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Biosimilars poised to save $54 billion over the next decade
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Golimumab earns new FDA approvals
The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).
Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.
“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.
Read the revised prescribing information for Simponi Aria here.
The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).
Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.
“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.
Read the revised prescribing information for Simponi Aria here.
The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).
Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.
“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.
Read the revised prescribing information for Simponi Aria here.
High ‘nocebo’ effect observed when patients knowingly switch to a biosimilar
Evidence suggests that patients who switch from an originator biologic to open-label treatment with its biosimilar have an increase in subjective but not objective assessments and also discontinue the drug at a high rate, possibly reflecting a “nocebo” response to switching.
If patients’ own negative expectations induced “negative symptoms (hyperalgesia or adverse events) during treatment, the so-called nocebo response,” and was the main contributing factor to the high discontinuation rate, then it will be very important for clinicians to improve communication with patients and their expectations in order to raise acceptance and persistence rates, the investigators said.
Of the 47 patients who discontinued CT-P13, 26 did so because of a perceived lack of effect, 11 because of adverse events, and 10 because of a combination of both of these factors.
Univariate Cox regression analyses showed that shorter infliximab infusion interval, higher 28-joint Disease Activity Scores (DAS28, based on either C-reactive protein [CRP] or erythrocyte sedimentation rate), higher swollen joint count, and patients’ global disease activity score at baseline were associated with CT-P13 discontinuation.
However, patients’ and clinicians’ awareness of the switch could have influenced these factors, the investigators said. For instance, they found that patients who discontinued CT-P13 reported a significant increase in “subjective” assessments such as tender joint count and patient’s global disease activity but not “objective” measures such as swollen joint count or CRP.
While the mean Bath Ankylosing Spondylitis Disease Activity Index score increased from 3.8 to 4.3, the mean DAS28-CRP in rheumatoid arthritis and psoriatic arthritis patients remained stable at 2.2 from baseline to month 6; CRP and anti-infliximab antibody levels also did not change.
“If immunogenicity would have caused CT-P13 discontinuation, we would have expected to find more patients with objectively active disease and/or allergic reactions,” the study authors wrote.
Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
Evidence suggests that patients who switch from an originator biologic to open-label treatment with its biosimilar have an increase in subjective but not objective assessments and also discontinue the drug at a high rate, possibly reflecting a “nocebo” response to switching.
If patients’ own negative expectations induced “negative symptoms (hyperalgesia or adverse events) during treatment, the so-called nocebo response,” and was the main contributing factor to the high discontinuation rate, then it will be very important for clinicians to improve communication with patients and their expectations in order to raise acceptance and persistence rates, the investigators said.
Of the 47 patients who discontinued CT-P13, 26 did so because of a perceived lack of effect, 11 because of adverse events, and 10 because of a combination of both of these factors.
Univariate Cox regression analyses showed that shorter infliximab infusion interval, higher 28-joint Disease Activity Scores (DAS28, based on either C-reactive protein [CRP] or erythrocyte sedimentation rate), higher swollen joint count, and patients’ global disease activity score at baseline were associated with CT-P13 discontinuation.
However, patients’ and clinicians’ awareness of the switch could have influenced these factors, the investigators said. For instance, they found that patients who discontinued CT-P13 reported a significant increase in “subjective” assessments such as tender joint count and patient’s global disease activity but not “objective” measures such as swollen joint count or CRP.
While the mean Bath Ankylosing Spondylitis Disease Activity Index score increased from 3.8 to 4.3, the mean DAS28-CRP in rheumatoid arthritis and psoriatic arthritis patients remained stable at 2.2 from baseline to month 6; CRP and anti-infliximab antibody levels also did not change.
“If immunogenicity would have caused CT-P13 discontinuation, we would have expected to find more patients with objectively active disease and/or allergic reactions,” the study authors wrote.
Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
Evidence suggests that patients who switch from an originator biologic to open-label treatment with its biosimilar have an increase in subjective but not objective assessments and also discontinue the drug at a high rate, possibly reflecting a “nocebo” response to switching.
If patients’ own negative expectations induced “negative symptoms (hyperalgesia or adverse events) during treatment, the so-called nocebo response,” and was the main contributing factor to the high discontinuation rate, then it will be very important for clinicians to improve communication with patients and their expectations in order to raise acceptance and persistence rates, the investigators said.
Of the 47 patients who discontinued CT-P13, 26 did so because of a perceived lack of effect, 11 because of adverse events, and 10 because of a combination of both of these factors.
Univariate Cox regression analyses showed that shorter infliximab infusion interval, higher 28-joint Disease Activity Scores (DAS28, based on either C-reactive protein [CRP] or erythrocyte sedimentation rate), higher swollen joint count, and patients’ global disease activity score at baseline were associated with CT-P13 discontinuation.
However, patients’ and clinicians’ awareness of the switch could have influenced these factors, the investigators said. For instance, they found that patients who discontinued CT-P13 reported a significant increase in “subjective” assessments such as tender joint count and patient’s global disease activity but not “objective” measures such as swollen joint count or CRP.
While the mean Bath Ankylosing Spondylitis Disease Activity Index score increased from 3.8 to 4.3, the mean DAS28-CRP in rheumatoid arthritis and psoriatic arthritis patients remained stable at 2.2 from baseline to month 6; CRP and anti-infliximab antibody levels also did not change.
“If immunogenicity would have caused CT-P13 discontinuation, we would have expected to find more patients with objectively active disease and/or allergic reactions,” the study authors wrote.
Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: Nearly a quarter of 192 patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, who knowingly switched from originator infliximab to its biosimilar CT-P13 discontinued the biosimilar during 6 months of follow-up.
Data source: A multicenter, prospective cohort study of 192 infliximab-treated patients who transitioned to the infliximab biosimilar CT-P13.
Disclosures: Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
Thoracic syndesmophytes common in ankylosing spondylitis
Thoracic syndesmophytes are common in ankylosing spondylitis, even in the absence of lumbar syndesmophytes, according to a study published in the Journal of Rheumatology.
Sovira Tan, PhD, and his colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases wrote that the current standard for radiographic assessment of ankylosing spondylitis scores only the cervical and lumbar spine because of difficulties visualizing the thoracic spine.
“Consequently, the involvement of the thoracic spine with syndesmophytes has not been widely studied,” they wrote. “If syndesmophytes differentially develop in the thoracic spine, exclusion of this large region may affect the validity of spinal fusion biomarker studies.”
In this study, 18 patients with ankylosing spondylitis who did not show complete lumbar fusion on radiographs underwent thoracolumbar CT and lumbar radiography (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.170340). The patients had ankylosing spondylitis for a mean duration of about 19 years, and 11 were treated with tumor necrosis factor inhibitors.
Researchers found syndesmophytes were common overall in intervertebral disc spaces, ranging from 56% to 89%. The rate of syndesmophytes peaked around the thoracolumbar junction, and bridging was both more evident and more extensive in the superior thoracic levels, compared with the lumbar levels.
In all the patients, thoracic syndesmophytes on the CT scan were at least as common as lumbar, and patients with extensive syndesmophytes at multiple lumbar locations typically also had the same in the thoracic region.
However, there were also patients with no, or very few, lumbar syndesmophytes on CT who still had thoracic syndesmophytes, some of which were extensive.
“Importantly, if syndesmophytes were observed on a lumbar radiograph, one could expect there to be syndesmophytes in the thoracic spine, but not the converse,” the authors wrote. “Several patients with normal lumbar radiographs had substantial thoracic syndesmophytes.”
The authors commented that because of its two-dimensional character, radiography has a relatively low sensitivity for detecting syndesmophytes, compared with CT. This could explain why patients with any syndesmophytes in the lumbar region on radiography also had them in the thoracic CT scans.
“By the time syndesmophytes are detectable on lumbar radiographs, structural damage may already have occurred in large portions of the thoracolumbar spine.”
They acknowledged that their method was a research tool and not intended for clinical practice, but also pointed out that CT technology had improved to allow more extensive spine coverage, at an equal effective dose, without compromising scan quality.
The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
Thoracic syndesmophytes are common in ankylosing spondylitis, even in the absence of lumbar syndesmophytes, according to a study published in the Journal of Rheumatology.
Sovira Tan, PhD, and his colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases wrote that the current standard for radiographic assessment of ankylosing spondylitis scores only the cervical and lumbar spine because of difficulties visualizing the thoracic spine.
“Consequently, the involvement of the thoracic spine with syndesmophytes has not been widely studied,” they wrote. “If syndesmophytes differentially develop in the thoracic spine, exclusion of this large region may affect the validity of spinal fusion biomarker studies.”
In this study, 18 patients with ankylosing spondylitis who did not show complete lumbar fusion on radiographs underwent thoracolumbar CT and lumbar radiography (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.170340). The patients had ankylosing spondylitis for a mean duration of about 19 years, and 11 were treated with tumor necrosis factor inhibitors.
Researchers found syndesmophytes were common overall in intervertebral disc spaces, ranging from 56% to 89%. The rate of syndesmophytes peaked around the thoracolumbar junction, and bridging was both more evident and more extensive in the superior thoracic levels, compared with the lumbar levels.
In all the patients, thoracic syndesmophytes on the CT scan were at least as common as lumbar, and patients with extensive syndesmophytes at multiple lumbar locations typically also had the same in the thoracic region.
However, there were also patients with no, or very few, lumbar syndesmophytes on CT who still had thoracic syndesmophytes, some of which were extensive.
“Importantly, if syndesmophytes were observed on a lumbar radiograph, one could expect there to be syndesmophytes in the thoracic spine, but not the converse,” the authors wrote. “Several patients with normal lumbar radiographs had substantial thoracic syndesmophytes.”
The authors commented that because of its two-dimensional character, radiography has a relatively low sensitivity for detecting syndesmophytes, compared with CT. This could explain why patients with any syndesmophytes in the lumbar region on radiography also had them in the thoracic CT scans.
“By the time syndesmophytes are detectable on lumbar radiographs, structural damage may already have occurred in large portions of the thoracolumbar spine.”
They acknowledged that their method was a research tool and not intended for clinical practice, but also pointed out that CT technology had improved to allow more extensive spine coverage, at an equal effective dose, without compromising scan quality.
The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
Thoracic syndesmophytes are common in ankylosing spondylitis, even in the absence of lumbar syndesmophytes, according to a study published in the Journal of Rheumatology.
Sovira Tan, PhD, and his colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases wrote that the current standard for radiographic assessment of ankylosing spondylitis scores only the cervical and lumbar spine because of difficulties visualizing the thoracic spine.
“Consequently, the involvement of the thoracic spine with syndesmophytes has not been widely studied,” they wrote. “If syndesmophytes differentially develop in the thoracic spine, exclusion of this large region may affect the validity of spinal fusion biomarker studies.”
In this study, 18 patients with ankylosing spondylitis who did not show complete lumbar fusion on radiographs underwent thoracolumbar CT and lumbar radiography (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.170340). The patients had ankylosing spondylitis for a mean duration of about 19 years, and 11 were treated with tumor necrosis factor inhibitors.
Researchers found syndesmophytes were common overall in intervertebral disc spaces, ranging from 56% to 89%. The rate of syndesmophytes peaked around the thoracolumbar junction, and bridging was both more evident and more extensive in the superior thoracic levels, compared with the lumbar levels.
In all the patients, thoracic syndesmophytes on the CT scan were at least as common as lumbar, and patients with extensive syndesmophytes at multiple lumbar locations typically also had the same in the thoracic region.
However, there were also patients with no, or very few, lumbar syndesmophytes on CT who still had thoracic syndesmophytes, some of which were extensive.
“Importantly, if syndesmophytes were observed on a lumbar radiograph, one could expect there to be syndesmophytes in the thoracic spine, but not the converse,” the authors wrote. “Several patients with normal lumbar radiographs had substantial thoracic syndesmophytes.”
The authors commented that because of its two-dimensional character, radiography has a relatively low sensitivity for detecting syndesmophytes, compared with CT. This could explain why patients with any syndesmophytes in the lumbar region on radiography also had them in the thoracic CT scans.
“By the time syndesmophytes are detectable on lumbar radiographs, structural damage may already have occurred in large portions of the thoracolumbar spine.”
They acknowledged that their method was a research tool and not intended for clinical practice, but also pointed out that CT technology had improved to allow more extensive spine coverage, at an equal effective dose, without compromising scan quality.
The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point:
Major finding: Within individual patients, CT-detected syndesmophytes were either more common in or equally present in thoracic intervertebral disc spaces, compared with lumbar.
Data source: CT and radiography study of 18 patients with ankylosing spondylitis.
Disclosures: The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
Launch of adalimumab biosimilar Amjevita postponed
Amgen, maker of the adalimumab biosimilar Amjevita (adalimumab-atto) has reached an agreement with AbbVie, manufacturer of the originator adalimumab Humira, that halts marketing of Amjevita in the United States until 2023 and in Europe until 2018, according to a company statement.
The deal between the two manufacturers settles a patent infringement lawsuit that AbbVie brought against Amgen after it received Food and Drug Administration approval in September 2016 for seven of Humira’s nine indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and polyarticular juvenile idiopathic arthritis. Amjevita is not approved for two of Humira’s indications, hidradenitis suppurativa and uveitis.
Amgen said in its statement that AbbVie will grant patent licenses for the use and sale of Amjevita worldwide, on a country-by-country basis, with current expectations that marketing will begin in Europe on Oct. 16, 2018, and in the United States on Jan. 31, 2023. Amjevita is named Amgevita in Europe.
Amgen, maker of the adalimumab biosimilar Amjevita (adalimumab-atto) has reached an agreement with AbbVie, manufacturer of the originator adalimumab Humira, that halts marketing of Amjevita in the United States until 2023 and in Europe until 2018, according to a company statement.
The deal between the two manufacturers settles a patent infringement lawsuit that AbbVie brought against Amgen after it received Food and Drug Administration approval in September 2016 for seven of Humira’s nine indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and polyarticular juvenile idiopathic arthritis. Amjevita is not approved for two of Humira’s indications, hidradenitis suppurativa and uveitis.
Amgen said in its statement that AbbVie will grant patent licenses for the use and sale of Amjevita worldwide, on a country-by-country basis, with current expectations that marketing will begin in Europe on Oct. 16, 2018, and in the United States on Jan. 31, 2023. Amjevita is named Amgevita in Europe.
Amgen, maker of the adalimumab biosimilar Amjevita (adalimumab-atto) has reached an agreement with AbbVie, manufacturer of the originator adalimumab Humira, that halts marketing of Amjevita in the United States until 2023 and in Europe until 2018, according to a company statement.
The deal between the two manufacturers settles a patent infringement lawsuit that AbbVie brought against Amgen after it received Food and Drug Administration approval in September 2016 for seven of Humira’s nine indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and polyarticular juvenile idiopathic arthritis. Amjevita is not approved for two of Humira’s indications, hidradenitis suppurativa and uveitis.
Amgen said in its statement that AbbVie will grant patent licenses for the use and sale of Amjevita worldwide, on a country-by-country basis, with current expectations that marketing will begin in Europe on Oct. 16, 2018, and in the United States on Jan. 31, 2023. Amjevita is named Amgevita in Europe.
Immunogenicity concerns for biosimilars so far don’t go beyond originator biologics
A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.
In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).
“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).
One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.
The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.
What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”
Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.
There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.
Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.
In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).
“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).
One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.
The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.
What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”
Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.
There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.
Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.
In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).
“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).
One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.
The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.
What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”
Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.
There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.
Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
Early ankylosing spondylitis treatment stops transition from inflammatory to bone-forming fatty lesions
Structural damage in axial and peripheral ankylosing spondylitis is the result of a combination of destruction and new bone formation, which can be halted if treated early and for long enough, according to Dirk Elewaut, MD, PhD.
“There is a longstanding paradox in the field of ankylosing spondylitis, as to whether there is a strict relationship between the inflammation that leads to the signs and symptoms in patients, and the structural progression,” said Dr. Elewaut, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “ ”
One key reason why the early TNF inhibition trials showed no effect of treatment on structural progression stemmed from inadequate study design. “The original studies were underpowered, and the patients used NSAIDs,” he said. “We also know that the anti-inflammatory effect [of TNF inhibition] is not 100%. So you have a clear drop in inflammation with biologics, but it’s not completely stopped. This led to a lot of speculation as to whether inflammation and ankyloses are coupled or not.”
More recently, researchers have honed in on the transition from acute inflammatory lesions visible on MRI by bone marrow edema to so-called fatty lesions, which are also visible on MRI. They have observed that fatty lesions are associated with new bone formation. “Lesions containing more fat are thought to be more difficult to modulate by biological therapy,” Dr. Elewaut said. “Once you have a fatty lesion, you have some kind of metabolic disease of the bone, and it’s a one-way road to the development of new syndesmophytes. So in other words, it is essential to assess the relationship between inflammation and new bone formation with both the STIR [short tau inversion recovery images] and T1-weighted MRI.”
A working hypothesis among AS researchers is that the effect of anti-TNF therapy on radiologic progression depends on the relative number of acute and mature inflammatory lesions that individual patients have. “Early diagnosis is a prerequisite for advances in disease modification,” he said. At least three “windows of opportunity” for disease modification exist, Dr. Elewaut continued. One is that the link between inflammation as measured by clinical parameters and new bone formation will be more evident in early AS. The second is that early treatment of patients with axial AS and spinal inflammation with anti-TNF agents will prevent new bone formation. The third is that reduction of new bone formation in established AS will be observed only with long-term anti-TNF therapy after mature lesions have resolved/repaired, and no new inflammatory lesions are being formed. One study found that patients with a delay of more than 10 years starting anti-TNF therapy were more likely to progress, compared with patients who received therapy earlier (odds ratio, 2.4; P = .03; see Arthritis Rheum. 2013;65:645-54). “The message here is quite clear,” Dr. Elewaut said. “The earlier we treat intensively, the better impact you have on structural outcomes.”
In a trial known as CRESPA (Clinical Remission in peripheral SPondyloArthritis), researchers including Dr. Elewaut evaluated the efficacy and safety of golimumab (Simponi) to induce clinical remission in patients with early, active peripheral AS (Ann Rheum Dis. 2017;76:1389-95). In all, 60 patients were randomized to golimumab or placebo for 24 weeks. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission, compared with placebo (75% vs. 20%, respectively; P less than .001). At week 12, similar results were observed (70% vs. 15%; P less than .001).
“These were very striking results in this early disease population,” Dr. Elewaut said. In a follow-up analysis, the researchers withdrew therapy in patients who reached clinical remission, to see what would happen. “At 1.5 years of follow-up, 57% of patients are in drug-free remission,” Dr. Elewaut said. “This is interesting and suggests that at least in a fraction of those patients, you can actually achieve a drug-free remission.” Predictors for relapse included pre-existing psoriasis and having more than five swollen joints.
Dr. Elewaut disclosed that he is a member of the speakers bureau for AbbVie, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.
Structural damage in axial and peripheral ankylosing spondylitis is the result of a combination of destruction and new bone formation, which can be halted if treated early and for long enough, according to Dirk Elewaut, MD, PhD.
“There is a longstanding paradox in the field of ankylosing spondylitis, as to whether there is a strict relationship between the inflammation that leads to the signs and symptoms in patients, and the structural progression,” said Dr. Elewaut, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “ ”
One key reason why the early TNF inhibition trials showed no effect of treatment on structural progression stemmed from inadequate study design. “The original studies were underpowered, and the patients used NSAIDs,” he said. “We also know that the anti-inflammatory effect [of TNF inhibition] is not 100%. So you have a clear drop in inflammation with biologics, but it’s not completely stopped. This led to a lot of speculation as to whether inflammation and ankyloses are coupled or not.”
More recently, researchers have honed in on the transition from acute inflammatory lesions visible on MRI by bone marrow edema to so-called fatty lesions, which are also visible on MRI. They have observed that fatty lesions are associated with new bone formation. “Lesions containing more fat are thought to be more difficult to modulate by biological therapy,” Dr. Elewaut said. “Once you have a fatty lesion, you have some kind of metabolic disease of the bone, and it’s a one-way road to the development of new syndesmophytes. So in other words, it is essential to assess the relationship between inflammation and new bone formation with both the STIR [short tau inversion recovery images] and T1-weighted MRI.”
A working hypothesis among AS researchers is that the effect of anti-TNF therapy on radiologic progression depends on the relative number of acute and mature inflammatory lesions that individual patients have. “Early diagnosis is a prerequisite for advances in disease modification,” he said. At least three “windows of opportunity” for disease modification exist, Dr. Elewaut continued. One is that the link between inflammation as measured by clinical parameters and new bone formation will be more evident in early AS. The second is that early treatment of patients with axial AS and spinal inflammation with anti-TNF agents will prevent new bone formation. The third is that reduction of new bone formation in established AS will be observed only with long-term anti-TNF therapy after mature lesions have resolved/repaired, and no new inflammatory lesions are being formed. One study found that patients with a delay of more than 10 years starting anti-TNF therapy were more likely to progress, compared with patients who received therapy earlier (odds ratio, 2.4; P = .03; see Arthritis Rheum. 2013;65:645-54). “The message here is quite clear,” Dr. Elewaut said. “The earlier we treat intensively, the better impact you have on structural outcomes.”
In a trial known as CRESPA (Clinical Remission in peripheral SPondyloArthritis), researchers including Dr. Elewaut evaluated the efficacy and safety of golimumab (Simponi) to induce clinical remission in patients with early, active peripheral AS (Ann Rheum Dis. 2017;76:1389-95). In all, 60 patients were randomized to golimumab or placebo for 24 weeks. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission, compared with placebo (75% vs. 20%, respectively; P less than .001). At week 12, similar results were observed (70% vs. 15%; P less than .001).
“These were very striking results in this early disease population,” Dr. Elewaut said. In a follow-up analysis, the researchers withdrew therapy in patients who reached clinical remission, to see what would happen. “At 1.5 years of follow-up, 57% of patients are in drug-free remission,” Dr. Elewaut said. “This is interesting and suggests that at least in a fraction of those patients, you can actually achieve a drug-free remission.” Predictors for relapse included pre-existing psoriasis and having more than five swollen joints.
Dr. Elewaut disclosed that he is a member of the speakers bureau for AbbVie, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.
Structural damage in axial and peripheral ankylosing spondylitis is the result of a combination of destruction and new bone formation, which can be halted if treated early and for long enough, according to Dirk Elewaut, MD, PhD.
“There is a longstanding paradox in the field of ankylosing spondylitis, as to whether there is a strict relationship between the inflammation that leads to the signs and symptoms in patients, and the structural progression,” said Dr. Elewaut, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “ ”
One key reason why the early TNF inhibition trials showed no effect of treatment on structural progression stemmed from inadequate study design. “The original studies were underpowered, and the patients used NSAIDs,” he said. “We also know that the anti-inflammatory effect [of TNF inhibition] is not 100%. So you have a clear drop in inflammation with biologics, but it’s not completely stopped. This led to a lot of speculation as to whether inflammation and ankyloses are coupled or not.”
More recently, researchers have honed in on the transition from acute inflammatory lesions visible on MRI by bone marrow edema to so-called fatty lesions, which are also visible on MRI. They have observed that fatty lesions are associated with new bone formation. “Lesions containing more fat are thought to be more difficult to modulate by biological therapy,” Dr. Elewaut said. “Once you have a fatty lesion, you have some kind of metabolic disease of the bone, and it’s a one-way road to the development of new syndesmophytes. So in other words, it is essential to assess the relationship between inflammation and new bone formation with both the STIR [short tau inversion recovery images] and T1-weighted MRI.”
A working hypothesis among AS researchers is that the effect of anti-TNF therapy on radiologic progression depends on the relative number of acute and mature inflammatory lesions that individual patients have. “Early diagnosis is a prerequisite for advances in disease modification,” he said. At least three “windows of opportunity” for disease modification exist, Dr. Elewaut continued. One is that the link between inflammation as measured by clinical parameters and new bone formation will be more evident in early AS. The second is that early treatment of patients with axial AS and spinal inflammation with anti-TNF agents will prevent new bone formation. The third is that reduction of new bone formation in established AS will be observed only with long-term anti-TNF therapy after mature lesions have resolved/repaired, and no new inflammatory lesions are being formed. One study found that patients with a delay of more than 10 years starting anti-TNF therapy were more likely to progress, compared with patients who received therapy earlier (odds ratio, 2.4; P = .03; see Arthritis Rheum. 2013;65:645-54). “The message here is quite clear,” Dr. Elewaut said. “The earlier we treat intensively, the better impact you have on structural outcomes.”
In a trial known as CRESPA (Clinical Remission in peripheral SPondyloArthritis), researchers including Dr. Elewaut evaluated the efficacy and safety of golimumab (Simponi) to induce clinical remission in patients with early, active peripheral AS (Ann Rheum Dis. 2017;76:1389-95). In all, 60 patients were randomized to golimumab or placebo for 24 weeks. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission, compared with placebo (75% vs. 20%, respectively; P less than .001). At week 12, similar results were observed (70% vs. 15%; P less than .001).
“These were very striking results in this early disease population,” Dr. Elewaut said. In a follow-up analysis, the researchers withdrew therapy in patients who reached clinical remission, to see what would happen. “At 1.5 years of follow-up, 57% of patients are in drug-free remission,” Dr. Elewaut said. “This is interesting and suggests that at least in a fraction of those patients, you can actually achieve a drug-free remission.” Predictors for relapse included pre-existing psoriasis and having more than five swollen joints.
Dr. Elewaut disclosed that he is a member of the speakers bureau for AbbVie, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
Ultrasound’s value for arthralgia may be to rule out IA
Ultrasound evaluations to look for subclinical inflammation in joints of patients with arthralgia appear best at ruling out inflammatory arthritis (IA) 1 year in the future rather than ruling it in, according to findings from a multicenter cohort study published online in Arthritis Research and Therapy.
The imaging modality’s ability to identify those who will not go on to develop IA complemented the serologic and clinical factors that help to discriminate the individuals with arthralgia who are most at risk of the condition.
The ultimate goal of using imaging such as ultrasound in patients with arthralgia is to identify those who would benefit from starting treatment with disease-modifying antirheumatic drugs as early as possible to potentially improve outcomes, but it also could help to discriminate between the anti-citrullinated protein antibody (ACPA)-positive and seronegative individuals without clinical signs of inflammation at baseline who may progress from arthralgia to IA.
“Although ACPA positivity is a very good predictor for those patients who will develop IA within 1 year, it is still difficult to identify the exact individuals who will develop IA, because any ACPA-positive individual has an a priori chance of 50% of developing IA. In seronegative patients, the prediction of IA is even more difficult, because only 5% develop IA within the subsequent year. Imaging techniques have been shown to be able to detect synovitis before its clinical appearance and could be of help in identifying those at risk of IA,” the investigators wrote (Arthritis Res Ther. 2017;19:202. doi: 10.1186/s13075-017-1405-y).
Dr. van der Ven and her associates found that 31 (16%) of 196 patients who had arthralgia for less than 1 year in the hands, feet, or shoulders went on to develop IA after 1 year of follow-up. In this group of 196 patients at baseline, 72 (37%) had synovitis on ultrasound – defined as a greyscale grade of 2 or 3 and/or the presence of power Doppler signal (grade 1, 2, or 3) – including 32 with a positive power Doppler. A total of 18 patients were lost to follow-up during the first 6 months and another 19 were lost during months 6-12.
Rheumatologists who were unaware of ultrasound findings had to confirm soft-tissue swelling as arthritis at 1 year to classify it as incident IA. The positive predictive value of ultrasound for IA was only 26% when at least 1 joint out of 26 assessed was positive, but the negative predictive value when no joints were positive on ultrasound was 89%.
Overall, at 1 year, 15 of the 31 patients with IA had started therapy with a disease-modifying antirheumatic drug and 22 did not have a definite diagnosis; 12 had monoarthritis and 10 had polyarthritis. The remaining nine patients included four with rheumatoid arthritis, four with psoriatic arthritis, and one with spondyloarthritis.
At baseline, individuals with IA were more often older (mean age 50 vs. 44 years; P = .005), had synovitis on ultrasound (59% vs. 32%; P = .007), and had a positive power Doppler signal (31% vs. 12%; P = .012). A multivariate analysis revealed that IA at 1 year of follow-up could be independently predicted according to age (odds ratio, 1.06), morning stiffness lasting more than 30 minutes (OR, 2.80), ACPA positivity (OR, 2.35), and synovitis on ultrasound (OR, 2.65).
The investigators noted that the study’s limitations relate to requirements for patients to have at least two painful joints in hands, feet, or shoulders at baseline and two criteria related to inflammation. The possible inflammation-related criteria required for entry included morning stiffness for more than 1 hour, inability to clench a fist in the morning, pain when shaking someone’s hand, pins and needles in the fingers, difficulties wearing rings or shoes, family history of rheumatoid arthritis, and/or unexplained fatigue for less than 1 year.
Rheumatologists who enrolled patients into the cohort also may have “recruited clinically suspected patients with possibly more severe symptoms,” the investigators noted. Another potential source of bias related to the group of 38 patients who chose not to participate: It’s possible these patients had less severe symptoms than those who participated in the study.
The study was funded by an investigator-initiated grant from Pfizer. The authors declared that they have no competing interests.
Ultrasound evaluations to look for subclinical inflammation in joints of patients with arthralgia appear best at ruling out inflammatory arthritis (IA) 1 year in the future rather than ruling it in, according to findings from a multicenter cohort study published online in Arthritis Research and Therapy.
The imaging modality’s ability to identify those who will not go on to develop IA complemented the serologic and clinical factors that help to discriminate the individuals with arthralgia who are most at risk of the condition.
The ultimate goal of using imaging such as ultrasound in patients with arthralgia is to identify those who would benefit from starting treatment with disease-modifying antirheumatic drugs as early as possible to potentially improve outcomes, but it also could help to discriminate between the anti-citrullinated protein antibody (ACPA)-positive and seronegative individuals without clinical signs of inflammation at baseline who may progress from arthralgia to IA.
“Although ACPA positivity is a very good predictor for those patients who will develop IA within 1 year, it is still difficult to identify the exact individuals who will develop IA, because any ACPA-positive individual has an a priori chance of 50% of developing IA. In seronegative patients, the prediction of IA is even more difficult, because only 5% develop IA within the subsequent year. Imaging techniques have been shown to be able to detect synovitis before its clinical appearance and could be of help in identifying those at risk of IA,” the investigators wrote (Arthritis Res Ther. 2017;19:202. doi: 10.1186/s13075-017-1405-y).
Dr. van der Ven and her associates found that 31 (16%) of 196 patients who had arthralgia for less than 1 year in the hands, feet, or shoulders went on to develop IA after 1 year of follow-up. In this group of 196 patients at baseline, 72 (37%) had synovitis on ultrasound – defined as a greyscale grade of 2 or 3 and/or the presence of power Doppler signal (grade 1, 2, or 3) – including 32 with a positive power Doppler. A total of 18 patients were lost to follow-up during the first 6 months and another 19 were lost during months 6-12.
Rheumatologists who were unaware of ultrasound findings had to confirm soft-tissue swelling as arthritis at 1 year to classify it as incident IA. The positive predictive value of ultrasound for IA was only 26% when at least 1 joint out of 26 assessed was positive, but the negative predictive value when no joints were positive on ultrasound was 89%.
Overall, at 1 year, 15 of the 31 patients with IA had started therapy with a disease-modifying antirheumatic drug and 22 did not have a definite diagnosis; 12 had monoarthritis and 10 had polyarthritis. The remaining nine patients included four with rheumatoid arthritis, four with psoriatic arthritis, and one with spondyloarthritis.
At baseline, individuals with IA were more often older (mean age 50 vs. 44 years; P = .005), had synovitis on ultrasound (59% vs. 32%; P = .007), and had a positive power Doppler signal (31% vs. 12%; P = .012). A multivariate analysis revealed that IA at 1 year of follow-up could be independently predicted according to age (odds ratio, 1.06), morning stiffness lasting more than 30 minutes (OR, 2.80), ACPA positivity (OR, 2.35), and synovitis on ultrasound (OR, 2.65).
The investigators noted that the study’s limitations relate to requirements for patients to have at least two painful joints in hands, feet, or shoulders at baseline and two criteria related to inflammation. The possible inflammation-related criteria required for entry included morning stiffness for more than 1 hour, inability to clench a fist in the morning, pain when shaking someone’s hand, pins and needles in the fingers, difficulties wearing rings or shoes, family history of rheumatoid arthritis, and/or unexplained fatigue for less than 1 year.
Rheumatologists who enrolled patients into the cohort also may have “recruited clinically suspected patients with possibly more severe symptoms,” the investigators noted. Another potential source of bias related to the group of 38 patients who chose not to participate: It’s possible these patients had less severe symptoms than those who participated in the study.
The study was funded by an investigator-initiated grant from Pfizer. The authors declared that they have no competing interests.
Ultrasound evaluations to look for subclinical inflammation in joints of patients with arthralgia appear best at ruling out inflammatory arthritis (IA) 1 year in the future rather than ruling it in, according to findings from a multicenter cohort study published online in Arthritis Research and Therapy.
The imaging modality’s ability to identify those who will not go on to develop IA complemented the serologic and clinical factors that help to discriminate the individuals with arthralgia who are most at risk of the condition.
The ultimate goal of using imaging such as ultrasound in patients with arthralgia is to identify those who would benefit from starting treatment with disease-modifying antirheumatic drugs as early as possible to potentially improve outcomes, but it also could help to discriminate between the anti-citrullinated protein antibody (ACPA)-positive and seronegative individuals without clinical signs of inflammation at baseline who may progress from arthralgia to IA.
“Although ACPA positivity is a very good predictor for those patients who will develop IA within 1 year, it is still difficult to identify the exact individuals who will develop IA, because any ACPA-positive individual has an a priori chance of 50% of developing IA. In seronegative patients, the prediction of IA is even more difficult, because only 5% develop IA within the subsequent year. Imaging techniques have been shown to be able to detect synovitis before its clinical appearance and could be of help in identifying those at risk of IA,” the investigators wrote (Arthritis Res Ther. 2017;19:202. doi: 10.1186/s13075-017-1405-y).
Dr. van der Ven and her associates found that 31 (16%) of 196 patients who had arthralgia for less than 1 year in the hands, feet, or shoulders went on to develop IA after 1 year of follow-up. In this group of 196 patients at baseline, 72 (37%) had synovitis on ultrasound – defined as a greyscale grade of 2 or 3 and/or the presence of power Doppler signal (grade 1, 2, or 3) – including 32 with a positive power Doppler. A total of 18 patients were lost to follow-up during the first 6 months and another 19 were lost during months 6-12.
Rheumatologists who were unaware of ultrasound findings had to confirm soft-tissue swelling as arthritis at 1 year to classify it as incident IA. The positive predictive value of ultrasound for IA was only 26% when at least 1 joint out of 26 assessed was positive, but the negative predictive value when no joints were positive on ultrasound was 89%.
Overall, at 1 year, 15 of the 31 patients with IA had started therapy with a disease-modifying antirheumatic drug and 22 did not have a definite diagnosis; 12 had monoarthritis and 10 had polyarthritis. The remaining nine patients included four with rheumatoid arthritis, four with psoriatic arthritis, and one with spondyloarthritis.
At baseline, individuals with IA were more often older (mean age 50 vs. 44 years; P = .005), had synovitis on ultrasound (59% vs. 32%; P = .007), and had a positive power Doppler signal (31% vs. 12%; P = .012). A multivariate analysis revealed that IA at 1 year of follow-up could be independently predicted according to age (odds ratio, 1.06), morning stiffness lasting more than 30 minutes (OR, 2.80), ACPA positivity (OR, 2.35), and synovitis on ultrasound (OR, 2.65).
The investigators noted that the study’s limitations relate to requirements for patients to have at least two painful joints in hands, feet, or shoulders at baseline and two criteria related to inflammation. The possible inflammation-related criteria required for entry included morning stiffness for more than 1 hour, inability to clench a fist in the morning, pain when shaking someone’s hand, pins and needles in the fingers, difficulties wearing rings or shoes, family history of rheumatoid arthritis, and/or unexplained fatigue for less than 1 year.
Rheumatologists who enrolled patients into the cohort also may have “recruited clinically suspected patients with possibly more severe symptoms,” the investigators noted. Another potential source of bias related to the group of 38 patients who chose not to participate: It’s possible these patients had less severe symptoms than those who participated in the study.
The study was funded by an investigator-initiated grant from Pfizer. The authors declared that they have no competing interests.
FROM ARTHRITIS RESEARCH AND THERAPY
Key clinical point:
Major finding: The positive predictive value of ultrasound for IA was only 26% when at least 1 joint out of 26 assessed was positive, but the negative predictive value when no joints were positive on ultrasound was 89%.
Data source: A multicenter cohort study of 196 patients with arthralgia in at least two joints for less than 1 year.
Disclosures: The study was funded by an investigator-initiated grant from Pfizer. The authors declared that they have no competing interests.
New recommendations tout biosimilars for rheumatologic diseases
The available evidence is sufficient to support switching appropriate patients with rheumatologic diseases from a bio-originator agent to an approved biosimilar agent, according to new consensus-based recommendations from an international multidisciplinary task force.
“Treatment with biological agents has dramatically improved the outcome for patients with inflammatory diseases. However, the high cost of these medications has limited access for many patients,” Jonathan Kay, MD, of UMass Memorial Medical Center and the University of Massachusetts, Worcester, and his colleagues wrote on behalf of the Task Force on the Use of Biosimilars to Treat Rheumatological Diseases. Biosimilars of agents no longer protected by patent allow for increased availability at lower costs, they noted. In the European Union, the United States, Japan, and other countries, biosimilars of adalimumab, etanercept, infliximab, and rituximab have been approved, and those for which the bio-originator is no longer protected by patent have been marketed.
The task force, convened in 2016 to address the matter at an international level, included 25 experts from Europe, Japan, and the United States, including 17 rheumatologists, a rheumatologist/regulator, a dermatologist, a gastroenterologist, 2 pharmacologists, 2 patients, and a research fellow. The task force identified five overarching principles and made eight specific recommendations, based on expert opinion and an extensive literature review that yielded 29 relevant full-text papers and 20 relevant abstracts from the 2015 and 2016 American College of Rheumatology and European League Against Rheumatism annual meetings (Ann Rheum Dis. 2017 Sep 2. doi: 10.1136/annrheumdis-2017-211937).
“This statement was intended both to guide clinicians and to serve as a framework for future educational efforts,” they wrote.
The experts based all five overarching principles for the use of biosimilars on level 5, grade D evidence, indicating that they were derived mainly from expert opinion. They determined that:
- Treatment of rheumatic diseases is based on a shared decision-making process between patients and their rheumatologists.
- The contextual aspects of the health care system should be taken into consideration when treatment decisions are made.
- A biosimilar, as approved by authorities in a highly regulated area, is neither better nor worse in efficacy and is not inferior in safety to its bio-originator.
- Patients and health care providers should be informed about the nature of biosimilars, their approval process, and their safety and efficacy.
- Harmonized methods should be established to obtain reliable pharmacovigilance data, including traceability, about both biosimilars and bio-originators.
These principles represent the key issues regarding biosimilars as identified by the task force. As for the specific recommendations, the task force agreed that:
1. The availability of biosimilars must significantly lower the cost of treating an individual patient and increase access to optimal therapy for all patients with rheumatic diseases (level 5, grade D evidence).
2. Approved biosimilars can be used to treat appropriate patients in the same way as their bio-originators (level 1b, grade A evidence, indicating that the recommendation is based on an individual randomized, controlled trial and that the level 1 evidence is consistent).
3. Antidrug antibodies to biosimilars need not be measured in clinical practice as no significant differences have been detected between biosimilars and their bio-originators (level 2b, grade B evidence, indicating that the recommendation is based on an individual cohort study/low-quality randomized, controlled trial and consistent level 2 or 3 evidence).
4. Relevant preclinical and phase 1 data on a biosimilar should be available when phase 3 data are published (level 5, grade D evidence).
5. Confirmation of efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the bio-originator has been approved because biosimilars are equivalent in physiochemical, functional, and pharmacokinetic properties to the bio-originator (level 5, grade D evidence).
6. Available evidence suggests that a single switch from a bio-originator to one of its biosimilars is safe and effective; there is no reason to expect a different clinical outcome. However, patient perspectives must be considered (level 1b, grade A evidence).
7. Multiple switching between biosimilars and their bio-originators or other biosimilars should be assessed in registries (level 5, grade D evidence).
8. No switch to or among biosimilars should be initiated without the prior awareness of the patient and the treating health care provider (level 5, grade D evidence).
Differing opinions about the use of biosimilars as published by various subspecialty organizations highlight a lack of confidence among many clinicians with respect to appropriate use of the products, but that is changing amid a rapidly growing body of evidence, the task force said. The group achieved a high level of agreement about both the evaluation of biosimilars and their use to treat rheumatologic diseases, reaching 100% consensus for six of the recommendations and 91% and 96% for the other two.
“Data available as of December 2016 support the use of biosimilars by rheumatologists to encourage a fair and competitive market for biologics. Biosimilars now provide an opportunity to expand access to effective but expensive medications, increasing the number of available treatment choices and helping to control rapidly increasing drug expenditures,” they concluded.
The task force’s work was funded by an unrestricted educational grant from Amgen. Dr. Kay and his coauthors reported financial relationships with multiple pharmaceutical companies, many of which are developing biosimilars.
The available evidence is sufficient to support switching appropriate patients with rheumatologic diseases from a bio-originator agent to an approved biosimilar agent, according to new consensus-based recommendations from an international multidisciplinary task force.
“Treatment with biological agents has dramatically improved the outcome for patients with inflammatory diseases. However, the high cost of these medications has limited access for many patients,” Jonathan Kay, MD, of UMass Memorial Medical Center and the University of Massachusetts, Worcester, and his colleagues wrote on behalf of the Task Force on the Use of Biosimilars to Treat Rheumatological Diseases. Biosimilars of agents no longer protected by patent allow for increased availability at lower costs, they noted. In the European Union, the United States, Japan, and other countries, biosimilars of adalimumab, etanercept, infliximab, and rituximab have been approved, and those for which the bio-originator is no longer protected by patent have been marketed.
The task force, convened in 2016 to address the matter at an international level, included 25 experts from Europe, Japan, and the United States, including 17 rheumatologists, a rheumatologist/regulator, a dermatologist, a gastroenterologist, 2 pharmacologists, 2 patients, and a research fellow. The task force identified five overarching principles and made eight specific recommendations, based on expert opinion and an extensive literature review that yielded 29 relevant full-text papers and 20 relevant abstracts from the 2015 and 2016 American College of Rheumatology and European League Against Rheumatism annual meetings (Ann Rheum Dis. 2017 Sep 2. doi: 10.1136/annrheumdis-2017-211937).
“This statement was intended both to guide clinicians and to serve as a framework for future educational efforts,” they wrote.
The experts based all five overarching principles for the use of biosimilars on level 5, grade D evidence, indicating that they were derived mainly from expert opinion. They determined that:
- Treatment of rheumatic diseases is based on a shared decision-making process between patients and their rheumatologists.
- The contextual aspects of the health care system should be taken into consideration when treatment decisions are made.
- A biosimilar, as approved by authorities in a highly regulated area, is neither better nor worse in efficacy and is not inferior in safety to its bio-originator.
- Patients and health care providers should be informed about the nature of biosimilars, their approval process, and their safety and efficacy.
- Harmonized methods should be established to obtain reliable pharmacovigilance data, including traceability, about both biosimilars and bio-originators.
These principles represent the key issues regarding biosimilars as identified by the task force. As for the specific recommendations, the task force agreed that:
1. The availability of biosimilars must significantly lower the cost of treating an individual patient and increase access to optimal therapy for all patients with rheumatic diseases (level 5, grade D evidence).
2. Approved biosimilars can be used to treat appropriate patients in the same way as their bio-originators (level 1b, grade A evidence, indicating that the recommendation is based on an individual randomized, controlled trial and that the level 1 evidence is consistent).
3. Antidrug antibodies to biosimilars need not be measured in clinical practice as no significant differences have been detected between biosimilars and their bio-originators (level 2b, grade B evidence, indicating that the recommendation is based on an individual cohort study/low-quality randomized, controlled trial and consistent level 2 or 3 evidence).
4. Relevant preclinical and phase 1 data on a biosimilar should be available when phase 3 data are published (level 5, grade D evidence).
5. Confirmation of efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the bio-originator has been approved because biosimilars are equivalent in physiochemical, functional, and pharmacokinetic properties to the bio-originator (level 5, grade D evidence).
6. Available evidence suggests that a single switch from a bio-originator to one of its biosimilars is safe and effective; there is no reason to expect a different clinical outcome. However, patient perspectives must be considered (level 1b, grade A evidence).
7. Multiple switching between biosimilars and their bio-originators or other biosimilars should be assessed in registries (level 5, grade D evidence).
8. No switch to or among biosimilars should be initiated without the prior awareness of the patient and the treating health care provider (level 5, grade D evidence).
Differing opinions about the use of biosimilars as published by various subspecialty organizations highlight a lack of confidence among many clinicians with respect to appropriate use of the products, but that is changing amid a rapidly growing body of evidence, the task force said. The group achieved a high level of agreement about both the evaluation of biosimilars and their use to treat rheumatologic diseases, reaching 100% consensus for six of the recommendations and 91% and 96% for the other two.
“Data available as of December 2016 support the use of biosimilars by rheumatologists to encourage a fair and competitive market for biologics. Biosimilars now provide an opportunity to expand access to effective but expensive medications, increasing the number of available treatment choices and helping to control rapidly increasing drug expenditures,” they concluded.
The task force’s work was funded by an unrestricted educational grant from Amgen. Dr. Kay and his coauthors reported financial relationships with multiple pharmaceutical companies, many of which are developing biosimilars.
The available evidence is sufficient to support switching appropriate patients with rheumatologic diseases from a bio-originator agent to an approved biosimilar agent, according to new consensus-based recommendations from an international multidisciplinary task force.
“Treatment with biological agents has dramatically improved the outcome for patients with inflammatory diseases. However, the high cost of these medications has limited access for many patients,” Jonathan Kay, MD, of UMass Memorial Medical Center and the University of Massachusetts, Worcester, and his colleagues wrote on behalf of the Task Force on the Use of Biosimilars to Treat Rheumatological Diseases. Biosimilars of agents no longer protected by patent allow for increased availability at lower costs, they noted. In the European Union, the United States, Japan, and other countries, biosimilars of adalimumab, etanercept, infliximab, and rituximab have been approved, and those for which the bio-originator is no longer protected by patent have been marketed.
The task force, convened in 2016 to address the matter at an international level, included 25 experts from Europe, Japan, and the United States, including 17 rheumatologists, a rheumatologist/regulator, a dermatologist, a gastroenterologist, 2 pharmacologists, 2 patients, and a research fellow. The task force identified five overarching principles and made eight specific recommendations, based on expert opinion and an extensive literature review that yielded 29 relevant full-text papers and 20 relevant abstracts from the 2015 and 2016 American College of Rheumatology and European League Against Rheumatism annual meetings (Ann Rheum Dis. 2017 Sep 2. doi: 10.1136/annrheumdis-2017-211937).
“This statement was intended both to guide clinicians and to serve as a framework for future educational efforts,” they wrote.
The experts based all five overarching principles for the use of biosimilars on level 5, grade D evidence, indicating that they were derived mainly from expert opinion. They determined that:
- Treatment of rheumatic diseases is based on a shared decision-making process between patients and their rheumatologists.
- The contextual aspects of the health care system should be taken into consideration when treatment decisions are made.
- A biosimilar, as approved by authorities in a highly regulated area, is neither better nor worse in efficacy and is not inferior in safety to its bio-originator.
- Patients and health care providers should be informed about the nature of biosimilars, their approval process, and their safety and efficacy.
- Harmonized methods should be established to obtain reliable pharmacovigilance data, including traceability, about both biosimilars and bio-originators.
These principles represent the key issues regarding biosimilars as identified by the task force. As for the specific recommendations, the task force agreed that:
1. The availability of biosimilars must significantly lower the cost of treating an individual patient and increase access to optimal therapy for all patients with rheumatic diseases (level 5, grade D evidence).
2. Approved biosimilars can be used to treat appropriate patients in the same way as their bio-originators (level 1b, grade A evidence, indicating that the recommendation is based on an individual randomized, controlled trial and that the level 1 evidence is consistent).
3. Antidrug antibodies to biosimilars need not be measured in clinical practice as no significant differences have been detected between biosimilars and their bio-originators (level 2b, grade B evidence, indicating that the recommendation is based on an individual cohort study/low-quality randomized, controlled trial and consistent level 2 or 3 evidence).
4. Relevant preclinical and phase 1 data on a biosimilar should be available when phase 3 data are published (level 5, grade D evidence).
5. Confirmation of efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the bio-originator has been approved because biosimilars are equivalent in physiochemical, functional, and pharmacokinetic properties to the bio-originator (level 5, grade D evidence).
6. Available evidence suggests that a single switch from a bio-originator to one of its biosimilars is safe and effective; there is no reason to expect a different clinical outcome. However, patient perspectives must be considered (level 1b, grade A evidence).
7. Multiple switching between biosimilars and their bio-originators or other biosimilars should be assessed in registries (level 5, grade D evidence).
8. No switch to or among biosimilars should be initiated without the prior awareness of the patient and the treating health care provider (level 5, grade D evidence).
Differing opinions about the use of biosimilars as published by various subspecialty organizations highlight a lack of confidence among many clinicians with respect to appropriate use of the products, but that is changing amid a rapidly growing body of evidence, the task force said. The group achieved a high level of agreement about both the evaluation of biosimilars and their use to treat rheumatologic diseases, reaching 100% consensus for six of the recommendations and 91% and 96% for the other two.
“Data available as of December 2016 support the use of biosimilars by rheumatologists to encourage a fair and competitive market for biologics. Biosimilars now provide an opportunity to expand access to effective but expensive medications, increasing the number of available treatment choices and helping to control rapidly increasing drug expenditures,” they concluded.
The task force’s work was funded by an unrestricted educational grant from Amgen. Dr. Kay and his coauthors reported financial relationships with multiple pharmaceutical companies, many of which are developing biosimilars.
FROM ANNALS OF THE RHEUMATIC DISEASES
FDA approves second adalimumab biosimilar for multiple conditions
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.