User login
Nonspecific musculoskeletal symptoms might indicate early PsA
People with psoriatic arthritis can be symptomatic for years before the condition is diagnosed, according to two recent reports.
There are no reliable diagnostic biomarkers, and sometimes patients have vague symptoms with only minimal physical findings, which makes it hard for physicians to recognize the problem and refer to rheumatology.
In the meantime, the longer it takes to diagnose psoriatic arthritis (PsA) and treat it properly, the worse off patients are when it’s finally caught. They “present with a greater rate of clinical progression and worse physical function, compared with patients with an undelayed diagnosis,” and more radiographic joint damage, according to investigators led by rheumatologist Alexis Ogdie, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia.
Dr. Ogdie’s study in BMC Rheumatology, and a second one from Arthritis Care & Research, both described the early phase of psoriatic arthritis, before formal diagnosis, to help with early recognition.
Delay associated with misdiagnosis
Dr. Ogdie’s team surveyed 203 adults with PsA – average age of 52 years, mostly white, and over 80% women – about their diagnosis history. The time between seeking medical attention for PsA-related symptoms and receiving a diagnosis was less than 6 months for 69 participants, 6 months to 4 years for 68, and 5 years or more for 66.
Typical symptoms, like joint pain, swollen joints, reduced range of motion, and dactylitis, were associated with quicker diagnosis. Turning early to dermatologists and rheumatologists – instead of general practitioners, orthopedics, chiropractors, and others – sped diagnosis, as well. People diagnosed within 6 months also tended to be slightly older, were less likely to be disabled or unemployed, have more education, and were more likely to make $100,000 per year or more.
Vaguer symptoms, such as stiffness, fatigue, and enthesitis-associated foot pain, delayed diagnosis. The longer PsA went unrecognized, the more likely people were to be misdiagnosed with osteoarthritis, psychosomatic disorders, and other problems.
“Increased recognition of heterogeneous symptoms associated with PsA, as well as understanding existing diagnostic barriers, may lead to prompt diagnosis and initiation of appropriate treatment that may improve outcomes,” the investigators concluded.
A prodromal phase
In the Arthritis Care & Research study, investigators led by Lihi Eder, MD, PhD, codirector of the cardio-rheumatology program at Women’s College Hospital, Toronto, used health records and databases to compare primary care histories of 462 Canadian PsA patients in the 5 years before they were diagnosed with 2,310 age- and sex-matched controls without PsA and treated by the same family physicians. The mean age in the study was 54 years, and just over half the subjects were women. Socioeconomic status and rurality were similar between the two groups.
The mean time from the initial primary care visit for a musculoskeletal complaint to rheumatology referral was 513 days among PsA patients, “which was substantially longer than for other inflammatory arthritic conditions, such as rheumatoid arthritis,” Dr. Eder and associates noted.
PsA patients were more than twice as likely to visit primary care for nonspecific musculoskeletal issues in the year before their diagnosis, and more likely in the 5 years prior. The odds of visits to musculoskeletal specialists, joint injections, joint imaging, and ED visits, was also higher as early as 5 years before PsA recognition, and hinted at the impending diagnosis.
“Our study characterized a prediagnosis period in PsA and supports the notion that a prodromal PsA phase occurs in a significant proportion of patients. ... This pattern reveals some of the underlying causes of diagnosis delays of PsA and highlights the need for diagnostic strategies and novel reliable biomarkers to aid in early diagnosis of PsA,” the investigators concluded.
Dr. Ogdie and colleagues suggested that community case searches, public awareness programs, patient education, and referral guidelines for primary care providers might help. They also suggested greater use of validated screening tools, such as the Psoriasis Epidemiology Screening Tool, in primary care.
Dr. Eder had no disclosures, and her study was funded by the Canadian Rheumatology Association. Dr. Ogdie’s study was funded by Novartis, maker of secukinumab (Cosentyx), which is indicated for PsA. She is a consultant for Novartis and has received grant support from the company. One author is an employee.
SOURCES: Ogdie A et al. BMC Rheumatol. 2020 Jan 10. doi: 10.1186/s41927-019-0102-7; Eder L et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24146.
People with psoriatic arthritis can be symptomatic for years before the condition is diagnosed, according to two recent reports.
There are no reliable diagnostic biomarkers, and sometimes patients have vague symptoms with only minimal physical findings, which makes it hard for physicians to recognize the problem and refer to rheumatology.
In the meantime, the longer it takes to diagnose psoriatic arthritis (PsA) and treat it properly, the worse off patients are when it’s finally caught. They “present with a greater rate of clinical progression and worse physical function, compared with patients with an undelayed diagnosis,” and more radiographic joint damage, according to investigators led by rheumatologist Alexis Ogdie, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia.
Dr. Ogdie’s study in BMC Rheumatology, and a second one from Arthritis Care & Research, both described the early phase of psoriatic arthritis, before formal diagnosis, to help with early recognition.
Delay associated with misdiagnosis
Dr. Ogdie’s team surveyed 203 adults with PsA – average age of 52 years, mostly white, and over 80% women – about their diagnosis history. The time between seeking medical attention for PsA-related symptoms and receiving a diagnosis was less than 6 months for 69 participants, 6 months to 4 years for 68, and 5 years or more for 66.
Typical symptoms, like joint pain, swollen joints, reduced range of motion, and dactylitis, were associated with quicker diagnosis. Turning early to dermatologists and rheumatologists – instead of general practitioners, orthopedics, chiropractors, and others – sped diagnosis, as well. People diagnosed within 6 months also tended to be slightly older, were less likely to be disabled or unemployed, have more education, and were more likely to make $100,000 per year or more.
Vaguer symptoms, such as stiffness, fatigue, and enthesitis-associated foot pain, delayed diagnosis. The longer PsA went unrecognized, the more likely people were to be misdiagnosed with osteoarthritis, psychosomatic disorders, and other problems.
“Increased recognition of heterogeneous symptoms associated with PsA, as well as understanding existing diagnostic barriers, may lead to prompt diagnosis and initiation of appropriate treatment that may improve outcomes,” the investigators concluded.
A prodromal phase
In the Arthritis Care & Research study, investigators led by Lihi Eder, MD, PhD, codirector of the cardio-rheumatology program at Women’s College Hospital, Toronto, used health records and databases to compare primary care histories of 462 Canadian PsA patients in the 5 years before they were diagnosed with 2,310 age- and sex-matched controls without PsA and treated by the same family physicians. The mean age in the study was 54 years, and just over half the subjects were women. Socioeconomic status and rurality were similar between the two groups.
The mean time from the initial primary care visit for a musculoskeletal complaint to rheumatology referral was 513 days among PsA patients, “which was substantially longer than for other inflammatory arthritic conditions, such as rheumatoid arthritis,” Dr. Eder and associates noted.
PsA patients were more than twice as likely to visit primary care for nonspecific musculoskeletal issues in the year before their diagnosis, and more likely in the 5 years prior. The odds of visits to musculoskeletal specialists, joint injections, joint imaging, and ED visits, was also higher as early as 5 years before PsA recognition, and hinted at the impending diagnosis.
“Our study characterized a prediagnosis period in PsA and supports the notion that a prodromal PsA phase occurs in a significant proportion of patients. ... This pattern reveals some of the underlying causes of diagnosis delays of PsA and highlights the need for diagnostic strategies and novel reliable biomarkers to aid in early diagnosis of PsA,” the investigators concluded.
Dr. Ogdie and colleagues suggested that community case searches, public awareness programs, patient education, and referral guidelines for primary care providers might help. They also suggested greater use of validated screening tools, such as the Psoriasis Epidemiology Screening Tool, in primary care.
Dr. Eder had no disclosures, and her study was funded by the Canadian Rheumatology Association. Dr. Ogdie’s study was funded by Novartis, maker of secukinumab (Cosentyx), which is indicated for PsA. She is a consultant for Novartis and has received grant support from the company. One author is an employee.
SOURCES: Ogdie A et al. BMC Rheumatol. 2020 Jan 10. doi: 10.1186/s41927-019-0102-7; Eder L et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24146.
People with psoriatic arthritis can be symptomatic for years before the condition is diagnosed, according to two recent reports.
There are no reliable diagnostic biomarkers, and sometimes patients have vague symptoms with only minimal physical findings, which makes it hard for physicians to recognize the problem and refer to rheumatology.
In the meantime, the longer it takes to diagnose psoriatic arthritis (PsA) and treat it properly, the worse off patients are when it’s finally caught. They “present with a greater rate of clinical progression and worse physical function, compared with patients with an undelayed diagnosis,” and more radiographic joint damage, according to investigators led by rheumatologist Alexis Ogdie, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia.
Dr. Ogdie’s study in BMC Rheumatology, and a second one from Arthritis Care & Research, both described the early phase of psoriatic arthritis, before formal diagnosis, to help with early recognition.
Delay associated with misdiagnosis
Dr. Ogdie’s team surveyed 203 adults with PsA – average age of 52 years, mostly white, and over 80% women – about their diagnosis history. The time between seeking medical attention for PsA-related symptoms and receiving a diagnosis was less than 6 months for 69 participants, 6 months to 4 years for 68, and 5 years or more for 66.
Typical symptoms, like joint pain, swollen joints, reduced range of motion, and dactylitis, were associated with quicker diagnosis. Turning early to dermatologists and rheumatologists – instead of general practitioners, orthopedics, chiropractors, and others – sped diagnosis, as well. People diagnosed within 6 months also tended to be slightly older, were less likely to be disabled or unemployed, have more education, and were more likely to make $100,000 per year or more.
Vaguer symptoms, such as stiffness, fatigue, and enthesitis-associated foot pain, delayed diagnosis. The longer PsA went unrecognized, the more likely people were to be misdiagnosed with osteoarthritis, psychosomatic disorders, and other problems.
“Increased recognition of heterogeneous symptoms associated with PsA, as well as understanding existing diagnostic barriers, may lead to prompt diagnosis and initiation of appropriate treatment that may improve outcomes,” the investigators concluded.
A prodromal phase
In the Arthritis Care & Research study, investigators led by Lihi Eder, MD, PhD, codirector of the cardio-rheumatology program at Women’s College Hospital, Toronto, used health records and databases to compare primary care histories of 462 Canadian PsA patients in the 5 years before they were diagnosed with 2,310 age- and sex-matched controls without PsA and treated by the same family physicians. The mean age in the study was 54 years, and just over half the subjects were women. Socioeconomic status and rurality were similar between the two groups.
The mean time from the initial primary care visit for a musculoskeletal complaint to rheumatology referral was 513 days among PsA patients, “which was substantially longer than for other inflammatory arthritic conditions, such as rheumatoid arthritis,” Dr. Eder and associates noted.
PsA patients were more than twice as likely to visit primary care for nonspecific musculoskeletal issues in the year before their diagnosis, and more likely in the 5 years prior. The odds of visits to musculoskeletal specialists, joint injections, joint imaging, and ED visits, was also higher as early as 5 years before PsA recognition, and hinted at the impending diagnosis.
“Our study characterized a prediagnosis period in PsA and supports the notion that a prodromal PsA phase occurs in a significant proportion of patients. ... This pattern reveals some of the underlying causes of diagnosis delays of PsA and highlights the need for diagnostic strategies and novel reliable biomarkers to aid in early diagnosis of PsA,” the investigators concluded.
Dr. Ogdie and colleagues suggested that community case searches, public awareness programs, patient education, and referral guidelines for primary care providers might help. They also suggested greater use of validated screening tools, such as the Psoriasis Epidemiology Screening Tool, in primary care.
Dr. Eder had no disclosures, and her study was funded by the Canadian Rheumatology Association. Dr. Ogdie’s study was funded by Novartis, maker of secukinumab (Cosentyx), which is indicated for PsA. She is a consultant for Novartis and has received grant support from the company. One author is an employee.
SOURCES: Ogdie A et al. BMC Rheumatol. 2020 Jan 10. doi: 10.1186/s41927-019-0102-7; Eder L et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24146.
FROM BMC RHEUMATOLOGY AND ARTHRITIS CARE & RESEARCH
Meta-analysis eyes impact of adherence to HCQ among SLE patients
Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.
Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.
“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”
For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.
The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.
In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”
Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A1C.’ ”
She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.
In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”
The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.
SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.
Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.
Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.
“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”
For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.
The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.
In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”
Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A1C.’ ”
She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.
In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”
The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.
SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.
Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.
Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.
“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”
For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.
The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.
In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”
Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A1C.’ ”
She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.
In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”
The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.
SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.
FROM ARTHRITIS CARE & RESEARCH
Value of very early etanercept plus methotrexate not confirmed in real-world RA trial
, investigators say.
A remission rate of 52% was seen with first-line etanercept plus methotrexate, compared with 38% for a strategy of methotrexate escalated to add etanercept in patients not in remission at 24 weeks in the study, known as VEDERA (Very Early Versus Delayed Etanercept in Patients With RA).
Investigators said a difference of 14 percentage points between remission rates was comparable to what was seen among patients with early RA in an earlier randomized trial of etanercept plus methotrexate versus methotrexate monotherapy.
However, the difference was not on par with the “larger than standard” effect of about 30% seen in an exploratory analysis of the very early RA subset in that previous study, according to VEDERA study authors, led by Paul Emery, MD, of the University of Leeds (England).
Taken together, the results highlight a “ceiling effect” in achieving remission in this real-life, treatment-naive cohort, Dr. Emery and coauthors noted in their report, which appears in Annals of the Rheumatic Diseases.
The study population aligned with real-world clinical practice, according to the investigators, who noted that half the cohort had at least one comorbidity.
“This may have partly driven the generally poorer than expected performance, the exact mechanisms for which are unclear,” they wrote in their discussion of results.
Delaying etanercept until failure of methotrexate, instead of giving both drugs up front, was linked to poorer etanercept response in an exploratory analysis of VEDERA. However, Dr. Emery and coinvestigators noted that this finding “requires validation and further investigation.”
While first-line etanercept plus methotrexate is a “clinically appropriate approach” in early RA, results of the VEDERA study don’t help to inform clinicians as to when it would be prudent to select that therapeutic approach, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles.
“Whether you’re treating with methotrexate or methotrexate plus etanercept, they do pretty well,” Dr. Furst said in an interview. “What that says to me is when you have patients with very early RA and the disease is moderately active, you should really try methotrexate before you add expensive other drugs.”
The phase 4, open-label, randomized VEDERA trial included 120 adult patients with new-onset early RA with symptom duration of less than 12 months. All patients in VEDERA had a 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or greater and clinical evidence of synovitis. They were all positive for anti-citrullinated peptide antibody or rheumatoid factor, or had evidence of disease activity in at least one joint by power Doppler ultrasonography.
The patients were randomized to 48 weeks of treatment with either first-line etanercept plus methotrexate, or with methotrexate in a treat-to-target strategy that called for the addition of etanercept if the DAS28-ESR was still 2.6 or greater at 24 weeks.
Based on results of the earlier trial, known as COMET, a confirmatory remission rate in the etanercept plus methotrexate arm was anticipated to be 70%, versus 40% for the methotrexate treat-to-target arm, investigators said in a discussion of their statistical methods.
Study results did not confirm a large effect size, according to the investigators. By week 48, DAS28-ESR remission was achieved in 52% of patients in the first-line etanercept plus methotrexate arm, versus 38% in the methotrexate treat-to-target arm, for an absolute difference of 14 percentage points (odds ratio, 1.73; 95% confidence interval, 0.81-3.70; P = .160).
In early, new-onset RA, remission is the goal, Dr. Emery and coauthors said. The proportions of patients in remission in both arms are “suboptimal rates for the contemporary era,” they wrote.
The escalation to etanercept at week 24 did not improve remission rates appreciably, with about 60% still failing to achieve that endpoint. However, an exploratory analysis suggested the subsequent 24 weeks of etanercept exposure in those escalated patients was associated with a lower rate of remission, compared with 24 weeks of etanercept in the front-line approach, investigators said.
In that analysis, the adjusted odds ratio of achieving DAS28-ESR remission was 2.84 (95% CI, 0.84-9.60) in favor of the first-line etanercept approach.
Dr. Furst said in the interview that the VEDERA results are subject to the inherent biases of an open-label study. He also suggested that further investigations could compare the two first-line treatment approaches specifically in very early RA patients with markers of more severe disease.
“That’s the only way I would think we might gain a little bit more, but so far, these data don’t support getting terribly aggressive,” he said.
The study was funded through an investigator-sponsored research grant provided by Pfizer. Three authors disclosed financial relationships with multiple pharmaceutical companies that market drugs for RA, including Pfizer.
SOURCE: Emery P et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216539.
, investigators say.
A remission rate of 52% was seen with first-line etanercept plus methotrexate, compared with 38% for a strategy of methotrexate escalated to add etanercept in patients not in remission at 24 weeks in the study, known as VEDERA (Very Early Versus Delayed Etanercept in Patients With RA).
Investigators said a difference of 14 percentage points between remission rates was comparable to what was seen among patients with early RA in an earlier randomized trial of etanercept plus methotrexate versus methotrexate monotherapy.
However, the difference was not on par with the “larger than standard” effect of about 30% seen in an exploratory analysis of the very early RA subset in that previous study, according to VEDERA study authors, led by Paul Emery, MD, of the University of Leeds (England).
Taken together, the results highlight a “ceiling effect” in achieving remission in this real-life, treatment-naive cohort, Dr. Emery and coauthors noted in their report, which appears in Annals of the Rheumatic Diseases.
The study population aligned with real-world clinical practice, according to the investigators, who noted that half the cohort had at least one comorbidity.
“This may have partly driven the generally poorer than expected performance, the exact mechanisms for which are unclear,” they wrote in their discussion of results.
Delaying etanercept until failure of methotrexate, instead of giving both drugs up front, was linked to poorer etanercept response in an exploratory analysis of VEDERA. However, Dr. Emery and coinvestigators noted that this finding “requires validation and further investigation.”
While first-line etanercept plus methotrexate is a “clinically appropriate approach” in early RA, results of the VEDERA study don’t help to inform clinicians as to when it would be prudent to select that therapeutic approach, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles.
“Whether you’re treating with methotrexate or methotrexate plus etanercept, they do pretty well,” Dr. Furst said in an interview. “What that says to me is when you have patients with very early RA and the disease is moderately active, you should really try methotrexate before you add expensive other drugs.”
The phase 4, open-label, randomized VEDERA trial included 120 adult patients with new-onset early RA with symptom duration of less than 12 months. All patients in VEDERA had a 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or greater and clinical evidence of synovitis. They were all positive for anti-citrullinated peptide antibody or rheumatoid factor, or had evidence of disease activity in at least one joint by power Doppler ultrasonography.
The patients were randomized to 48 weeks of treatment with either first-line etanercept plus methotrexate, or with methotrexate in a treat-to-target strategy that called for the addition of etanercept if the DAS28-ESR was still 2.6 or greater at 24 weeks.
Based on results of the earlier trial, known as COMET, a confirmatory remission rate in the etanercept plus methotrexate arm was anticipated to be 70%, versus 40% for the methotrexate treat-to-target arm, investigators said in a discussion of their statistical methods.
Study results did not confirm a large effect size, according to the investigators. By week 48, DAS28-ESR remission was achieved in 52% of patients in the first-line etanercept plus methotrexate arm, versus 38% in the methotrexate treat-to-target arm, for an absolute difference of 14 percentage points (odds ratio, 1.73; 95% confidence interval, 0.81-3.70; P = .160).
In early, new-onset RA, remission is the goal, Dr. Emery and coauthors said. The proportions of patients in remission in both arms are “suboptimal rates for the contemporary era,” they wrote.
The escalation to etanercept at week 24 did not improve remission rates appreciably, with about 60% still failing to achieve that endpoint. However, an exploratory analysis suggested the subsequent 24 weeks of etanercept exposure in those escalated patients was associated with a lower rate of remission, compared with 24 weeks of etanercept in the front-line approach, investigators said.
In that analysis, the adjusted odds ratio of achieving DAS28-ESR remission was 2.84 (95% CI, 0.84-9.60) in favor of the first-line etanercept approach.
Dr. Furst said in the interview that the VEDERA results are subject to the inherent biases of an open-label study. He also suggested that further investigations could compare the two first-line treatment approaches specifically in very early RA patients with markers of more severe disease.
“That’s the only way I would think we might gain a little bit more, but so far, these data don’t support getting terribly aggressive,” he said.
The study was funded through an investigator-sponsored research grant provided by Pfizer. Three authors disclosed financial relationships with multiple pharmaceutical companies that market drugs for RA, including Pfizer.
SOURCE: Emery P et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216539.
, investigators say.
A remission rate of 52% was seen with first-line etanercept plus methotrexate, compared with 38% for a strategy of methotrexate escalated to add etanercept in patients not in remission at 24 weeks in the study, known as VEDERA (Very Early Versus Delayed Etanercept in Patients With RA).
Investigators said a difference of 14 percentage points between remission rates was comparable to what was seen among patients with early RA in an earlier randomized trial of etanercept plus methotrexate versus methotrexate monotherapy.
However, the difference was not on par with the “larger than standard” effect of about 30% seen in an exploratory analysis of the very early RA subset in that previous study, according to VEDERA study authors, led by Paul Emery, MD, of the University of Leeds (England).
Taken together, the results highlight a “ceiling effect” in achieving remission in this real-life, treatment-naive cohort, Dr. Emery and coauthors noted in their report, which appears in Annals of the Rheumatic Diseases.
The study population aligned with real-world clinical practice, according to the investigators, who noted that half the cohort had at least one comorbidity.
“This may have partly driven the generally poorer than expected performance, the exact mechanisms for which are unclear,” they wrote in their discussion of results.
Delaying etanercept until failure of methotrexate, instead of giving both drugs up front, was linked to poorer etanercept response in an exploratory analysis of VEDERA. However, Dr. Emery and coinvestigators noted that this finding “requires validation and further investigation.”
While first-line etanercept plus methotrexate is a “clinically appropriate approach” in early RA, results of the VEDERA study don’t help to inform clinicians as to when it would be prudent to select that therapeutic approach, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles.
“Whether you’re treating with methotrexate or methotrexate plus etanercept, they do pretty well,” Dr. Furst said in an interview. “What that says to me is when you have patients with very early RA and the disease is moderately active, you should really try methotrexate before you add expensive other drugs.”
The phase 4, open-label, randomized VEDERA trial included 120 adult patients with new-onset early RA with symptom duration of less than 12 months. All patients in VEDERA had a 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or greater and clinical evidence of synovitis. They were all positive for anti-citrullinated peptide antibody or rheumatoid factor, or had evidence of disease activity in at least one joint by power Doppler ultrasonography.
The patients were randomized to 48 weeks of treatment with either first-line etanercept plus methotrexate, or with methotrexate in a treat-to-target strategy that called for the addition of etanercept if the DAS28-ESR was still 2.6 or greater at 24 weeks.
Based on results of the earlier trial, known as COMET, a confirmatory remission rate in the etanercept plus methotrexate arm was anticipated to be 70%, versus 40% for the methotrexate treat-to-target arm, investigators said in a discussion of their statistical methods.
Study results did not confirm a large effect size, according to the investigators. By week 48, DAS28-ESR remission was achieved in 52% of patients in the first-line etanercept plus methotrexate arm, versus 38% in the methotrexate treat-to-target arm, for an absolute difference of 14 percentage points (odds ratio, 1.73; 95% confidence interval, 0.81-3.70; P = .160).
In early, new-onset RA, remission is the goal, Dr. Emery and coauthors said. The proportions of patients in remission in both arms are “suboptimal rates for the contemporary era,” they wrote.
The escalation to etanercept at week 24 did not improve remission rates appreciably, with about 60% still failing to achieve that endpoint. However, an exploratory analysis suggested the subsequent 24 weeks of etanercept exposure in those escalated patients was associated with a lower rate of remission, compared with 24 weeks of etanercept in the front-line approach, investigators said.
In that analysis, the adjusted odds ratio of achieving DAS28-ESR remission was 2.84 (95% CI, 0.84-9.60) in favor of the first-line etanercept approach.
Dr. Furst said in the interview that the VEDERA results are subject to the inherent biases of an open-label study. He also suggested that further investigations could compare the two first-line treatment approaches specifically in very early RA patients with markers of more severe disease.
“That’s the only way I would think we might gain a little bit more, but so far, these data don’t support getting terribly aggressive,” he said.
The study was funded through an investigator-sponsored research grant provided by Pfizer. Three authors disclosed financial relationships with multiple pharmaceutical companies that market drugs for RA, including Pfizer.
SOURCE: Emery P et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216539.
FROM ANNALS OF THE RHEUMATIC DISEASES
Hypertensive disorders of pregnancy in SLE contribute to later CV outcomes
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
FROM ARTHRITIS CARE & RESEARCH
Multiple assessment measures can hone RA treatment
Combining the measures of the Clinical Disease Activity Index and the Disease Activity Score in 28 joints provides an opportunity adjust treatment for patients with RA, based on data from a cross-sectional study of 1,585 adults.
Although the Clinical Disease Activity Index (CDAI) is considered more stringent, comparisons with the Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) outside of clinical trials are limited, wrote Satoshi Takanashi, MD, of Keio University School of Medicine in Tokyo, and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from 1,585 consecutive RA patients seen at Keio University Hospital in Tokyo. The average age of the patients was 64 years, 84% were women, and the average duration of disease was 12 years.
Overall, more patients met the CDAI remission criteria but not the DAS28-ESR criteria, with the exception of patients treated with an interleukin-6 inhibitor.
Of the patients in remission based on CDAI, the proportion who were not in DAS28-ESR remission was 19.4% for those treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 18.2% for tumor necrosis factor inhibitors, 4.2% for IL-6 inhibitors, 27.6% for CTLA4-Ig fusion protein, and 33.3% for Janus kinase inhibitors.
Of the patients in DAS28-ESR remission, those not also in CDAI remission totaled 11.7% with csDMARDs, 15.4% with tumor necrosis factor inhibitors, 29.5% with IL-6 inhibitors, 16.0% with CTLA4-Ig, and 14.3% with Janus kinase inhibitors.
“The fact that many patients fulfilled the CDAI but not DAS28-ESR remission could be explained by several reasons including residual synovitis in joints that are not included in the main 28 joints, which could lead to an increase in acute phase reactants and elevate only DAS28-ESR, extra-articular involvement or other comorbidities that could elevate the C-reactive protein irrelevant to arthritis,” the researchers noted. The prevalence of complications was higher in patients in CDAI remission and DAS28-ESR nonremission independent of rheumatoid or nonrheumatoid comorbid conditions, they added.
The findings were limited by several factors, including the cross-sectional study design that did not evaluate longitudinal radiological and functional progression, the researchers wrote.
“However, patients in both CDAI and DAS28-ESR remission were apparently in better condition than those who met either criteria; therefore, in the management of rheumatoid arthritis, assessing patients with two composite measures can yield important opportunities to consider what causes the discrepancy between the measures and adjust treatment appropriately,” they concluded.
The authors did not report having a specific grant for this research. Two of the paper’s three authors disclosed relationships with multiple companies that market drugs for RA.
SOURCE: Takanashi S et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216607.
Combining the measures of the Clinical Disease Activity Index and the Disease Activity Score in 28 joints provides an opportunity adjust treatment for patients with RA, based on data from a cross-sectional study of 1,585 adults.
Although the Clinical Disease Activity Index (CDAI) is considered more stringent, comparisons with the Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) outside of clinical trials are limited, wrote Satoshi Takanashi, MD, of Keio University School of Medicine in Tokyo, and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from 1,585 consecutive RA patients seen at Keio University Hospital in Tokyo. The average age of the patients was 64 years, 84% were women, and the average duration of disease was 12 years.
Overall, more patients met the CDAI remission criteria but not the DAS28-ESR criteria, with the exception of patients treated with an interleukin-6 inhibitor.
Of the patients in remission based on CDAI, the proportion who were not in DAS28-ESR remission was 19.4% for those treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 18.2% for tumor necrosis factor inhibitors, 4.2% for IL-6 inhibitors, 27.6% for CTLA4-Ig fusion protein, and 33.3% for Janus kinase inhibitors.
Of the patients in DAS28-ESR remission, those not also in CDAI remission totaled 11.7% with csDMARDs, 15.4% with tumor necrosis factor inhibitors, 29.5% with IL-6 inhibitors, 16.0% with CTLA4-Ig, and 14.3% with Janus kinase inhibitors.
“The fact that many patients fulfilled the CDAI but not DAS28-ESR remission could be explained by several reasons including residual synovitis in joints that are not included in the main 28 joints, which could lead to an increase in acute phase reactants and elevate only DAS28-ESR, extra-articular involvement or other comorbidities that could elevate the C-reactive protein irrelevant to arthritis,” the researchers noted. The prevalence of complications was higher in patients in CDAI remission and DAS28-ESR nonremission independent of rheumatoid or nonrheumatoid comorbid conditions, they added.
The findings were limited by several factors, including the cross-sectional study design that did not evaluate longitudinal radiological and functional progression, the researchers wrote.
“However, patients in both CDAI and DAS28-ESR remission were apparently in better condition than those who met either criteria; therefore, in the management of rheumatoid arthritis, assessing patients with two composite measures can yield important opportunities to consider what causes the discrepancy between the measures and adjust treatment appropriately,” they concluded.
The authors did not report having a specific grant for this research. Two of the paper’s three authors disclosed relationships with multiple companies that market drugs for RA.
SOURCE: Takanashi S et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216607.
Combining the measures of the Clinical Disease Activity Index and the Disease Activity Score in 28 joints provides an opportunity adjust treatment for patients with RA, based on data from a cross-sectional study of 1,585 adults.
Although the Clinical Disease Activity Index (CDAI) is considered more stringent, comparisons with the Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) outside of clinical trials are limited, wrote Satoshi Takanashi, MD, of Keio University School of Medicine in Tokyo, and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from 1,585 consecutive RA patients seen at Keio University Hospital in Tokyo. The average age of the patients was 64 years, 84% were women, and the average duration of disease was 12 years.
Overall, more patients met the CDAI remission criteria but not the DAS28-ESR criteria, with the exception of patients treated with an interleukin-6 inhibitor.
Of the patients in remission based on CDAI, the proportion who were not in DAS28-ESR remission was 19.4% for those treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 18.2% for tumor necrosis factor inhibitors, 4.2% for IL-6 inhibitors, 27.6% for CTLA4-Ig fusion protein, and 33.3% for Janus kinase inhibitors.
Of the patients in DAS28-ESR remission, those not also in CDAI remission totaled 11.7% with csDMARDs, 15.4% with tumor necrosis factor inhibitors, 29.5% with IL-6 inhibitors, 16.0% with CTLA4-Ig, and 14.3% with Janus kinase inhibitors.
“The fact that many patients fulfilled the CDAI but not DAS28-ESR remission could be explained by several reasons including residual synovitis in joints that are not included in the main 28 joints, which could lead to an increase in acute phase reactants and elevate only DAS28-ESR, extra-articular involvement or other comorbidities that could elevate the C-reactive protein irrelevant to arthritis,” the researchers noted. The prevalence of complications was higher in patients in CDAI remission and DAS28-ESR nonremission independent of rheumatoid or nonrheumatoid comorbid conditions, they added.
The findings were limited by several factors, including the cross-sectional study design that did not evaluate longitudinal radiological and functional progression, the researchers wrote.
“However, patients in both CDAI and DAS28-ESR remission were apparently in better condition than those who met either criteria; therefore, in the management of rheumatoid arthritis, assessing patients with two composite measures can yield important opportunities to consider what causes the discrepancy between the measures and adjust treatment appropriately,” they concluded.
The authors did not report having a specific grant for this research. Two of the paper’s three authors disclosed relationships with multiple companies that market drugs for RA.
SOURCE: Takanashi S et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216607.
FROM ANNALS OF THE RHEUMATIC DISEASES
Zoledronate promotes postdenosumab bone retention
Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.
Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.
In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.
At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.
All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.
The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.
A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”
The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.
SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.
Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.
Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.
In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.
At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.
All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.
The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.
A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”
The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.
SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.
Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.
Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.
In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.
At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.
All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.
The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.
A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”
The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.
SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
Psoriasis: A look back over the past 50 years, and forward to next steps
Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.
Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.
“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.
“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”
said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.
There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.
In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”
In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.
“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.
Enter the biologics era
The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.
Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.
His colleague Alice B. Gottlieb, MD, PhD, was among the pioneers in the development of TNF blockers for the treatment of psoriasis. Her seminal, investigator-initiated paper on the efficacy and safety of infliximab (Remicade) monotherapy for plaque-type psoriasis published in the Lancet in 2001 helped launch the current era in which many psoriasis patients achieve 100% PASI responses with limited side effects, he said, explaining that subsequent research elucidated the role of IL-12 and -23 – leading to effective treatments like ustekinumab (Stelara), and later IL-17, which is, “in fact, the molecule closest to the pathogenesis of psoriasis.”
“If you block IL-17, you get rid of psoriasis,” he said, noting that there are now several companies with approved antibodies to IL-17. “Taltz [ixekizumab] and Cosentyx [secukinumab] are the leading ones, and Siliq [brodalumab] blocks the receptor for IL-17, so it is very effective.”
Another novel biologic – bimekizumab – is on the horizon. It blocks both IL-17a and IL-17f, and appears highly effective in psoriasis and psoriatic arthritis (PsA). “Biologics were the real start of the [psoriasis treatment] revolution,” he said. “When I started out I would speak at patient meetings and the patients were angry at their physicians; they thought they weren’t aggressive enough, they were very frustrated.”
Dr. Lebwohl described patients he would see at annual National Psoriasis Foundation meetings: “There were patients in wheel chairs, because they couldn’t walk. They would be red and scaly all over ... you could have literally swept up scale like it was snow after one of those meetings.
“You go forward to around 2010 – nobody’s in wheelchairs anymore, everybody has clear skin, and it’s become a party; patients are no longer angry – they are thrilled with the results they are getting from much safer and much more effective drugs,” he said. “So it’s been a pleasure taking care of those patients and going from a very difficult time of treating them, to a time where we’ve done a great job treating them.”
Dr. Lebwohl noted that a “large number of dermatologists have been involved with the development of these drugs and making sure they succeed, and that has also been a pleasure to see.”
Dr. Gottlieb, who Dr. Lebwohl has described as “a superstar” in the fields of dermatology and rheumatology, is one such researcher. In an interview, she looked back on her work and the ways that her work “opened the field,” led to many of her trainees also doing “great work,” and changed the lives of patients.
“It’s nice to feel that I really did change, fundamentally, how psoriasis patients are treated,” said Dr. Gottlieb, who is a clinical professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai. “That obviously feels great.”
She recalled a patient – “a 6-foot-5 biker with bad psoriasis” – who “literally, the minute the door closed, he was crying about how horrible his disease was.”
“And I cleared him ... and then you get big hugs – it just feels extremely good ... giving somebody their life back,” she said.
Dr. Gottlieb has been involved in much of the work in developing biologics for psoriasis, including the ongoing work with bimekizumab for PsA as mentioned by Dr. Lebwohl.
If the phase 2 data with bimekizumab are replicated in the ongoing phase 3 trials now underway at her center, “that can really raise the bar ... so if it’s reproducible, it’s very exciting.”
“It’s exciting to have an IL-23 blocker that, at least in clinical trials, showed inhibition of radiographic progression [in PsA],” she said. “That’s guselkumab those data are already out, and I was involved with that.”
The early work of Dr. Gottlieb and others has also “spread to other diseases,” like hidradenitis suppurativa and atopic dermatitis, she said, noting that numerous studies are underway.
Aside from curing all patients, her ultimate goal is getting to a point where psoriasis has no effect on patients’ quality of life.
“And I see it already,” she said. “It’s happening, and it’s nice to see that it’s happening in children now, too; several of the drugs are approved in kids.”
Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.
“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”
It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.
“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”
Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.
Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.
Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.
Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.
Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.
“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.
Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.
He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.
It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”
“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.
That research is underway, and the future looks bright – and clear.
“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”
In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”
All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.
Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.
Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.
“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.
“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”
said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.
There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.
In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”
In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.
“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.
Enter the biologics era
The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.
Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.
His colleague Alice B. Gottlieb, MD, PhD, was among the pioneers in the development of TNF blockers for the treatment of psoriasis. Her seminal, investigator-initiated paper on the efficacy and safety of infliximab (Remicade) monotherapy for plaque-type psoriasis published in the Lancet in 2001 helped launch the current era in which many psoriasis patients achieve 100% PASI responses with limited side effects, he said, explaining that subsequent research elucidated the role of IL-12 and -23 – leading to effective treatments like ustekinumab (Stelara), and later IL-17, which is, “in fact, the molecule closest to the pathogenesis of psoriasis.”
“If you block IL-17, you get rid of psoriasis,” he said, noting that there are now several companies with approved antibodies to IL-17. “Taltz [ixekizumab] and Cosentyx [secukinumab] are the leading ones, and Siliq [brodalumab] blocks the receptor for IL-17, so it is very effective.”
Another novel biologic – bimekizumab – is on the horizon. It blocks both IL-17a and IL-17f, and appears highly effective in psoriasis and psoriatic arthritis (PsA). “Biologics were the real start of the [psoriasis treatment] revolution,” he said. “When I started out I would speak at patient meetings and the patients were angry at their physicians; they thought they weren’t aggressive enough, they were very frustrated.”
Dr. Lebwohl described patients he would see at annual National Psoriasis Foundation meetings: “There were patients in wheel chairs, because they couldn’t walk. They would be red and scaly all over ... you could have literally swept up scale like it was snow after one of those meetings.
“You go forward to around 2010 – nobody’s in wheelchairs anymore, everybody has clear skin, and it’s become a party; patients are no longer angry – they are thrilled with the results they are getting from much safer and much more effective drugs,” he said. “So it’s been a pleasure taking care of those patients and going from a very difficult time of treating them, to a time where we’ve done a great job treating them.”
Dr. Lebwohl noted that a “large number of dermatologists have been involved with the development of these drugs and making sure they succeed, and that has also been a pleasure to see.”
Dr. Gottlieb, who Dr. Lebwohl has described as “a superstar” in the fields of dermatology and rheumatology, is one such researcher. In an interview, she looked back on her work and the ways that her work “opened the field,” led to many of her trainees also doing “great work,” and changed the lives of patients.
“It’s nice to feel that I really did change, fundamentally, how psoriasis patients are treated,” said Dr. Gottlieb, who is a clinical professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai. “That obviously feels great.”
She recalled a patient – “a 6-foot-5 biker with bad psoriasis” – who “literally, the minute the door closed, he was crying about how horrible his disease was.”
“And I cleared him ... and then you get big hugs – it just feels extremely good ... giving somebody their life back,” she said.
Dr. Gottlieb has been involved in much of the work in developing biologics for psoriasis, including the ongoing work with bimekizumab for PsA as mentioned by Dr. Lebwohl.
If the phase 2 data with bimekizumab are replicated in the ongoing phase 3 trials now underway at her center, “that can really raise the bar ... so if it’s reproducible, it’s very exciting.”
“It’s exciting to have an IL-23 blocker that, at least in clinical trials, showed inhibition of radiographic progression [in PsA],” she said. “That’s guselkumab those data are already out, and I was involved with that.”
The early work of Dr. Gottlieb and others has also “spread to other diseases,” like hidradenitis suppurativa and atopic dermatitis, she said, noting that numerous studies are underway.
Aside from curing all patients, her ultimate goal is getting to a point where psoriasis has no effect on patients’ quality of life.
“And I see it already,” she said. “It’s happening, and it’s nice to see that it’s happening in children now, too; several of the drugs are approved in kids.”
Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.
“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”
It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.
“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”
Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.
Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.
Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.
Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.
Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.
“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.
Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.
He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.
It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”
“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.
That research is underway, and the future looks bright – and clear.
“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”
In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”
All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.
Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.
Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.
“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.
“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”
said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.
There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.
In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”
In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.
“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.
Enter the biologics era
The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.
Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.
His colleague Alice B. Gottlieb, MD, PhD, was among the pioneers in the development of TNF blockers for the treatment of psoriasis. Her seminal, investigator-initiated paper on the efficacy and safety of infliximab (Remicade) monotherapy for plaque-type psoriasis published in the Lancet in 2001 helped launch the current era in which many psoriasis patients achieve 100% PASI responses with limited side effects, he said, explaining that subsequent research elucidated the role of IL-12 and -23 – leading to effective treatments like ustekinumab (Stelara), and later IL-17, which is, “in fact, the molecule closest to the pathogenesis of psoriasis.”
“If you block IL-17, you get rid of psoriasis,” he said, noting that there are now several companies with approved antibodies to IL-17. “Taltz [ixekizumab] and Cosentyx [secukinumab] are the leading ones, and Siliq [brodalumab] blocks the receptor for IL-17, so it is very effective.”
Another novel biologic – bimekizumab – is on the horizon. It blocks both IL-17a and IL-17f, and appears highly effective in psoriasis and psoriatic arthritis (PsA). “Biologics were the real start of the [psoriasis treatment] revolution,” he said. “When I started out I would speak at patient meetings and the patients were angry at their physicians; they thought they weren’t aggressive enough, they were very frustrated.”
Dr. Lebwohl described patients he would see at annual National Psoriasis Foundation meetings: “There were patients in wheel chairs, because they couldn’t walk. They would be red and scaly all over ... you could have literally swept up scale like it was snow after one of those meetings.
“You go forward to around 2010 – nobody’s in wheelchairs anymore, everybody has clear skin, and it’s become a party; patients are no longer angry – they are thrilled with the results they are getting from much safer and much more effective drugs,” he said. “So it’s been a pleasure taking care of those patients and going from a very difficult time of treating them, to a time where we’ve done a great job treating them.”
Dr. Lebwohl noted that a “large number of dermatologists have been involved with the development of these drugs and making sure they succeed, and that has also been a pleasure to see.”
Dr. Gottlieb, who Dr. Lebwohl has described as “a superstar” in the fields of dermatology and rheumatology, is one such researcher. In an interview, she looked back on her work and the ways that her work “opened the field,” led to many of her trainees also doing “great work,” and changed the lives of patients.
“It’s nice to feel that I really did change, fundamentally, how psoriasis patients are treated,” said Dr. Gottlieb, who is a clinical professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai. “That obviously feels great.”
She recalled a patient – “a 6-foot-5 biker with bad psoriasis” – who “literally, the minute the door closed, he was crying about how horrible his disease was.”
“And I cleared him ... and then you get big hugs – it just feels extremely good ... giving somebody their life back,” she said.
Dr. Gottlieb has been involved in much of the work in developing biologics for psoriasis, including the ongoing work with bimekizumab for PsA as mentioned by Dr. Lebwohl.
If the phase 2 data with bimekizumab are replicated in the ongoing phase 3 trials now underway at her center, “that can really raise the bar ... so if it’s reproducible, it’s very exciting.”
“It’s exciting to have an IL-23 blocker that, at least in clinical trials, showed inhibition of radiographic progression [in PsA],” she said. “That’s guselkumab those data are already out, and I was involved with that.”
The early work of Dr. Gottlieb and others has also “spread to other diseases,” like hidradenitis suppurativa and atopic dermatitis, she said, noting that numerous studies are underway.
Aside from curing all patients, her ultimate goal is getting to a point where psoriasis has no effect on patients’ quality of life.
“And I see it already,” she said. “It’s happening, and it’s nice to see that it’s happening in children now, too; several of the drugs are approved in kids.”
Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.
“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”
It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.
“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”
Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.
Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.
Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.
Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.
Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.
“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.
Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.
He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.
It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”
“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.
That research is underway, and the future looks bright – and clear.
“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”
In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”
All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.
Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
ATLANTA – Psoriasis type and patient age at presentation among patients with psoriatic arthritis predict the timing of arthritis symptom synchronicity, according to findings from the Psoriatic Arthritis Registry of Turkey International Database.
However, in those who develop arthritis symptoms first, age at onset is not predictive of psoriatic arthritis (PsA) symptom synchronicity, Umut Kalyoncu, MD, reported at the annual meeting of the American College of Rheumatology.
Of 1,631 patients from the registry, 1,251 had psoriasis first, 71 had arthritis first, and 309 had synchronous onset, which was defined as the onset of both psoriasis and arthritis symptoms within a 12-month period. The time from skin disease to PsA was 155.6 months, –67.4 months, and 1.8 months, among the groups, respectively, and the mean age at PsA onset was similar, ranging from about 41 to 42 years in those who developed arthritis first, said Dr. Kalyoncu, of the department of rheumatology at Hacettepe University, Ankara, Turkey.
However, the mean age of PsA onset among those who developed psoriasis first was 29.4 years, compared with 46.3 years in those who developed arthritis first.
“So there is a really big difference between psoriasis beginning age,” he said.
PsA types also differed by onset symptoms: Axial involvement was more common with arthritis-first onset at 38.0%, compared with 28.8% for psoriasis first and 27.8% for synchronous onset). Oligoarthritis occurred more often with arthritis-first onset (45.1% vs. 30.7% and 29.4%, respectively), and polyarthritis occurred less often with arthritis-first onset (33.8% vs. 49.4% and 47.6%, respectively), he said.
Psoriasis type also differed among the groups: Pustular skin involvement was more common in arthritis-first patients (18.3% vs. 11.9% and 16.5% of psoriasis-first and synchronous-onset patients), scalp lesions as the initial lesion were more common in psoriasis-first patients (48.3% vs. 35.2% of arthritis-first patients and 39.8% of synchronous-onset patients), and genital involvement was present more often in arthritis-first patients (12.7% vs. 6.2% and 4.9% of psoriasis-first and synchronous-onset patients).
Early-onset (type 1) psoriasis was more common in psoriasis-first patients (74% vs. 28.1% and 51.8% of arthritis-first and synchronous-onset patients), whereas late-onset (type 2) psoriasis was more common in arthritis-first patients (71.9% vs. 26.0% and 48.2% for psoriasis-first and synchronous-onset patients).
A family history of psoriasis or PsA was more common in psoriasis-first patients (35.6% vs. 26.3% and 28.2% of arthritis-first and synchronous-onset patients), Dr. Kalyoncu said.
Treatment types did not differ between the groups.
Multiple linear regression analysis for the time elapsed from psoriasis to PsA symptom synchronicity, with all other independent variables set to baseline values, showed an overall intercept interval of 66 months, but with nail involvement, family history, or plaque psoriasis, the interval was extended by 28, 24, and 20 months, respectively. However, the presence of pustular psoriasis decreased the intercept interval by 28 months.
A temporal relationship between the onset of skin psoriasis and PsA is a well-known feature of psoriatic disease, with prior studies showing that the majority of cases involve psoriasis-first onset, Dr. Kalyoncu said, adding that heterogeneity in musculoskeletal and skin involvement is also a known feature.
However, little is known about the role of genetics, he noted.
Therefore, he and his colleagues used the Psoriatic Arthritis Registry of Turkey International Database, which was established in 2014 and now also includes data from patients in Canada and Italy, to explore the associations between disease characteristics and the temporal relationship of skin and musculoskeletal disease.
Based on the findings, age at the onset of psoriasis was the main factor that determined PsA symptom synchronicity, he said.
“We know that HLA-Cw6 is important in genetic susceptibility of psoriatic arthritis, but it is important only for early-onset arthritis, not late-onset psoriasis,” Dr. Kalyoncu said. “So our results make an indirect contribution [to the understanding of] these genetic and immunochemical differences between early-onset and late-onset psoriasis, and we need further future studies about this topic.”
Dr. Kalyoncu reported having no relevant disclosures.
SOURCE: Kalyoncu U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2854.
ATLANTA – Psoriasis type and patient age at presentation among patients with psoriatic arthritis predict the timing of arthritis symptom synchronicity, according to findings from the Psoriatic Arthritis Registry of Turkey International Database.
However, in those who develop arthritis symptoms first, age at onset is not predictive of psoriatic arthritis (PsA) symptom synchronicity, Umut Kalyoncu, MD, reported at the annual meeting of the American College of Rheumatology.
Of 1,631 patients from the registry, 1,251 had psoriasis first, 71 had arthritis first, and 309 had synchronous onset, which was defined as the onset of both psoriasis and arthritis symptoms within a 12-month period. The time from skin disease to PsA was 155.6 months, –67.4 months, and 1.8 months, among the groups, respectively, and the mean age at PsA onset was similar, ranging from about 41 to 42 years in those who developed arthritis first, said Dr. Kalyoncu, of the department of rheumatology at Hacettepe University, Ankara, Turkey.
However, the mean age of PsA onset among those who developed psoriasis first was 29.4 years, compared with 46.3 years in those who developed arthritis first.
“So there is a really big difference between psoriasis beginning age,” he said.
PsA types also differed by onset symptoms: Axial involvement was more common with arthritis-first onset at 38.0%, compared with 28.8% for psoriasis first and 27.8% for synchronous onset). Oligoarthritis occurred more often with arthritis-first onset (45.1% vs. 30.7% and 29.4%, respectively), and polyarthritis occurred less often with arthritis-first onset (33.8% vs. 49.4% and 47.6%, respectively), he said.
Psoriasis type also differed among the groups: Pustular skin involvement was more common in arthritis-first patients (18.3% vs. 11.9% and 16.5% of psoriasis-first and synchronous-onset patients), scalp lesions as the initial lesion were more common in psoriasis-first patients (48.3% vs. 35.2% of arthritis-first patients and 39.8% of synchronous-onset patients), and genital involvement was present more often in arthritis-first patients (12.7% vs. 6.2% and 4.9% of psoriasis-first and synchronous-onset patients).
Early-onset (type 1) psoriasis was more common in psoriasis-first patients (74% vs. 28.1% and 51.8% of arthritis-first and synchronous-onset patients), whereas late-onset (type 2) psoriasis was more common in arthritis-first patients (71.9% vs. 26.0% and 48.2% for psoriasis-first and synchronous-onset patients).
A family history of psoriasis or PsA was more common in psoriasis-first patients (35.6% vs. 26.3% and 28.2% of arthritis-first and synchronous-onset patients), Dr. Kalyoncu said.
Treatment types did not differ between the groups.
Multiple linear regression analysis for the time elapsed from psoriasis to PsA symptom synchronicity, with all other independent variables set to baseline values, showed an overall intercept interval of 66 months, but with nail involvement, family history, or plaque psoriasis, the interval was extended by 28, 24, and 20 months, respectively. However, the presence of pustular psoriasis decreased the intercept interval by 28 months.
A temporal relationship between the onset of skin psoriasis and PsA is a well-known feature of psoriatic disease, with prior studies showing that the majority of cases involve psoriasis-first onset, Dr. Kalyoncu said, adding that heterogeneity in musculoskeletal and skin involvement is also a known feature.
However, little is known about the role of genetics, he noted.
Therefore, he and his colleagues used the Psoriatic Arthritis Registry of Turkey International Database, which was established in 2014 and now also includes data from patients in Canada and Italy, to explore the associations between disease characteristics and the temporal relationship of skin and musculoskeletal disease.
Based on the findings, age at the onset of psoriasis was the main factor that determined PsA symptom synchronicity, he said.
“We know that HLA-Cw6 is important in genetic susceptibility of psoriatic arthritis, but it is important only for early-onset arthritis, not late-onset psoriasis,” Dr. Kalyoncu said. “So our results make an indirect contribution [to the understanding of] these genetic and immunochemical differences between early-onset and late-onset psoriasis, and we need further future studies about this topic.”
Dr. Kalyoncu reported having no relevant disclosures.
SOURCE: Kalyoncu U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2854.
ATLANTA – Psoriasis type and patient age at presentation among patients with psoriatic arthritis predict the timing of arthritis symptom synchronicity, according to findings from the Psoriatic Arthritis Registry of Turkey International Database.
However, in those who develop arthritis symptoms first, age at onset is not predictive of psoriatic arthritis (PsA) symptom synchronicity, Umut Kalyoncu, MD, reported at the annual meeting of the American College of Rheumatology.
Of 1,631 patients from the registry, 1,251 had psoriasis first, 71 had arthritis first, and 309 had synchronous onset, which was defined as the onset of both psoriasis and arthritis symptoms within a 12-month period. The time from skin disease to PsA was 155.6 months, –67.4 months, and 1.8 months, among the groups, respectively, and the mean age at PsA onset was similar, ranging from about 41 to 42 years in those who developed arthritis first, said Dr. Kalyoncu, of the department of rheumatology at Hacettepe University, Ankara, Turkey.
However, the mean age of PsA onset among those who developed psoriasis first was 29.4 years, compared with 46.3 years in those who developed arthritis first.
“So there is a really big difference between psoriasis beginning age,” he said.
PsA types also differed by onset symptoms: Axial involvement was more common with arthritis-first onset at 38.0%, compared with 28.8% for psoriasis first and 27.8% for synchronous onset). Oligoarthritis occurred more often with arthritis-first onset (45.1% vs. 30.7% and 29.4%, respectively), and polyarthritis occurred less often with arthritis-first onset (33.8% vs. 49.4% and 47.6%, respectively), he said.
Psoriasis type also differed among the groups: Pustular skin involvement was more common in arthritis-first patients (18.3% vs. 11.9% and 16.5% of psoriasis-first and synchronous-onset patients), scalp lesions as the initial lesion were more common in psoriasis-first patients (48.3% vs. 35.2% of arthritis-first patients and 39.8% of synchronous-onset patients), and genital involvement was present more often in arthritis-first patients (12.7% vs. 6.2% and 4.9% of psoriasis-first and synchronous-onset patients).
Early-onset (type 1) psoriasis was more common in psoriasis-first patients (74% vs. 28.1% and 51.8% of arthritis-first and synchronous-onset patients), whereas late-onset (type 2) psoriasis was more common in arthritis-first patients (71.9% vs. 26.0% and 48.2% for psoriasis-first and synchronous-onset patients).
A family history of psoriasis or PsA was more common in psoriasis-first patients (35.6% vs. 26.3% and 28.2% of arthritis-first and synchronous-onset patients), Dr. Kalyoncu said.
Treatment types did not differ between the groups.
Multiple linear regression analysis for the time elapsed from psoriasis to PsA symptom synchronicity, with all other independent variables set to baseline values, showed an overall intercept interval of 66 months, but with nail involvement, family history, or plaque psoriasis, the interval was extended by 28, 24, and 20 months, respectively. However, the presence of pustular psoriasis decreased the intercept interval by 28 months.
A temporal relationship between the onset of skin psoriasis and PsA is a well-known feature of psoriatic disease, with prior studies showing that the majority of cases involve psoriasis-first onset, Dr. Kalyoncu said, adding that heterogeneity in musculoskeletal and skin involvement is also a known feature.
However, little is known about the role of genetics, he noted.
Therefore, he and his colleagues used the Psoriatic Arthritis Registry of Turkey International Database, which was established in 2014 and now also includes data from patients in Canada and Italy, to explore the associations between disease characteristics and the temporal relationship of skin and musculoskeletal disease.
Based on the findings, age at the onset of psoriasis was the main factor that determined PsA symptom synchronicity, he said.
“We know that HLA-Cw6 is important in genetic susceptibility of psoriatic arthritis, but it is important only for early-onset arthritis, not late-onset psoriasis,” Dr. Kalyoncu said. “So our results make an indirect contribution [to the understanding of] these genetic and immunochemical differences between early-onset and late-onset psoriasis, and we need further future studies about this topic.”
Dr. Kalyoncu reported having no relevant disclosures.
SOURCE: Kalyoncu U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2854.
REPORTING FROM ACR 2019
What happens to clinically suspected arthralgia patients without RA?
About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.
“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.
The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.
Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.
There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.
“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.
The study was sponsored by the European Research Council. The authors had no relevant disclosures.
SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.
About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.
“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.
The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.
Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.
There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.
“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.
The study was sponsored by the European Research Council. The authors had no relevant disclosures.
SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.
About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.
“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.
The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.
Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.
There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.
“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.
The study was sponsored by the European Research Council. The authors had no relevant disclosures.
SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.
FROM ARTHRITIS RESEARCH & THERAPY
Value analysis of JAK inhibitors for RA hampered by limited data
Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.
ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.
Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
A pricey comparator
In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.
The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.
“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
Weighing efficacy and cost
Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.
CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).
Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”
After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:
- Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
- Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
- Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.
The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.
ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.
These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.
ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.
Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.
Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.
The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.
ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.
These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.
ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.
Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.
Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.
The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.
ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.
These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.
ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.
Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.
Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.
Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.
ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.
Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
A pricey comparator
In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.
The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.
“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
Weighing efficacy and cost
Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.
CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).
Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”
After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:
- Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
- Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
- Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.
Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.
ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.
Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
A pricey comparator
In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.
The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.
“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
Weighing efficacy and cost
Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.
CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).
Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”
After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:
- Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
- Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
- Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.