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The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.
“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and , S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.
The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.
The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.
“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.
Immunogenicity
Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”
Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
Extrapolation of indications
The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.
However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
Substitution, interchangeability, and switching
The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.
While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.
Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.
While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.
“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
Costs
The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.
“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”
It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.
No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.
SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402
The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.
“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and , S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.
The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.
The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.
“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.
Immunogenicity
Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”
Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
Extrapolation of indications
The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.
However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
Substitution, interchangeability, and switching
The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.
While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.
Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.
While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.
“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
Costs
The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.
“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”
It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.
No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.
SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402
The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.
“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and , S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.
The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.
The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.
“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.
Immunogenicity
Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”
Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
Extrapolation of indications
The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.
However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
Substitution, interchangeability, and switching
The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.
While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.
Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.
While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.
“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
Costs
The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.
“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”
It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.
No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.
SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402
FROM ARTHRITIS & RHEUMATOLOGY