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Ustekinumab trumps TNF-blockade for enthesitis in patients with psoriatic arthritis
MADRID – The anti-IL-23 antibody ustekinumab cleared enthesitis significantly better than did TNF-blockade in a small, open-label trial of patients with psoriatic arthritis
After 6 months on the drug, 71% of those taking the antibody achieved a score of 0 on the Spondyloarthritis Research Consortium of Canada (SPARCC) scale, representing a complete absence of enthesitis, Elizabeth Araujo, MD, said at the European Congress of Rheumatology. Just 38% of those on TNF-inhibitors achieved that score.
Enthesitis is often more bothersome to arthritis patients than their primary disease, said Dr. Araujo of the Centre of Internal Medicine, Universitätsklinikum Erlangen, Germany.
“Despite being a hallmark of PsA patients, enthesitis still receives rather peripheral attention as an outcome, especially when compared with ‘classical’ arthritis. Nonetheless, in clinical practice, enthesitis is an important factor for PsA-associated pain in many patients,” explained Dr. Araujo.
Yet it’s frequently ignored or under-treated. When it is addressed, enthesitis is often treated using TNF-inhibitors. But recent increases in the treatment options for PsA patients got Dr. Araujo thinking that PsA patients with enthesitis might respond better to a different therapy.
She investigated this with the open-label ECLIPSA trial, which randomized 51 PsA patients (47 with active enthesitis) to a 6-month treatment regimen of ustekinumab or a TNF-inhibitor. The primary endpoint of the observational study was a SPARCC score of 0.
Patients were a mean of 61 years, with a mean disease duration of 2.5 years. The mean baseline SPARCC score was 4. The mean Psoriatic Area and Severity Score (PASI) was 3.
Patients’ arthritis symptoms responded equally well to both drugs, with similar marked decreases in tender and swollen joint counts. But there was a clear, significant between-group separation on the SPARCC score, with 71% of the ustekinumab group reaching a 0 compared to 38% of the TNF-inhibition group.
Ustekinumab also effected better skin clearance than TNF-inhibition, she said. Among the TNF-inhibition group, about 20% achieved a PASI 90 and 20%, a PASI 100. Among those taking ustekinumab, about 80% achieved a PASI 90 and 55% a PASI 100.
The data point the way to more stratified treatment approaches for PsA patients, where PsA that predominantly involves enthesitis is treated by drugs like ustekinumab, Dr. Araujo said. Since both TNF-inhibitors and ustekinumab are approved for treatment of PsA, treatment could be tailored.
“Stratification of PsA patients according to clinical features (enthesitis driven vs. arthritis driven) appears within reach and will allow a more selective use of cytokine-blocking agents in PsA in the future,” said Dr. Araujo.
“More attention on enthesial-driven PsA patients is needed in the future as this patient group is well known to clinicians working in the PsA field but is massively underrepresented in clinical studies. Comparative studies of biological [disease-modifying antirheumatic drugs] in PsA need to take into account the differences in the clinical profile of PsA patients and should not be confined to the traditional polyarticular arthritis–driven disease population,” she added.
Dr. Araujo had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – The anti-IL-23 antibody ustekinumab cleared enthesitis significantly better than did TNF-blockade in a small, open-label trial of patients with psoriatic arthritis
After 6 months on the drug, 71% of those taking the antibody achieved a score of 0 on the Spondyloarthritis Research Consortium of Canada (SPARCC) scale, representing a complete absence of enthesitis, Elizabeth Araujo, MD, said at the European Congress of Rheumatology. Just 38% of those on TNF-inhibitors achieved that score.
Enthesitis is often more bothersome to arthritis patients than their primary disease, said Dr. Araujo of the Centre of Internal Medicine, Universitätsklinikum Erlangen, Germany.
“Despite being a hallmark of PsA patients, enthesitis still receives rather peripheral attention as an outcome, especially when compared with ‘classical’ arthritis. Nonetheless, in clinical practice, enthesitis is an important factor for PsA-associated pain in many patients,” explained Dr. Araujo.
Yet it’s frequently ignored or under-treated. When it is addressed, enthesitis is often treated using TNF-inhibitors. But recent increases in the treatment options for PsA patients got Dr. Araujo thinking that PsA patients with enthesitis might respond better to a different therapy.
She investigated this with the open-label ECLIPSA trial, which randomized 51 PsA patients (47 with active enthesitis) to a 6-month treatment regimen of ustekinumab or a TNF-inhibitor. The primary endpoint of the observational study was a SPARCC score of 0.
Patients were a mean of 61 years, with a mean disease duration of 2.5 years. The mean baseline SPARCC score was 4. The mean Psoriatic Area and Severity Score (PASI) was 3.
Patients’ arthritis symptoms responded equally well to both drugs, with similar marked decreases in tender and swollen joint counts. But there was a clear, significant between-group separation on the SPARCC score, with 71% of the ustekinumab group reaching a 0 compared to 38% of the TNF-inhibition group.
Ustekinumab also effected better skin clearance than TNF-inhibition, she said. Among the TNF-inhibition group, about 20% achieved a PASI 90 and 20%, a PASI 100. Among those taking ustekinumab, about 80% achieved a PASI 90 and 55% a PASI 100.
The data point the way to more stratified treatment approaches for PsA patients, where PsA that predominantly involves enthesitis is treated by drugs like ustekinumab, Dr. Araujo said. Since both TNF-inhibitors and ustekinumab are approved for treatment of PsA, treatment could be tailored.
“Stratification of PsA patients according to clinical features (enthesitis driven vs. arthritis driven) appears within reach and will allow a more selective use of cytokine-blocking agents in PsA in the future,” said Dr. Araujo.
“More attention on enthesial-driven PsA patients is needed in the future as this patient group is well known to clinicians working in the PsA field but is massively underrepresented in clinical studies. Comparative studies of biological [disease-modifying antirheumatic drugs] in PsA need to take into account the differences in the clinical profile of PsA patients and should not be confined to the traditional polyarticular arthritis–driven disease population,” she added.
Dr. Araujo had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – The anti-IL-23 antibody ustekinumab cleared enthesitis significantly better than did TNF-blockade in a small, open-label trial of patients with psoriatic arthritis
After 6 months on the drug, 71% of those taking the antibody achieved a score of 0 on the Spondyloarthritis Research Consortium of Canada (SPARCC) scale, representing a complete absence of enthesitis, Elizabeth Araujo, MD, said at the European Congress of Rheumatology. Just 38% of those on TNF-inhibitors achieved that score.
Enthesitis is often more bothersome to arthritis patients than their primary disease, said Dr. Araujo of the Centre of Internal Medicine, Universitätsklinikum Erlangen, Germany.
“Despite being a hallmark of PsA patients, enthesitis still receives rather peripheral attention as an outcome, especially when compared with ‘classical’ arthritis. Nonetheless, in clinical practice, enthesitis is an important factor for PsA-associated pain in many patients,” explained Dr. Araujo.
Yet it’s frequently ignored or under-treated. When it is addressed, enthesitis is often treated using TNF-inhibitors. But recent increases in the treatment options for PsA patients got Dr. Araujo thinking that PsA patients with enthesitis might respond better to a different therapy.
She investigated this with the open-label ECLIPSA trial, which randomized 51 PsA patients (47 with active enthesitis) to a 6-month treatment regimen of ustekinumab or a TNF-inhibitor. The primary endpoint of the observational study was a SPARCC score of 0.
Patients were a mean of 61 years, with a mean disease duration of 2.5 years. The mean baseline SPARCC score was 4. The mean Psoriatic Area and Severity Score (PASI) was 3.
Patients’ arthritis symptoms responded equally well to both drugs, with similar marked decreases in tender and swollen joint counts. But there was a clear, significant between-group separation on the SPARCC score, with 71% of the ustekinumab group reaching a 0 compared to 38% of the TNF-inhibition group.
Ustekinumab also effected better skin clearance than TNF-inhibition, she said. Among the TNF-inhibition group, about 20% achieved a PASI 90 and 20%, a PASI 100. Among those taking ustekinumab, about 80% achieved a PASI 90 and 55% a PASI 100.
The data point the way to more stratified treatment approaches for PsA patients, where PsA that predominantly involves enthesitis is treated by drugs like ustekinumab, Dr. Araujo said. Since both TNF-inhibitors and ustekinumab are approved for treatment of PsA, treatment could be tailored.
“Stratification of PsA patients according to clinical features (enthesitis driven vs. arthritis driven) appears within reach and will allow a more selective use of cytokine-blocking agents in PsA in the future,” said Dr. Araujo.
“More attention on enthesial-driven PsA patients is needed in the future as this patient group is well known to clinicians working in the PsA field but is massively underrepresented in clinical studies. Comparative studies of biological [disease-modifying antirheumatic drugs] in PsA need to take into account the differences in the clinical profile of PsA patients and should not be confined to the traditional polyarticular arthritis–driven disease population,” she added.
Dr. Araujo had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT EULAR 2017
Key clinical point:
Major finding: After 6 months, 71% of those taking ustekinumab and 38% of those taking TNF-blockers achieved total enthesitis clearance.
Data source: The open-label trial randomized 51 patients - 47 of whom had active enthesitis.
Disclosures: Dr. Araujo had no financial disclosures.
VIDEO: Guselkumab bests placebo in psoriatic arthritis
MADRID – Guselkumab, an IL-23 blocker that has proved its mettle in psoriasis, also posted excellent results in an early-phase psoriatic arthritis trial.
The fully human monoclonal antibody, which is being developed by Janssen, targets the p19 subunit of interleukin-23, Atul Deodhar, MD, said at the European Congress of Rheumatology. The 52-week phase 2a study randomized 149 patients to 100 mg guselkumab or placebo given subcutaneously at baseline and week 4, then every 8 weeks, for 24 weeks. Patients who didn’t respond adequately in either arm could begin using ustekinumab. After 24 weeks, everyone remaining in the placebo group switched to guselkumab, and patients in both arms continued open-label treatment until 52 weeks.
Dr. Deodhar of the Oregon Health and Science University, Portland, reported 24-week outcomes. A full year of data will be presented at the American College of Rheumatology meeting in San Diego in November.
Guselkumab aced the study’s primary endpoint – ACR 20 response by week 24 (58% vs. 18% with the placebo, P less than .001). Improvement developed rapidly, with a significant separation between the groups by week 4 (21% vs. 0%; P less than .001). It also succeeded on the secondary endpoints of ACR 50 response (34% vs. 10%) and ACR 70 (14% vs. 2%). The antibody also significantly outperformed placebo on the Health Assessment Questionnaire Disability Index (HAQ-DI), 36-Item Short Form Health Survey (SF-36), and Minimal Disease Activity score. Skin clearance was strikingly good, Dr. Deodhar said: 39% achieved complete clearance, with a Psoriasis Area and Severity Index (PASI) score of 100; 66% achieved a PASI of 90; and 79% acheived a PASI of 75.
Guselkumab also significantly improved enthesitis – a symptom that can be terribly troubling for patients with psoriatic arthritis. Enthesitis was present in 106 at baseline. By 24 weeks, it had resolved in 56.6% of those taking the antibody and 29% of those taking the placebo (P = .012.).
A phase III trial in psoriatic arthritis will be forthcoming, Dr. Deodhar said.
Dr. Deodhar has received research funding and is a consultant for Janssen and other pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
MADRID – Guselkumab, an IL-23 blocker that has proved its mettle in psoriasis, also posted excellent results in an early-phase psoriatic arthritis trial.
The fully human monoclonal antibody, which is being developed by Janssen, targets the p19 subunit of interleukin-23, Atul Deodhar, MD, said at the European Congress of Rheumatology. The 52-week phase 2a study randomized 149 patients to 100 mg guselkumab or placebo given subcutaneously at baseline and week 4, then every 8 weeks, for 24 weeks. Patients who didn’t respond adequately in either arm could begin using ustekinumab. After 24 weeks, everyone remaining in the placebo group switched to guselkumab, and patients in both arms continued open-label treatment until 52 weeks.
Dr. Deodhar of the Oregon Health and Science University, Portland, reported 24-week outcomes. A full year of data will be presented at the American College of Rheumatology meeting in San Diego in November.
Guselkumab aced the study’s primary endpoint – ACR 20 response by week 24 (58% vs. 18% with the placebo, P less than .001). Improvement developed rapidly, with a significant separation between the groups by week 4 (21% vs. 0%; P less than .001). It also succeeded on the secondary endpoints of ACR 50 response (34% vs. 10%) and ACR 70 (14% vs. 2%). The antibody also significantly outperformed placebo on the Health Assessment Questionnaire Disability Index (HAQ-DI), 36-Item Short Form Health Survey (SF-36), and Minimal Disease Activity score. Skin clearance was strikingly good, Dr. Deodhar said: 39% achieved complete clearance, with a Psoriasis Area and Severity Index (PASI) score of 100; 66% achieved a PASI of 90; and 79% acheived a PASI of 75.
Guselkumab also significantly improved enthesitis – a symptom that can be terribly troubling for patients with psoriatic arthritis. Enthesitis was present in 106 at baseline. By 24 weeks, it had resolved in 56.6% of those taking the antibody and 29% of those taking the placebo (P = .012.).
A phase III trial in psoriatic arthritis will be forthcoming, Dr. Deodhar said.
Dr. Deodhar has received research funding and is a consultant for Janssen and other pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
MADRID – Guselkumab, an IL-23 blocker that has proved its mettle in psoriasis, also posted excellent results in an early-phase psoriatic arthritis trial.
The fully human monoclonal antibody, which is being developed by Janssen, targets the p19 subunit of interleukin-23, Atul Deodhar, MD, said at the European Congress of Rheumatology. The 52-week phase 2a study randomized 149 patients to 100 mg guselkumab or placebo given subcutaneously at baseline and week 4, then every 8 weeks, for 24 weeks. Patients who didn’t respond adequately in either arm could begin using ustekinumab. After 24 weeks, everyone remaining in the placebo group switched to guselkumab, and patients in both arms continued open-label treatment until 52 weeks.
Dr. Deodhar of the Oregon Health and Science University, Portland, reported 24-week outcomes. A full year of data will be presented at the American College of Rheumatology meeting in San Diego in November.
Guselkumab aced the study’s primary endpoint – ACR 20 response by week 24 (58% vs. 18% with the placebo, P less than .001). Improvement developed rapidly, with a significant separation between the groups by week 4 (21% vs. 0%; P less than .001). It also succeeded on the secondary endpoints of ACR 50 response (34% vs. 10%) and ACR 70 (14% vs. 2%). The antibody also significantly outperformed placebo on the Health Assessment Questionnaire Disability Index (HAQ-DI), 36-Item Short Form Health Survey (SF-36), and Minimal Disease Activity score. Skin clearance was strikingly good, Dr. Deodhar said: 39% achieved complete clearance, with a Psoriasis Area and Severity Index (PASI) score of 100; 66% achieved a PASI of 90; and 79% acheived a PASI of 75.
Guselkumab also significantly improved enthesitis – a symptom that can be terribly troubling for patients with psoriatic arthritis. Enthesitis was present in 106 at baseline. By 24 weeks, it had resolved in 56.6% of those taking the antibody and 29% of those taking the placebo (P = .012.).
A phase III trial in psoriatic arthritis will be forthcoming, Dr. Deodhar said.
Dr. Deodhar has received research funding and is a consultant for Janssen and other pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: ACR 20 response at 24 weeks was 58% in the treated group, vs. 18% in the placebo group.
Data source: The 52-week 2a study randomized 149 patients to guselkumab or placebo.
Disclosures: Dr. Deodhar has received research monies and is a consultant for Janssen, which is developing guselkumab.
VIDEO: Troponin acts as atherosclerotic biomarker in patients with lupus
MADRID – Measuring levels of troponin, a well-known cardiac biomarker, could help identify patients with systemic lupus erythematosus (SLE) at particularly high risk for cardiovascular (CV) events, according to the results of a cross-sectional study presented at the European Congress of Rheumatology.
Karim Sacré, MD, presented the findings of the study that looked for possible biomarkers of atherosclerosis in patients with SLE and provide preliminary evidence that high-sensitivity troponin T (HS-cTnT) was predictive regardless of whether or not patients already had visible atherosclerotic plaques on vascular ultrasound.
“Patients with SLE have been known to be at risk for cardiovascular disease for at least a decade,” Dr. Sacré of Bichat Hospital, University of Paris-Diderot, France, said in an interview at the meeting. Today, SLE is considered an independent risk factor for CV events, much like diabetes, he added.
However, determining which patients with lupus will and which will not develop cardiac problems is still tricky in routine practice. This is because the traditional ways of assessing CV events do not fully account for the increased risk seen in lupus patients. Indeed, the Framingham risk score, which is based on several risk factors such as tobacco use, hypertension, and dyslipidemia, has been shown to underestimate the cardiovascular risk of lupus patients, he observed.
“So, we need something that will help clinicians to better define the real risk of cardiovascular disease in such populations,” he said at an earlier press conference.
Thus, the objective of the study he presented was to try to find a biomarker in the blood that might aid clinicians in identifying which patients who had SLE and no obvious cardiac symptoms might be at risk for future CV events.
The study involved 63 patients with SLE who were consecutively recruited and 18 individuals without SLE who were used as controls. None had any symptoms of cardiovascular disease at recruitment, and all were assessed prospectively by vascular ultrasound for the presence of atherosclerotic plaques in the carotid artery.
The concentration of HS-cTnT was measured in the serum by using an electrochemiluminescence method, which could detect a concentration level greater than 3 ng/L .
At recruitment, the Framingham risk score was low (2.1) in both patients and controls, none of whom showed any signs of already having cardiovascular disease. The results of the carotid ultrasound, however, showed a different story for the SLE patients, with 23 (36.5%) identified as having carotid plaques, compared with just 2 (11.1%) of the control group.
Serum HS-cTNT could be detected in more SLE patients than controls (58.7% vs. 33.3%; P = .057), and the SLE patients who had detectable levels were nine times more likely than controls to have a carotid plaque, Dr. Sacré reported, although the 95% confidence interval was wide (1.55 to 90.07; P = .033).
Interestingly, a higher percentage of SLE patients with carotid plaques than those without had detectable HS-cTNT (87% vs. 42.5%; P less than .001). Conversely, more patients with detectable HS-cTnT than without had a carotid plaque (54.5% vs. 11.5%; P less than .001).
In multivariate analyses, only SLE status and age were significantly associated with having carotid plaques, and body mass index and HS-cTnT (P = .033) were statistically associated with the presence of carotid plaques in SLE patients.
The research is, of course, preliminary, Dr. Sacré emphasized, and further investigation is needed. The study looked at subclinical disease rather than actual CV events, and that is something to look at next in a larger cohort of patients with a longer follow-up period, he said.
Dr. Sacré disclosed that he had received support for travel to the EULAR Congress from Roche Diagnostics France.
*This story was updated 6/20/2017.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Measuring levels of troponin, a well-known cardiac biomarker, could help identify patients with systemic lupus erythematosus (SLE) at particularly high risk for cardiovascular (CV) events, according to the results of a cross-sectional study presented at the European Congress of Rheumatology.
Karim Sacré, MD, presented the findings of the study that looked for possible biomarkers of atherosclerosis in patients with SLE and provide preliminary evidence that high-sensitivity troponin T (HS-cTnT) was predictive regardless of whether or not patients already had visible atherosclerotic plaques on vascular ultrasound.
“Patients with SLE have been known to be at risk for cardiovascular disease for at least a decade,” Dr. Sacré of Bichat Hospital, University of Paris-Diderot, France, said in an interview at the meeting. Today, SLE is considered an independent risk factor for CV events, much like diabetes, he added.
However, determining which patients with lupus will and which will not develop cardiac problems is still tricky in routine practice. This is because the traditional ways of assessing CV events do not fully account for the increased risk seen in lupus patients. Indeed, the Framingham risk score, which is based on several risk factors such as tobacco use, hypertension, and dyslipidemia, has been shown to underestimate the cardiovascular risk of lupus patients, he observed.
“So, we need something that will help clinicians to better define the real risk of cardiovascular disease in such populations,” he said at an earlier press conference.
Thus, the objective of the study he presented was to try to find a biomarker in the blood that might aid clinicians in identifying which patients who had SLE and no obvious cardiac symptoms might be at risk for future CV events.
The study involved 63 patients with SLE who were consecutively recruited and 18 individuals without SLE who were used as controls. None had any symptoms of cardiovascular disease at recruitment, and all were assessed prospectively by vascular ultrasound for the presence of atherosclerotic plaques in the carotid artery.
The concentration of HS-cTnT was measured in the serum by using an electrochemiluminescence method, which could detect a concentration level greater than 3 ng/L .
At recruitment, the Framingham risk score was low (2.1) in both patients and controls, none of whom showed any signs of already having cardiovascular disease. The results of the carotid ultrasound, however, showed a different story for the SLE patients, with 23 (36.5%) identified as having carotid plaques, compared with just 2 (11.1%) of the control group.
Serum HS-cTNT could be detected in more SLE patients than controls (58.7% vs. 33.3%; P = .057), and the SLE patients who had detectable levels were nine times more likely than controls to have a carotid plaque, Dr. Sacré reported, although the 95% confidence interval was wide (1.55 to 90.07; P = .033).
Interestingly, a higher percentage of SLE patients with carotid plaques than those without had detectable HS-cTNT (87% vs. 42.5%; P less than .001). Conversely, more patients with detectable HS-cTnT than without had a carotid plaque (54.5% vs. 11.5%; P less than .001).
In multivariate analyses, only SLE status and age were significantly associated with having carotid plaques, and body mass index and HS-cTnT (P = .033) were statistically associated with the presence of carotid plaques in SLE patients.
The research is, of course, preliminary, Dr. Sacré emphasized, and further investigation is needed. The study looked at subclinical disease rather than actual CV events, and that is something to look at next in a larger cohort of patients with a longer follow-up period, he said.
Dr. Sacré disclosed that he had received support for travel to the EULAR Congress from Roche Diagnostics France.
*This story was updated 6/20/2017.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Measuring levels of troponin, a well-known cardiac biomarker, could help identify patients with systemic lupus erythematosus (SLE) at particularly high risk for cardiovascular (CV) events, according to the results of a cross-sectional study presented at the European Congress of Rheumatology.
Karim Sacré, MD, presented the findings of the study that looked for possible biomarkers of atherosclerosis in patients with SLE and provide preliminary evidence that high-sensitivity troponin T (HS-cTnT) was predictive regardless of whether or not patients already had visible atherosclerotic plaques on vascular ultrasound.
“Patients with SLE have been known to be at risk for cardiovascular disease for at least a decade,” Dr. Sacré of Bichat Hospital, University of Paris-Diderot, France, said in an interview at the meeting. Today, SLE is considered an independent risk factor for CV events, much like diabetes, he added.
However, determining which patients with lupus will and which will not develop cardiac problems is still tricky in routine practice. This is because the traditional ways of assessing CV events do not fully account for the increased risk seen in lupus patients. Indeed, the Framingham risk score, which is based on several risk factors such as tobacco use, hypertension, and dyslipidemia, has been shown to underestimate the cardiovascular risk of lupus patients, he observed.
“So, we need something that will help clinicians to better define the real risk of cardiovascular disease in such populations,” he said at an earlier press conference.
Thus, the objective of the study he presented was to try to find a biomarker in the blood that might aid clinicians in identifying which patients who had SLE and no obvious cardiac symptoms might be at risk for future CV events.
The study involved 63 patients with SLE who were consecutively recruited and 18 individuals without SLE who were used as controls. None had any symptoms of cardiovascular disease at recruitment, and all were assessed prospectively by vascular ultrasound for the presence of atherosclerotic plaques in the carotid artery.
The concentration of HS-cTnT was measured in the serum by using an electrochemiluminescence method, which could detect a concentration level greater than 3 ng/L .
At recruitment, the Framingham risk score was low (2.1) in both patients and controls, none of whom showed any signs of already having cardiovascular disease. The results of the carotid ultrasound, however, showed a different story for the SLE patients, with 23 (36.5%) identified as having carotid plaques, compared with just 2 (11.1%) of the control group.
Serum HS-cTNT could be detected in more SLE patients than controls (58.7% vs. 33.3%; P = .057), and the SLE patients who had detectable levels were nine times more likely than controls to have a carotid plaque, Dr. Sacré reported, although the 95% confidence interval was wide (1.55 to 90.07; P = .033).
Interestingly, a higher percentage of SLE patients with carotid plaques than those without had detectable HS-cTNT (87% vs. 42.5%; P less than .001). Conversely, more patients with detectable HS-cTnT than without had a carotid plaque (54.5% vs. 11.5%; P less than .001).
In multivariate analyses, only SLE status and age were significantly associated with having carotid plaques, and body mass index and HS-cTnT (P = .033) were statistically associated with the presence of carotid plaques in SLE patients.
The research is, of course, preliminary, Dr. Sacré emphasized, and further investigation is needed. The study looked at subclinical disease rather than actual CV events, and that is something to look at next in a larger cohort of patients with a longer follow-up period, he said.
Dr. Sacré disclosed that he had received support for travel to the EULAR Congress from Roche Diagnostics France.
*This story was updated 6/20/2017.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EULAR 2017 CONGRESS
VIDEO: Rheumatology biosimilars gain U.S. momentum
MADRID – With biosimilar infliximab on the U.S. market since November 2016 and producing an immediate, albeit modest, price drop for this tumor necrosis factor inhibitor (TNFi) and a second biosimilar infliximab now approved by the Food and Drug Administration and awaiting market entry, biosimilars are in a new phase of integration into U.S. practice.
“Physicians are willing to prescribe Inflectra,” the first biosimilar infliximab and the first TNFi to be sold in the United States last November, Jonathan Kay, MD, said in a video interview during the European Congress of Rheumatology. “Rheumatologists who were initially skeptical are now on the bandwagon and willing to prescribe biosimilars,” said Dr. Kay, a rheumatologist who has often consulted on biosimilar issues and has recently spoken to rheumatologists at various state society meetings to explain the U.S. biosimilar regulatory concepts and spread the message of the societal value of these agents.
“This is not a quick and casual drug evaluation” that produces “knockoff drugs,” but a “careful and extensive” FDA review that results in drugs that are equivalent in efficacy, safety, and immunogenicity to the reference drug and only compete on price, he explained.
When Pfizer began marketing Inflectra last Fall, it set the drug’s list price 15% lower than the list price at the time for Remicade, the reference-product infliximab. However, complex pricing and rebate strategies actually led to Remicade selling for a lower price than Inflectra, at least for some U.S. hospitals, including the University of Massachusetts in Worcester, where Dr. Kay is a professor of medicine.
“The effect of biosimilars is to reduce the cost to patients of an effective treatment. Whether that cost is for the reference drug or for the biosimilar drug doesn’t matter [from society’s perspective] as long as patients are able to receive an effective therapy at a [more] affordable cost, making the effective therapy available to more patients,” he said.
While Inflectra’s price impact my have been modest so far, the biosimilar effect on infliximab’s cost may soon intensify now that a second biosimilar of this TNFi, Renflexis – made by Samsung Bioepis and with U.S. marketing by Merck, received FDA approval on April 21, 2017. Until recently, U.S. pharmaceutical regulations had been understood to require a 180-day hiatus between FDA marketing approval for a biosimilar and the start of U.S. sales. But, on June 12, 2017, the U.S. Supreme Court, in a 9-0 decision, ruled that this 180-day wait was not required, making it possible for U.S. marketing of Renflexis to begin soon. (In mid-June, a statement on the Merck U.S. website for Renflexis says that the product is not currently available.)
Availability of a second biosimilar infliximab “is likely to drive the price down rapidly,” predicted Dr. Kay, citing what happened when multiple biosimilars for a reference drug came onto the European market.
Two other biosimilar TNFi have also received FDA marketing approvals but remain on hold as patent issues and litigation barriers play out. Erelzi – biosimilar etanercept – received FDA approval in August 2016, and Amjevita, biosimilar adalimumab, received FDA approval last September.
The efficacy and safety of Inflectra specifically, and by extension all biosimilars, received a recent boost with publication of findings from a randomized study with 482 patients that provided a real-world test of the core principle of biosimilar equivalence. After Inflectra came onto the Norwegian market, during July 2014 to August 2015, Norwegian researchers ran the NOR-SWTICH trial, which randomized patients who were on stable treatment with Remicade for a variety of indications (including 41% with a rheumatologic disease) to either stay on Remicade or to abruptly switch to treatment with Inflectra. During 1-year follow-up, the incidence of adverse effects and of episodes of disease worsening were virtually identical in the two treatment arms (Lancet. 2017 June 10;389[10086]:2304-16).
Dr. Kay has been a consultant to several companies that develop or market biosimilars, including Samsung Bioepis, Amgen, Pfizer, and Sandoz (Novartis), and to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen, Roche, and UCB.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – With biosimilar infliximab on the U.S. market since November 2016 and producing an immediate, albeit modest, price drop for this tumor necrosis factor inhibitor (TNFi) and a second biosimilar infliximab now approved by the Food and Drug Administration and awaiting market entry, biosimilars are in a new phase of integration into U.S. practice.
“Physicians are willing to prescribe Inflectra,” the first biosimilar infliximab and the first TNFi to be sold in the United States last November, Jonathan Kay, MD, said in a video interview during the European Congress of Rheumatology. “Rheumatologists who were initially skeptical are now on the bandwagon and willing to prescribe biosimilars,” said Dr. Kay, a rheumatologist who has often consulted on biosimilar issues and has recently spoken to rheumatologists at various state society meetings to explain the U.S. biosimilar regulatory concepts and spread the message of the societal value of these agents.
“This is not a quick and casual drug evaluation” that produces “knockoff drugs,” but a “careful and extensive” FDA review that results in drugs that are equivalent in efficacy, safety, and immunogenicity to the reference drug and only compete on price, he explained.
When Pfizer began marketing Inflectra last Fall, it set the drug’s list price 15% lower than the list price at the time for Remicade, the reference-product infliximab. However, complex pricing and rebate strategies actually led to Remicade selling for a lower price than Inflectra, at least for some U.S. hospitals, including the University of Massachusetts in Worcester, where Dr. Kay is a professor of medicine.
“The effect of biosimilars is to reduce the cost to patients of an effective treatment. Whether that cost is for the reference drug or for the biosimilar drug doesn’t matter [from society’s perspective] as long as patients are able to receive an effective therapy at a [more] affordable cost, making the effective therapy available to more patients,” he said.
While Inflectra’s price impact my have been modest so far, the biosimilar effect on infliximab’s cost may soon intensify now that a second biosimilar of this TNFi, Renflexis – made by Samsung Bioepis and with U.S. marketing by Merck, received FDA approval on April 21, 2017. Until recently, U.S. pharmaceutical regulations had been understood to require a 180-day hiatus between FDA marketing approval for a biosimilar and the start of U.S. sales. But, on June 12, 2017, the U.S. Supreme Court, in a 9-0 decision, ruled that this 180-day wait was not required, making it possible for U.S. marketing of Renflexis to begin soon. (In mid-June, a statement on the Merck U.S. website for Renflexis says that the product is not currently available.)
Availability of a second biosimilar infliximab “is likely to drive the price down rapidly,” predicted Dr. Kay, citing what happened when multiple biosimilars for a reference drug came onto the European market.
Two other biosimilar TNFi have also received FDA marketing approvals but remain on hold as patent issues and litigation barriers play out. Erelzi – biosimilar etanercept – received FDA approval in August 2016, and Amjevita, biosimilar adalimumab, received FDA approval last September.
The efficacy and safety of Inflectra specifically, and by extension all biosimilars, received a recent boost with publication of findings from a randomized study with 482 patients that provided a real-world test of the core principle of biosimilar equivalence. After Inflectra came onto the Norwegian market, during July 2014 to August 2015, Norwegian researchers ran the NOR-SWTICH trial, which randomized patients who were on stable treatment with Remicade for a variety of indications (including 41% with a rheumatologic disease) to either stay on Remicade or to abruptly switch to treatment with Inflectra. During 1-year follow-up, the incidence of adverse effects and of episodes of disease worsening were virtually identical in the two treatment arms (Lancet. 2017 June 10;389[10086]:2304-16).
Dr. Kay has been a consultant to several companies that develop or market biosimilars, including Samsung Bioepis, Amgen, Pfizer, and Sandoz (Novartis), and to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen, Roche, and UCB.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – With biosimilar infliximab on the U.S. market since November 2016 and producing an immediate, albeit modest, price drop for this tumor necrosis factor inhibitor (TNFi) and a second biosimilar infliximab now approved by the Food and Drug Administration and awaiting market entry, biosimilars are in a new phase of integration into U.S. practice.
“Physicians are willing to prescribe Inflectra,” the first biosimilar infliximab and the first TNFi to be sold in the United States last November, Jonathan Kay, MD, said in a video interview during the European Congress of Rheumatology. “Rheumatologists who were initially skeptical are now on the bandwagon and willing to prescribe biosimilars,” said Dr. Kay, a rheumatologist who has often consulted on biosimilar issues and has recently spoken to rheumatologists at various state society meetings to explain the U.S. biosimilar regulatory concepts and spread the message of the societal value of these agents.
“This is not a quick and casual drug evaluation” that produces “knockoff drugs,” but a “careful and extensive” FDA review that results in drugs that are equivalent in efficacy, safety, and immunogenicity to the reference drug and only compete on price, he explained.
When Pfizer began marketing Inflectra last Fall, it set the drug’s list price 15% lower than the list price at the time for Remicade, the reference-product infliximab. However, complex pricing and rebate strategies actually led to Remicade selling for a lower price than Inflectra, at least for some U.S. hospitals, including the University of Massachusetts in Worcester, where Dr. Kay is a professor of medicine.
“The effect of biosimilars is to reduce the cost to patients of an effective treatment. Whether that cost is for the reference drug or for the biosimilar drug doesn’t matter [from society’s perspective] as long as patients are able to receive an effective therapy at a [more] affordable cost, making the effective therapy available to more patients,” he said.
While Inflectra’s price impact my have been modest so far, the biosimilar effect on infliximab’s cost may soon intensify now that a second biosimilar of this TNFi, Renflexis – made by Samsung Bioepis and with U.S. marketing by Merck, received FDA approval on April 21, 2017. Until recently, U.S. pharmaceutical regulations had been understood to require a 180-day hiatus between FDA marketing approval for a biosimilar and the start of U.S. sales. But, on June 12, 2017, the U.S. Supreme Court, in a 9-0 decision, ruled that this 180-day wait was not required, making it possible for U.S. marketing of Renflexis to begin soon. (In mid-June, a statement on the Merck U.S. website for Renflexis says that the product is not currently available.)
Availability of a second biosimilar infliximab “is likely to drive the price down rapidly,” predicted Dr. Kay, citing what happened when multiple biosimilars for a reference drug came onto the European market.
Two other biosimilar TNFi have also received FDA marketing approvals but remain on hold as patent issues and litigation barriers play out. Erelzi – biosimilar etanercept – received FDA approval in August 2016, and Amjevita, biosimilar adalimumab, received FDA approval last September.
The efficacy and safety of Inflectra specifically, and by extension all biosimilars, received a recent boost with publication of findings from a randomized study with 482 patients that provided a real-world test of the core principle of biosimilar equivalence. After Inflectra came onto the Norwegian market, during July 2014 to August 2015, Norwegian researchers ran the NOR-SWTICH trial, which randomized patients who were on stable treatment with Remicade for a variety of indications (including 41% with a rheumatologic disease) to either stay on Remicade or to abruptly switch to treatment with Inflectra. During 1-year follow-up, the incidence of adverse effects and of episodes of disease worsening were virtually identical in the two treatment arms (Lancet. 2017 June 10;389[10086]:2304-16).
Dr. Kay has been a consultant to several companies that develop or market biosimilars, including Samsung Bioepis, Amgen, Pfizer, and Sandoz (Novartis), and to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen, Roche, and UCB.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR 2017 CONGRESS
VIDEO: Adding ultrasound to treat to target doesn’t improve RA remission outcomes
MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.
In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.
“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”
Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.
Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.
Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.
To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.
As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.
In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.
The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.
Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”
But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.
“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”
Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.
Dr. Sepriano and his associates had no conflicts of interest to declare.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.
In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.
“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”
Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.
Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.
Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.
To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.
As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.
In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.
The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.
Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”
But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.
“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”
Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.
Dr. Sepriano and his associates had no conflicts of interest to declare.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.
In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.
“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”
Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.
Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.
Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.
To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.
As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.
In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.
The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.
Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”
But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.
“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”
Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.
Dr. Sepriano and his associates had no conflicts of interest to declare.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Adding ultrasound to the treatment protocol actually reduced the likelihood of patients achieving remission by up to 66%, depending on the remission assessment used.
Data source: The observational study comprised 130 patients and more than 1,000 clinical visits.
Disclosures: Dr. Sepriano had no financial disclosures.
Pain often persists despite biologic treatment in PsA
MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.
At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.
In an interview. Dr. Conaghan said that it’s important for clinicians not to assume that pain in a PsA patient on a biologic means that the drug is not working.
“The main limitation of our study is that we haven’t worked out how well-controlled patients’ psoriatic arthritis is, so, although we know they’re on a biologic for more than 3 months, we don’t know if they were responding well to it.” But, even in the absence of systemic inflammation, he said, there are other potential causes for pain that should not be overlooked.
“There’s no reason why PsA patients wouldn’t have pain due to tendinitis, enthesitis, and osteoarthritis – the same mechanical-type joint pain that we see in the whole community of people over 40,” Dr. Conaghan said. “I am concerned that, once we give someone a label of inflammatory arthritis, we stop looking at all the other things that can happen to their musculoskeletal system.”
Moreover, he said, “people who’ve had arthritis severe enough to need a biologic treatment will have muscle deconditioning and weakness. It’s very common that PsA patients have trouble opening jars and getting out of chairs.”
Such weakness “can lead to mechanical joint pain, which fortunately can be improved – along with the pain – through muscle strengthening and rehabilitation.”
For their study, Dr. Conaghan and his colleagues collected information from clinicians on treatment and from patients. The questionnaires incorporated several measures of disability, pain, functional impairment, and health-related quality of life that have been validated for use in PsA patients.
Severe pain was significantly associated with increased use of prescription nonsteroidal anti-inflammatory drugs and opioids, as well as nonprescription pain medication. Patients 65 years and older had a significantly greater likelihood of being unemployed or retired because of PsA if they reported severe pain, compared with those reporting mild or moderate pain.
A number of quality of life and work-related measures were also associated with pain severity. Dr. Conaghan and his colleagues found that the risk of disability increased with bodily pain, and more severe pain was associated with greater activity impairment, worse social functioning, more work impairment, and work time missed, among other measures (P less than .0001 for all).
“What we saw is that, the more pain you have, the more your world shrinks in,” Dr. Conaghan said.
Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.
At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.
In an interview. Dr. Conaghan said that it’s important for clinicians not to assume that pain in a PsA patient on a biologic means that the drug is not working.
“The main limitation of our study is that we haven’t worked out how well-controlled patients’ psoriatic arthritis is, so, although we know they’re on a biologic for more than 3 months, we don’t know if they were responding well to it.” But, even in the absence of systemic inflammation, he said, there are other potential causes for pain that should not be overlooked.
“There’s no reason why PsA patients wouldn’t have pain due to tendinitis, enthesitis, and osteoarthritis – the same mechanical-type joint pain that we see in the whole community of people over 40,” Dr. Conaghan said. “I am concerned that, once we give someone a label of inflammatory arthritis, we stop looking at all the other things that can happen to their musculoskeletal system.”
Moreover, he said, “people who’ve had arthritis severe enough to need a biologic treatment will have muscle deconditioning and weakness. It’s very common that PsA patients have trouble opening jars and getting out of chairs.”
Such weakness “can lead to mechanical joint pain, which fortunately can be improved – along with the pain – through muscle strengthening and rehabilitation.”
For their study, Dr. Conaghan and his colleagues collected information from clinicians on treatment and from patients. The questionnaires incorporated several measures of disability, pain, functional impairment, and health-related quality of life that have been validated for use in PsA patients.
Severe pain was significantly associated with increased use of prescription nonsteroidal anti-inflammatory drugs and opioids, as well as nonprescription pain medication. Patients 65 years and older had a significantly greater likelihood of being unemployed or retired because of PsA if they reported severe pain, compared with those reporting mild or moderate pain.
A number of quality of life and work-related measures were also associated with pain severity. Dr. Conaghan and his colleagues found that the risk of disability increased with bodily pain, and more severe pain was associated with greater activity impairment, worse social functioning, more work impairment, and work time missed, among other measures (P less than .0001 for all).
“What we saw is that, the more pain you have, the more your world shrinks in,” Dr. Conaghan said.
Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.
At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.
In an interview. Dr. Conaghan said that it’s important for clinicians not to assume that pain in a PsA patient on a biologic means that the drug is not working.
“The main limitation of our study is that we haven’t worked out how well-controlled patients’ psoriatic arthritis is, so, although we know they’re on a biologic for more than 3 months, we don’t know if they were responding well to it.” But, even in the absence of systemic inflammation, he said, there are other potential causes for pain that should not be overlooked.
“There’s no reason why PsA patients wouldn’t have pain due to tendinitis, enthesitis, and osteoarthritis – the same mechanical-type joint pain that we see in the whole community of people over 40,” Dr. Conaghan said. “I am concerned that, once we give someone a label of inflammatory arthritis, we stop looking at all the other things that can happen to their musculoskeletal system.”
Moreover, he said, “people who’ve had arthritis severe enough to need a biologic treatment will have muscle deconditioning and weakness. It’s very common that PsA patients have trouble opening jars and getting out of chairs.”
Such weakness “can lead to mechanical joint pain, which fortunately can be improved – along with the pain – through muscle strengthening and rehabilitation.”
For their study, Dr. Conaghan and his colleagues collected information from clinicians on treatment and from patients. The questionnaires incorporated several measures of disability, pain, functional impairment, and health-related quality of life that have been validated for use in PsA patients.
Severe pain was significantly associated with increased use of prescription nonsteroidal anti-inflammatory drugs and opioids, as well as nonprescription pain medication. Patients 65 years and older had a significantly greater likelihood of being unemployed or retired because of PsA if they reported severe pain, compared with those reporting mild or moderate pain.
A number of quality of life and work-related measures were also associated with pain severity. Dr. Conaghan and his colleagues found that the risk of disability increased with bodily pain, and more severe pain was associated with greater activity impairment, worse social functioning, more work impairment, and work time missed, among other measures (P less than .0001 for all).
“What we saw is that, the more pain you have, the more your world shrinks in,” Dr. Conaghan said.
Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Overall, 37% of PsA patients reported severe pain despite treatment with biologic agents.
Data source: A multinational survey of 782 consecutive PsA patients on biologic agents.
Disclosures: Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
Studies provide insight into link between cancer immunotherapy and autoimmune disease
MADRID – Rheumatologists all over the world are beginning to find that the new class of anticancer immune checkpoint inhibitor therapies have the potential to elicit symptoms of rheumatoid arthritis (RA) and other rheumatic diseases in patients with no previous history of them, and two reports from the European Congress of Rheumatology provide typical examples.
These immune checkpoint inhibitor (ICI) agents, which include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), target regulatory pathways in T cells to boost antitumor immune responses, leading to improved survival for many cancer patients, but the induction of rheumatic disease can sometimes lead to the suspension of the agents, according to investigators.
“This phenomenon was unknown to me and my group before [February 2016], when we started noting referrals of patients from oncology,” Dr. Calabrese said. “We were seeing symptoms of everything from Sjögren’s syndrome to inflammatory arthritis and myositis in patients being treated with these drugs for their cancer.” The same year, Dr. Calabrese and her team began coordinating an ongoing study to assess these patients.
Dr. Calabrese said that the cohort has shown so far that patients who develop autoimmune disease after immune checkpoint inhibitors “require much higher doses – of steroids in particular – to treat their symptoms,” and this can all too often result in being taken out of a clinical trial or having to stop cancer treatment.
Most of the patients in the cohort were treated with steroids only, while three patients received biologic agents, and four received methotrexate or antimalarials.
Dr. Calabrese said that the serology results were available for all the patients in the cohort and “were largely unremarkable.”
She noted that the rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment. “We have some patients that have been off their checkpoint inhibitors for over a year and still have symptoms, so it’s looking like it might be a more long-term effect,” she said.
“In my unit, we also manage patients with myeloma, and I developed a weekly consultation with a cancer center,” Dr. Belkhir said. In 2015, she saw her first patient with RA and no previous history who had been treated with checkpoint inhibitors. That patient’s symptoms resolved after treatment with nonsteroidal anti-inflammatory drugs alone.
Dr. Belkhir is sharing results from this and five other patients presenting with symptoms of RA after their cancer treatment with immune checkpoint inhibitors, taken from a larger cohort of patients (n = 13) with a spectrum of rheumatic disease–like adverse effects. None of the six patients in this study had a previous clinical history of RA. They manifested their RA symptoms after a median of 1 month on cancer immunotherapy.
Some were able to continue their checkpoint inhibitors and be treated simultaneously for RA with steroids, antimalarials, methotrexate, and NSAIDs, Dr. Belkhir said. None received biologic agents, and each medication strategy, she said, was arrived at in consultation with the treating oncologist.
Dr. Belkhir’s team also looked closely at serology and found all six patients to be at least weakly, and mostly strongly, seropositive for RA. Three patients underwent testing for anticyclic citrullinated protein antibodies prior to starting cancer immunotherapy and two of these three were anti-CCP positive. Now, she said, the oncologists she’s working with are testing for anticyclic citrullinated peptides and rheumatoid factor prior to initiating cancer immunotherapy, so that this relationship is better understood.
“It is possible that antibodies were already present and that the anti-PD1 immunotherapy,” one type of immune checkpoint inhibitor, “acted as a trigger for the disease.” Animal studies have suggested a role for PD1 in the development of autoimmune disease, “but it’s not well investigated,” Dr. Belkhir said.
Dr. Belkhir and Dr. Calabrese both acknowledged that the understanding of checkpoint inhibitor–induced autoimmune disease is in its infancy. Clinical trials largely missed the phenomenon, the researchers said, because the trials were not designed to capture musculoskeletal adverse effects with the same granularity as other serious adverse events.
“This will be a long discussion in the months and the years ahead with oncologists,” Dr. Belkhir said.
Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
MADRID – Rheumatologists all over the world are beginning to find that the new class of anticancer immune checkpoint inhibitor therapies have the potential to elicit symptoms of rheumatoid arthritis (RA) and other rheumatic diseases in patients with no previous history of them, and two reports from the European Congress of Rheumatology provide typical examples.
These immune checkpoint inhibitor (ICI) agents, which include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), target regulatory pathways in T cells to boost antitumor immune responses, leading to improved survival for many cancer patients, but the induction of rheumatic disease can sometimes lead to the suspension of the agents, according to investigators.
“This phenomenon was unknown to me and my group before [February 2016], when we started noting referrals of patients from oncology,” Dr. Calabrese said. “We were seeing symptoms of everything from Sjögren’s syndrome to inflammatory arthritis and myositis in patients being treated with these drugs for their cancer.” The same year, Dr. Calabrese and her team began coordinating an ongoing study to assess these patients.
Dr. Calabrese said that the cohort has shown so far that patients who develop autoimmune disease after immune checkpoint inhibitors “require much higher doses – of steroids in particular – to treat their symptoms,” and this can all too often result in being taken out of a clinical trial or having to stop cancer treatment.
Most of the patients in the cohort were treated with steroids only, while three patients received biologic agents, and four received methotrexate or antimalarials.
Dr. Calabrese said that the serology results were available for all the patients in the cohort and “were largely unremarkable.”
She noted that the rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment. “We have some patients that have been off their checkpoint inhibitors for over a year and still have symptoms, so it’s looking like it might be a more long-term effect,” she said.
“In my unit, we also manage patients with myeloma, and I developed a weekly consultation with a cancer center,” Dr. Belkhir said. In 2015, she saw her first patient with RA and no previous history who had been treated with checkpoint inhibitors. That patient’s symptoms resolved after treatment with nonsteroidal anti-inflammatory drugs alone.
Dr. Belkhir is sharing results from this and five other patients presenting with symptoms of RA after their cancer treatment with immune checkpoint inhibitors, taken from a larger cohort of patients (n = 13) with a spectrum of rheumatic disease–like adverse effects. None of the six patients in this study had a previous clinical history of RA. They manifested their RA symptoms after a median of 1 month on cancer immunotherapy.
Some were able to continue their checkpoint inhibitors and be treated simultaneously for RA with steroids, antimalarials, methotrexate, and NSAIDs, Dr. Belkhir said. None received biologic agents, and each medication strategy, she said, was arrived at in consultation with the treating oncologist.
Dr. Belkhir’s team also looked closely at serology and found all six patients to be at least weakly, and mostly strongly, seropositive for RA. Three patients underwent testing for anticyclic citrullinated protein antibodies prior to starting cancer immunotherapy and two of these three were anti-CCP positive. Now, she said, the oncologists she’s working with are testing for anticyclic citrullinated peptides and rheumatoid factor prior to initiating cancer immunotherapy, so that this relationship is better understood.
“It is possible that antibodies were already present and that the anti-PD1 immunotherapy,” one type of immune checkpoint inhibitor, “acted as a trigger for the disease.” Animal studies have suggested a role for PD1 in the development of autoimmune disease, “but it’s not well investigated,” Dr. Belkhir said.
Dr. Belkhir and Dr. Calabrese both acknowledged that the understanding of checkpoint inhibitor–induced autoimmune disease is in its infancy. Clinical trials largely missed the phenomenon, the researchers said, because the trials were not designed to capture musculoskeletal adverse effects with the same granularity as other serious adverse events.
“This will be a long discussion in the months and the years ahead with oncologists,” Dr. Belkhir said.
Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
MADRID – Rheumatologists all over the world are beginning to find that the new class of anticancer immune checkpoint inhibitor therapies have the potential to elicit symptoms of rheumatoid arthritis (RA) and other rheumatic diseases in patients with no previous history of them, and two reports from the European Congress of Rheumatology provide typical examples.
These immune checkpoint inhibitor (ICI) agents, which include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), target regulatory pathways in T cells to boost antitumor immune responses, leading to improved survival for many cancer patients, but the induction of rheumatic disease can sometimes lead to the suspension of the agents, according to investigators.
“This phenomenon was unknown to me and my group before [February 2016], when we started noting referrals of patients from oncology,” Dr. Calabrese said. “We were seeing symptoms of everything from Sjögren’s syndrome to inflammatory arthritis and myositis in patients being treated with these drugs for their cancer.” The same year, Dr. Calabrese and her team began coordinating an ongoing study to assess these patients.
Dr. Calabrese said that the cohort has shown so far that patients who develop autoimmune disease after immune checkpoint inhibitors “require much higher doses – of steroids in particular – to treat their symptoms,” and this can all too often result in being taken out of a clinical trial or having to stop cancer treatment.
Most of the patients in the cohort were treated with steroids only, while three patients received biologic agents, and four received methotrexate or antimalarials.
Dr. Calabrese said that the serology results were available for all the patients in the cohort and “were largely unremarkable.”
She noted that the rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment. “We have some patients that have been off their checkpoint inhibitors for over a year and still have symptoms, so it’s looking like it might be a more long-term effect,” she said.
“In my unit, we also manage patients with myeloma, and I developed a weekly consultation with a cancer center,” Dr. Belkhir said. In 2015, she saw her first patient with RA and no previous history who had been treated with checkpoint inhibitors. That patient’s symptoms resolved after treatment with nonsteroidal anti-inflammatory drugs alone.
Dr. Belkhir is sharing results from this and five other patients presenting with symptoms of RA after their cancer treatment with immune checkpoint inhibitors, taken from a larger cohort of patients (n = 13) with a spectrum of rheumatic disease–like adverse effects. None of the six patients in this study had a previous clinical history of RA. They manifested their RA symptoms after a median of 1 month on cancer immunotherapy.
Some were able to continue their checkpoint inhibitors and be treated simultaneously for RA with steroids, antimalarials, methotrexate, and NSAIDs, Dr. Belkhir said. None received biologic agents, and each medication strategy, she said, was arrived at in consultation with the treating oncologist.
Dr. Belkhir’s team also looked closely at serology and found all six patients to be at least weakly, and mostly strongly, seropositive for RA. Three patients underwent testing for anticyclic citrullinated protein antibodies prior to starting cancer immunotherapy and two of these three were anti-CCP positive. Now, she said, the oncologists she’s working with are testing for anticyclic citrullinated peptides and rheumatoid factor prior to initiating cancer immunotherapy, so that this relationship is better understood.
“It is possible that antibodies were already present and that the anti-PD1 immunotherapy,” one type of immune checkpoint inhibitor, “acted as a trigger for the disease.” Animal studies have suggested a role for PD1 in the development of autoimmune disease, “but it’s not well investigated,” Dr. Belkhir said.
Dr. Belkhir and Dr. Calabrese both acknowledged that the understanding of checkpoint inhibitor–induced autoimmune disease is in its infancy. Clinical trials largely missed the phenomenon, the researchers said, because the trials were not designed to capture musculoskeletal adverse effects with the same granularity as other serious adverse events.
“This will be a long discussion in the months and the years ahead with oncologists,” Dr. Belkhir said.
Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment, and some were able to continue their checkpoint inhibitors and be treated simultaneously for RA.
Data source: Two retrospective cohort reviews of patients on immune checkpoint inhibitors.
Disclosures: Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
Prophylaxis prevents PCP in rheumatic disease patients
MADRID – The benefits of primary prophylaxis for pneumocystis pneumonia (PCP) outweighed the risks of treatment in patients taking prolonged, high-dose corticosteroids for various rheumatic diseases in a study presented at the European Congress of Rheumatology.
In a single-center, retrospective cohort study of 1,522 corticosteroid treatment episodes in 1,092 patients with a variety of rheumatic conditions given over a 12-year follow-up period, the estimated incidence of PCP was 2.37 per 100 person-years.
Significantly fewer cases of PCP occurred at 1 year, however, in the 262 patients who were cotreated with the antibiotic combination of trimethoprim and sulfamethoxazole (TMP-SMX), than in the 1,260 patients who received no such antibiotic prophylaxis in addition to their steroid therapy.
The adjusted hazard ratio (HR) for no PCP at 1 year of follow-up in the prophylaxis group, versus the no prophylaxis group, was 0.096 (P = .022).
The TMP-SMX combination also significantly reduced the mortality associated with PCP, with an adjusted HR of 0.09, versus no prophylaxis (P = .023).
“Pneumocystis pneumonia is a major opportunistic infection in immunocompromised patients associated with high morbidity and mortality,” explained the presenting study investigator Jun Won Park, MD, of Seoul National University Hospital in the Republic of Korea.
Dr. Park added that corticosteroid therapy was an important risk factor for PCP but that the risk-benefit ratio had not been evaluated sufficiently in patients with rheumatic diseases and that there was “different opinion among rheumatologists regarding [the value of] PCP prophylaxis.”
The current study aimed to see if primary antibiotic prophylaxis could prevent PCP in patients with rheumatic diseases, which included patients with systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis, and Behçet’s disease.
For inclusion, patients had to have been treated with prednisolone at a dose of 30 mg/day or more (or its equivalent) for at least 4 weeks and observed for 1 year. Patients with a prior history of PCP or conditions associated with this opportunistic infection, such as HIV, cancer, or solid organ or hematopoietic stem cell transplantation, were excluded.
Dr. Park reported that PCP prophylaxis was given at the discretion of the treating physician, and the mean duration of TMP-SMX was 230 days.
In the prophylaxis group, 34 adverse drug reactions occurred. Two of these reactions were serious – one case of pancytopenia and one case of Steven’s Johnson syndrome – but both resolved after the antibiotic treatment was discontinued.
A sensitivity analysis was performed, giving consistent results, and a risk-benefit analysis showed that the number needed to treat to prevent one case of PCP was 52, considering all rheumatic disease studied, while the number needed to cause one serious adverse drug reaction was 131.
Taken together, these results suggest a role for TMP-SMX as primary prophylaxis for PCP in patients with rheumatic diseases who need prolonged treatment with high-dose corticosteroids, Dr. Park said.
Dr. Park reported having no relevant financial disclosures.
MADRID – The benefits of primary prophylaxis for pneumocystis pneumonia (PCP) outweighed the risks of treatment in patients taking prolonged, high-dose corticosteroids for various rheumatic diseases in a study presented at the European Congress of Rheumatology.
In a single-center, retrospective cohort study of 1,522 corticosteroid treatment episodes in 1,092 patients with a variety of rheumatic conditions given over a 12-year follow-up period, the estimated incidence of PCP was 2.37 per 100 person-years.
Significantly fewer cases of PCP occurred at 1 year, however, in the 262 patients who were cotreated with the antibiotic combination of trimethoprim and sulfamethoxazole (TMP-SMX), than in the 1,260 patients who received no such antibiotic prophylaxis in addition to their steroid therapy.
The adjusted hazard ratio (HR) for no PCP at 1 year of follow-up in the prophylaxis group, versus the no prophylaxis group, was 0.096 (P = .022).
The TMP-SMX combination also significantly reduced the mortality associated with PCP, with an adjusted HR of 0.09, versus no prophylaxis (P = .023).
“Pneumocystis pneumonia is a major opportunistic infection in immunocompromised patients associated with high morbidity and mortality,” explained the presenting study investigator Jun Won Park, MD, of Seoul National University Hospital in the Republic of Korea.
Dr. Park added that corticosteroid therapy was an important risk factor for PCP but that the risk-benefit ratio had not been evaluated sufficiently in patients with rheumatic diseases and that there was “different opinion among rheumatologists regarding [the value of] PCP prophylaxis.”
The current study aimed to see if primary antibiotic prophylaxis could prevent PCP in patients with rheumatic diseases, which included patients with systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis, and Behçet’s disease.
For inclusion, patients had to have been treated with prednisolone at a dose of 30 mg/day or more (or its equivalent) for at least 4 weeks and observed for 1 year. Patients with a prior history of PCP or conditions associated with this opportunistic infection, such as HIV, cancer, or solid organ or hematopoietic stem cell transplantation, were excluded.
Dr. Park reported that PCP prophylaxis was given at the discretion of the treating physician, and the mean duration of TMP-SMX was 230 days.
In the prophylaxis group, 34 adverse drug reactions occurred. Two of these reactions were serious – one case of pancytopenia and one case of Steven’s Johnson syndrome – but both resolved after the antibiotic treatment was discontinued.
A sensitivity analysis was performed, giving consistent results, and a risk-benefit analysis showed that the number needed to treat to prevent one case of PCP was 52, considering all rheumatic disease studied, while the number needed to cause one serious adverse drug reaction was 131.
Taken together, these results suggest a role for TMP-SMX as primary prophylaxis for PCP in patients with rheumatic diseases who need prolonged treatment with high-dose corticosteroids, Dr. Park said.
Dr. Park reported having no relevant financial disclosures.
MADRID – The benefits of primary prophylaxis for pneumocystis pneumonia (PCP) outweighed the risks of treatment in patients taking prolonged, high-dose corticosteroids for various rheumatic diseases in a study presented at the European Congress of Rheumatology.
In a single-center, retrospective cohort study of 1,522 corticosteroid treatment episodes in 1,092 patients with a variety of rheumatic conditions given over a 12-year follow-up period, the estimated incidence of PCP was 2.37 per 100 person-years.
Significantly fewer cases of PCP occurred at 1 year, however, in the 262 patients who were cotreated with the antibiotic combination of trimethoprim and sulfamethoxazole (TMP-SMX), than in the 1,260 patients who received no such antibiotic prophylaxis in addition to their steroid therapy.
The adjusted hazard ratio (HR) for no PCP at 1 year of follow-up in the prophylaxis group, versus the no prophylaxis group, was 0.096 (P = .022).
The TMP-SMX combination also significantly reduced the mortality associated with PCP, with an adjusted HR of 0.09, versus no prophylaxis (P = .023).
“Pneumocystis pneumonia is a major opportunistic infection in immunocompromised patients associated with high morbidity and mortality,” explained the presenting study investigator Jun Won Park, MD, of Seoul National University Hospital in the Republic of Korea.
Dr. Park added that corticosteroid therapy was an important risk factor for PCP but that the risk-benefit ratio had not been evaluated sufficiently in patients with rheumatic diseases and that there was “different opinion among rheumatologists regarding [the value of] PCP prophylaxis.”
The current study aimed to see if primary antibiotic prophylaxis could prevent PCP in patients with rheumatic diseases, which included patients with systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis, and Behçet’s disease.
For inclusion, patients had to have been treated with prednisolone at a dose of 30 mg/day or more (or its equivalent) for at least 4 weeks and observed for 1 year. Patients with a prior history of PCP or conditions associated with this opportunistic infection, such as HIV, cancer, or solid organ or hematopoietic stem cell transplantation, were excluded.
Dr. Park reported that PCP prophylaxis was given at the discretion of the treating physician, and the mean duration of TMP-SMX was 230 days.
In the prophylaxis group, 34 adverse drug reactions occurred. Two of these reactions were serious – one case of pancytopenia and one case of Steven’s Johnson syndrome – but both resolved after the antibiotic treatment was discontinued.
A sensitivity analysis was performed, giving consistent results, and a risk-benefit analysis showed that the number needed to treat to prevent one case of PCP was 52, considering all rheumatic disease studied, while the number needed to cause one serious adverse drug reaction was 131.
Taken together, these results suggest a role for TMP-SMX as primary prophylaxis for PCP in patients with rheumatic diseases who need prolonged treatment with high-dose corticosteroids, Dr. Park said.
Dr. Park reported having no relevant financial disclosures.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The adjusted hazard ratio (HR) for no PCP at 1 year of follow-up in the prophylaxis group, versus the no prophylaxis group, was 0.096 (P = .022).
Data source: A single-center, retrospective cohort study of 1,522 episodes of prolonged, high-dose steroid use in 1,092 patients with various rheumatic diseases.
Disclosures: Dr. Park reported having no relevant financial disclosures.
Romosozumab cuts new vertebral fracture risk by 73%, but safety data are concerning
MADRID – Romosozumab, an investigational bone-building agent, reduced new vertebral fractures by 73% among postmenopausal women with osteoporosis.
Compared with placebo, the monoclonal antibody also reduced the risk of a clinical fracture by 36% after 12 months of treatment, Piet Geusens, MD, said at the European Congress of Rheumatology. The effect was maintained at 24 months, with a 50% reduction in fracture risk, said Dr. Geusens of Maastricht University, the Netherlands.
Romosozumab also significantly reduced clinical and nonvertebral fractures and increased bone mineral density at the total hip, femoral neck, and lumbar spine in the phase III FRAME study, cosponsored by Amgen and UCB Pharma.
But recently, the finding of increased cardiovascular events in another highly anticipated phase III study of romosozumab cast a cloud of doubt over its rising star. During an interview at EULAR, a UCB company spokesman said the company no longer anticipates a 2017 Food and Drug Administration approval.
FRAME randomized 7,180 postmenopausal women with osteoporosis to monthly injections of romosozumab 210 mg or placebo for 12 months; after that, patients who had been taking placebo switched to denosumab. Dr. Geusens presented only the first year’s placebo-controlled portion. The full FRAME study was published in the New England Journal of Medicine last September (doi: 10.1056/NEJMoa1607948).
At baseline, the women had a mean bone mineral density T score of –2.7 at the lumbar spine, –2.4 at the total hip, and –2.7 at the femoral neck. Mean age was 71 years. About 20% of the women had a previous vertebral fracture, and 22% a previous nonvertebral fracture. The mean FRAX (fracture risk assessment tool) score was 13.4 in both groups.
After 12 months, a new vertebral fracture had occurred in 59 women taking placebo and 16 taking romosozumab (1.8% vs. 0.5%). This amounted to a 73% risk reduction, Dr. Geusens said. Although he did not present 24-month data, the published article cited the antibody’s sustained effect, with a 50% risk reduction evident after the 12-month comparison with denosumab.
The drug also exerted its benefit quickly, Dr. Geusens said. Most of the fractures in the active group occurred in the first 6 months of treatment, with only two additional fractures later.
Romosozumab also was associated with a 36% decrease in the risk of clinical fracture by 12 months (1.6% vs. 2.5% placebo). There was also a positive effect on nonvertebral fractures, which constituted more than 85% of the clinical fractures. Nonvertebral fractures occurred in 56 of those taking the antibody and 75 of those taking placebo (1.6% vs. 2.1%; hazard ratio [HR], .75).
By 12 months, bone mineral density had increased in the romosozumab group by 13% more than in the placebo group at the lumbar spine, by 7% more at the total hip, and by 6% more at the femoral neck.
Dr. Geusens did not address the adverse event profile during his talk. However, according to the published study, romosozumab was generally well tolerated. Serious hypersensitivity events occurred in seven romosozumab patients. Injection site reactions were mostly mild and occurred in 5% of the active group and 3% of the placebo group.
Two patients taking romosozumab experienced osteonecrosis of the jaw; both incidences occurred during the second 12 months and in conjunction with dental issues (tooth extraction and poorly fitted dentures). Anti-romosozumab antibodies developed in 18% and neutralizing antibodies in 0.7%.
Serious cardiovascular events occurred in about 1% of each treatment group, with 17 among those taking romosozumab and15 cardiovascular deaths among those taking placebo – not a significant difference.
UCB and Amgen were pleased with FRAME’s results and, last July, submitted a Biologics License Application to the FDA based on the positive data. A 2017 approval was anticipated, UCB spokesman Scott Fleming said in an interview. But in May, the primary safety analysis of another phase III study, ARCH, threw a monkey wrench in the works.
ARCH compared romosozumab to alendronate in 4,100 postmenopausal women with osteoporosis. ARCH met its primary and secondary endpoints, reducing the incidence of new vertebral fractures by 50%, clinical fractures by 27%, and nonvertebral fractures by 19%. But significantly more women taking the antibody experienced an adjudicated serious cardiovascular event (2.5% vs. 1.9% on alendronate).
On May 21, the companies said these new data would delay romosozumab’s progress toward approval, despite the fact that the submission was based on FRAMES’s positive safety and efficacy data.
Mr. Fleming confirmed this in an interview.
“Amgen has agreed with the FDA that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization, and as a result we do not expect approval of romosozumab in the U.S. to occur in 2017,” he said. “Patient safety is of utmost importance and whilst the cardiac imbalance observed in ARCH was not seen in FRAME, it is important and our responsibility to better understand this imbalance. Further analysis of the ARCH study data is ongoing and will be submitted to a future medical conference and for publication.”
Dr. Geusens refused to comment on the cardiovascular adverse events, saying he had not seen the ARCH data; nor did he explain the cardiovascular events that did occur in FRAME.
Romosozumab also is being reviewed in Canada and Japan; those processes are still underway. Mr. Fleming said the companies are preparing a European Medicines Agency application as well. “The preparation for the European regulatory submission will continue as planned – second half of 2017,” he said.
Dr. Geusens has received research support from Amgen and other pharmaceutical companies. He is a consultant for Amgen and a member of its speakers bureau.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Romosozumab, an investigational bone-building agent, reduced new vertebral fractures by 73% among postmenopausal women with osteoporosis.
Compared with placebo, the monoclonal antibody also reduced the risk of a clinical fracture by 36% after 12 months of treatment, Piet Geusens, MD, said at the European Congress of Rheumatology. The effect was maintained at 24 months, with a 50% reduction in fracture risk, said Dr. Geusens of Maastricht University, the Netherlands.
Romosozumab also significantly reduced clinical and nonvertebral fractures and increased bone mineral density at the total hip, femoral neck, and lumbar spine in the phase III FRAME study, cosponsored by Amgen and UCB Pharma.
But recently, the finding of increased cardiovascular events in another highly anticipated phase III study of romosozumab cast a cloud of doubt over its rising star. During an interview at EULAR, a UCB company spokesman said the company no longer anticipates a 2017 Food and Drug Administration approval.
FRAME randomized 7,180 postmenopausal women with osteoporosis to monthly injections of romosozumab 210 mg or placebo for 12 months; after that, patients who had been taking placebo switched to denosumab. Dr. Geusens presented only the first year’s placebo-controlled portion. The full FRAME study was published in the New England Journal of Medicine last September (doi: 10.1056/NEJMoa1607948).
At baseline, the women had a mean bone mineral density T score of –2.7 at the lumbar spine, –2.4 at the total hip, and –2.7 at the femoral neck. Mean age was 71 years. About 20% of the women had a previous vertebral fracture, and 22% a previous nonvertebral fracture. The mean FRAX (fracture risk assessment tool) score was 13.4 in both groups.
After 12 months, a new vertebral fracture had occurred in 59 women taking placebo and 16 taking romosozumab (1.8% vs. 0.5%). This amounted to a 73% risk reduction, Dr. Geusens said. Although he did not present 24-month data, the published article cited the antibody’s sustained effect, with a 50% risk reduction evident after the 12-month comparison with denosumab.
The drug also exerted its benefit quickly, Dr. Geusens said. Most of the fractures in the active group occurred in the first 6 months of treatment, with only two additional fractures later.
Romosozumab also was associated with a 36% decrease in the risk of clinical fracture by 12 months (1.6% vs. 2.5% placebo). There was also a positive effect on nonvertebral fractures, which constituted more than 85% of the clinical fractures. Nonvertebral fractures occurred in 56 of those taking the antibody and 75 of those taking placebo (1.6% vs. 2.1%; hazard ratio [HR], .75).
By 12 months, bone mineral density had increased in the romosozumab group by 13% more than in the placebo group at the lumbar spine, by 7% more at the total hip, and by 6% more at the femoral neck.
Dr. Geusens did not address the adverse event profile during his talk. However, according to the published study, romosozumab was generally well tolerated. Serious hypersensitivity events occurred in seven romosozumab patients. Injection site reactions were mostly mild and occurred in 5% of the active group and 3% of the placebo group.
Two patients taking romosozumab experienced osteonecrosis of the jaw; both incidences occurred during the second 12 months and in conjunction with dental issues (tooth extraction and poorly fitted dentures). Anti-romosozumab antibodies developed in 18% and neutralizing antibodies in 0.7%.
Serious cardiovascular events occurred in about 1% of each treatment group, with 17 among those taking romosozumab and15 cardiovascular deaths among those taking placebo – not a significant difference.
UCB and Amgen were pleased with FRAME’s results and, last July, submitted a Biologics License Application to the FDA based on the positive data. A 2017 approval was anticipated, UCB spokesman Scott Fleming said in an interview. But in May, the primary safety analysis of another phase III study, ARCH, threw a monkey wrench in the works.
ARCH compared romosozumab to alendronate in 4,100 postmenopausal women with osteoporosis. ARCH met its primary and secondary endpoints, reducing the incidence of new vertebral fractures by 50%, clinical fractures by 27%, and nonvertebral fractures by 19%. But significantly more women taking the antibody experienced an adjudicated serious cardiovascular event (2.5% vs. 1.9% on alendronate).
On May 21, the companies said these new data would delay romosozumab’s progress toward approval, despite the fact that the submission was based on FRAMES’s positive safety and efficacy data.
Mr. Fleming confirmed this in an interview.
“Amgen has agreed with the FDA that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization, and as a result we do not expect approval of romosozumab in the U.S. to occur in 2017,” he said. “Patient safety is of utmost importance and whilst the cardiac imbalance observed in ARCH was not seen in FRAME, it is important and our responsibility to better understand this imbalance. Further analysis of the ARCH study data is ongoing and will be submitted to a future medical conference and for publication.”
Dr. Geusens refused to comment on the cardiovascular adverse events, saying he had not seen the ARCH data; nor did he explain the cardiovascular events that did occur in FRAME.
Romosozumab also is being reviewed in Canada and Japan; those processes are still underway. Mr. Fleming said the companies are preparing a European Medicines Agency application as well. “The preparation for the European regulatory submission will continue as planned – second half of 2017,” he said.
Dr. Geusens has received research support from Amgen and other pharmaceutical companies. He is a consultant for Amgen and a member of its speakers bureau.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Romosozumab, an investigational bone-building agent, reduced new vertebral fractures by 73% among postmenopausal women with osteoporosis.
Compared with placebo, the monoclonal antibody also reduced the risk of a clinical fracture by 36% after 12 months of treatment, Piet Geusens, MD, said at the European Congress of Rheumatology. The effect was maintained at 24 months, with a 50% reduction in fracture risk, said Dr. Geusens of Maastricht University, the Netherlands.
Romosozumab also significantly reduced clinical and nonvertebral fractures and increased bone mineral density at the total hip, femoral neck, and lumbar spine in the phase III FRAME study, cosponsored by Amgen and UCB Pharma.
But recently, the finding of increased cardiovascular events in another highly anticipated phase III study of romosozumab cast a cloud of doubt over its rising star. During an interview at EULAR, a UCB company spokesman said the company no longer anticipates a 2017 Food and Drug Administration approval.
FRAME randomized 7,180 postmenopausal women with osteoporosis to monthly injections of romosozumab 210 mg or placebo for 12 months; after that, patients who had been taking placebo switched to denosumab. Dr. Geusens presented only the first year’s placebo-controlled portion. The full FRAME study was published in the New England Journal of Medicine last September (doi: 10.1056/NEJMoa1607948).
At baseline, the women had a mean bone mineral density T score of –2.7 at the lumbar spine, –2.4 at the total hip, and –2.7 at the femoral neck. Mean age was 71 years. About 20% of the women had a previous vertebral fracture, and 22% a previous nonvertebral fracture. The mean FRAX (fracture risk assessment tool) score was 13.4 in both groups.
After 12 months, a new vertebral fracture had occurred in 59 women taking placebo and 16 taking romosozumab (1.8% vs. 0.5%). This amounted to a 73% risk reduction, Dr. Geusens said. Although he did not present 24-month data, the published article cited the antibody’s sustained effect, with a 50% risk reduction evident after the 12-month comparison with denosumab.
The drug also exerted its benefit quickly, Dr. Geusens said. Most of the fractures in the active group occurred in the first 6 months of treatment, with only two additional fractures later.
Romosozumab also was associated with a 36% decrease in the risk of clinical fracture by 12 months (1.6% vs. 2.5% placebo). There was also a positive effect on nonvertebral fractures, which constituted more than 85% of the clinical fractures. Nonvertebral fractures occurred in 56 of those taking the antibody and 75 of those taking placebo (1.6% vs. 2.1%; hazard ratio [HR], .75).
By 12 months, bone mineral density had increased in the romosozumab group by 13% more than in the placebo group at the lumbar spine, by 7% more at the total hip, and by 6% more at the femoral neck.
Dr. Geusens did not address the adverse event profile during his talk. However, according to the published study, romosozumab was generally well tolerated. Serious hypersensitivity events occurred in seven romosozumab patients. Injection site reactions were mostly mild and occurred in 5% of the active group and 3% of the placebo group.
Two patients taking romosozumab experienced osteonecrosis of the jaw; both incidences occurred during the second 12 months and in conjunction with dental issues (tooth extraction and poorly fitted dentures). Anti-romosozumab antibodies developed in 18% and neutralizing antibodies in 0.7%.
Serious cardiovascular events occurred in about 1% of each treatment group, with 17 among those taking romosozumab and15 cardiovascular deaths among those taking placebo – not a significant difference.
UCB and Amgen were pleased with FRAME’s results and, last July, submitted a Biologics License Application to the FDA based on the positive data. A 2017 approval was anticipated, UCB spokesman Scott Fleming said in an interview. But in May, the primary safety analysis of another phase III study, ARCH, threw a monkey wrench in the works.
ARCH compared romosozumab to alendronate in 4,100 postmenopausal women with osteoporosis. ARCH met its primary and secondary endpoints, reducing the incidence of new vertebral fractures by 50%, clinical fractures by 27%, and nonvertebral fractures by 19%. But significantly more women taking the antibody experienced an adjudicated serious cardiovascular event (2.5% vs. 1.9% on alendronate).
On May 21, the companies said these new data would delay romosozumab’s progress toward approval, despite the fact that the submission was based on FRAMES’s positive safety and efficacy data.
Mr. Fleming confirmed this in an interview.
“Amgen has agreed with the FDA that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization, and as a result we do not expect approval of romosozumab in the U.S. to occur in 2017,” he said. “Patient safety is of utmost importance and whilst the cardiac imbalance observed in ARCH was not seen in FRAME, it is important and our responsibility to better understand this imbalance. Further analysis of the ARCH study data is ongoing and will be submitted to a future medical conference and for publication.”
Dr. Geusens refused to comment on the cardiovascular adverse events, saying he had not seen the ARCH data; nor did he explain the cardiovascular events that did occur in FRAME.
Romosozumab also is being reviewed in Canada and Japan; those processes are still underway. Mr. Fleming said the companies are preparing a European Medicines Agency application as well. “The preparation for the European regulatory submission will continue as planned – second half of 2017,” he said.
Dr. Geusens has received research support from Amgen and other pharmaceutical companies. He is a consultant for Amgen and a member of its speakers bureau.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Compared with placebo, the antibody reduced the risk of a new-onset vertebral fracture by 73% over 1 year.
Data source: FRAME, which randomized 7,180 women to monthly injections of 210 mg romosozumab or placebo for 12 months; for an additional 12 months, those taking placebo switched to denosumab.
Disclosures: Amgen and UCB Pharma are codeveloping the drug. Dr. Geusens is a consultant and speaker for Amgen, and has received research from the company.
VIDEO: No cancer risk found from biological DMARDs
MADRID – Additional real-world evidence confirmed that biological disease modifying drugs used to treat rheumatoid arthritis produced no spikes in new cancers or in cancer recurrences in registry data from tens of thousands of Swedish patients.
Among rheumatoid arthritis patients with a history of cancer, patients treated with a tumor necrosis factor inhibitor (TNFi) were not at an increased risk for cancer recurrence, Johan Askling, MD, said at the European Congress of Rheumatology. In a second study, patients with rheumatoid arthritis (RA) treated with a non-TNFi, biological, disease-modifying drug, specifically abatacept, rituximab, or tocilizumab, had no significantly different rate of new cancer onset when compared with RA patients who never received a biological disease modifying drug nor when compared with the general Swedish adult population, said Dr. Askling, a professor of clinical epidemiology at the Karolinska Institute in Stockholm.
“Five-year data are a good start, but we need data on 30-year risk,” Dr. Askling said in an interview.
The cancer-recurrence risk study with TNFi treatment used data collected by the Swedish national outpatient care registry on nearly 62,000 people, the Swedish cancer registry, and a rheumatology treatment registry called ARTIS. It also included patients treated during 2001-2014. From these sources, the researchers identified 446 RA patients with a history of at least one cancer who then began treatment with any type of TNFi and matched these cases with 1,278 similar RA patients with a cancer history who had never received a biologic drug. On average, the patients were nearly 10 years removed from their initial cancer diagnoses, and the average duration on TNFi treatment was nearly 5 years.
The adjusted hazard ratio for cancer recurrence among the TNFi recipients was reduced by a nominal 30%, compared with that of the controls, a difference that was not statistically significant, Dr. Askling reported.
The second study used data from similar sources for patients treated during 2006-2014 and included nearly 100,000 Swedes from the general population, more than 42,000 RA patients who did not receive a biological drug, more than 14,000 treated with either a first or second TNFi drug, and 1,693 patients treated with tocilizumab (Actemra), 1,894 on abatacept (Orencia), and 3,119 on rituximab (Rituxan).
The rates of new onset cancer in any of these treatment groups, including the patients on tocilizumab, abatacept, or rituximab, was not significantly different from the rate among RA patients who never received a biologic drug, nor from the general Swedish population rate, Dr. Askling said.
This is “one of the first large-scale assessments” of the cancer risk posed by non-TNFi biological drugs, aside from what was reported from the pivotal trials for these drugs, Dr. Askling said.
Dr. Askling has received research support from AbbVie, Lilly, MSD, Pfizer, Roche, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Rheumatologists began having concerns about the possible impact of biological drugs on cancer when these types of drugs first became available 20 or more years ago. Registries have allowed us to follow these patients, and, so far, we have consistently seen that the risk for cancer is very low. The major adverse effect from treatment with biological drugs is infection.
The most confirmed finding has been that biologic drugs do not cause new cancers. We have known less about the risk patients with a history of cancer face for recurrence by taking a biological drug. The data on this have so far been scarce. Most guidelines advise that, when patients have had cancer, the possible use of a biologic drug should be the subject of a shared-decision discussion with the patient. The new data reported by Dr. Askling add to the risk information we have available to discuss with patients.
The risk that biologic drugs poses for infections is more complex. The infection risk also depends on a patient’s use of glucocorticoids, their age, and their comorbidities. The infection risk faced by a patient from treatment with a biological drug requires an individualized discussion that takes into account the severity of all the relevant risk factors.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
João E. Fonseca, MD is a professor of rheumatology at the University of Lisbon. He has been a speaker for or has received research funding from Abbvie, MSD, Pfizer, Roche, and UCB. He made these comments in a video interview.
Rheumatologists began having concerns about the possible impact of biological drugs on cancer when these types of drugs first became available 20 or more years ago. Registries have allowed us to follow these patients, and, so far, we have consistently seen that the risk for cancer is very low. The major adverse effect from treatment with biological drugs is infection.
The most confirmed finding has been that biologic drugs do not cause new cancers. We have known less about the risk patients with a history of cancer face for recurrence by taking a biological drug. The data on this have so far been scarce. Most guidelines advise that, when patients have had cancer, the possible use of a biologic drug should be the subject of a shared-decision discussion with the patient. The new data reported by Dr. Askling add to the risk information we have available to discuss with patients.
The risk that biologic drugs poses for infections is more complex. The infection risk also depends on a patient’s use of glucocorticoids, their age, and their comorbidities. The infection risk faced by a patient from treatment with a biological drug requires an individualized discussion that takes into account the severity of all the relevant risk factors.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
João E. Fonseca, MD is a professor of rheumatology at the University of Lisbon. He has been a speaker for or has received research funding from Abbvie, MSD, Pfizer, Roche, and UCB. He made these comments in a video interview.
Rheumatologists began having concerns about the possible impact of biological drugs on cancer when these types of drugs first became available 20 or more years ago. Registries have allowed us to follow these patients, and, so far, we have consistently seen that the risk for cancer is very low. The major adverse effect from treatment with biological drugs is infection.
The most confirmed finding has been that biologic drugs do not cause new cancers. We have known less about the risk patients with a history of cancer face for recurrence by taking a biological drug. The data on this have so far been scarce. Most guidelines advise that, when patients have had cancer, the possible use of a biologic drug should be the subject of a shared-decision discussion with the patient. The new data reported by Dr. Askling add to the risk information we have available to discuss with patients.
The risk that biologic drugs poses for infections is more complex. The infection risk also depends on a patient’s use of glucocorticoids, their age, and their comorbidities. The infection risk faced by a patient from treatment with a biological drug requires an individualized discussion that takes into account the severity of all the relevant risk factors.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
João E. Fonseca, MD is a professor of rheumatology at the University of Lisbon. He has been a speaker for or has received research funding from Abbvie, MSD, Pfizer, Roche, and UCB. He made these comments in a video interview.
MADRID – Additional real-world evidence confirmed that biological disease modifying drugs used to treat rheumatoid arthritis produced no spikes in new cancers or in cancer recurrences in registry data from tens of thousands of Swedish patients.
Among rheumatoid arthritis patients with a history of cancer, patients treated with a tumor necrosis factor inhibitor (TNFi) were not at an increased risk for cancer recurrence, Johan Askling, MD, said at the European Congress of Rheumatology. In a second study, patients with rheumatoid arthritis (RA) treated with a non-TNFi, biological, disease-modifying drug, specifically abatacept, rituximab, or tocilizumab, had no significantly different rate of new cancer onset when compared with RA patients who never received a biological disease modifying drug nor when compared with the general Swedish adult population, said Dr. Askling, a professor of clinical epidemiology at the Karolinska Institute in Stockholm.
“Five-year data are a good start, but we need data on 30-year risk,” Dr. Askling said in an interview.
The cancer-recurrence risk study with TNFi treatment used data collected by the Swedish national outpatient care registry on nearly 62,000 people, the Swedish cancer registry, and a rheumatology treatment registry called ARTIS. It also included patients treated during 2001-2014. From these sources, the researchers identified 446 RA patients with a history of at least one cancer who then began treatment with any type of TNFi and matched these cases with 1,278 similar RA patients with a cancer history who had never received a biologic drug. On average, the patients were nearly 10 years removed from their initial cancer diagnoses, and the average duration on TNFi treatment was nearly 5 years.
The adjusted hazard ratio for cancer recurrence among the TNFi recipients was reduced by a nominal 30%, compared with that of the controls, a difference that was not statistically significant, Dr. Askling reported.
The second study used data from similar sources for patients treated during 2006-2014 and included nearly 100,000 Swedes from the general population, more than 42,000 RA patients who did not receive a biological drug, more than 14,000 treated with either a first or second TNFi drug, and 1,693 patients treated with tocilizumab (Actemra), 1,894 on abatacept (Orencia), and 3,119 on rituximab (Rituxan).
The rates of new onset cancer in any of these treatment groups, including the patients on tocilizumab, abatacept, or rituximab, was not significantly different from the rate among RA patients who never received a biologic drug, nor from the general Swedish population rate, Dr. Askling said.
This is “one of the first large-scale assessments” of the cancer risk posed by non-TNFi biological drugs, aside from what was reported from the pivotal trials for these drugs, Dr. Askling said.
Dr. Askling has received research support from AbbVie, Lilly, MSD, Pfizer, Roche, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Additional real-world evidence confirmed that biological disease modifying drugs used to treat rheumatoid arthritis produced no spikes in new cancers or in cancer recurrences in registry data from tens of thousands of Swedish patients.
Among rheumatoid arthritis patients with a history of cancer, patients treated with a tumor necrosis factor inhibitor (TNFi) were not at an increased risk for cancer recurrence, Johan Askling, MD, said at the European Congress of Rheumatology. In a second study, patients with rheumatoid arthritis (RA) treated with a non-TNFi, biological, disease-modifying drug, specifically abatacept, rituximab, or tocilizumab, had no significantly different rate of new cancer onset when compared with RA patients who never received a biological disease modifying drug nor when compared with the general Swedish adult population, said Dr. Askling, a professor of clinical epidemiology at the Karolinska Institute in Stockholm.
“Five-year data are a good start, but we need data on 30-year risk,” Dr. Askling said in an interview.
The cancer-recurrence risk study with TNFi treatment used data collected by the Swedish national outpatient care registry on nearly 62,000 people, the Swedish cancer registry, and a rheumatology treatment registry called ARTIS. It also included patients treated during 2001-2014. From these sources, the researchers identified 446 RA patients with a history of at least one cancer who then began treatment with any type of TNFi and matched these cases with 1,278 similar RA patients with a cancer history who had never received a biologic drug. On average, the patients were nearly 10 years removed from their initial cancer diagnoses, and the average duration on TNFi treatment was nearly 5 years.
The adjusted hazard ratio for cancer recurrence among the TNFi recipients was reduced by a nominal 30%, compared with that of the controls, a difference that was not statistically significant, Dr. Askling reported.
The second study used data from similar sources for patients treated during 2006-2014 and included nearly 100,000 Swedes from the general population, more than 42,000 RA patients who did not receive a biological drug, more than 14,000 treated with either a first or second TNFi drug, and 1,693 patients treated with tocilizumab (Actemra), 1,894 on abatacept (Orencia), and 3,119 on rituximab (Rituxan).
The rates of new onset cancer in any of these treatment groups, including the patients on tocilizumab, abatacept, or rituximab, was not significantly different from the rate among RA patients who never received a biologic drug, nor from the general Swedish population rate, Dr. Askling said.
This is “one of the first large-scale assessments” of the cancer risk posed by non-TNFi biological drugs, aside from what was reported from the pivotal trials for these drugs, Dr. Askling said.
Dr. Askling has received research support from AbbVie, Lilly, MSD, Pfizer, Roche, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Former cancer patients on a TNFi had no increased cancer recurrences, compared with patients on other rheumatic treatments.
Data source: Data from the Swedish national registries.
Disclosures: Dr. Askling has received research support from AbbVie, Lilly, MSD, Pfizer, Roche, and UCB.