating psoriasis. In contrast with prior systematic reviews of efficacy and safety of biosimilars for psoriasis this was not focused on the effect of switching from originator to biosimilar treatments but on outcomes with the inclusion of both new users and switchers with an updated search.

This research was authored by Zenas Z.N. Yiu, MBChB, PhD, from the Dermatopharmacology Unit of the Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust.

“Currently, biosimilars of adalimumab, etanercept, and infliximab are available for the treatment of patients with psoriasis, with ustekinumab biosimilar candidates under investigation,” Yiu and colleagues wrote. “The aim of this systematic literature review was to summarize and critically evaluate the evidence for the use of biosimilars in the treatment of patients with psoriasis.”

Study Background

The investigators analyzed a total of 14 trials and 3 cohort studies to examine the efficacy and safety of various biosimilar drugs in treatment of psoriasis. Out of these trials, 10 focused on adalimumab, 2 on etanercept, 1 on infliximab, and 1 on ustekinumab.

The cohort studies investigated the effectiveness and safety of adalimumab, etanercept, infliximab, and a combination of infliximab and etanercept. The search for relevant studies was performed in August of 2022 using several databases, including EMBASE, MEDLINE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register.

To assess the quality of eligible studies, the Cochrane Risk of Bias 2 and ROBINS-I tools were utilized by the investigators. The analysis of the collected data was then carried out between September and November of 2022.

1. Findings for Biosimilars of Adalimumab:

The team could not identify any robust evidence from randomized controlled trials (RCTs) that showed a significant difference in efficacy or safety between biosimilars of adalimumab (such as BCD-057 and GP2017) and the originator Humira.
Switching to adalimumab biosimilars was found to be less effective in lowering Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores compared to continuous originator adalimumab, but these differences were not clinically significant.

2. Findings for Biosimilars of Etanercept:

The investigators found that the etanercept biosimilar CHS-0214 demonstrated better efficacy in achieving PASI75 compared to the originator drug Enbrel.

3. Findings for Biosimilars of Infliximab:

No robust evidence that the investigators could identify from RCTs was found regarding the efficacy and safety of biosimilars of infliximab (such as CT-P43, flixabi/renflexis, ixifi/zessly) compared to the originator drug Remicade.

4. Findings for Biosimilars of Ustekinumab:

The research team noted as well that the new ustekinumab biosimilar CT-P43 showed improved efficacy in achievement of PASI75 compared to the originator drug Stelara.

General Findings and Conclusions

The overall available clinical evidence for the use of biosimilars in psoriasis treatment was shown by the investigators to be both scarce and of lower quality. Out of the 3 included cohort trials, 2 studies had serious risks of bias due to a lack of adjustment for baseline confounders.

One showed a higher risk of adverse events when switching to adalimumab biosimilars (GP2017 and SB5) compared to continuous originator adalimumab, but the difference was reported by the research team not to be clinically significant.²

When comparing biosimilars to originators in those who were new to originator treatment (starters), the investigators found there were no major differences in the rates of achieving a 75% improvement in PASI scores or the risks of adverse events at both week 16 and week 52.

Similarly, when comparing patients who switched from originator to biosimilar treatment with those who continued on originator treatment, no substantial differences were found in terms of efficacy or safety outcomes.

The findings from the cohort studies aligned with these results, as they also demonstrated no substantial differences between the originator drugs and biosimilars. However, 1 of the studies did report a higher occurrence of adverse events in patients who switched to biosimilars of adalimumab after 12 months.

“Most of the available evidence for the use of biosimilars in psoriasis treatment was based on RCTs where high-quality and long-term clinical evidence was lacking,” they wrote. “Future studies are needed to examine the long-term effectiveness and safety of biosimilars for psoriasis treatment in clinical settings.”

References

1. ^{Phan DB, Elyoussfi S, Stevenson M, Lunt M, Warren RB, Yiu ZZN. Biosimilars for the Treatment of Psoriasis: A Systematic Review of Clinical Trials and Observational Studies. JAMA Dermatol. Published online May 31, 2023. doi:10.1001/jamadermatol.2023.1338.}
2. ^{Loft N, Egeberg A, Rasmussen MK, et al. Outcomes following a mandatory nonmedical switch from adalimumab originator to adalimumab biosimilars in patients with psoriasis. JAMA Dermatol. 2021;157(6):676-683. doi:10.1001/jamadermatol.2021.0221.}