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Biosimilar immunogenicity studies produce no surprises
AT EULAR 2017
MADRID – Two biosimilar tumor necrosis factor inhibitor (TNFi) products are no more immunogenic than their reference biologic counterparts in patients with rheumatoid arthritis, according to the results of two studies presented at the European Congress of Rheumatology.
Results of one study, which involved 544 RA patients, showed 33.1% treated with SB5, a biosimilar candidate for adalimumab (Humira), and 32% of those who were treated with reference adalimumab developed antidrug antibodies (ADAbs) after 24 weeks’ treatment.
In the second study, which involved 596 RA patients, significantly fewer treated with SB4, a biosimilar candidate for etanercept (Enbrel) developed ADAbs versus reference etanercept (0.7% vs. 13.1%, P less than .001).
In both studies the development of ADAbs with the biosimilar or reference products was found to attenuate the clinical responses seen, with trends towards lower American College of Rheumatology (ACR) scores with higher levels of ADAbs.
Dr. Kay observed that for both SB5 and adalimumab, efficacy at week 24 was higher among patients who achieved drug trough levels of 1.274 microg/mL or more than this threshold set for achieving a good EULAR response. At week 24, 32.9% and 43.2% of patients treated with the biosimilar adalimumab and reference adalimumab, respectively, had drug trough levels greater than or equal to the threshold, and achieved a good EULAR response, with 61.7% and 51.8% achieving a moderate EULAR response, and 5.4% and 5% no EULAR response. Dr. Kay also reported that similar percentages of patients treated with the biosimilar and reference adalimumab achieved a low disease activity (LDA) score or were in remission at 24 weeks if the drug trough levels were 1.274 microg/mL or above, at 32.9% and 43.2% for LDA and 20.8% and 25.9% for remission.
“Efficacy tended to be lower in patients with ADAbs,” Dr. Vencovský, who is vice-director of the Institute of Rheumatology, Charles University in Prague, Czech Republic, said. For both the ACR50 and ACR70 responses at week 24, no differences were seen between the patients who received biosimilar or reference etanercept. The impact on the ACR20 response could not be evaluated in the biosimilar group due to the low incidence of ADAbs, Dr. Vencovský said. The effect of injection site reactions on efficacy was also studied, and while no correlation was found between injection site reactions and the development of ADAbs, efficacy did tend to be slightly lower in some parameters measured in the patients who experienced injection site reactions. Dr. Vencovský reported that fewer patients treated with the biosimilar candidate experienced injection site reactions than those with the reference etanercept (3% vs. 16%).
The study presented by Dr. Kay is currently under consideration for publication and has previously been presented at the American College of Rheumatology.
Samsung Biopics sponsored the studies. The company has several biosimilar products in the pipeline, including SB2, which is a biosimilar for infliximab (Remicade) that was approved for use in the United States in April 2017. Although not yet available in the U.S., the company’s biosimilar adalimumab (SB5) is undergoing regulatory review by the European Medicines Agency (EMA) and it’s biosimilar etanercept is available in Europe as Benpali and Canada as Brenzys.
Dr. Kay has received research support paid to his institution from AbbVie, Genentech, Pfizer, Roche Laboratories, and UCB. He has also acted as a consultant to several companies that develop or market biosimilars including Samsung Bioepis who make the two biosimilar products mentioned in this report. Dr. Vencovský disclosed acting as a consultant to Samsung Bioepis and to Biogen, and acting as a speaker for UCB, Pfizer, AbbVie, MSD, Novartis, and Eli Lilly.
AT EULAR 2017
MADRID – Two biosimilar tumor necrosis factor inhibitor (TNFi) products are no more immunogenic than their reference biologic counterparts in patients with rheumatoid arthritis, according to the results of two studies presented at the European Congress of Rheumatology.
Results of one study, which involved 544 RA patients, showed 33.1% treated with SB5, a biosimilar candidate for adalimumab (Humira), and 32% of those who were treated with reference adalimumab developed antidrug antibodies (ADAbs) after 24 weeks’ treatment.
In the second study, which involved 596 RA patients, significantly fewer treated with SB4, a biosimilar candidate for etanercept (Enbrel) developed ADAbs versus reference etanercept (0.7% vs. 13.1%, P less than .001).
In both studies the development of ADAbs with the biosimilar or reference products was found to attenuate the clinical responses seen, with trends towards lower American College of Rheumatology (ACR) scores with higher levels of ADAbs.
Dr. Kay observed that for both SB5 and adalimumab, efficacy at week 24 was higher among patients who achieved drug trough levels of 1.274 microg/mL or more than this threshold set for achieving a good EULAR response. At week 24, 32.9% and 43.2% of patients treated with the biosimilar adalimumab and reference adalimumab, respectively, had drug trough levels greater than or equal to the threshold, and achieved a good EULAR response, with 61.7% and 51.8% achieving a moderate EULAR response, and 5.4% and 5% no EULAR response. Dr. Kay also reported that similar percentages of patients treated with the biosimilar and reference adalimumab achieved a low disease activity (LDA) score or were in remission at 24 weeks if the drug trough levels were 1.274 microg/mL or above, at 32.9% and 43.2% for LDA and 20.8% and 25.9% for remission.
“Efficacy tended to be lower in patients with ADAbs,” Dr. Vencovský, who is vice-director of the Institute of Rheumatology, Charles University in Prague, Czech Republic, said. For both the ACR50 and ACR70 responses at week 24, no differences were seen between the patients who received biosimilar or reference etanercept. The impact on the ACR20 response could not be evaluated in the biosimilar group due to the low incidence of ADAbs, Dr. Vencovský said. The effect of injection site reactions on efficacy was also studied, and while no correlation was found between injection site reactions and the development of ADAbs, efficacy did tend to be slightly lower in some parameters measured in the patients who experienced injection site reactions. Dr. Vencovský reported that fewer patients treated with the biosimilar candidate experienced injection site reactions than those with the reference etanercept (3% vs. 16%).
The study presented by Dr. Kay is currently under consideration for publication and has previously been presented at the American College of Rheumatology.
Samsung Biopics sponsored the studies. The company has several biosimilar products in the pipeline, including SB2, which is a biosimilar for infliximab (Remicade) that was approved for use in the United States in April 2017. Although not yet available in the U.S., the company’s biosimilar adalimumab (SB5) is undergoing regulatory review by the European Medicines Agency (EMA) and it’s biosimilar etanercept is available in Europe as Benpali and Canada as Brenzys.
Dr. Kay has received research support paid to his institution from AbbVie, Genentech, Pfizer, Roche Laboratories, and UCB. He has also acted as a consultant to several companies that develop or market biosimilars including Samsung Bioepis who make the two biosimilar products mentioned in this report. Dr. Vencovský disclosed acting as a consultant to Samsung Bioepis and to Biogen, and acting as a speaker for UCB, Pfizer, AbbVie, MSD, Novartis, and Eli Lilly.
AT EULAR 2017
MADRID – Two biosimilar tumor necrosis factor inhibitor (TNFi) products are no more immunogenic than their reference biologic counterparts in patients with rheumatoid arthritis, according to the results of two studies presented at the European Congress of Rheumatology.
Results of one study, which involved 544 RA patients, showed 33.1% treated with SB5, a biosimilar candidate for adalimumab (Humira), and 32% of those who were treated with reference adalimumab developed antidrug antibodies (ADAbs) after 24 weeks’ treatment.
In the second study, which involved 596 RA patients, significantly fewer treated with SB4, a biosimilar candidate for etanercept (Enbrel) developed ADAbs versus reference etanercept (0.7% vs. 13.1%, P less than .001).
In both studies the development of ADAbs with the biosimilar or reference products was found to attenuate the clinical responses seen, with trends towards lower American College of Rheumatology (ACR) scores with higher levels of ADAbs.
Dr. Kay observed that for both SB5 and adalimumab, efficacy at week 24 was higher among patients who achieved drug trough levels of 1.274 microg/mL or more than this threshold set for achieving a good EULAR response. At week 24, 32.9% and 43.2% of patients treated with the biosimilar adalimumab and reference adalimumab, respectively, had drug trough levels greater than or equal to the threshold, and achieved a good EULAR response, with 61.7% and 51.8% achieving a moderate EULAR response, and 5.4% and 5% no EULAR response. Dr. Kay also reported that similar percentages of patients treated with the biosimilar and reference adalimumab achieved a low disease activity (LDA) score or were in remission at 24 weeks if the drug trough levels were 1.274 microg/mL or above, at 32.9% and 43.2% for LDA and 20.8% and 25.9% for remission.
“Efficacy tended to be lower in patients with ADAbs,” Dr. Vencovský, who is vice-director of the Institute of Rheumatology, Charles University in Prague, Czech Republic, said. For both the ACR50 and ACR70 responses at week 24, no differences were seen between the patients who received biosimilar or reference etanercept. The impact on the ACR20 response could not be evaluated in the biosimilar group due to the low incidence of ADAbs, Dr. Vencovský said. The effect of injection site reactions on efficacy was also studied, and while no correlation was found between injection site reactions and the development of ADAbs, efficacy did tend to be slightly lower in some parameters measured in the patients who experienced injection site reactions. Dr. Vencovský reported that fewer patients treated with the biosimilar candidate experienced injection site reactions than those with the reference etanercept (3% vs. 16%).
The study presented by Dr. Kay is currently under consideration for publication and has previously been presented at the American College of Rheumatology.
Samsung Biopics sponsored the studies. The company has several biosimilar products in the pipeline, including SB2, which is a biosimilar for infliximab (Remicade) that was approved for use in the United States in April 2017. Although not yet available in the U.S., the company’s biosimilar adalimumab (SB5) is undergoing regulatory review by the European Medicines Agency (EMA) and it’s biosimilar etanercept is available in Europe as Benpali and Canada as Brenzys.
Dr. Kay has received research support paid to his institution from AbbVie, Genentech, Pfizer, Roche Laboratories, and UCB. He has also acted as a consultant to several companies that develop or market biosimilars including Samsung Bioepis who make the two biosimilar products mentioned in this report. Dr. Vencovský disclosed acting as a consultant to Samsung Bioepis and to Biogen, and acting as a speaker for UCB, Pfizer, AbbVie, MSD, Novartis, and Eli Lilly.
Key clinical point:
Major finding: Around one-third of biosimilar and reference adalimumab-treated patients developed anti-drug antibodies, while significantly fewer patients treated with biosimilar etanercept versus reference etanercept did so (0.7% vs. 13/1%, P less than .001).
Data source: Two studies in patients with rheumatoid arthritis treated with biosimilar adalimumab or biosimilar etanercept or the reference products.
Disclosures: Samsung Bioepis sponsored the studies. Dr. Kay has received research support paid to his institution from AbbVie, Pfizer, Genentech, Roche Laboratories, and UCB. He has also acted as a consultant to several companies that develop or market biosimilars including Samsung Bioepis who make the two biosimilar products mentioned in this report. Dr. Vencovský disclosed acting as a consultant to Samsung Bioepis and to Biogen, and acting as a speaker for UCB, Pfizer, AbbVie, MSD, Novartis, and Eli Lilly.
Biologics, TNF-inhibitors confer no excess cancer risks upon RA patients
MADRID – Biologics and tumor necrosis factor–inhibitors confer very little – if any – risk of malignancy upon those who take them for rheumatoid arthritis, according to a large Swedish registry study.
A doubling in the risk of squamous cell carcinoma among those who took abatacept was the only significant finding in the 8-year study of almost 70,000 subjects, Hjalmar Wadstrom, said at the European Congress of Rheumatology. And while he said the finding could be spurious, he stressed that it can’t be ignored.
“We think this finding should be interpreted cautiously,” said Mr. Wadstrom, a doctoral student at the Karolinska Institute, Stockholm. “These patients are seen frequently, and this increase in sqaumous cell carcinoma could be related to this multiple screening, or due to study bias. But of course, we cannot disregard it. It should be validated and further examined.”
The study plumbed several national patient registries and administrative databases for its cohort. It comprised 22,500 patients who, from 2006 to 2014, took tocilizumab, abatacept, or rituximab; or a TNF-inhibitor as a first or second disease-modifying antirheumatic drug. These were compared to 46,600 patients who took synthetic DMARDS during the same period and to a matched general population cohort (107,500). The mean age of all groups was about 59 years.
The primary outcome was a first-ever solid or hematologic malignancy excluding nonmelanoma skin cancer. The fully adjusted risk model controlled for age, sex, educational level, comorbidities, seropositivity, number of hospitalizations and days spent in inpatient care, use of prednisone at baseline, use of nonsteroidal anti-inflammatory drugs at baseline, number of prescription drugs at baseline, and sick leave and disability.
A first invasive solid tumor or hematologic malignancy occurred in 50 patients taking tocilizumab; 61 taking abatacept; 141 taking rituximab; 478 taking a TNF-inhibitor as the first biologic DMARD; and 169 taking a TNF-inhibitor as the second DMARD. There was no statistically significant difference between any of these groups, when they were compared either to each other, to those taking a conventional synthetic DMARD, or to the general population.
The doubled risk of squamous cell carcinoma associated with abatacept (HR 2.2) was the only significant positive finding the secondary analysis, Dr. Wadstrom said.
He had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Biologics and tumor necrosis factor–inhibitors confer very little – if any – risk of malignancy upon those who take them for rheumatoid arthritis, according to a large Swedish registry study.
A doubling in the risk of squamous cell carcinoma among those who took abatacept was the only significant finding in the 8-year study of almost 70,000 subjects, Hjalmar Wadstrom, said at the European Congress of Rheumatology. And while he said the finding could be spurious, he stressed that it can’t be ignored.
“We think this finding should be interpreted cautiously,” said Mr. Wadstrom, a doctoral student at the Karolinska Institute, Stockholm. “These patients are seen frequently, and this increase in sqaumous cell carcinoma could be related to this multiple screening, or due to study bias. But of course, we cannot disregard it. It should be validated and further examined.”
The study plumbed several national patient registries and administrative databases for its cohort. It comprised 22,500 patients who, from 2006 to 2014, took tocilizumab, abatacept, or rituximab; or a TNF-inhibitor as a first or second disease-modifying antirheumatic drug. These were compared to 46,600 patients who took synthetic DMARDS during the same period and to a matched general population cohort (107,500). The mean age of all groups was about 59 years.
The primary outcome was a first-ever solid or hematologic malignancy excluding nonmelanoma skin cancer. The fully adjusted risk model controlled for age, sex, educational level, comorbidities, seropositivity, number of hospitalizations and days spent in inpatient care, use of prednisone at baseline, use of nonsteroidal anti-inflammatory drugs at baseline, number of prescription drugs at baseline, and sick leave and disability.
A first invasive solid tumor or hematologic malignancy occurred in 50 patients taking tocilizumab; 61 taking abatacept; 141 taking rituximab; 478 taking a TNF-inhibitor as the first biologic DMARD; and 169 taking a TNF-inhibitor as the second DMARD. There was no statistically significant difference between any of these groups, when they were compared either to each other, to those taking a conventional synthetic DMARD, or to the general population.
The doubled risk of squamous cell carcinoma associated with abatacept (HR 2.2) was the only significant positive finding the secondary analysis, Dr. Wadstrom said.
He had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Biologics and tumor necrosis factor–inhibitors confer very little – if any – risk of malignancy upon those who take them for rheumatoid arthritis, according to a large Swedish registry study.
A doubling in the risk of squamous cell carcinoma among those who took abatacept was the only significant finding in the 8-year study of almost 70,000 subjects, Hjalmar Wadstrom, said at the European Congress of Rheumatology. And while he said the finding could be spurious, he stressed that it can’t be ignored.
“We think this finding should be interpreted cautiously,” said Mr. Wadstrom, a doctoral student at the Karolinska Institute, Stockholm. “These patients are seen frequently, and this increase in sqaumous cell carcinoma could be related to this multiple screening, or due to study bias. But of course, we cannot disregard it. It should be validated and further examined.”
The study plumbed several national patient registries and administrative databases for its cohort. It comprised 22,500 patients who, from 2006 to 2014, took tocilizumab, abatacept, or rituximab; or a TNF-inhibitor as a first or second disease-modifying antirheumatic drug. These were compared to 46,600 patients who took synthetic DMARDS during the same period and to a matched general population cohort (107,500). The mean age of all groups was about 59 years.
The primary outcome was a first-ever solid or hematologic malignancy excluding nonmelanoma skin cancer. The fully adjusted risk model controlled for age, sex, educational level, comorbidities, seropositivity, number of hospitalizations and days spent in inpatient care, use of prednisone at baseline, use of nonsteroidal anti-inflammatory drugs at baseline, number of prescription drugs at baseline, and sick leave and disability.
A first invasive solid tumor or hematologic malignancy occurred in 50 patients taking tocilizumab; 61 taking abatacept; 141 taking rituximab; 478 taking a TNF-inhibitor as the first biologic DMARD; and 169 taking a TNF-inhibitor as the second DMARD. There was no statistically significant difference between any of these groups, when they were compared either to each other, to those taking a conventional synthetic DMARD, or to the general population.
The doubled risk of squamous cell carcinoma associated with abatacept (HR 2.2) was the only significant positive finding the secondary analysis, Dr. Wadstrom said.
He had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT EULAR 2017
Key clinical point:
Major finding: A twofold increased risk of squamous cell carcinoma was associated with abatacept.
Data source: The Swedish study examined almost 70,000 people in various national registries and health care databases.
Disclosures: Mr. Wadstrom had no financial disclosures.
Safety data review finds no increased risk of infection from abatacept
MADRID – Abatacept doesn’t appear to increase the risk of opportunistic infections among patients with rheumatoid arthritis, Kevin Winthrop, MD, reported at the European Congress of Rheumatology.
After reviewing all of the extant safety data on the drug – all of its clinical trial and open-label study data, and case reports of abatacept-associated adverse events – Dr. Winthrop concluded that infections, including tuberculosis, fungal overgrowth, herpes simplex and herpes zoster, occur either with similar frequency or less often than among those taking placebo.
“In fact, there is a sense that abatacept is actually safer,” than some other disease-modifying antirheumatic drugs,” said Dr. Winthrop, an infectious disease specialist at Oregon Health and Science University, Portland. However, there are few data comparing safety among the agents – something he said should be examined in more detail.
His review encompassed 16 clinical trials comprising 7,044 patients who took the drug (21,330 patient/years of abatacept exposure) and 1,485 patients who took placebo. He conducted two analyses: one for opportunistic bacterial and fungal infections, and one for herpes simplex and herpes zoster.
The first analysis found 45 opportunistic bacterial or fungal infections among those taking abatacept – an incidence rate of 0.21/ 100 person-years. There were seven such infections in the placebo group – an incidence rate of 0.56/100 person-years. This difference was statistically significant.
In the abatacept cohort, there were two cases of bronchopulmonary aspergilliosis (IR 0.01) and three fungal eye infections (IR 0.01). There was also one case of gastrointestinal candidiasis; one fungal esophagitis; one cryptococcal meningitis; two pneumonias (one pseudomonal and one caused by Pneumocystis jirovecii); and two cases of respiratory monoliasis. All of these infections had an incidence rate of less than 0.01/100 person-years.
There were 17 tuberculosis cases (IR 0.08/100 person-years). Three cases were latent. Six of the cases were pulmonary and five were extrapulmonary. Two cases were unspecified. All occurred in regions with high or moderate endemic tuberculosis levels.
A meta-regression analysis examined the risk of opportunistic infections in the patients taken from the placebo-controlled clinical trials only (2,653 abatacept, 1,485 placebo). The estimated frequency of an opportunistic infection was 0.15% among those taking the drug and 0.48% among those taking placebo.
The herpes analysis examined the placebo-controlled clinical trial population as well. There were 57 cases of herpes simplex (IR 2.5/100 person-years) among those taking abatacept and 22 among those taking placebo (IR 1.8/100 person-years). The difference was not statistically significant.
There were 44 cases of herpes zoster among those taking abatacept (IR 1.9/100 person-years) and 21 among those taking placebo (IR 1.7/100 person-years).
“Basically, I think what we’re seeing here is a whole lot of nothing,” Dr. Winthrop said.
Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Abatacept doesn’t appear to increase the risk of opportunistic infections among patients with rheumatoid arthritis, Kevin Winthrop, MD, reported at the European Congress of Rheumatology.
After reviewing all of the extant safety data on the drug – all of its clinical trial and open-label study data, and case reports of abatacept-associated adverse events – Dr. Winthrop concluded that infections, including tuberculosis, fungal overgrowth, herpes simplex and herpes zoster, occur either with similar frequency or less often than among those taking placebo.
“In fact, there is a sense that abatacept is actually safer,” than some other disease-modifying antirheumatic drugs,” said Dr. Winthrop, an infectious disease specialist at Oregon Health and Science University, Portland. However, there are few data comparing safety among the agents – something he said should be examined in more detail.
His review encompassed 16 clinical trials comprising 7,044 patients who took the drug (21,330 patient/years of abatacept exposure) and 1,485 patients who took placebo. He conducted two analyses: one for opportunistic bacterial and fungal infections, and one for herpes simplex and herpes zoster.
The first analysis found 45 opportunistic bacterial or fungal infections among those taking abatacept – an incidence rate of 0.21/ 100 person-years. There were seven such infections in the placebo group – an incidence rate of 0.56/100 person-years. This difference was statistically significant.
In the abatacept cohort, there were two cases of bronchopulmonary aspergilliosis (IR 0.01) and three fungal eye infections (IR 0.01). There was also one case of gastrointestinal candidiasis; one fungal esophagitis; one cryptococcal meningitis; two pneumonias (one pseudomonal and one caused by Pneumocystis jirovecii); and two cases of respiratory monoliasis. All of these infections had an incidence rate of less than 0.01/100 person-years.
There were 17 tuberculosis cases (IR 0.08/100 person-years). Three cases were latent. Six of the cases were pulmonary and five were extrapulmonary. Two cases were unspecified. All occurred in regions with high or moderate endemic tuberculosis levels.
A meta-regression analysis examined the risk of opportunistic infections in the patients taken from the placebo-controlled clinical trials only (2,653 abatacept, 1,485 placebo). The estimated frequency of an opportunistic infection was 0.15% among those taking the drug and 0.48% among those taking placebo.
The herpes analysis examined the placebo-controlled clinical trial population as well. There were 57 cases of herpes simplex (IR 2.5/100 person-years) among those taking abatacept and 22 among those taking placebo (IR 1.8/100 person-years). The difference was not statistically significant.
There were 44 cases of herpes zoster among those taking abatacept (IR 1.9/100 person-years) and 21 among those taking placebo (IR 1.7/100 person-years).
“Basically, I think what we’re seeing here is a whole lot of nothing,” Dr. Winthrop said.
Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Abatacept doesn’t appear to increase the risk of opportunistic infections among patients with rheumatoid arthritis, Kevin Winthrop, MD, reported at the European Congress of Rheumatology.
After reviewing all of the extant safety data on the drug – all of its clinical trial and open-label study data, and case reports of abatacept-associated adverse events – Dr. Winthrop concluded that infections, including tuberculosis, fungal overgrowth, herpes simplex and herpes zoster, occur either with similar frequency or less often than among those taking placebo.
“In fact, there is a sense that abatacept is actually safer,” than some other disease-modifying antirheumatic drugs,” said Dr. Winthrop, an infectious disease specialist at Oregon Health and Science University, Portland. However, there are few data comparing safety among the agents – something he said should be examined in more detail.
His review encompassed 16 clinical trials comprising 7,044 patients who took the drug (21,330 patient/years of abatacept exposure) and 1,485 patients who took placebo. He conducted two analyses: one for opportunistic bacterial and fungal infections, and one for herpes simplex and herpes zoster.
The first analysis found 45 opportunistic bacterial or fungal infections among those taking abatacept – an incidence rate of 0.21/ 100 person-years. There were seven such infections in the placebo group – an incidence rate of 0.56/100 person-years. This difference was statistically significant.
In the abatacept cohort, there were two cases of bronchopulmonary aspergilliosis (IR 0.01) and three fungal eye infections (IR 0.01). There was also one case of gastrointestinal candidiasis; one fungal esophagitis; one cryptococcal meningitis; two pneumonias (one pseudomonal and one caused by Pneumocystis jirovecii); and two cases of respiratory monoliasis. All of these infections had an incidence rate of less than 0.01/100 person-years.
There were 17 tuberculosis cases (IR 0.08/100 person-years). Three cases were latent. Six of the cases were pulmonary and five were extrapulmonary. Two cases were unspecified. All occurred in regions with high or moderate endemic tuberculosis levels.
A meta-regression analysis examined the risk of opportunistic infections in the patients taken from the placebo-controlled clinical trials only (2,653 abatacept, 1,485 placebo). The estimated frequency of an opportunistic infection was 0.15% among those taking the drug and 0.48% among those taking placebo.
The herpes analysis examined the placebo-controlled clinical trial population as well. There were 57 cases of herpes simplex (IR 2.5/100 person-years) among those taking abatacept and 22 among those taking placebo (IR 1.8/100 person-years). The difference was not statistically significant.
There were 44 cases of herpes zoster among those taking abatacept (IR 1.9/100 person-years) and 21 among those taking placebo (IR 1.7/100 person-years).
“Basically, I think what we’re seeing here is a whole lot of nothing,” Dr. Winthrop said.
Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT EULAR 2017
Key clinical point:
Major finding: The overall incidence rate for opportunistic infection was 0.21/100 person-years for abatacept and 0.56 for placebo.
Data source: The review comprised 7,044 who took abatacept and 1,485 who took placebo.
Disclosures: Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.
Apremilast eases PsA symptoms in patients who are naive to biologics
MADRID – Aprelimast rapidly improved symptoms for patients with active psoriatic arthritis who were naive to biologics, whether or not they were on background methotrexate.
Response to the phosphodiesterase 4-inhibitor also increased with time, Peter Nash, MD, said at the European Congress of Rheumatology. By 2 weeks, 16% had achieved an ACR20 response. By 24 weeks, that had risen to 43%, and at 52 weeks, was 67%. Many patients responded even better, with 37% achieving an ACR50 response and 21% and ACR70 response by the end of the phase III placebo-controlled trial, said Dr. Nash of the University of Queensland, Brisbane, Australia.
ACTIVE randomized 229 patients with active psoriatic arthritis (PsA) to either placebo or 30 mg apremilast twice daily. The primary endpoint was ACR20 response at week 16. At that time, patients who had not improved by at least 10% were offered early escape into active therapy.
Patients were a mean of 49 years old, with mean disease duration of 4 years. This is considerably shorter than the duration seen in many PsA trials, Dr. Nash said. It was a reflection of the study requirement that patients have taken no more than one synthetic disease-modifying antirheumatic agent (sDMARD) and no biologics for their disease.
The active and placebo groups separated very early in this study, with 16% of the apremilast group achieving an ACR 20 response by 2 weeks compared to 6% taking placebo. The response curves remained significantly separated throughout the entire study. By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20. At this point, 11 of those taking apremilast asked for early escape and went on open-label apremilast at the same dose; 35 taking placebo were switched to open-label apremilast.
By 24 weeks, the ACR20 responses were 44% in the apremilast group and 25% in the placebo group. That response rate continued to rise over the year of treatment. By week 52, 67% of patients who had been on the study drug since the beginning had an ACR20, 37% an ACR50, and 21% an ACR70 response. ACR response was just as good in patients who were taking background methotrexate as those who were not, Dr. Nash said.
Compared to placebo, apremilast was associated with significantly more improvement on the Disease Activity Score-28 (CRP). Again, the response curves separated significantly by 2 weeks (–0.59 apremilast vs. –0.31 placebo) and continued to separate at 16 weeks (–1.07 vs. –0.39), and 24 weeks (–1.26 vs. –0.76). At 52 weeks, among those who had been initially randomized to apremilast, the mean DAS-28 (CRP) score had changed –1.71 from baseline.
The drug also significantly improved enthesitis relative to placebo, with rapid onset of action that continued to improve by week 24. The adverse event profile was good, Dr. Nash said. There were no opportunistic infections and no reactivations of tuberculosis. Ten in the active group and five in the placebo group withdrew due to an adverse event. Diarrhea and headache were the most common issues. Diarrhea occurred in 11% of the placebo group and 15% of the apremilast group; headache in 4% of the placebo group and 7% of the apremilast group. These were more common in the beginning of the study and tended to resolve with time, Dr. Nash said.
Thirty patients in the study had a history of depression and of these, two had a depression flare that lead to withdrawal from the study. Weight loss of at least 10% occurred in 5% of those taking apremilast.
Celgene sponsored the study. Dr. Nash has received research support from the company.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Aprelimast rapidly improved symptoms for patients with active psoriatic arthritis who were naive to biologics, whether or not they were on background methotrexate.
Response to the phosphodiesterase 4-inhibitor also increased with time, Peter Nash, MD, said at the European Congress of Rheumatology. By 2 weeks, 16% had achieved an ACR20 response. By 24 weeks, that had risen to 43%, and at 52 weeks, was 67%. Many patients responded even better, with 37% achieving an ACR50 response and 21% and ACR70 response by the end of the phase III placebo-controlled trial, said Dr. Nash of the University of Queensland, Brisbane, Australia.
ACTIVE randomized 229 patients with active psoriatic arthritis (PsA) to either placebo or 30 mg apremilast twice daily. The primary endpoint was ACR20 response at week 16. At that time, patients who had not improved by at least 10% were offered early escape into active therapy.
Patients were a mean of 49 years old, with mean disease duration of 4 years. This is considerably shorter than the duration seen in many PsA trials, Dr. Nash said. It was a reflection of the study requirement that patients have taken no more than one synthetic disease-modifying antirheumatic agent (sDMARD) and no biologics for their disease.
The active and placebo groups separated very early in this study, with 16% of the apremilast group achieving an ACR 20 response by 2 weeks compared to 6% taking placebo. The response curves remained significantly separated throughout the entire study. By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20. At this point, 11 of those taking apremilast asked for early escape and went on open-label apremilast at the same dose; 35 taking placebo were switched to open-label apremilast.
By 24 weeks, the ACR20 responses were 44% in the apremilast group and 25% in the placebo group. That response rate continued to rise over the year of treatment. By week 52, 67% of patients who had been on the study drug since the beginning had an ACR20, 37% an ACR50, and 21% an ACR70 response. ACR response was just as good in patients who were taking background methotrexate as those who were not, Dr. Nash said.
Compared to placebo, apremilast was associated with significantly more improvement on the Disease Activity Score-28 (CRP). Again, the response curves separated significantly by 2 weeks (–0.59 apremilast vs. –0.31 placebo) and continued to separate at 16 weeks (–1.07 vs. –0.39), and 24 weeks (–1.26 vs. –0.76). At 52 weeks, among those who had been initially randomized to apremilast, the mean DAS-28 (CRP) score had changed –1.71 from baseline.
The drug also significantly improved enthesitis relative to placebo, with rapid onset of action that continued to improve by week 24. The adverse event profile was good, Dr. Nash said. There were no opportunistic infections and no reactivations of tuberculosis. Ten in the active group and five in the placebo group withdrew due to an adverse event. Diarrhea and headache were the most common issues. Diarrhea occurred in 11% of the placebo group and 15% of the apremilast group; headache in 4% of the placebo group and 7% of the apremilast group. These were more common in the beginning of the study and tended to resolve with time, Dr. Nash said.
Thirty patients in the study had a history of depression and of these, two had a depression flare that lead to withdrawal from the study. Weight loss of at least 10% occurred in 5% of those taking apremilast.
Celgene sponsored the study. Dr. Nash has received research support from the company.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – Aprelimast rapidly improved symptoms for patients with active psoriatic arthritis who were naive to biologics, whether or not they were on background methotrexate.
Response to the phosphodiesterase 4-inhibitor also increased with time, Peter Nash, MD, said at the European Congress of Rheumatology. By 2 weeks, 16% had achieved an ACR20 response. By 24 weeks, that had risen to 43%, and at 52 weeks, was 67%. Many patients responded even better, with 37% achieving an ACR50 response and 21% and ACR70 response by the end of the phase III placebo-controlled trial, said Dr. Nash of the University of Queensland, Brisbane, Australia.
ACTIVE randomized 229 patients with active psoriatic arthritis (PsA) to either placebo or 30 mg apremilast twice daily. The primary endpoint was ACR20 response at week 16. At that time, patients who had not improved by at least 10% were offered early escape into active therapy.
Patients were a mean of 49 years old, with mean disease duration of 4 years. This is considerably shorter than the duration seen in many PsA trials, Dr. Nash said. It was a reflection of the study requirement that patients have taken no more than one synthetic disease-modifying antirheumatic agent (sDMARD) and no biologics for their disease.
The active and placebo groups separated very early in this study, with 16% of the apremilast group achieving an ACR 20 response by 2 weeks compared to 6% taking placebo. The response curves remained significantly separated throughout the entire study. By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20. At this point, 11 of those taking apremilast asked for early escape and went on open-label apremilast at the same dose; 35 taking placebo were switched to open-label apremilast.
By 24 weeks, the ACR20 responses were 44% in the apremilast group and 25% in the placebo group. That response rate continued to rise over the year of treatment. By week 52, 67% of patients who had been on the study drug since the beginning had an ACR20, 37% an ACR50, and 21% an ACR70 response. ACR response was just as good in patients who were taking background methotrexate as those who were not, Dr. Nash said.
Compared to placebo, apremilast was associated with significantly more improvement on the Disease Activity Score-28 (CRP). Again, the response curves separated significantly by 2 weeks (–0.59 apremilast vs. –0.31 placebo) and continued to separate at 16 weeks (–1.07 vs. –0.39), and 24 weeks (–1.26 vs. –0.76). At 52 weeks, among those who had been initially randomized to apremilast, the mean DAS-28 (CRP) score had changed –1.71 from baseline.
The drug also significantly improved enthesitis relative to placebo, with rapid onset of action that continued to improve by week 24. The adverse event profile was good, Dr. Nash said. There were no opportunistic infections and no reactivations of tuberculosis. Ten in the active group and five in the placebo group withdrew due to an adverse event. Diarrhea and headache were the most common issues. Diarrhea occurred in 11% of the placebo group and 15% of the apremilast group; headache in 4% of the placebo group and 7% of the apremilast group. These were more common in the beginning of the study and tended to resolve with time, Dr. Nash said.
Thirty patients in the study had a history of depression and of these, two had a depression flare that lead to withdrawal from the study. Weight loss of at least 10% occurred in 5% of those taking apremilast.
Celgene sponsored the study. Dr. Nash has received research support from the company.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT EULAR 2017
Key clinical point: Apremilast improved symptoms of psoriatic arthritis in patients who were naive to biologics.
Major finding: By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20.
Data source: The phase IIIb study randomized 229 patients to apremilast or placebo.
Disclosures: Celgene sponsored the trial. Dr. Nash has received research support from the company.
Panel revises spondyloarthritis treat-to-target recommendations
MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.
The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.
Among the evidence-based recommendations, the most striking was a new formulation for how to measure disease activity. The new recommendations call the ASDAS (Ankylosing Spondylitis Disease Activity Score) the “preferred” disease activity measure for patients with axial SpA and cite both the DAPSA (Disease Activity Index for Psoriatic Arthritis) as well as minimal disease activity as “considered to define the target” when treating PsA.
“This recommendation just made it,” squeaking onto the list with a 52% vote of approval from the task force members, said Dr. van der Heijde. “It had the longest discussion,” with a significant minority of panelists taking a different view.
ASDAS shook out as the preferred measure for axial SpA because of evidence linking a patient’s ASDAS with syndesmophyte formation. “The idea is that by targeting ASDAS you should have better outcomes,” she explained.
“Applying a treat-to-target approach in axial SpA is feasible but requires systematic collection of outcome parameters in daily practice,” such as ASDAS, said Dr. Dougados, professor of rheumatology at Cochin Hospital in Paris. Another piece currently lacking in the case for treat-to-target is demonstration of the clinical benefit from this approach in a trial, he added.
According to Dr. van der Heijde, the other four recommendations that now have evidence backup are:
- Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
- An alternative treatment target for PsA may be low or minimal disease activity.
- Measure disease activity by clinical signs and symptoms and by acute phase reactants.
- Once a treatment target is reached it should be maintained.
The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.
Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The evidence we now have is the difference between the new recommendations and the prior version. We have evidence from trials in patients with psoriatic arthritis using minimal disease activity as a target. And we have indirect evidence from observational studies in patients with SpA that suggest the higher the ASDAS, the more progression occurs. In addition, results reported at the EULAR 2017 Congress showed that reductions in the ASDAS appeared to correlate with the effect of a tumor necrosis factor inhibitor on reduced radiographic progression in patients with ankylosing spondylitis. But this is just an association; data from a randomized, prospective trial should be available next year.
The recommendations say to manage patients with axial SpA or psoriatic arthritis by treating them to a target. To do that a clinician needs a standardized assessment of a patient’s disease and to perform follow-up measurements to see if the target is met. The data Dr. Dougados cited from Paris document that assessments such as an ASDAS are rarely made. Getting an ASDAS means knowing either a patient’s C-reactive protein level or erythrocyte sedimentation rate. That requires blood work before a clinic visit, something patients often don’t want.
Will these recommendations change practice and make the ASDAS more widely used? That depends to some extent on whether any benefits or penalties linked to ASDAS use go into place.
Next year, we expect to see results from trials that are testing whether the treat-to-target approach produces better outcomes. Evidence like that will be important to further spur adoption.
Lianne S. Gensler, MD , is director of the ankylosing spondylitis clinic at the University of California, San Francisco. She has been a consultant to Novartis and Janssen and has received research support from AbbVie and UCB. Dr. Gensler was a member of the task force that issued the revised recommendations. She made these comments in an interview.
The evidence we now have is the difference between the new recommendations and the prior version. We have evidence from trials in patients with psoriatic arthritis using minimal disease activity as a target. And we have indirect evidence from observational studies in patients with SpA that suggest the higher the ASDAS, the more progression occurs. In addition, results reported at the EULAR 2017 Congress showed that reductions in the ASDAS appeared to correlate with the effect of a tumor necrosis factor inhibitor on reduced radiographic progression in patients with ankylosing spondylitis. But this is just an association; data from a randomized, prospective trial should be available next year.
The recommendations say to manage patients with axial SpA or psoriatic arthritis by treating them to a target. To do that a clinician needs a standardized assessment of a patient’s disease and to perform follow-up measurements to see if the target is met. The data Dr. Dougados cited from Paris document that assessments such as an ASDAS are rarely made. Getting an ASDAS means knowing either a patient’s C-reactive protein level or erythrocyte sedimentation rate. That requires blood work before a clinic visit, something patients often don’t want.
Will these recommendations change practice and make the ASDAS more widely used? That depends to some extent on whether any benefits or penalties linked to ASDAS use go into place.
Next year, we expect to see results from trials that are testing whether the treat-to-target approach produces better outcomes. Evidence like that will be important to further spur adoption.
Lianne S. Gensler, MD , is director of the ankylosing spondylitis clinic at the University of California, San Francisco. She has been a consultant to Novartis and Janssen and has received research support from AbbVie and UCB. Dr. Gensler was a member of the task force that issued the revised recommendations. She made these comments in an interview.
The evidence we now have is the difference between the new recommendations and the prior version. We have evidence from trials in patients with psoriatic arthritis using minimal disease activity as a target. And we have indirect evidence from observational studies in patients with SpA that suggest the higher the ASDAS, the more progression occurs. In addition, results reported at the EULAR 2017 Congress showed that reductions in the ASDAS appeared to correlate with the effect of a tumor necrosis factor inhibitor on reduced radiographic progression in patients with ankylosing spondylitis. But this is just an association; data from a randomized, prospective trial should be available next year.
The recommendations say to manage patients with axial SpA or psoriatic arthritis by treating them to a target. To do that a clinician needs a standardized assessment of a patient’s disease and to perform follow-up measurements to see if the target is met. The data Dr. Dougados cited from Paris document that assessments such as an ASDAS are rarely made. Getting an ASDAS means knowing either a patient’s C-reactive protein level or erythrocyte sedimentation rate. That requires blood work before a clinic visit, something patients often don’t want.
Will these recommendations change practice and make the ASDAS more widely used? That depends to some extent on whether any benefits or penalties linked to ASDAS use go into place.
Next year, we expect to see results from trials that are testing whether the treat-to-target approach produces better outcomes. Evidence like that will be important to further spur adoption.
Lianne S. Gensler, MD , is director of the ankylosing spondylitis clinic at the University of California, San Francisco. She has been a consultant to Novartis and Janssen and has received research support from AbbVie and UCB. Dr. Gensler was a member of the task force that issued the revised recommendations. She made these comments in an interview.
MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.
The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.
Among the evidence-based recommendations, the most striking was a new formulation for how to measure disease activity. The new recommendations call the ASDAS (Ankylosing Spondylitis Disease Activity Score) the “preferred” disease activity measure for patients with axial SpA and cite both the DAPSA (Disease Activity Index for Psoriatic Arthritis) as well as minimal disease activity as “considered to define the target” when treating PsA.
“This recommendation just made it,” squeaking onto the list with a 52% vote of approval from the task force members, said Dr. van der Heijde. “It had the longest discussion,” with a significant minority of panelists taking a different view.
ASDAS shook out as the preferred measure for axial SpA because of evidence linking a patient’s ASDAS with syndesmophyte formation. “The idea is that by targeting ASDAS you should have better outcomes,” she explained.
“Applying a treat-to-target approach in axial SpA is feasible but requires systematic collection of outcome parameters in daily practice,” such as ASDAS, said Dr. Dougados, professor of rheumatology at Cochin Hospital in Paris. Another piece currently lacking in the case for treat-to-target is demonstration of the clinical benefit from this approach in a trial, he added.
According to Dr. van der Heijde, the other four recommendations that now have evidence backup are:
- Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
- An alternative treatment target for PsA may be low or minimal disease activity.
- Measure disease activity by clinical signs and symptoms and by acute phase reactants.
- Once a treatment target is reached it should be maintained.
The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.
Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.
The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.
Among the evidence-based recommendations, the most striking was a new formulation for how to measure disease activity. The new recommendations call the ASDAS (Ankylosing Spondylitis Disease Activity Score) the “preferred” disease activity measure for patients with axial SpA and cite both the DAPSA (Disease Activity Index for Psoriatic Arthritis) as well as minimal disease activity as “considered to define the target” when treating PsA.
“This recommendation just made it,” squeaking onto the list with a 52% vote of approval from the task force members, said Dr. van der Heijde. “It had the longest discussion,” with a significant minority of panelists taking a different view.
ASDAS shook out as the preferred measure for axial SpA because of evidence linking a patient’s ASDAS with syndesmophyte formation. “The idea is that by targeting ASDAS you should have better outcomes,” she explained.
“Applying a treat-to-target approach in axial SpA is feasible but requires systematic collection of outcome parameters in daily practice,” such as ASDAS, said Dr. Dougados, professor of rheumatology at Cochin Hospital in Paris. Another piece currently lacking in the case for treat-to-target is demonstration of the clinical benefit from this approach in a trial, he added.
According to Dr. van der Heijde, the other four recommendations that now have evidence backup are:
- Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
- An alternative treatment target for PsA may be low or minimal disease activity.
- Measure disease activity by clinical signs and symptoms and by acute phase reactants.
- Once a treatment target is reached it should be maintained.
The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.
Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR 2017 CONGRESS
In Sweden, very few osteoporotic fractures prompt treatment within 12 months
MADRID – In Sweden, less than 7% of those who experience an osteoporotic fracture receive osteoporosis treatment within the first year, when the risk of a second fracture is the highest.
Women are more likely than are men to get a prescription, but people older than 80 years, and those with dementia or low socioeconomic status, are less likely to receive one, Anna Spångeus, MD, PhD, said at the European Congress of Rheumatology.
She expressed particular concern about the age differential observed in the study. “These drugs are equally as effective in the aged as in younger subjects. … It’s quite reasonable for a women aged 80-85 years to have treatment if she has a lower biological age and a good survival time that would allow her to benefit from the treatment.”
The investigators took advantage of Sweden’s multiple, inked national health registries to examine the rates of new osteoporosis prescriptions in treatment-naive patients who experienced a first osteoporotic bone fracture. Prescribing information came from the Prescribed Drug Register, which covers 100% of outpatient pharmacies. This database doesn’t include medications dispensed in hospitals, though, or intravenous osteoporotic treatments – a weakness of the study, Dr. Spångeus noted. The 6-year study period covered 2006-2012.
In all, almost 260,000 Swedish citizens naive to osteoporosis treatment had an osteoporotic bone fracture during that period. Most of these (68%) were women; the mean age was 73 years. Of these, 16,970 (6.6%) received therapy for osteoporosis within the first year after their fracture.
Vertebral fractures were the most likely to prompt treatment (21%). Only about 5% of all other fracture types prompted an osteoporosis treatment prescription, despite a clear clinical link to the disorder, Dr. Spångeus said. “Almost four times as many patients with clinical vertebral fractures initiated osteoporosis treatment in the year after the fracture. In contrast, treatment after hip fracture was significantly lower, despite the high subsequent risk.”
A good bit of news emerged when she parsed the group by comorbidities: 18% of patients with rheumatoid arthritis got an osteoporosis prescription, suggesting that clinicians were aware of the risk to bone posed by glucocorticoid therapy. Of all fracture patients on glucocorticoids, 17% got a prescription after their break. Only 6% of those not taking glucocorticoids got an osteoporosis medication.
Patients with chronic pulmonary diseases also tended to be treated more often, with about 10% getting a prescription. But those with dementia were much less likely to receive a prescription (1.5%), as were patients with any kind of social dependency – a marker of lower socioeconomic status (2%).
In an age analysis, patients aged 70-80 years were most often treated (19%). The youngest patients (50-60 years) and the oldest (90 and older) were the least likely to be treated (4% and 1.6%). About 6% of those aged 80-90 years were treated.
Women were almost four times more likely to get a prescription than were men (8.5% vs. 2.3%; odds ratio, 3.7). “This was concerning, because about a third of our cohort consisted of men,” Dr. Spångeus said. “Men do develop osteoporotic bone fractures, but this is not being recognized.”
The study was funded by an unrestricted grant from UCB Pharma. Dr. Spångeus disclosed that she has received research funding from Amgen and Eli Lilly.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
MADRID – In Sweden, less than 7% of those who experience an osteoporotic fracture receive osteoporosis treatment within the first year, when the risk of a second fracture is the highest.
Women are more likely than are men to get a prescription, but people older than 80 years, and those with dementia or low socioeconomic status, are less likely to receive one, Anna Spångeus, MD, PhD, said at the European Congress of Rheumatology.
She expressed particular concern about the age differential observed in the study. “These drugs are equally as effective in the aged as in younger subjects. … It’s quite reasonable for a women aged 80-85 years to have treatment if she has a lower biological age and a good survival time that would allow her to benefit from the treatment.”
The investigators took advantage of Sweden’s multiple, inked national health registries to examine the rates of new osteoporosis prescriptions in treatment-naive patients who experienced a first osteoporotic bone fracture. Prescribing information came from the Prescribed Drug Register, which covers 100% of outpatient pharmacies. This database doesn’t include medications dispensed in hospitals, though, or intravenous osteoporotic treatments – a weakness of the study, Dr. Spångeus noted. The 6-year study period covered 2006-2012.
In all, almost 260,000 Swedish citizens naive to osteoporosis treatment had an osteoporotic bone fracture during that period. Most of these (68%) were women; the mean age was 73 years. Of these, 16,970 (6.6%) received therapy for osteoporosis within the first year after their fracture.
Vertebral fractures were the most likely to prompt treatment (21%). Only about 5% of all other fracture types prompted an osteoporosis treatment prescription, despite a clear clinical link to the disorder, Dr. Spångeus said. “Almost four times as many patients with clinical vertebral fractures initiated osteoporosis treatment in the year after the fracture. In contrast, treatment after hip fracture was significantly lower, despite the high subsequent risk.”
A good bit of news emerged when she parsed the group by comorbidities: 18% of patients with rheumatoid arthritis got an osteoporosis prescription, suggesting that clinicians were aware of the risk to bone posed by glucocorticoid therapy. Of all fracture patients on glucocorticoids, 17% got a prescription after their break. Only 6% of those not taking glucocorticoids got an osteoporosis medication.
Patients with chronic pulmonary diseases also tended to be treated more often, with about 10% getting a prescription. But those with dementia were much less likely to receive a prescription (1.5%), as were patients with any kind of social dependency – a marker of lower socioeconomic status (2%).
In an age analysis, patients aged 70-80 years were most often treated (19%). The youngest patients (50-60 years) and the oldest (90 and older) were the least likely to be treated (4% and 1.6%). About 6% of those aged 80-90 years were treated.
Women were almost four times more likely to get a prescription than were men (8.5% vs. 2.3%; odds ratio, 3.7). “This was concerning, because about a third of our cohort consisted of men,” Dr. Spångeus said. “Men do develop osteoporotic bone fractures, but this is not being recognized.”
The study was funded by an unrestricted grant from UCB Pharma. Dr. Spångeus disclosed that she has received research funding from Amgen and Eli Lilly.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
MADRID – In Sweden, less than 7% of those who experience an osteoporotic fracture receive osteoporosis treatment within the first year, when the risk of a second fracture is the highest.
Women are more likely than are men to get a prescription, but people older than 80 years, and those with dementia or low socioeconomic status, are less likely to receive one, Anna Spångeus, MD, PhD, said at the European Congress of Rheumatology.
She expressed particular concern about the age differential observed in the study. “These drugs are equally as effective in the aged as in younger subjects. … It’s quite reasonable for a women aged 80-85 years to have treatment if she has a lower biological age and a good survival time that would allow her to benefit from the treatment.”
The investigators took advantage of Sweden’s multiple, inked national health registries to examine the rates of new osteoporosis prescriptions in treatment-naive patients who experienced a first osteoporotic bone fracture. Prescribing information came from the Prescribed Drug Register, which covers 100% of outpatient pharmacies. This database doesn’t include medications dispensed in hospitals, though, or intravenous osteoporotic treatments – a weakness of the study, Dr. Spångeus noted. The 6-year study period covered 2006-2012.
In all, almost 260,000 Swedish citizens naive to osteoporosis treatment had an osteoporotic bone fracture during that period. Most of these (68%) were women; the mean age was 73 years. Of these, 16,970 (6.6%) received therapy for osteoporosis within the first year after their fracture.
Vertebral fractures were the most likely to prompt treatment (21%). Only about 5% of all other fracture types prompted an osteoporosis treatment prescription, despite a clear clinical link to the disorder, Dr. Spångeus said. “Almost four times as many patients with clinical vertebral fractures initiated osteoporosis treatment in the year after the fracture. In contrast, treatment after hip fracture was significantly lower, despite the high subsequent risk.”
A good bit of news emerged when she parsed the group by comorbidities: 18% of patients with rheumatoid arthritis got an osteoporosis prescription, suggesting that clinicians were aware of the risk to bone posed by glucocorticoid therapy. Of all fracture patients on glucocorticoids, 17% got a prescription after their break. Only 6% of those not taking glucocorticoids got an osteoporosis medication.
Patients with chronic pulmonary diseases also tended to be treated more often, with about 10% getting a prescription. But those with dementia were much less likely to receive a prescription (1.5%), as were patients with any kind of social dependency – a marker of lower socioeconomic status (2%).
In an age analysis, patients aged 70-80 years were most often treated (19%). The youngest patients (50-60 years) and the oldest (90 and older) were the least likely to be treated (4% and 1.6%). About 6% of those aged 80-90 years were treated.
Women were almost four times more likely to get a prescription than were men (8.5% vs. 2.3%; odds ratio, 3.7). “This was concerning, because about a third of our cohort consisted of men,” Dr. Spångeus said. “Men do develop osteoporotic bone fractures, but this is not being recognized.”
The study was funded by an unrestricted grant from UCB Pharma. Dr. Spångeus disclosed that she has received research funding from Amgen and Eli Lilly.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Only 6.6% of patients who were naive to osteoporotic therapy and experienced a break received a prescription.
Data source: The national registry study, comprising about 290,000 patients.
Disclosures: UCB Pharma sponsored the study with an unrestricted grant. Dr. Spångeus has received research funding from Amgen and Eli Lilly.
Knee OA structural defects predict pain trajectories
The presence of bone marrow lesions and cartilage defects on baseline MRI scans of knee osteoarthritis (OA) patients may help to predict moderate to severe pain trajectories, based on data from a population-based study presented here at the European Congress of Rheumatology.
Three pain trajectories were identified: 52% of the patients reported stable mild pain over time, 33% reported moderate pain over time, and 15% reported fluctuating or severe pain over time.
“Knee pain is the most prominent symptom of knee osteoarthritis,” Dr. Pan said in an interview. “It is also a main reason for people to seek joint replacement. Despite this, the causes of knee pain are poorly understood. Therapy will only improve if we understand this better.”
Dr. Pan and his colleagues studied 1,099 adults with knee OA who participated in a population-based study. The mean age was 63 years (ranging from 51 to 81 years). A total of 875 participants were assessed using the knee pain components of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 2.6 years’ follow-up, 768 at 5.1 years’ follow-up, and 563 at 10.7 years’ follow-up.
Knee OA was assessed at baseline by x-ray, and T1-weighted or T2-weighted MRI scans of the right knee were used to assess knee structural pathology. The researchers applied group-based trajectory modeling to identify pain trajectories.
“We identified three distinct trajectories over time,” Dr. Pan said. “Remarkably, structural, environmental, sociodemographic, and psychological factors are associated with a more ‘severe pain’ trajectory, suggesting that pain course is determined by an integrated mix of all these factors.”
Dr. Pan added: “We already know that structural damage is a major driver in the development and maintenance of pain severity, but less is known about the other factors.”
The researchers found a significant dose-response relationship between the number of knee structural abnormalities, including cartilage defects and bone marrow lesions, and the ‘moderate pain’ and ‘severe pain’ trajectories (P less than .001 comparing both categories to the ‘mild pain’ trajectory).
Other factors that were significantly associated with both moderate and severe pain, compared with mild pain, included higher body mass index (overweight but not obese), emotional problems, and musculoskeletal diseases.
The findings provide support to the concept that “pain experience is both complex and individual in nature, suggesting the clinician should target treatments according to which of these factors predominate in the individual,” Dr. Pan said.
Future research may aim to develop “a predictive model that could be utilized in clinical practice and target therapies based on these trajectories.”
Dr. Pan had no financial conflicts to disclose.
The presence of bone marrow lesions and cartilage defects on baseline MRI scans of knee osteoarthritis (OA) patients may help to predict moderate to severe pain trajectories, based on data from a population-based study presented here at the European Congress of Rheumatology.
Three pain trajectories were identified: 52% of the patients reported stable mild pain over time, 33% reported moderate pain over time, and 15% reported fluctuating or severe pain over time.
“Knee pain is the most prominent symptom of knee osteoarthritis,” Dr. Pan said in an interview. “It is also a main reason for people to seek joint replacement. Despite this, the causes of knee pain are poorly understood. Therapy will only improve if we understand this better.”
Dr. Pan and his colleagues studied 1,099 adults with knee OA who participated in a population-based study. The mean age was 63 years (ranging from 51 to 81 years). A total of 875 participants were assessed using the knee pain components of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 2.6 years’ follow-up, 768 at 5.1 years’ follow-up, and 563 at 10.7 years’ follow-up.
Knee OA was assessed at baseline by x-ray, and T1-weighted or T2-weighted MRI scans of the right knee were used to assess knee structural pathology. The researchers applied group-based trajectory modeling to identify pain trajectories.
“We identified three distinct trajectories over time,” Dr. Pan said. “Remarkably, structural, environmental, sociodemographic, and psychological factors are associated with a more ‘severe pain’ trajectory, suggesting that pain course is determined by an integrated mix of all these factors.”
Dr. Pan added: “We already know that structural damage is a major driver in the development and maintenance of pain severity, but less is known about the other factors.”
The researchers found a significant dose-response relationship between the number of knee structural abnormalities, including cartilage defects and bone marrow lesions, and the ‘moderate pain’ and ‘severe pain’ trajectories (P less than .001 comparing both categories to the ‘mild pain’ trajectory).
Other factors that were significantly associated with both moderate and severe pain, compared with mild pain, included higher body mass index (overweight but not obese), emotional problems, and musculoskeletal diseases.
The findings provide support to the concept that “pain experience is both complex and individual in nature, suggesting the clinician should target treatments according to which of these factors predominate in the individual,” Dr. Pan said.
Future research may aim to develop “a predictive model that could be utilized in clinical practice and target therapies based on these trajectories.”
Dr. Pan had no financial conflicts to disclose.
The presence of bone marrow lesions and cartilage defects on baseline MRI scans of knee osteoarthritis (OA) patients may help to predict moderate to severe pain trajectories, based on data from a population-based study presented here at the European Congress of Rheumatology.
Three pain trajectories were identified: 52% of the patients reported stable mild pain over time, 33% reported moderate pain over time, and 15% reported fluctuating or severe pain over time.
“Knee pain is the most prominent symptom of knee osteoarthritis,” Dr. Pan said in an interview. “It is also a main reason for people to seek joint replacement. Despite this, the causes of knee pain are poorly understood. Therapy will only improve if we understand this better.”
Dr. Pan and his colleagues studied 1,099 adults with knee OA who participated in a population-based study. The mean age was 63 years (ranging from 51 to 81 years). A total of 875 participants were assessed using the knee pain components of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 2.6 years’ follow-up, 768 at 5.1 years’ follow-up, and 563 at 10.7 years’ follow-up.
Knee OA was assessed at baseline by x-ray, and T1-weighted or T2-weighted MRI scans of the right knee were used to assess knee structural pathology. The researchers applied group-based trajectory modeling to identify pain trajectories.
“We identified three distinct trajectories over time,” Dr. Pan said. “Remarkably, structural, environmental, sociodemographic, and psychological factors are associated with a more ‘severe pain’ trajectory, suggesting that pain course is determined by an integrated mix of all these factors.”
Dr. Pan added: “We already know that structural damage is a major driver in the development and maintenance of pain severity, but less is known about the other factors.”
The researchers found a significant dose-response relationship between the number of knee structural abnormalities, including cartilage defects and bone marrow lesions, and the ‘moderate pain’ and ‘severe pain’ trajectories (P less than .001 comparing both categories to the ‘mild pain’ trajectory).
Other factors that were significantly associated with both moderate and severe pain, compared with mild pain, included higher body mass index (overweight but not obese), emotional problems, and musculoskeletal diseases.
The findings provide support to the concept that “pain experience is both complex and individual in nature, suggesting the clinician should target treatments according to which of these factors predominate in the individual,” Dr. Pan said.
Future research may aim to develop “a predictive model that could be utilized in clinical practice and target therapies based on these trajectories.”
Dr. Pan had no financial conflicts to disclose.
FROM THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Three pain trajectories were identified: stable mild pain (52% of patients), moderate pain (33%), and fluctuating or severe pain (15%).
Data source: Population-based cohort study of 1,099 patients with knee OA.
Disclosures: The presenter had no financial conflicts to disclose.
VIDEO: Tocilizumab tested in children with sJIA under 2 years old
MADRID – The results of the first trial of a biologic agent in children less than 2 years of age with systemic juvenile idiopathic arthritis (sJIA) suggest that tocilizumab is likely to be effective in this age group.
“sJIA is the most severe form of childhood arthritis, and as you are aware, it’s the most difficult to treat as well,” said Navita L. Mallalieu, PhD, director of clinical pharmacology at Roche Innovation Center New York, the company that funded the study.
Tocilizumab (Actemra) has been available for the treatment of sJIA, both in the United States and the European Union since 2011, she observed at the European Congress of Rheumatology, but only for children aged 2 years or older at the current time.
Because of this prior history of use in sJIA, “we have confidence in the safety profile, and so we were able to go to the next step of testing children who were even younger than 2 years of age,” Dr. Mallalieu said in a video interview.
[polldaddy:9771949]
Dr. Mallalieu presented findings from an open-label, single-arm, phase I trial that evaluated a 12 mg/kg dosing regimen of tocilizumab, which was given intravenously every 2 weeks for 12 weeks. Eleven children were studied who had a mean age of 1.3 years and active disease for at least 1 month despite treatment with glucocorticoids or nonsteroidal anti-inflammatory drugs.
The primary endpoint was the pharmacokinetics of tocilizumab in this younger patient population, and secondary endpoints were safety, pharmacodynamics, and exploring the efficacy over 12 weeks on top of stable background therapy, she explained.
Results showed that tocilizumab in children under 2 years of age could achieve pharmacokinetics similar to those seen in older children in the TENDER trial (N Engl J Med. 2012;367:2385-95), which is the trial that helped the biologic get licensed for use in the older sJIA population. Reductions in soluble interleukin-6 receptor, C-reactive protein, and the erythrocyte sedimentation rate were seen, again to a similar extent as seen in the TENDER trial. There was also an indication that similar reductions in the Juvenile Arthritis Disease Activity Score (JADAS)-71 score could be achieved, Dr. Mallalieu reported.
While the pattern and nature of adverse events were similar to those seen in the TENDER trial, there were more cases of hypersensitivity in this phase I study. Four cases of hypersensitivity were clinically confirmed, three of which were deemed serious. The three serious cases were observed at day 15, with two of the cases associated with multiple signs and symptoms that were confounded by either subclinical macrophage activation syndrome (MAS) or a faster infusion rate. One patient had urticaria and was hospitalized for observation.
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 – The results of the first trial of a biologic agent in children less than 2 years of age with systemic juvenile idiopathic arthritis (sJIA) suggest that tocilizumab is likely to be effective in this age group.
“sJIA is the most severe form of childhood arthritis, and as you are aware, it’s the most difficult to treat as well,” said Navita L. Mallalieu, PhD, director of clinical pharmacology at Roche Innovation Center New York, the company that funded the study.
Tocilizumab (Actemra) has been available for the treatment of sJIA, both in the United States and the European Union since 2011, she observed at the European Congress of Rheumatology, but only for children aged 2 years or older at the current time.
Because of this prior history of use in sJIA, “we have confidence in the safety profile, and so we were able to go to the next step of testing children who were even younger than 2 years of age,” Dr. Mallalieu said in a video interview.
[polldaddy:9771949]
Dr. Mallalieu presented findings from an open-label, single-arm, phase I trial that evaluated a 12 mg/kg dosing regimen of tocilizumab, which was given intravenously every 2 weeks for 12 weeks. Eleven children were studied who had a mean age of 1.3 years and active disease for at least 1 month despite treatment with glucocorticoids or nonsteroidal anti-inflammatory drugs.
The primary endpoint was the pharmacokinetics of tocilizumab in this younger patient population, and secondary endpoints were safety, pharmacodynamics, and exploring the efficacy over 12 weeks on top of stable background therapy, she explained.
Results showed that tocilizumab in children under 2 years of age could achieve pharmacokinetics similar to those seen in older children in the TENDER trial (N Engl J Med. 2012;367:2385-95), which is the trial that helped the biologic get licensed for use in the older sJIA population. Reductions in soluble interleukin-6 receptor, C-reactive protein, and the erythrocyte sedimentation rate were seen, again to a similar extent as seen in the TENDER trial. There was also an indication that similar reductions in the Juvenile Arthritis Disease Activity Score (JADAS)-71 score could be achieved, Dr. Mallalieu reported.
While the pattern and nature of adverse events were similar to those seen in the TENDER trial, there were more cases of hypersensitivity in this phase I study. Four cases of hypersensitivity were clinically confirmed, three of which were deemed serious. The three serious cases were observed at day 15, with two of the cases associated with multiple signs and symptoms that were confounded by either subclinical macrophage activation syndrome (MAS) or a faster infusion rate. One patient had urticaria and was hospitalized for observation.
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 – The results of the first trial of a biologic agent in children less than 2 years of age with systemic juvenile idiopathic arthritis (sJIA) suggest that tocilizumab is likely to be effective in this age group.
“sJIA is the most severe form of childhood arthritis, and as you are aware, it’s the most difficult to treat as well,” said Navita L. Mallalieu, PhD, director of clinical pharmacology at Roche Innovation Center New York, the company that funded the study.
Tocilizumab (Actemra) has been available for the treatment of sJIA, both in the United States and the European Union since 2011, she observed at the European Congress of Rheumatology, but only for children aged 2 years or older at the current time.
Because of this prior history of use in sJIA, “we have confidence in the safety profile, and so we were able to go to the next step of testing children who were even younger than 2 years of age,” Dr. Mallalieu said in a video interview.
[polldaddy:9771949]
Dr. Mallalieu presented findings from an open-label, single-arm, phase I trial that evaluated a 12 mg/kg dosing regimen of tocilizumab, which was given intravenously every 2 weeks for 12 weeks. Eleven children were studied who had a mean age of 1.3 years and active disease for at least 1 month despite treatment with glucocorticoids or nonsteroidal anti-inflammatory drugs.
The primary endpoint was the pharmacokinetics of tocilizumab in this younger patient population, and secondary endpoints were safety, pharmacodynamics, and exploring the efficacy over 12 weeks on top of stable background therapy, she explained.
Results showed that tocilizumab in children under 2 years of age could achieve pharmacokinetics similar to those seen in older children in the TENDER trial (N Engl J Med. 2012;367:2385-95), which is the trial that helped the biologic get licensed for use in the older sJIA population. Reductions in soluble interleukin-6 receptor, C-reactive protein, and the erythrocyte sedimentation rate were seen, again to a similar extent as seen in the TENDER trial. There was also an indication that similar reductions in the Juvenile Arthritis Disease Activity Score (JADAS)-71 score could be achieved, Dr. Mallalieu reported.
While the pattern and nature of adverse events were similar to those seen in the TENDER trial, there were more cases of hypersensitivity in this phase I study. Four cases of hypersensitivity were clinically confirmed, three of which were deemed serious. The three serious cases were observed at day 15, with two of the cases associated with multiple signs and symptoms that were confounded by either subclinical macrophage activation syndrome (MAS) or a faster infusion rate. One patient had urticaria and was hospitalized for observation.
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: Similar pharmacokinetics were observed in children under 2 years of age as those seen in a prior study of older children.
Data source: Open-label, single-arm, phase I trial that evaluated a 12-mg/kg dosing regimen of tocilizumab given intravenously every 2 weeks for 12 weeks.
Disclosures: Roche funded the study. The presenter is an employee of Roche.
VIDEO: Childhood second-hand smoke boosts RA incidence
MADRID – Second-hand smoke exposure to children was about as potent a trigger for future rheumatoid arthritis as active smoking by an adult, based on an analysis of data collected from more than 70,000 French women followed for an average of more than 20 years
“This is the first demonstration of a rheumatoid arthritis risk associated with passive smoking,” Raphaèle Seror, MD, said at the European Congress of Rheumatology.
“This is an important finding because we can avoid passive smoke exposure,” Dr. Seror added in a video interview . The imperative to eliminate second-hand smoke exposure to children is particularly acute for those with a genetic risk for developing rheumatoid arthritis (RA), specifically children with a parent diagnosed with RA, suggested Dr. Seror, a professor of rheumatology at the University of Paris–South.
She and her associates used data collected in the E3N, a longitudinal French epidemiological study that enrolled nearly 100,000 women in 1990 when they were 40-65 years old and collected health data by questionnaire every 2-3 years for an average of 21 years. They identified from this cohort women with “confirmed” RA based on a self report of having incident RA during follow-up plus a coincident record of reimbursement for a prescription for an RA-specific treatment, such as methotrexate or a biological disease-modifying drug.
This identified 389 women with confirmed incident RA, including 350 with a complete smoking history that made the current analysis possible. The study also included 70,248 women who did not develop RA and who had provided a complete smoking history.
The analysis showed that women who reported a history of second-hand smoke exposure estimated at more than an hour daily as children but without a history of active smoking had a 43% higher rate of incident RA compared with never smoker women without a history of passive smoke exposure, Dr. Seror reported. This association just missed reaching statistical significance, a limitation that Dr. Seror attributed to a power issue as the analysis included only 30 women who had incident RA and a history of second-hand smoke exposure without adult smoke exposure. By comparison, women in the study with a history of active smoking without childhood exposure linked had a 37% increased incidence of RA, a finding that confirmed the well-known link between smoking and RA incidence.
The study also found that women with both second-hand smoke exposure as children and adult smoking linked with a 73% higher RA incidence, an indication that the contributions from second-hand smoke in children and active smoking by adults were not only similar in magnitude but also worked additively to promote RA development.
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 – Second-hand smoke exposure to children was about as potent a trigger for future rheumatoid arthritis as active smoking by an adult, based on an analysis of data collected from more than 70,000 French women followed for an average of more than 20 years
“This is the first demonstration of a rheumatoid arthritis risk associated with passive smoking,” Raphaèle Seror, MD, said at the European Congress of Rheumatology.
“This is an important finding because we can avoid passive smoke exposure,” Dr. Seror added in a video interview . The imperative to eliminate second-hand smoke exposure to children is particularly acute for those with a genetic risk for developing rheumatoid arthritis (RA), specifically children with a parent diagnosed with RA, suggested Dr. Seror, a professor of rheumatology at the University of Paris–South.
She and her associates used data collected in the E3N, a longitudinal French epidemiological study that enrolled nearly 100,000 women in 1990 when they were 40-65 years old and collected health data by questionnaire every 2-3 years for an average of 21 years. They identified from this cohort women with “confirmed” RA based on a self report of having incident RA during follow-up plus a coincident record of reimbursement for a prescription for an RA-specific treatment, such as methotrexate or a biological disease-modifying drug.
This identified 389 women with confirmed incident RA, including 350 with a complete smoking history that made the current analysis possible. The study also included 70,248 women who did not develop RA and who had provided a complete smoking history.
The analysis showed that women who reported a history of second-hand smoke exposure estimated at more than an hour daily as children but without a history of active smoking had a 43% higher rate of incident RA compared with never smoker women without a history of passive smoke exposure, Dr. Seror reported. This association just missed reaching statistical significance, a limitation that Dr. Seror attributed to a power issue as the analysis included only 30 women who had incident RA and a history of second-hand smoke exposure without adult smoke exposure. By comparison, women in the study with a history of active smoking without childhood exposure linked had a 37% increased incidence of RA, a finding that confirmed the well-known link between smoking and RA incidence.
The study also found that women with both second-hand smoke exposure as children and adult smoking linked with a 73% higher RA incidence, an indication that the contributions from second-hand smoke in children and active smoking by adults were not only similar in magnitude but also worked additively to promote RA development.
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 – Second-hand smoke exposure to children was about as potent a trigger for future rheumatoid arthritis as active smoking by an adult, based on an analysis of data collected from more than 70,000 French women followed for an average of more than 20 years
“This is the first demonstration of a rheumatoid arthritis risk associated with passive smoking,” Raphaèle Seror, MD, said at the European Congress of Rheumatology.
“This is an important finding because we can avoid passive smoke exposure,” Dr. Seror added in a video interview . The imperative to eliminate second-hand smoke exposure to children is particularly acute for those with a genetic risk for developing rheumatoid arthritis (RA), specifically children with a parent diagnosed with RA, suggested Dr. Seror, a professor of rheumatology at the University of Paris–South.
She and her associates used data collected in the E3N, a longitudinal French epidemiological study that enrolled nearly 100,000 women in 1990 when they were 40-65 years old and collected health data by questionnaire every 2-3 years for an average of 21 years. They identified from this cohort women with “confirmed” RA based on a self report of having incident RA during follow-up plus a coincident record of reimbursement for a prescription for an RA-specific treatment, such as methotrexate or a biological disease-modifying drug.
This identified 389 women with confirmed incident RA, including 350 with a complete smoking history that made the current analysis possible. The study also included 70,248 women who did not develop RA and who had provided a complete smoking history.
The analysis showed that women who reported a history of second-hand smoke exposure estimated at more than an hour daily as children but without a history of active smoking had a 43% higher rate of incident RA compared with never smoker women without a history of passive smoke exposure, Dr. Seror reported. This association just missed reaching statistical significance, a limitation that Dr. Seror attributed to a power issue as the analysis included only 30 women who had incident RA and a history of second-hand smoke exposure without adult smoke exposure. By comparison, women in the study with a history of active smoking without childhood exposure linked had a 37% increased incidence of RA, a finding that confirmed the well-known link between smoking and RA incidence.
The study also found that women with both second-hand smoke exposure as children and adult smoking linked with a 73% higher RA incidence, an indication that the contributions from second-hand smoke in children and active smoking by adults were not only similar in magnitude but also worked additively to promote RA development.
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
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Women with significant second-hand smoke exposure as children had a 43% increased rate of incident rheumatoid arthritis.
Data source: E3N, a prospective, longitudinal, observational study of nearly 100,000 French women begun in 1990.
Disclosures: Dr. Seror had no relevant disclosures.
Comorbidities emerge in adulthood for many patients with JIA
MADRID – More than half of young adults with juvenile idiopathic arthritis have comorbid conditions that impact their daily quality of life.
The issues range from directly disease-related – like uveitis – to more tangentially associated problems, like depression, Kirsten Minden, MD, said at the European Congress of Rheumatology.
She discussed the findings of two large German registries, Biologika in der Kinder-Rheumatologie (BiKeR) and Juvenile Arthritis-Methotrexate/Biologics Long-Term Observation (JUMBO).
Children enter BiKeR as soon as they receive a JIA diagnosis; they transfer to JuMBO when they turn 18 years old. Since 2001, 1,022 children have transitioned from the pediatric to young adult databases.
These patients are largely female (68%), with a mean age of 23 years and a mean disease duration of 13 years. Most (77%) had received at least one biologic disease-modifying antirheumatic drug; the mean number of those drugs received was 3. They were diagnosed with a wide variety of JIA subtypes: polyarthritis RF-negative (27%); enthesitis-related (20%); extended oligoarthritis (17%); polyarthritis RF-positive (9%); psoriatic arthritis (9%); persistent oligoarthritis (9%); and systemic arthritis (5%). The remainder had other subtypes.
More than half of the patients had at least one comorbidity; the mean number of issues per patient was two. Eye disorders were most common (17%), with uveitis making up 16% of that. Immune disorders were also common (12%). Psychiatric disorders occurred in 10%, with most of that (9%) being depression. Another 9% had skin or subcutaneous tissue disorders, including psoriasis (3%).
Autoimmune thyroiditis occurred in 2.5%, as did inflammatory bowel disease. General gastrointestinal disorders were present in 5%.
Men and women experienced different comorbidity clusters. Depression was more common among women (12% vs. 3%), as were pain disorders (6% vs. 2%) and autoimmune disorders (3% vs. 1%). Men, however, experienced more inflammatory bowel disease than women (4% vs. 2%).
Comorbidities were also expressed differently among the different JIA subtypes. Those with systemic disease were more likely to have hypertension (21%), osteoporosis (10%), and amyloidosis (4%). Uveitis was most common among those with extended oligoarthritis (35%). Psoriasis was most common among those with psoriatic arthritis (20%).
A progressive enrollment assessment showed some encouraging trends, however. The patients who enrolled in the earliest epoch (2001-2005) were also oldest at initial assessment (26). The majority of those (71%) had at least one comorbidity. But from 2006-2009, patients were younger when assessed, and fewer had comorbidities (55%). In the last epoch of 2010-2016, patients were a mean of 20 when assessed, and about 45% endorsed at least one comorbidity.
Hypertension, uveitis, and depression have all decreased since the first epoch, Dr. Minden noted. Hypertension has gone down from a rate of 21% in 2001-2005 to 13% most recently. Depression declined from 11.5%-6%, and uveitis, from 17%-2%.
This improvement, she said, may reflect newer trends in earlier diagnosis, earlier treatment, and more effective disease-modifying drugs.
“Age and disease duration do play a role in the presence of comorbidities, but whether the lower rates are due to younger age now is questionable,” she said. “It may be that the decreasing rates are due to earlier and better treatment strategies, and we are analyzing this now.”
A key finding supports this hypothesis, she noted.
“When we look at the presence of short stature over time, we can be encouraged about this. In the earliest period, 5% had short stature. That is now seen in less than 1% of our patients enrolled in the last decade.”
Dr. Minden is on the speakers bureau of Pfizer, Roche, and Pharm-Allergan. BiKeR is funded by unconditional grants from AbbVie, Germany, Novartis, Germany, and Roche, Germany, JuMBO by unconditional grants from AbbVie, Pfizer, and Roche.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – More than half of young adults with juvenile idiopathic arthritis have comorbid conditions that impact their daily quality of life.
The issues range from directly disease-related – like uveitis – to more tangentially associated problems, like depression, Kirsten Minden, MD, said at the European Congress of Rheumatology.
She discussed the findings of two large German registries, Biologika in der Kinder-Rheumatologie (BiKeR) and Juvenile Arthritis-Methotrexate/Biologics Long-Term Observation (JUMBO).
Children enter BiKeR as soon as they receive a JIA diagnosis; they transfer to JuMBO when they turn 18 years old. Since 2001, 1,022 children have transitioned from the pediatric to young adult databases.
These patients are largely female (68%), with a mean age of 23 years and a mean disease duration of 13 years. Most (77%) had received at least one biologic disease-modifying antirheumatic drug; the mean number of those drugs received was 3. They were diagnosed with a wide variety of JIA subtypes: polyarthritis RF-negative (27%); enthesitis-related (20%); extended oligoarthritis (17%); polyarthritis RF-positive (9%); psoriatic arthritis (9%); persistent oligoarthritis (9%); and systemic arthritis (5%). The remainder had other subtypes.
More than half of the patients had at least one comorbidity; the mean number of issues per patient was two. Eye disorders were most common (17%), with uveitis making up 16% of that. Immune disorders were also common (12%). Psychiatric disorders occurred in 10%, with most of that (9%) being depression. Another 9% had skin or subcutaneous tissue disorders, including psoriasis (3%).
Autoimmune thyroiditis occurred in 2.5%, as did inflammatory bowel disease. General gastrointestinal disorders were present in 5%.
Men and women experienced different comorbidity clusters. Depression was more common among women (12% vs. 3%), as were pain disorders (6% vs. 2%) and autoimmune disorders (3% vs. 1%). Men, however, experienced more inflammatory bowel disease than women (4% vs. 2%).
Comorbidities were also expressed differently among the different JIA subtypes. Those with systemic disease were more likely to have hypertension (21%), osteoporosis (10%), and amyloidosis (4%). Uveitis was most common among those with extended oligoarthritis (35%). Psoriasis was most common among those with psoriatic arthritis (20%).
A progressive enrollment assessment showed some encouraging trends, however. The patients who enrolled in the earliest epoch (2001-2005) were also oldest at initial assessment (26). The majority of those (71%) had at least one comorbidity. But from 2006-2009, patients were younger when assessed, and fewer had comorbidities (55%). In the last epoch of 2010-2016, patients were a mean of 20 when assessed, and about 45% endorsed at least one comorbidity.
Hypertension, uveitis, and depression have all decreased since the first epoch, Dr. Minden noted. Hypertension has gone down from a rate of 21% in 2001-2005 to 13% most recently. Depression declined from 11.5%-6%, and uveitis, from 17%-2%.
This improvement, she said, may reflect newer trends in earlier diagnosis, earlier treatment, and more effective disease-modifying drugs.
“Age and disease duration do play a role in the presence of comorbidities, but whether the lower rates are due to younger age now is questionable,” she said. “It may be that the decreasing rates are due to earlier and better treatment strategies, and we are analyzing this now.”
A key finding supports this hypothesis, she noted.
“When we look at the presence of short stature over time, we can be encouraged about this. In the earliest period, 5% had short stature. That is now seen in less than 1% of our patients enrolled in the last decade.”
Dr. Minden is on the speakers bureau of Pfizer, Roche, and Pharm-Allergan. BiKeR is funded by unconditional grants from AbbVie, Germany, Novartis, Germany, and Roche, Germany, JuMBO by unconditional grants from AbbVie, Pfizer, and Roche.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – More than half of young adults with juvenile idiopathic arthritis have comorbid conditions that impact their daily quality of life.
The issues range from directly disease-related – like uveitis – to more tangentially associated problems, like depression, Kirsten Minden, MD, said at the European Congress of Rheumatology.
She discussed the findings of two large German registries, Biologika in der Kinder-Rheumatologie (BiKeR) and Juvenile Arthritis-Methotrexate/Biologics Long-Term Observation (JUMBO).
Children enter BiKeR as soon as they receive a JIA diagnosis; they transfer to JuMBO when they turn 18 years old. Since 2001, 1,022 children have transitioned from the pediatric to young adult databases.
These patients are largely female (68%), with a mean age of 23 years and a mean disease duration of 13 years. Most (77%) had received at least one biologic disease-modifying antirheumatic drug; the mean number of those drugs received was 3. They were diagnosed with a wide variety of JIA subtypes: polyarthritis RF-negative (27%); enthesitis-related (20%); extended oligoarthritis (17%); polyarthritis RF-positive (9%); psoriatic arthritis (9%); persistent oligoarthritis (9%); and systemic arthritis (5%). The remainder had other subtypes.
More than half of the patients had at least one comorbidity; the mean number of issues per patient was two. Eye disorders were most common (17%), with uveitis making up 16% of that. Immune disorders were also common (12%). Psychiatric disorders occurred in 10%, with most of that (9%) being depression. Another 9% had skin or subcutaneous tissue disorders, including psoriasis (3%).
Autoimmune thyroiditis occurred in 2.5%, as did inflammatory bowel disease. General gastrointestinal disorders were present in 5%.
Men and women experienced different comorbidity clusters. Depression was more common among women (12% vs. 3%), as were pain disorders (6% vs. 2%) and autoimmune disorders (3% vs. 1%). Men, however, experienced more inflammatory bowel disease than women (4% vs. 2%).
Comorbidities were also expressed differently among the different JIA subtypes. Those with systemic disease were more likely to have hypertension (21%), osteoporosis (10%), and amyloidosis (4%). Uveitis was most common among those with extended oligoarthritis (35%). Psoriasis was most common among those with psoriatic arthritis (20%).
A progressive enrollment assessment showed some encouraging trends, however. The patients who enrolled in the earliest epoch (2001-2005) were also oldest at initial assessment (26). The majority of those (71%) had at least one comorbidity. But from 2006-2009, patients were younger when assessed, and fewer had comorbidities (55%). In the last epoch of 2010-2016, patients were a mean of 20 when assessed, and about 45% endorsed at least one comorbidity.
Hypertension, uveitis, and depression have all decreased since the first epoch, Dr. Minden noted. Hypertension has gone down from a rate of 21% in 2001-2005 to 13% most recently. Depression declined from 11.5%-6%, and uveitis, from 17%-2%.
This improvement, she said, may reflect newer trends in earlier diagnosis, earlier treatment, and more effective disease-modifying drugs.
“Age and disease duration do play a role in the presence of comorbidities, but whether the lower rates are due to younger age now is questionable,” she said. “It may be that the decreasing rates are due to earlier and better treatment strategies, and we are analyzing this now.”
A key finding supports this hypothesis, she noted.
“When we look at the presence of short stature over time, we can be encouraged about this. In the earliest period, 5% had short stature. That is now seen in less than 1% of our patients enrolled in the last decade.”
Dr. Minden is on the speakers bureau of Pfizer, Roche, and Pharm-Allergan. BiKeR is funded by unconditional grants from AbbVie, Germany, Novartis, Germany, and Roche, Germany, JuMBO by unconditional grants from AbbVie, Pfizer, and Roche.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: More than half of these patients (54%) have at least one comorbidity that interferes with their quality of life.
Data source: The JuMBO registry used in the study comprised 1,022 patients.
Disclosures: Dr. Minden is on the speakers bureau of Pfizer, Roche, and Pharm-Allergan. BiKeR is funded by unconditional grants from AbbVie, Germany, Novartis, Germany, and Roche, Germany; JuMBO by unconditional grants from AbbVie, Pfizer, and Roch