Biosimilars for psoriasis matched the performance of the original products for skin clearance, but evidence from real-world comparisons remains limited, a systematic review of published studies showed.
No clinically or statistically significant differences occurred between biosimilars and originators at 16 or 52 weeks. No appreciable differences existed for comparisons of biosimilars for adalimumab, infliximab, ustekinumab, or etanercept and their respective original biologics. Results also did not differ in studies involving patients with no prior exposure to a biologic agent or those who were switched from one biologic to another.
Where multiple products for the same biologic were available, limited evidence suggested differences in efficacy and adverse events (AEs) related to specific biosimilars, but more studies based in clinical settings are needed to confirm the findings, reported Zenas Z.N. Yiu, MBChB, PhD, of Salford Royal Hospital in England, and coauthors in JAMA Dermatology
"Most of the available evidence for the use of biosimilars in psoriasis treatment was based on RCTs [randomized controlled trials], where high-quality and long-term clinical evidence was lacking," the authors concluded. "Future studies are needed to examine the long-term effectiveness and safety of biosimilars for psoriasis treatment in clinical settings."
Limitations of Evidence
In the absence of that evidence, "biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve accessibility for biologic treatments," they noted. The available data also showed that "switching from originators to biosimilars had no effect on treatment efficacy and safety. Thus, switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs."
Although biologic agents have transformed the treatment of psoriasis and other inflammatory conditions, the attraction of biosimilar alternatives is a matter of cost, noted the authors of an accompanying editorial
"In the U.S., biologics comprise less than 3% of the volume of drugs on the market, but account for more than one third of all spending," wrote Luigi Naldi, MD, of Ospedale San Bortolo di Vicenza, and Antonio Addis, PharmD, of the Regional Health Service at ASL Roma 1, both in Italy. "The reasons for the high cost of biologics are manifold, including the complexity of their development process, lack of competition, and high demand for their use."
Multiple barriers have limited uptake of biosimilars in clinical practice, beginning with the general marketing issue of value associated with a "brand" product versus "copies," they continued. Clinicians' relative lack of understanding about the peculiarities of the development process for biosimilars is another potential barrier. Manufacturers of originator drugs have the capacity to extend patent rights for minor variations in a product and delay introduction of biosimilars for years.
Manufacturers of originators also negotiate discounts for the biologics, which can reduce the financial incentive to prescribe biosimilars.
"From a societal point of view, adopting biosimilars could provide advantages, including improved access to treatment for a larger basis of patients and cost savings on drugs," Naldi and Addis concluded. "The cost-effectiveness of an approach privileging, at start, a biosimilar choice, in comparison with alternative strategies capitalizing on drugs with a higher level of efficacy but lacking a biosimilar alternative remains to be determined in the long term."
Background, Findings
The biosimilar approval process allows extrapolation of evidence for approved indications of the originator without direct clinical trial investigation, Yiu and coauthors noted in the introduction to their study. Thus, biosimilars can be approved for psoriasis on the basis of extrapolated evidence from other diseases. As a result, the extent of evidence for biosimilars' safety and effectiveness in psoriasis remained unclear.To explore evidence for biosimilars specific to psoriasis, investigators performed a systematic review that included clinical trials and observational studies. They identified 14 clinical trials (10 involving adalimumab, two for etanercept, and one each for infliximab and ustekinumab) and three cohort studies involving adalimumab, etanercept, infliximab, and etanercept.
The data encompassed 12 trials that compared biosimilars with originators in patients with no prior exposure to an originator biological and 11 that compared switching from originator to biosimilar versus continuous treatment with the originator. The primary outcomes of interest were the proportion of patients achieving at least 75% improvement in the Psoriasis Area and Severity Index (PASI75) at 16 and 52 weeks, as well as AEs.
The results showed PASI75 response rates at 16 weeks ranging from 60.7% to 90.6% for biosimilars to adalimumab and from 61.5% to 91.7% for the originator. Two studies of biosimilars to etanercept showed 16-week PASI75 response rates of 56.1% and 76.7% versus 55.5% and 73.4% for the originator. A single study of ustekinumab showed PASI75 responses in 86.1% of patients treated with a biosimilar and 84.0% with the originator.
At week 52, PASI75 response rates ranged form 86.3% to 92.8% for adalimumab biosimilars and 84.9% to 93.9% for the originator. A single comparison of an etanercept biosimilar to the originator yielded PASI75 rates of 80.9% and 82.9%, respectively.
Studies evaluating switch from originator to a biosimilar versus continuous therapy with the originator yielded 32-week response rates of 87.0% to 91.3% for biosimilars and 88.2% to 93.2% for the originator. A single study of ustekinumab showed a 32-week PASI75 response rate of 92.6% with the switch to a biosimilar and 92.9% with continuous therapy. The 52-week response rates with adalimumab ranged from 84.2% to 94.8% for the biosimilars and 88.1% to 93.9% for the originator.
Safety analyses at 16 weeks showed no clear trend favoring biosimilars or originators with the possible exception of a trend favoring the biosimilars for serious AEs in trials involving patients with no prior exposure to a biologic agent.
"This systematic review found no robust evidence from RCTs to show that people with psoriasis who started or switched to biosimilars of adalimumab, etanercept, infliximab, and ustekinumab had a statistically or clinically significant difference in efficacy or safety compared with the originators Humira, Enbrel, Remicade, or Stelara," Yiu and coauthors concluded.
Disclosures
The study was supported by the Psoriasis Association and the NIHR Manchester Biomedical Research Centre.
Yiu reported no relevant relationships with industry.
Naldi disclosed relationships with Bristol Myers Squibb, AbbVie, Almirall, Eli Lilly, Janssen, LEO, and Novartis.
Primary Source
JAMA Dermatology
Source Reference: Phan DB, et al "Biosimilars for the treatment of psoriasis. A systematic review of clinical trials and observational studies" JAMA Dermatol 2023; DOI: 10.1001/jamadermatol.2023.1338.
Secondary Source
JAMA Dermatology
Source Reference: Naldi L, Addis A "Biosimilars for the treatment of psoriasis -- A systematic review of clinical trials and observational studies. Looking beyond single-trial evidence for a valuable choice" JAMA Dermatol 2023; DOI: 10.1001/jamadermatol.2023.1331.
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