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New RA JAK inhibitor, monoclonal antibody trial results scheduled for ACR 2017
New results from several investigational oral Janus kinase inhibitor trials and an antifractalkine monoclonal antibody trial for patients with rheumatoid arthritis will be made available for the first time to attendees of the annual meeting of the American College of Rheumatology on Nov. 6 and 7 in San Diego.
Selective JAK-1 inhibitor upadacitinib
Two double-blind, randomized, controlled phase 3 studies of the oral, selective JAK-1 inhibitor upadacitinib (ABT-494) will be presented at the meeting, both involving once-daily extended-release formulations of the drug at 15 mg or 30 mg. The first trial, to be presented during an ACR abstract session on Monday, Nov. 6, showed that the drug met ACR 20 response criteria at significantly higher rates than did placebo at week 12 (63.8% for 15 mg, 66.2% for 30 mg, and 35.7% for placebo) in 661 patients with active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients on the study drug also achieved low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28-CRP] of 3.2 or less) in higher proportions than did those who received placebo (48.4% for 15 mg, 47.9% for 30 mg, and 17.2% for placebo). More infections occurred in patients on 15 mg and 30 mg upadacitinib (29.0% and 31.5%, respectively), compared with placebo (21.3%), but there were no differences in serious infections. Three of the total four cases of herpes zoster infection were in patients taking upadacitinib.
A second upadacitinib trial, which involved patients on stable csDMARD therapy who could not tolerate or had disease refractory to a biologic DMARD, will be presented during a late-breaking poster session on Tuesday, Nov. 7. The study randomized 499 patients who had severe, refractory disease for a mean duration of 13 years. At 12 weeks, treatment with upadacitinib resulted in ACR 20 responses in 64.6% at 15 mg and 56.4% at 30 mg, compared with 28.4% for placebo. Responses at 12 weeks of 3.2 or less for DAS28-CRP also occurred at significantly higher rates of 43.3% for 15 mg and 42.4% for 30 mg, compared with 14.2% for placebo. Patients who were switched from placebo to active treatment at week 12 also achieved these responses at week 24, and the people who stayed on treatment with upadacitinib maintained or improved their response at week 24. More adverse events and infections tended to occur with upadacitinib at 30 mg than with 15 mg, and there were more herpes zoster infections with 30 mg (n = 4) vs. 15 mg (n = 1) and placebo (n = 1).
Antifractalkine monoclonal antibody
The Monday afternoon RA therapy abstract session will also feature the first-in-patient results at 52 weeks for the antifractalkine monoclonal antibody E6011 in an open-label phase 1/2 study of Japanese RA patients with active disease who had an inadequate response or intolerance to methotrexate or a TNF inhibitor. The results from the small trial of the biologic, which targets the chemokine that regulates chemotaxis and the adhesion of inflammatory cells that express CX3C chemokine receptor 1 (CX3CR1), indicate that the treatment has durable efficacy and is safe and well tolerated. Adverse events (AEs) developed in 84% of 28 patients who participated in the 52-week extension study, including a rate of 48% for treatment-emergent adverse events (TEAEs) and 14% for serious AEs. ACR 20 rates at week 52 ranged from 58% for 100 mg of E6011 to 73% for 200 mg and 60% for 400 mg.
Filgotinib safety in an extension trial
The long-term, open-label results from two phase 2b studies of the JAK-1 inhibitor filgotinib that’s in development for RA also will be presented during the same Monday abstract session. These safety data out to 84 weeks from the long-term extension study of the DARWIN 1 and 2 studies, called DARWIN 3, show that, among patients who received at least one dose of filgotinib 100 mg twice daily or 200 mg once daily in addition to methotrexate, the rate of TEAEs ranged from about 146 to 153 per 100 patient-years of exposure (PYE), including about 41-45 infections per 100 PYE. For filgotinib monotherapy, the rate of TEAEs was 150 per 100 PYE for 200 mg once daily, including 38 infections per 100 PYE.
Total cholesterol of 200-239 mg/dL occurred at a rate of about 79 per 100 PYE and a level of 240 mg/dL or greater was seen in 61-64 per 100 PYE for patients who took filgotinib plus methotrexate. Filgotinib monotherapy at 200 mg once daily gave rates of about 94 and 71 per 100 PYE for those respective total cholesterol levels.
New results from several investigational oral Janus kinase inhibitor trials and an antifractalkine monoclonal antibody trial for patients with rheumatoid arthritis will be made available for the first time to attendees of the annual meeting of the American College of Rheumatology on Nov. 6 and 7 in San Diego.
Selective JAK-1 inhibitor upadacitinib
Two double-blind, randomized, controlled phase 3 studies of the oral, selective JAK-1 inhibitor upadacitinib (ABT-494) will be presented at the meeting, both involving once-daily extended-release formulations of the drug at 15 mg or 30 mg. The first trial, to be presented during an ACR abstract session on Monday, Nov. 6, showed that the drug met ACR 20 response criteria at significantly higher rates than did placebo at week 12 (63.8% for 15 mg, 66.2% for 30 mg, and 35.7% for placebo) in 661 patients with active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients on the study drug also achieved low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28-CRP] of 3.2 or less) in higher proportions than did those who received placebo (48.4% for 15 mg, 47.9% for 30 mg, and 17.2% for placebo). More infections occurred in patients on 15 mg and 30 mg upadacitinib (29.0% and 31.5%, respectively), compared with placebo (21.3%), but there were no differences in serious infections. Three of the total four cases of herpes zoster infection were in patients taking upadacitinib.
A second upadacitinib trial, which involved patients on stable csDMARD therapy who could not tolerate or had disease refractory to a biologic DMARD, will be presented during a late-breaking poster session on Tuesday, Nov. 7. The study randomized 499 patients who had severe, refractory disease for a mean duration of 13 years. At 12 weeks, treatment with upadacitinib resulted in ACR 20 responses in 64.6% at 15 mg and 56.4% at 30 mg, compared with 28.4% for placebo. Responses at 12 weeks of 3.2 or less for DAS28-CRP also occurred at significantly higher rates of 43.3% for 15 mg and 42.4% for 30 mg, compared with 14.2% for placebo. Patients who were switched from placebo to active treatment at week 12 also achieved these responses at week 24, and the people who stayed on treatment with upadacitinib maintained or improved their response at week 24. More adverse events and infections tended to occur with upadacitinib at 30 mg than with 15 mg, and there were more herpes zoster infections with 30 mg (n = 4) vs. 15 mg (n = 1) and placebo (n = 1).
Antifractalkine monoclonal antibody
The Monday afternoon RA therapy abstract session will also feature the first-in-patient results at 52 weeks for the antifractalkine monoclonal antibody E6011 in an open-label phase 1/2 study of Japanese RA patients with active disease who had an inadequate response or intolerance to methotrexate or a TNF inhibitor. The results from the small trial of the biologic, which targets the chemokine that regulates chemotaxis and the adhesion of inflammatory cells that express CX3C chemokine receptor 1 (CX3CR1), indicate that the treatment has durable efficacy and is safe and well tolerated. Adverse events (AEs) developed in 84% of 28 patients who participated in the 52-week extension study, including a rate of 48% for treatment-emergent adverse events (TEAEs) and 14% for serious AEs. ACR 20 rates at week 52 ranged from 58% for 100 mg of E6011 to 73% for 200 mg and 60% for 400 mg.
Filgotinib safety in an extension trial
The long-term, open-label results from two phase 2b studies of the JAK-1 inhibitor filgotinib that’s in development for RA also will be presented during the same Monday abstract session. These safety data out to 84 weeks from the long-term extension study of the DARWIN 1 and 2 studies, called DARWIN 3, show that, among patients who received at least one dose of filgotinib 100 mg twice daily or 200 mg once daily in addition to methotrexate, the rate of TEAEs ranged from about 146 to 153 per 100 patient-years of exposure (PYE), including about 41-45 infections per 100 PYE. For filgotinib monotherapy, the rate of TEAEs was 150 per 100 PYE for 200 mg once daily, including 38 infections per 100 PYE.
Total cholesterol of 200-239 mg/dL occurred at a rate of about 79 per 100 PYE and a level of 240 mg/dL or greater was seen in 61-64 per 100 PYE for patients who took filgotinib plus methotrexate. Filgotinib monotherapy at 200 mg once daily gave rates of about 94 and 71 per 100 PYE for those respective total cholesterol levels.
New results from several investigational oral Janus kinase inhibitor trials and an antifractalkine monoclonal antibody trial for patients with rheumatoid arthritis will be made available for the first time to attendees of the annual meeting of the American College of Rheumatology on Nov. 6 and 7 in San Diego.
Selective JAK-1 inhibitor upadacitinib
Two double-blind, randomized, controlled phase 3 studies of the oral, selective JAK-1 inhibitor upadacitinib (ABT-494) will be presented at the meeting, both involving once-daily extended-release formulations of the drug at 15 mg or 30 mg. The first trial, to be presented during an ACR abstract session on Monday, Nov. 6, showed that the drug met ACR 20 response criteria at significantly higher rates than did placebo at week 12 (63.8% for 15 mg, 66.2% for 30 mg, and 35.7% for placebo) in 661 patients with active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients on the study drug also achieved low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28-CRP] of 3.2 or less) in higher proportions than did those who received placebo (48.4% for 15 mg, 47.9% for 30 mg, and 17.2% for placebo). More infections occurred in patients on 15 mg and 30 mg upadacitinib (29.0% and 31.5%, respectively), compared with placebo (21.3%), but there were no differences in serious infections. Three of the total four cases of herpes zoster infection were in patients taking upadacitinib.
A second upadacitinib trial, which involved patients on stable csDMARD therapy who could not tolerate or had disease refractory to a biologic DMARD, will be presented during a late-breaking poster session on Tuesday, Nov. 7. The study randomized 499 patients who had severe, refractory disease for a mean duration of 13 years. At 12 weeks, treatment with upadacitinib resulted in ACR 20 responses in 64.6% at 15 mg and 56.4% at 30 mg, compared with 28.4% for placebo. Responses at 12 weeks of 3.2 or less for DAS28-CRP also occurred at significantly higher rates of 43.3% for 15 mg and 42.4% for 30 mg, compared with 14.2% for placebo. Patients who were switched from placebo to active treatment at week 12 also achieved these responses at week 24, and the people who stayed on treatment with upadacitinib maintained or improved their response at week 24. More adverse events and infections tended to occur with upadacitinib at 30 mg than with 15 mg, and there were more herpes zoster infections with 30 mg (n = 4) vs. 15 mg (n = 1) and placebo (n = 1).
Antifractalkine monoclonal antibody
The Monday afternoon RA therapy abstract session will also feature the first-in-patient results at 52 weeks for the antifractalkine monoclonal antibody E6011 in an open-label phase 1/2 study of Japanese RA patients with active disease who had an inadequate response or intolerance to methotrexate or a TNF inhibitor. The results from the small trial of the biologic, which targets the chemokine that regulates chemotaxis and the adhesion of inflammatory cells that express CX3C chemokine receptor 1 (CX3CR1), indicate that the treatment has durable efficacy and is safe and well tolerated. Adverse events (AEs) developed in 84% of 28 patients who participated in the 52-week extension study, including a rate of 48% for treatment-emergent adverse events (TEAEs) and 14% for serious AEs. ACR 20 rates at week 52 ranged from 58% for 100 mg of E6011 to 73% for 200 mg and 60% for 400 mg.
Filgotinib safety in an extension trial
The long-term, open-label results from two phase 2b studies of the JAK-1 inhibitor filgotinib that’s in development for RA also will be presented during the same Monday abstract session. These safety data out to 84 weeks from the long-term extension study of the DARWIN 1 and 2 studies, called DARWIN 3, show that, among patients who received at least one dose of filgotinib 100 mg twice daily or 200 mg once daily in addition to methotrexate, the rate of TEAEs ranged from about 146 to 153 per 100 patient-years of exposure (PYE), including about 41-45 infections per 100 PYE. For filgotinib monotherapy, the rate of TEAEs was 150 per 100 PYE for 200 mg once daily, including 38 infections per 100 PYE.
Total cholesterol of 200-239 mg/dL occurred at a rate of about 79 per 100 PYE and a level of 240 mg/dL or greater was seen in 61-64 per 100 PYE for patients who took filgotinib plus methotrexate. Filgotinib monotherapy at 200 mg once daily gave rates of about 94 and 71 per 100 PYE for those respective total cholesterol levels.
FROM ACR 2017
Precision medicine’s future in rheumatic diseases outlined at ACR 2017
The treatment and prevention of rheumatic diseases through a precision medicine approach that takes into account individual variability in genes, environment, and lifestyle has not yet become a reality in clinical practice, but researchers in the field hope to demonstrate its potential at a course before and a session during the annual meeting of the American College of Rheumatology in San Diego.
In a 2-day premeeting course that begins on Friday, Nov. 3, a multidisciplinary faculty will discuss the technologies involved in precision medicine research; the complexities and challenges of identifying optimal drug treatments for rheumatic diseases; past, ongoing, and future research initiatives in precision medicine affecting rheumatic diseases; and how large data-set analysis and collaborative networks of researchers can shape its future.
Later, during the meeting on the afternoon of Monday, Nov. 6, an ACR session will look at how precision medicine research in patients with systemic lupus erythematosus (SLE) has laid groundwork to improve clinical trial design and the implementation of more tailored treatment for SLE and other complex autoimmune diseases.
The first day of the 2-day premeeting course will cover current approaches to studying familial and pediatric rheumatic diseases as well as an outline of how precision medicine could affect treatment approaches to SLE. Later in the day, presentations will focus on examples of personalized medicine approaches that have been derived from studies of cancer genomics and familial syndromes and the genetic underpinning of different responses to medications. The impact of direct-to-consumer genetic testing will also be discussed. Abstract presentations at the end of the day will focus on new genetic biomarkers that differentiate active disease from remission in granulomatosis with polyangiitis and mutations related to cancer-associated myositis.
The second day of the course on Saturday, Nov. 4, will focus on the technology behind precision medicine, followed by data analysis and integration into clinical practice. Technology presentations aim to demonstrate how transcriptional analysis of single immune cells and epigenetics in small numbers of cells can provide information about disease activity and prognosis. Examples of how multiple types of data can be integrated to form a picture of the pathogenesis of diseases such as rheumatoid arthritis will be discussed. Two abstract presentations will serve to show how analysis of tissue-specific serum biomarkers can identify rheumatoid arthritis patients with structural progression and how the presence of a specific antibody can predict better response to anti–tumor necrosis factor treatment and better disease control over time. In the afternoon, sessions will focus on analyzing single-cell data in key cell subpopulations in rheumatic disease and specifically address immune cell interactions across systems in SLE.
On Monday at 1:00 p.m., Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York will speak in the ACR session, “Precision Medicine for Rheumatic Disease: Closer Than You Think?” Dr. Pascual will provide an overview of her lab’s recent work in transcriptional profiling of pediatric SLE patients, which demonstrates the potential value of immunomonitoring in order to stratify patients into discrete molecular groups to make clinical trial design better and offer more targeted therapies.
The treatment and prevention of rheumatic diseases through a precision medicine approach that takes into account individual variability in genes, environment, and lifestyle has not yet become a reality in clinical practice, but researchers in the field hope to demonstrate its potential at a course before and a session during the annual meeting of the American College of Rheumatology in San Diego.
In a 2-day premeeting course that begins on Friday, Nov. 3, a multidisciplinary faculty will discuss the technologies involved in precision medicine research; the complexities and challenges of identifying optimal drug treatments for rheumatic diseases; past, ongoing, and future research initiatives in precision medicine affecting rheumatic diseases; and how large data-set analysis and collaborative networks of researchers can shape its future.
Later, during the meeting on the afternoon of Monday, Nov. 6, an ACR session will look at how precision medicine research in patients with systemic lupus erythematosus (SLE) has laid groundwork to improve clinical trial design and the implementation of more tailored treatment for SLE and other complex autoimmune diseases.
The first day of the 2-day premeeting course will cover current approaches to studying familial and pediatric rheumatic diseases as well as an outline of how precision medicine could affect treatment approaches to SLE. Later in the day, presentations will focus on examples of personalized medicine approaches that have been derived from studies of cancer genomics and familial syndromes and the genetic underpinning of different responses to medications. The impact of direct-to-consumer genetic testing will also be discussed. Abstract presentations at the end of the day will focus on new genetic biomarkers that differentiate active disease from remission in granulomatosis with polyangiitis and mutations related to cancer-associated myositis.
The second day of the course on Saturday, Nov. 4, will focus on the technology behind precision medicine, followed by data analysis and integration into clinical practice. Technology presentations aim to demonstrate how transcriptional analysis of single immune cells and epigenetics in small numbers of cells can provide information about disease activity and prognosis. Examples of how multiple types of data can be integrated to form a picture of the pathogenesis of diseases such as rheumatoid arthritis will be discussed. Two abstract presentations will serve to show how analysis of tissue-specific serum biomarkers can identify rheumatoid arthritis patients with structural progression and how the presence of a specific antibody can predict better response to anti–tumor necrosis factor treatment and better disease control over time. In the afternoon, sessions will focus on analyzing single-cell data in key cell subpopulations in rheumatic disease and specifically address immune cell interactions across systems in SLE.
On Monday at 1:00 p.m., Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York will speak in the ACR session, “Precision Medicine for Rheumatic Disease: Closer Than You Think?” Dr. Pascual will provide an overview of her lab’s recent work in transcriptional profiling of pediatric SLE patients, which demonstrates the potential value of immunomonitoring in order to stratify patients into discrete molecular groups to make clinical trial design better and offer more targeted therapies.
The treatment and prevention of rheumatic diseases through a precision medicine approach that takes into account individual variability in genes, environment, and lifestyle has not yet become a reality in clinical practice, but researchers in the field hope to demonstrate its potential at a course before and a session during the annual meeting of the American College of Rheumatology in San Diego.
In a 2-day premeeting course that begins on Friday, Nov. 3, a multidisciplinary faculty will discuss the technologies involved in precision medicine research; the complexities and challenges of identifying optimal drug treatments for rheumatic diseases; past, ongoing, and future research initiatives in precision medicine affecting rheumatic diseases; and how large data-set analysis and collaborative networks of researchers can shape its future.
Later, during the meeting on the afternoon of Monday, Nov. 6, an ACR session will look at how precision medicine research in patients with systemic lupus erythematosus (SLE) has laid groundwork to improve clinical trial design and the implementation of more tailored treatment for SLE and other complex autoimmune diseases.
The first day of the 2-day premeeting course will cover current approaches to studying familial and pediatric rheumatic diseases as well as an outline of how precision medicine could affect treatment approaches to SLE. Later in the day, presentations will focus on examples of personalized medicine approaches that have been derived from studies of cancer genomics and familial syndromes and the genetic underpinning of different responses to medications. The impact of direct-to-consumer genetic testing will also be discussed. Abstract presentations at the end of the day will focus on new genetic biomarkers that differentiate active disease from remission in granulomatosis with polyangiitis and mutations related to cancer-associated myositis.
The second day of the course on Saturday, Nov. 4, will focus on the technology behind precision medicine, followed by data analysis and integration into clinical practice. Technology presentations aim to demonstrate how transcriptional analysis of single immune cells and epigenetics in small numbers of cells can provide information about disease activity and prognosis. Examples of how multiple types of data can be integrated to form a picture of the pathogenesis of diseases such as rheumatoid arthritis will be discussed. Two abstract presentations will serve to show how analysis of tissue-specific serum biomarkers can identify rheumatoid arthritis patients with structural progression and how the presence of a specific antibody can predict better response to anti–tumor necrosis factor treatment and better disease control over time. In the afternoon, sessions will focus on analyzing single-cell data in key cell subpopulations in rheumatic disease and specifically address immune cell interactions across systems in SLE.
On Monday at 1:00 p.m., Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York will speak in the ACR session, “Precision Medicine for Rheumatic Disease: Closer Than You Think?” Dr. Pascual will provide an overview of her lab’s recent work in transcriptional profiling of pediatric SLE patients, which demonstrates the potential value of immunomonitoring in order to stratify patients into discrete molecular groups to make clinical trial design better and offer more targeted therapies.
FROM ACR 2017
“Great debates” at ACR 2017 address biosimilar switching, new curricular milestones
Two “Great Debates” at this year’s annual meeting of the American College of Rheumatology in San Diego will center on important, but completely separate, issues in rheumatology: whether it is safe to switch to a biosimilar and the relevance of curricular milestones in rheumatology training.
At 2:30 p.m. on Sunday, Nov. 5, a session titled “Biosimilars ... To Switch or Not to Switch? That Is the Question“ will pit Jonathan Kay, MD, against Roy Fleischmann, MD, to try to sway the audience to their point of view in the face of a small evidence base about the consequences of switching.
Dr. Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts, Worcester, where he directs clinical research in the division of rheumatology, will discuss and defend the usefulness of biosimilars for rheumatoid arthritis in his presentation, “The Data Supports That It Is Safe, Effective and Cost-Effective to Switch to a Biosimilar.” He has been greatly involved in clinical research on the development of biosimilars to treat rheumatic diseases in recent years.
In his presentation, “The Data Is Not Convincing. One Study Cannot Be Generalized to All Indications, and Some Studies Suggest That It Is Not Safe, Not Effective and Not Cost-Effective to Switch All Patients (YET) to a Biosimilar,” Dr. Fleischmann will discuss and defend the position that biosimilars are not yet well-enough researched to confidently allow switching. Dr. Fleischmann is clinical professor in the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas.
At 7:30 a.m. on Monday, Nov. 6, two clinician-educators will advocate for opposing opinions in “The Great (Educational) Debate: Milestones: Meaningful vs. Millstone.” The debate will focus on the relative merits of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, which in 2013 led to a paradigm shift in how training programs approach curriculum development, and how both trainees and their programs are assessed.
Calvin Brown, MD, professor of medicine in the division of rheumatology and director of the rheumatology training program at Northwestern University, Chicago, will describe the reported and perceived benefits of the milestones, while Simon Helfgott, MD, of Brigham and Women’s Hospital, Boston, will summarize the arguments that underlie the call for radical change in the milestones system of evaluation
Two “Great Debates” at this year’s annual meeting of the American College of Rheumatology in San Diego will center on important, but completely separate, issues in rheumatology: whether it is safe to switch to a biosimilar and the relevance of curricular milestones in rheumatology training.
At 2:30 p.m. on Sunday, Nov. 5, a session titled “Biosimilars ... To Switch or Not to Switch? That Is the Question“ will pit Jonathan Kay, MD, against Roy Fleischmann, MD, to try to sway the audience to their point of view in the face of a small evidence base about the consequences of switching.
Dr. Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts, Worcester, where he directs clinical research in the division of rheumatology, will discuss and defend the usefulness of biosimilars for rheumatoid arthritis in his presentation, “The Data Supports That It Is Safe, Effective and Cost-Effective to Switch to a Biosimilar.” He has been greatly involved in clinical research on the development of biosimilars to treat rheumatic diseases in recent years.
In his presentation, “The Data Is Not Convincing. One Study Cannot Be Generalized to All Indications, and Some Studies Suggest That It Is Not Safe, Not Effective and Not Cost-Effective to Switch All Patients (YET) to a Biosimilar,” Dr. Fleischmann will discuss and defend the position that biosimilars are not yet well-enough researched to confidently allow switching. Dr. Fleischmann is clinical professor in the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas.
At 7:30 a.m. on Monday, Nov. 6, two clinician-educators will advocate for opposing opinions in “The Great (Educational) Debate: Milestones: Meaningful vs. Millstone.” The debate will focus on the relative merits of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, which in 2013 led to a paradigm shift in how training programs approach curriculum development, and how both trainees and their programs are assessed.
Calvin Brown, MD, professor of medicine in the division of rheumatology and director of the rheumatology training program at Northwestern University, Chicago, will describe the reported and perceived benefits of the milestones, while Simon Helfgott, MD, of Brigham and Women’s Hospital, Boston, will summarize the arguments that underlie the call for radical change in the milestones system of evaluation
Two “Great Debates” at this year’s annual meeting of the American College of Rheumatology in San Diego will center on important, but completely separate, issues in rheumatology: whether it is safe to switch to a biosimilar and the relevance of curricular milestones in rheumatology training.
At 2:30 p.m. on Sunday, Nov. 5, a session titled “Biosimilars ... To Switch or Not to Switch? That Is the Question“ will pit Jonathan Kay, MD, against Roy Fleischmann, MD, to try to sway the audience to their point of view in the face of a small evidence base about the consequences of switching.
Dr. Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts, Worcester, where he directs clinical research in the division of rheumatology, will discuss and defend the usefulness of biosimilars for rheumatoid arthritis in his presentation, “The Data Supports That It Is Safe, Effective and Cost-Effective to Switch to a Biosimilar.” He has been greatly involved in clinical research on the development of biosimilars to treat rheumatic diseases in recent years.
In his presentation, “The Data Is Not Convincing. One Study Cannot Be Generalized to All Indications, and Some Studies Suggest That It Is Not Safe, Not Effective and Not Cost-Effective to Switch All Patients (YET) to a Biosimilar,” Dr. Fleischmann will discuss and defend the position that biosimilars are not yet well-enough researched to confidently allow switching. Dr. Fleischmann is clinical professor in the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas.
At 7:30 a.m. on Monday, Nov. 6, two clinician-educators will advocate for opposing opinions in “The Great (Educational) Debate: Milestones: Meaningful vs. Millstone.” The debate will focus on the relative merits of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, which in 2013 led to a paradigm shift in how training programs approach curriculum development, and how both trainees and their programs are assessed.
Calvin Brown, MD, professor of medicine in the division of rheumatology and director of the rheumatology training program at Northwestern University, Chicago, will describe the reported and perceived benefits of the milestones, while Simon Helfgott, MD, of Brigham and Women’s Hospital, Boston, will summarize the arguments that underlie the call for radical change in the milestones system of evaluation
FROM ACR 2017
In close vote, advisory panel prefers Shingrix over Zostavax
Herpes zoster subunit vaccine (Shingrix) was preferentially recommended over zoster vaccine live (Zostavax) for preventing herpes zoster and related complications Oct. 25 at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
Eight committee members voted for the recommendation, and seven voted against it.
In discussions leading up to the vote, some committee members cited potential supply issues, as well as the need for longer-term safety data, among other issues.
“I think it would be nice to see data on a larger population that is not just research-based, especially because we have very little data on ethnic minorities,” said Laura E. Riley, MD, of Harvard Medical School, Boston, who voted against the recommendation.
The vote comes several days after GlaxoSmithKline announced the Food and Drug Administration approval of Shingrix for the prevention of herpes zoster (shingles) in adults aged 50 years or older. In pooled clinical trial results, the vaccine demonstrated greater than 90% efficacy in all age groups, according to a company statement.
Shingrix is a non-live, recombinant subunit vaccine that is given in two doses, intramuscularly. Zostavax, also indicated in individuals aged 50 years or older, is a live attenuated virus vaccine.
In a related decision, ACIP voted 14-1 to recommend Shingrix for prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.
They also voted 12-3 to recommend Shingrix to prevent herpes zoster and its complications for immunocompetent adults who previously received Zostavax.
Herpes zoster subunit vaccine (Shingrix) was preferentially recommended over zoster vaccine live (Zostavax) for preventing herpes zoster and related complications Oct. 25 at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
Eight committee members voted for the recommendation, and seven voted against it.
In discussions leading up to the vote, some committee members cited potential supply issues, as well as the need for longer-term safety data, among other issues.
“I think it would be nice to see data on a larger population that is not just research-based, especially because we have very little data on ethnic minorities,” said Laura E. Riley, MD, of Harvard Medical School, Boston, who voted against the recommendation.
The vote comes several days after GlaxoSmithKline announced the Food and Drug Administration approval of Shingrix for the prevention of herpes zoster (shingles) in adults aged 50 years or older. In pooled clinical trial results, the vaccine demonstrated greater than 90% efficacy in all age groups, according to a company statement.
Shingrix is a non-live, recombinant subunit vaccine that is given in two doses, intramuscularly. Zostavax, also indicated in individuals aged 50 years or older, is a live attenuated virus vaccine.
In a related decision, ACIP voted 14-1 to recommend Shingrix for prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.
They also voted 12-3 to recommend Shingrix to prevent herpes zoster and its complications for immunocompetent adults who previously received Zostavax.
Herpes zoster subunit vaccine (Shingrix) was preferentially recommended over zoster vaccine live (Zostavax) for preventing herpes zoster and related complications Oct. 25 at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
Eight committee members voted for the recommendation, and seven voted against it.
In discussions leading up to the vote, some committee members cited potential supply issues, as well as the need for longer-term safety data, among other issues.
“I think it would be nice to see data on a larger population that is not just research-based, especially because we have very little data on ethnic minorities,” said Laura E. Riley, MD, of Harvard Medical School, Boston, who voted against the recommendation.
The vote comes several days after GlaxoSmithKline announced the Food and Drug Administration approval of Shingrix for the prevention of herpes zoster (shingles) in adults aged 50 years or older. In pooled clinical trial results, the vaccine demonstrated greater than 90% efficacy in all age groups, according to a company statement.
Shingrix is a non-live, recombinant subunit vaccine that is given in two doses, intramuscularly. Zostavax, also indicated in individuals aged 50 years or older, is a live attenuated virus vaccine.
In a related decision, ACIP voted 14-1 to recommend Shingrix for prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.
They also voted 12-3 to recommend Shingrix to prevent herpes zoster and its complications for immunocompetent adults who previously received Zostavax.
FROM AN ACIP MEETING
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.”
Rheumatoid arthritis increases risk of COPD hospitalizations
Individuals with rheumatoid arthritis (RA) had an increased risk of hospitalizations from chronic obstructive pulmonary disease (COPD) when compared with the general population in a Canadian retrospective, population-based cohort study.
The risk of COPD hospitalizations was 47% higher in individuals with RA. “This finding emphasizes the need to control inflammation in rheumatoid arthritis, not only to prevent joint damage, but also to prevent complications of systemic inflammation, including the development of comorbidities such as cardiovascular diseases and COPD,” wrote Diane Lacaille, MD, of the University of British Columbia, Vancouver, and her coauthors (Arthritis Care Res. 2017 Oct 19. doi: 10.1002/acr.23410).
Several previous studies have suggested a link between COPD and inflammation, Dr. Lacaille and her colleagues said. Accordingly, they sought to evaluate the risk of COPD hospitalizations in a cohort of 24,625 individuals with RA as compared with 25,396 general population controls randomly selected and matched based on age, sex, and index year. Most subjects in the analysis were female, and the mean age at onset of RA was 57.2 years.
The investigators reported an increased incidence of COPD in individuals with RA, compared with controls, based on an incident rate ratio (IRR) of 1.58 (95% confidence interval, 1.34-1.87) that dropped to 1.47 (95% CI, 1.24-1.74) after adjustment for potential confounders, including comorbidities and health services usage at baseline. The overall incidence rate for COPD was 2.07 per 1,000 patient-years for RA patients and 1.31 per 1,000 patient-years for controls.
When the model was stratified based on sex, COPD hospitalization risk was significantly increased in women (adjusted hazard ratio [HR], 1.61; 95% CI, 1.30-1.98), but not in men (adjusted HR, 1.25; 95% CI, 0.95-1.66), they said.
Data were not available on smoking, the main COPD risk factor, for the patients in this study; however, the increased risk of COPD hospitalizations in the RA group remained significant after modeling for smoking, according to the investigators.
Combined, these results have “notable implications for the clinical care of RA and COPD,” Dr. Lacaille and her coinvestigators said.
Both clinicians and people living with RA “should be aware of the increased risk of developing COPD and be vigilant in watching for early symptoms of COPD, so that appropriate diagnostic tests can be administered at the onset of early symptoms,” they wrote. “Early detection of COPD is essential so that effective treatments can be initiated before irreversible damage to the lungs occurs, to improve long-term outcomes.”
These findings strengthen the conclusions of two previous cross-sectional studies showing an association between RA and COPD prevalence, according to the investigators. In one study, RA patients in Israel who were receiving disease-modifying antirheumatic drugs had double the prevalence of COPD, compared with general population controls, according to authors of that study (Immunol Res. 2013;56[2-3]:261-6). Similarly, U.K. investigators compared 421 RA patients against controls and reported a twofold increase in obstructive pattern on screening spirometry in the RA group (Ann Rheum Dis. 2013;72:1517-23).
The current study from Dr. Lacaille and her coinvestigators was supported by funding from the Canadian Institute for Health Research. The authors reported that they had no financial disclosures, conflicts of interest, or benefits from commercial sources.
Individuals with rheumatoid arthritis (RA) had an increased risk of hospitalizations from chronic obstructive pulmonary disease (COPD) when compared with the general population in a Canadian retrospective, population-based cohort study.
The risk of COPD hospitalizations was 47% higher in individuals with RA. “This finding emphasizes the need to control inflammation in rheumatoid arthritis, not only to prevent joint damage, but also to prevent complications of systemic inflammation, including the development of comorbidities such as cardiovascular diseases and COPD,” wrote Diane Lacaille, MD, of the University of British Columbia, Vancouver, and her coauthors (Arthritis Care Res. 2017 Oct 19. doi: 10.1002/acr.23410).
Several previous studies have suggested a link between COPD and inflammation, Dr. Lacaille and her colleagues said. Accordingly, they sought to evaluate the risk of COPD hospitalizations in a cohort of 24,625 individuals with RA as compared with 25,396 general population controls randomly selected and matched based on age, sex, and index year. Most subjects in the analysis were female, and the mean age at onset of RA was 57.2 years.
The investigators reported an increased incidence of COPD in individuals with RA, compared with controls, based on an incident rate ratio (IRR) of 1.58 (95% confidence interval, 1.34-1.87) that dropped to 1.47 (95% CI, 1.24-1.74) after adjustment for potential confounders, including comorbidities and health services usage at baseline. The overall incidence rate for COPD was 2.07 per 1,000 patient-years for RA patients and 1.31 per 1,000 patient-years for controls.
When the model was stratified based on sex, COPD hospitalization risk was significantly increased in women (adjusted hazard ratio [HR], 1.61; 95% CI, 1.30-1.98), but not in men (adjusted HR, 1.25; 95% CI, 0.95-1.66), they said.
Data were not available on smoking, the main COPD risk factor, for the patients in this study; however, the increased risk of COPD hospitalizations in the RA group remained significant after modeling for smoking, according to the investigators.
Combined, these results have “notable implications for the clinical care of RA and COPD,” Dr. Lacaille and her coinvestigators said.
Both clinicians and people living with RA “should be aware of the increased risk of developing COPD and be vigilant in watching for early symptoms of COPD, so that appropriate diagnostic tests can be administered at the onset of early symptoms,” they wrote. “Early detection of COPD is essential so that effective treatments can be initiated before irreversible damage to the lungs occurs, to improve long-term outcomes.”
These findings strengthen the conclusions of two previous cross-sectional studies showing an association between RA and COPD prevalence, according to the investigators. In one study, RA patients in Israel who were receiving disease-modifying antirheumatic drugs had double the prevalence of COPD, compared with general population controls, according to authors of that study (Immunol Res. 2013;56[2-3]:261-6). Similarly, U.K. investigators compared 421 RA patients against controls and reported a twofold increase in obstructive pattern on screening spirometry in the RA group (Ann Rheum Dis. 2013;72:1517-23).
The current study from Dr. Lacaille and her coinvestigators was supported by funding from the Canadian Institute for Health Research. The authors reported that they had no financial disclosures, conflicts of interest, or benefits from commercial sources.
Individuals with rheumatoid arthritis (RA) had an increased risk of hospitalizations from chronic obstructive pulmonary disease (COPD) when compared with the general population in a Canadian retrospective, population-based cohort study.
The risk of COPD hospitalizations was 47% higher in individuals with RA. “This finding emphasizes the need to control inflammation in rheumatoid arthritis, not only to prevent joint damage, but also to prevent complications of systemic inflammation, including the development of comorbidities such as cardiovascular diseases and COPD,” wrote Diane Lacaille, MD, of the University of British Columbia, Vancouver, and her coauthors (Arthritis Care Res. 2017 Oct 19. doi: 10.1002/acr.23410).
Several previous studies have suggested a link between COPD and inflammation, Dr. Lacaille and her colleagues said. Accordingly, they sought to evaluate the risk of COPD hospitalizations in a cohort of 24,625 individuals with RA as compared with 25,396 general population controls randomly selected and matched based on age, sex, and index year. Most subjects in the analysis were female, and the mean age at onset of RA was 57.2 years.
The investigators reported an increased incidence of COPD in individuals with RA, compared with controls, based on an incident rate ratio (IRR) of 1.58 (95% confidence interval, 1.34-1.87) that dropped to 1.47 (95% CI, 1.24-1.74) after adjustment for potential confounders, including comorbidities and health services usage at baseline. The overall incidence rate for COPD was 2.07 per 1,000 patient-years for RA patients and 1.31 per 1,000 patient-years for controls.
When the model was stratified based on sex, COPD hospitalization risk was significantly increased in women (adjusted hazard ratio [HR], 1.61; 95% CI, 1.30-1.98), but not in men (adjusted HR, 1.25; 95% CI, 0.95-1.66), they said.
Data were not available on smoking, the main COPD risk factor, for the patients in this study; however, the increased risk of COPD hospitalizations in the RA group remained significant after modeling for smoking, according to the investigators.
Combined, these results have “notable implications for the clinical care of RA and COPD,” Dr. Lacaille and her coinvestigators said.
Both clinicians and people living with RA “should be aware of the increased risk of developing COPD and be vigilant in watching for early symptoms of COPD, so that appropriate diagnostic tests can be administered at the onset of early symptoms,” they wrote. “Early detection of COPD is essential so that effective treatments can be initiated before irreversible damage to the lungs occurs, to improve long-term outcomes.”
These findings strengthen the conclusions of two previous cross-sectional studies showing an association between RA and COPD prevalence, according to the investigators. In one study, RA patients in Israel who were receiving disease-modifying antirheumatic drugs had double the prevalence of COPD, compared with general population controls, according to authors of that study (Immunol Res. 2013;56[2-3]:261-6). Similarly, U.K. investigators compared 421 RA patients against controls and reported a twofold increase in obstructive pattern on screening spirometry in the RA group (Ann Rheum Dis. 2013;72:1517-23).
The current study from Dr. Lacaille and her coinvestigators was supported by funding from the Canadian Institute for Health Research. The authors reported that they had no financial disclosures, conflicts of interest, or benefits from commercial sources.
FROM Arthritis Care AND Research
Key clinical point:
Major finding: The risk of COPD hospitalizations was 47% higher in individuals with rheumatoid arthritis (adjusted hazard ratio, 1.47; 95% confidence interval, 1.34-1.87).
Data source: A retrospective cohort study including approximately 25,000 RA patients seen in British Columbia and a roughly equal number of controls.
Disclosures: The Canadian Institute for Health Research provided funding for the study. The authors reported that they had no financial disclosures, conflicts of interest, or benefits from commercial sources.
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.
Flu shots and persuasion
Compliant patients are all alike; every noncompliant patient is obstinate in his or her own way. Because of this, persuading patients to make good choices is rarely easy and never universal.
At Kaiser Permanente, we have begun in earnest providing flu shots. Every department participates (even dermatology) with a goal of vaccinating every eligible patient. Most patients want their shot. When patients decline, it’s game on. A rare few decline for justifiable reasons such as an allergy. Most say “no” for flawed reasons: “I never get the flu,” “The shot always gives me the flu,” and “I don’t believe in vaccines,” are common ones.
Fortunately, we can help them. Here are techniques I learned while working on my MBA that I’ve found useful in persuading patients to make better choices:
- The “everyone is doing it” technique. At KP, we’ve put up boards with the iconic goal thermometer showing how many flu shots we need to reach our objective. When patients see we’ve given over 1,000 shots in dermatology in just 2 weeks, this technique helps convince them. Patients prefer to be like others rather than to stand out, particularly when there is uncertainty.
- The “this is who you are technique.” Patients hate to be seen as inconsistent. In fact, we are all more likely to make a choice seen as consistent with who we are rather than change our mind, even if doing so is a better choice. Highlight how they have previously shown good decision making and healthy behaviors and point out how getting vaccinated is consonant with who they are. For example: “Being a vegan, you are clearly someone who takes care of her health. Getting the vaccine is similar to choosing to eat plants. It’s what healthy people like you do.”
- The “well, that’s not like you” technique. Here, you point out how their choice is inconsistent with their previous choices. You might say, “Why would you get the hepatitis A vaccine last week and not the flu shot today?” Like the previous technique, this creates cognitive dissonance. You might soften the approach by saying, “You might have thought this,” or “I’m sure you didn’t realize.”
- The emotional decision approach. Making the risk seem real and imminent can combat future discounting. One example might be: “We have had several people hospitalized and one death from the flu in San Diego already.” Use stories and descriptive language to make the risk salient.
- The use your authority approach. The long coat does matter. A more modern version of the paternalistic physician is referred to as “asymmetric” or “light paternalism,” and we should recognize that it might be used to save a life. One example is: “I advise you to get the flu shot because I care about you, and I’m worried you might end up in the hospital or worse if you don’t get it.” There’s a reason why tobacco companies once used doctors in white coats to sell cigarettes – we can be quite persuasive.
“A great deal of literature has been distributed, casting discredit upon the value of vaccination ... I do not see how any one ... who is familiar with the history of the subject, and who has any capacity left for clear judgment, can doubt its value.” – William Osler
Dr. Benabio is director of health care transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.
Compliant patients are all alike; every noncompliant patient is obstinate in his or her own way. Because of this, persuading patients to make good choices is rarely easy and never universal.
At Kaiser Permanente, we have begun in earnest providing flu shots. Every department participates (even dermatology) with a goal of vaccinating every eligible patient. Most patients want their shot. When patients decline, it’s game on. A rare few decline for justifiable reasons such as an allergy. Most say “no” for flawed reasons: “I never get the flu,” “The shot always gives me the flu,” and “I don’t believe in vaccines,” are common ones.
Fortunately, we can help them. Here are techniques I learned while working on my MBA that I’ve found useful in persuading patients to make better choices:
- The “everyone is doing it” technique. At KP, we’ve put up boards with the iconic goal thermometer showing how many flu shots we need to reach our objective. When patients see we’ve given over 1,000 shots in dermatology in just 2 weeks, this technique helps convince them. Patients prefer to be like others rather than to stand out, particularly when there is uncertainty.
- The “this is who you are technique.” Patients hate to be seen as inconsistent. In fact, we are all more likely to make a choice seen as consistent with who we are rather than change our mind, even if doing so is a better choice. Highlight how they have previously shown good decision making and healthy behaviors and point out how getting vaccinated is consonant with who they are. For example: “Being a vegan, you are clearly someone who takes care of her health. Getting the vaccine is similar to choosing to eat plants. It’s what healthy people like you do.”
- The “well, that’s not like you” technique. Here, you point out how their choice is inconsistent with their previous choices. You might say, “Why would you get the hepatitis A vaccine last week and not the flu shot today?” Like the previous technique, this creates cognitive dissonance. You might soften the approach by saying, “You might have thought this,” or “I’m sure you didn’t realize.”
- The emotional decision approach. Making the risk seem real and imminent can combat future discounting. One example might be: “We have had several people hospitalized and one death from the flu in San Diego already.” Use stories and descriptive language to make the risk salient.
- The use your authority approach. The long coat does matter. A more modern version of the paternalistic physician is referred to as “asymmetric” or “light paternalism,” and we should recognize that it might be used to save a life. One example is: “I advise you to get the flu shot because I care about you, and I’m worried you might end up in the hospital or worse if you don’t get it.” There’s a reason why tobacco companies once used doctors in white coats to sell cigarettes – we can be quite persuasive.
“A great deal of literature has been distributed, casting discredit upon the value of vaccination ... I do not see how any one ... who is familiar with the history of the subject, and who has any capacity left for clear judgment, can doubt its value.” – William Osler
Dr. Benabio is director of health care transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.
Compliant patients are all alike; every noncompliant patient is obstinate in his or her own way. Because of this, persuading patients to make good choices is rarely easy and never universal.
At Kaiser Permanente, we have begun in earnest providing flu shots. Every department participates (even dermatology) with a goal of vaccinating every eligible patient. Most patients want their shot. When patients decline, it’s game on. A rare few decline for justifiable reasons such as an allergy. Most say “no” for flawed reasons: “I never get the flu,” “The shot always gives me the flu,” and “I don’t believe in vaccines,” are common ones.
Fortunately, we can help them. Here are techniques I learned while working on my MBA that I’ve found useful in persuading patients to make better choices:
- The “everyone is doing it” technique. At KP, we’ve put up boards with the iconic goal thermometer showing how many flu shots we need to reach our objective. When patients see we’ve given over 1,000 shots in dermatology in just 2 weeks, this technique helps convince them. Patients prefer to be like others rather than to stand out, particularly when there is uncertainty.
- The “this is who you are technique.” Patients hate to be seen as inconsistent. In fact, we are all more likely to make a choice seen as consistent with who we are rather than change our mind, even if doing so is a better choice. Highlight how they have previously shown good decision making and healthy behaviors and point out how getting vaccinated is consonant with who they are. For example: “Being a vegan, you are clearly someone who takes care of her health. Getting the vaccine is similar to choosing to eat plants. It’s what healthy people like you do.”
- The “well, that’s not like you” technique. Here, you point out how their choice is inconsistent with their previous choices. You might say, “Why would you get the hepatitis A vaccine last week and not the flu shot today?” Like the previous technique, this creates cognitive dissonance. You might soften the approach by saying, “You might have thought this,” or “I’m sure you didn’t realize.”
- The emotional decision approach. Making the risk seem real and imminent can combat future discounting. One example might be: “We have had several people hospitalized and one death from the flu in San Diego already.” Use stories and descriptive language to make the risk salient.
- The use your authority approach. The long coat does matter. A more modern version of the paternalistic physician is referred to as “asymmetric” or “light paternalism,” and we should recognize that it might be used to save a life. One example is: “I advise you to get the flu shot because I care about you, and I’m worried you might end up in the hospital or worse if you don’t get it.” There’s a reason why tobacco companies once used doctors in white coats to sell cigarettes – we can be quite persuasive.
“A great deal of literature has been distributed, casting discredit upon the value of vaccination ... I do not see how any one ... who is familiar with the history of the subject, and who has any capacity left for clear judgment, can doubt its value.” – William Osler
Dr. Benabio is director of health care transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.
Too few RA patients get timely adjustment of DMARDs
Adjustment of disease-modifying antirheumatic drug (DMARD) therapy is not happening quickly enough for a substantial minority of rheumatoid arthritis patients with moderate to high disease activity, according to the findings of a registry study that is the first to evaluate this association.
Investigators led by Yomei Shaw, PhD, a research fellow with the National Data Bank for Rheumatic Diseases, retrospectively analyzed data from 538 patients in the university’s Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry who had moderate to high disease activity. Dr. Shaw conducted the study as a doctoral student in the department of health policy and management at the University of Pittsburgh.
In 40% of patients who had persistent disease activity of this severity, clinicians waited more than the 90 days recommended by treat-to-target (T2T) guidelines to adjust DMARDs, according to published results (Arthritis Care Res. 2017 Sep 21. doi: 10.1002/acr.23418). Such delay was more common for certain groups, including those on biologics and those who had rheumatoid arthritis (RA) for longer.
Compared with peers whose therapy was adjusted sooner, patients with such delayed adjustment were about one-quarter less likely to achieve low disease activity or remission during follow-up.
“The results of our survival analyses suggest that delays in DMARD adjustment of more than 3 months are common among RA patients with [moderate to high disease activity], highlighting an important potential gap in quality of care for these patients,” Dr. Shaw and her colleagues wrote.
They acknowledge that some of the delays in adjustment may have been unavoidable. For example, patients on biologic DMARDs may have needed insurance approval to start a new biologic, and patients with long-standing disease may have had fewer options remaining or symptoms that clinicians attributed to irreversible joint damage.
The study’s findings provide additional evidence of the importance of timely, guideline-adherent DMARD adjustment in reducing the amount of time patients spend in moderate to high disease activity, the investigators further contend.
“Promoting T2T in clinical practice requires coordinated change at the system, rheumatology practice, and individual levels,” such as consistently documenting the treatment target, assessing disease activity at every visit, and mandating a minimum visit frequency, they conclude.
Dr. Shaw and her colleagues studied patients having moderate to high disease activity, defined according to the 28-joint Disease Activity Score with C-reactive protein criteria (score of greater than 3.2).
The investigators reported a median time to adjustment of DMARD therapy of 154 days during 943.5 patient-years of follow-up. These adjustments could be adding, switching, or increasing the dose of a DMARD medication (excluding corticosteroids).
In multivariate analysis, patients had a longer time to DMARD adjustment if they were aged 75 years or older (subdistribution hazard ratio, 0.61; P = .02), had lower baseline disease activity (0.72; P less than .01), had longer duration of rheumatoid arthritis (0.98; P less than .01), or were receiving a biologic DMARD at baseline (0.71; P less than .01).
The median time to achieving low disease activity or remission was 301 days for the entire cohort. Patients had a longer time to achieve this goal if their DMARD therapy was not adjusted within 90 days (hazard ratio, 0.76; P = .01) or if they were African American (0.63; P = .01) or had higher baseline disease activity (0.75; P less than .01). They had a shorter time if they had better mental health (1.01; P = .03) or physical health (1.01; P = .02) as assessed with the 12-item Short Form Health Survey.
One of the study authors received research funding from Genentech and is currently employed by AbbVie. The registry used was funded by the National Institutes of Health and Genentech.
Randomized controlled trials demonstrate that statin lipid–lowering drugs reduce repeat cardiovascular events. Based on this evidence, clinicians agree that the vast majority of patients should receive statin lipid-lowering drugs after a CV event, and that providers not prescribing statins to these patients are providing suboptimal care.
By analogy, the data provided in this new analysis by Shaw and her colleagues suggests that many rheumatologists are providing suboptimal care. Many randomized, controlled trials testing a treat-to-target (T2T) paradigm demonstrate the clinical benefits of changing treatments for patients with rheumatoid arthritis who are in moderate or high disease activity. Yet, this analysis found many patients do not change treatments despite poor disease control. While the current study does not examine the reasons for suboptimal care, some correlates include:
• Patient preference to not change treatment;
• Provider desire to give treatments more time to work; and
• Health system issues such as drug payment complexities.
Continuing medical education may be necessary, but it is not a sufficient lever to push providers to implement T2T. Audit and feedback – providing individual providers with their performance metrics – alerts rheumatic disease providers when improvement is necessary. Yet, most providers need specific strategies within their practice to implement T2T. Collaborative learning between providers with a common purpose and coaches that understand the complexities of implementing T2T have been shown in the recently published TRACTION trial to produce improvements (Arthritis Rheumatol. 2017;69[7]:1374-80). The article by Shaw and her colleagues should sound the alarm to rheumatic disease providers: Care for RA needs improving if we want to produce optimal outcomes.
Daniel H. Solomon, MD, is a professor of medicine at Harvard University, and chief of the section of clinical sciences in the division of rheumatology at Brigham and Women’s Hospital, both in Boston. He has no relevant disclosures.
Randomized controlled trials demonstrate that statin lipid–lowering drugs reduce repeat cardiovascular events. Based on this evidence, clinicians agree that the vast majority of patients should receive statin lipid-lowering drugs after a CV event, and that providers not prescribing statins to these patients are providing suboptimal care.
By analogy, the data provided in this new analysis by Shaw and her colleagues suggests that many rheumatologists are providing suboptimal care. Many randomized, controlled trials testing a treat-to-target (T2T) paradigm demonstrate the clinical benefits of changing treatments for patients with rheumatoid arthritis who are in moderate or high disease activity. Yet, this analysis found many patients do not change treatments despite poor disease control. While the current study does not examine the reasons for suboptimal care, some correlates include:
• Patient preference to not change treatment;
• Provider desire to give treatments more time to work; and
• Health system issues such as drug payment complexities.
Continuing medical education may be necessary, but it is not a sufficient lever to push providers to implement T2T. Audit and feedback – providing individual providers with their performance metrics – alerts rheumatic disease providers when improvement is necessary. Yet, most providers need specific strategies within their practice to implement T2T. Collaborative learning between providers with a common purpose and coaches that understand the complexities of implementing T2T have been shown in the recently published TRACTION trial to produce improvements (Arthritis Rheumatol. 2017;69[7]:1374-80). The article by Shaw and her colleagues should sound the alarm to rheumatic disease providers: Care for RA needs improving if we want to produce optimal outcomes.
Daniel H. Solomon, MD, is a professor of medicine at Harvard University, and chief of the section of clinical sciences in the division of rheumatology at Brigham and Women’s Hospital, both in Boston. He has no relevant disclosures.
Randomized controlled trials demonstrate that statin lipid–lowering drugs reduce repeat cardiovascular events. Based on this evidence, clinicians agree that the vast majority of patients should receive statin lipid-lowering drugs after a CV event, and that providers not prescribing statins to these patients are providing suboptimal care.
By analogy, the data provided in this new analysis by Shaw and her colleagues suggests that many rheumatologists are providing suboptimal care. Many randomized, controlled trials testing a treat-to-target (T2T) paradigm demonstrate the clinical benefits of changing treatments for patients with rheumatoid arthritis who are in moderate or high disease activity. Yet, this analysis found many patients do not change treatments despite poor disease control. While the current study does not examine the reasons for suboptimal care, some correlates include:
• Patient preference to not change treatment;
• Provider desire to give treatments more time to work; and
• Health system issues such as drug payment complexities.
Continuing medical education may be necessary, but it is not a sufficient lever to push providers to implement T2T. Audit and feedback – providing individual providers with their performance metrics – alerts rheumatic disease providers when improvement is necessary. Yet, most providers need specific strategies within their practice to implement T2T. Collaborative learning between providers with a common purpose and coaches that understand the complexities of implementing T2T have been shown in the recently published TRACTION trial to produce improvements (Arthritis Rheumatol. 2017;69[7]:1374-80). The article by Shaw and her colleagues should sound the alarm to rheumatic disease providers: Care for RA needs improving if we want to produce optimal outcomes.
Daniel H. Solomon, MD, is a professor of medicine at Harvard University, and chief of the section of clinical sciences in the division of rheumatology at Brigham and Women’s Hospital, both in Boston. He has no relevant disclosures.
Adjustment of disease-modifying antirheumatic drug (DMARD) therapy is not happening quickly enough for a substantial minority of rheumatoid arthritis patients with moderate to high disease activity, according to the findings of a registry study that is the first to evaluate this association.
Investigators led by Yomei Shaw, PhD, a research fellow with the National Data Bank for Rheumatic Diseases, retrospectively analyzed data from 538 patients in the university’s Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry who had moderate to high disease activity. Dr. Shaw conducted the study as a doctoral student in the department of health policy and management at the University of Pittsburgh.
In 40% of patients who had persistent disease activity of this severity, clinicians waited more than the 90 days recommended by treat-to-target (T2T) guidelines to adjust DMARDs, according to published results (Arthritis Care Res. 2017 Sep 21. doi: 10.1002/acr.23418). Such delay was more common for certain groups, including those on biologics and those who had rheumatoid arthritis (RA) for longer.
Compared with peers whose therapy was adjusted sooner, patients with such delayed adjustment were about one-quarter less likely to achieve low disease activity or remission during follow-up.
“The results of our survival analyses suggest that delays in DMARD adjustment of more than 3 months are common among RA patients with [moderate to high disease activity], highlighting an important potential gap in quality of care for these patients,” Dr. Shaw and her colleagues wrote.
They acknowledge that some of the delays in adjustment may have been unavoidable. For example, patients on biologic DMARDs may have needed insurance approval to start a new biologic, and patients with long-standing disease may have had fewer options remaining or symptoms that clinicians attributed to irreversible joint damage.
The study’s findings provide additional evidence of the importance of timely, guideline-adherent DMARD adjustment in reducing the amount of time patients spend in moderate to high disease activity, the investigators further contend.
“Promoting T2T in clinical practice requires coordinated change at the system, rheumatology practice, and individual levels,” such as consistently documenting the treatment target, assessing disease activity at every visit, and mandating a minimum visit frequency, they conclude.
Dr. Shaw and her colleagues studied patients having moderate to high disease activity, defined according to the 28-joint Disease Activity Score with C-reactive protein criteria (score of greater than 3.2).
The investigators reported a median time to adjustment of DMARD therapy of 154 days during 943.5 patient-years of follow-up. These adjustments could be adding, switching, or increasing the dose of a DMARD medication (excluding corticosteroids).
In multivariate analysis, patients had a longer time to DMARD adjustment if they were aged 75 years or older (subdistribution hazard ratio, 0.61; P = .02), had lower baseline disease activity (0.72; P less than .01), had longer duration of rheumatoid arthritis (0.98; P less than .01), or were receiving a biologic DMARD at baseline (0.71; P less than .01).
The median time to achieving low disease activity or remission was 301 days for the entire cohort. Patients had a longer time to achieve this goal if their DMARD therapy was not adjusted within 90 days (hazard ratio, 0.76; P = .01) or if they were African American (0.63; P = .01) or had higher baseline disease activity (0.75; P less than .01). They had a shorter time if they had better mental health (1.01; P = .03) or physical health (1.01; P = .02) as assessed with the 12-item Short Form Health Survey.
One of the study authors received research funding from Genentech and is currently employed by AbbVie. The registry used was funded by the National Institutes of Health and Genentech.
Adjustment of disease-modifying antirheumatic drug (DMARD) therapy is not happening quickly enough for a substantial minority of rheumatoid arthritis patients with moderate to high disease activity, according to the findings of a registry study that is the first to evaluate this association.
Investigators led by Yomei Shaw, PhD, a research fellow with the National Data Bank for Rheumatic Diseases, retrospectively analyzed data from 538 patients in the university’s Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry who had moderate to high disease activity. Dr. Shaw conducted the study as a doctoral student in the department of health policy and management at the University of Pittsburgh.
In 40% of patients who had persistent disease activity of this severity, clinicians waited more than the 90 days recommended by treat-to-target (T2T) guidelines to adjust DMARDs, according to published results (Arthritis Care Res. 2017 Sep 21. doi: 10.1002/acr.23418). Such delay was more common for certain groups, including those on biologics and those who had rheumatoid arthritis (RA) for longer.
Compared with peers whose therapy was adjusted sooner, patients with such delayed adjustment were about one-quarter less likely to achieve low disease activity or remission during follow-up.
“The results of our survival analyses suggest that delays in DMARD adjustment of more than 3 months are common among RA patients with [moderate to high disease activity], highlighting an important potential gap in quality of care for these patients,” Dr. Shaw and her colleagues wrote.
They acknowledge that some of the delays in adjustment may have been unavoidable. For example, patients on biologic DMARDs may have needed insurance approval to start a new biologic, and patients with long-standing disease may have had fewer options remaining or symptoms that clinicians attributed to irreversible joint damage.
The study’s findings provide additional evidence of the importance of timely, guideline-adherent DMARD adjustment in reducing the amount of time patients spend in moderate to high disease activity, the investigators further contend.
“Promoting T2T in clinical practice requires coordinated change at the system, rheumatology practice, and individual levels,” such as consistently documenting the treatment target, assessing disease activity at every visit, and mandating a minimum visit frequency, they conclude.
Dr. Shaw and her colleagues studied patients having moderate to high disease activity, defined according to the 28-joint Disease Activity Score with C-reactive protein criteria (score of greater than 3.2).
The investigators reported a median time to adjustment of DMARD therapy of 154 days during 943.5 patient-years of follow-up. These adjustments could be adding, switching, or increasing the dose of a DMARD medication (excluding corticosteroids).
In multivariate analysis, patients had a longer time to DMARD adjustment if they were aged 75 years or older (subdistribution hazard ratio, 0.61; P = .02), had lower baseline disease activity (0.72; P less than .01), had longer duration of rheumatoid arthritis (0.98; P less than .01), or were receiving a biologic DMARD at baseline (0.71; P less than .01).
The median time to achieving low disease activity or remission was 301 days for the entire cohort. Patients had a longer time to achieve this goal if their DMARD therapy was not adjusted within 90 days (hazard ratio, 0.76; P = .01) or if they were African American (0.63; P = .01) or had higher baseline disease activity (0.75; P less than .01). They had a shorter time if they had better mental health (1.01; P = .03) or physical health (1.01; P = .02) as assessed with the 12-item Short Form Health Survey.
One of the study authors received research funding from Genentech and is currently employed by AbbVie. The registry used was funded by the National Institutes of Health and Genentech.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: In 40% of patients who had persistent disease activity of this severity, clinicians waited more than the 90 days recommended by treat-to-target guidelines to adjust DMARDs.
Data source: A retrospective cohort study of 538 patients with RA having moderate to high disease activity.
Disclosures: One of the study authors received research funding from Genentech and is currently employed by AbbVie. The study registry used was funded by the National Institutes of Health and Genentech.
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.