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Experts cite different approaches to try for methotrexate-related nausea, fatigue
Methotrexate-related nausea and fatigue are an issue for many rheumatology patients who otherwise benefit from the treatment, but
Subcutaneous dosing is one option suggested by panel members Christopher Ritchlin, MD, of the University of Rochester (N.Y.) and Douglas Veale, MD, of St. Vincent’s University Hospital, Dublin, who along with several other colleagues fielded questions during a discussion session at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“I like sub-Q,” agreed discussion moderator Michael E. Weinblatt, MD, of Brigham and Women’s Hospital, Boston. “But I actually would lower the dose sub-Q before I gave it because you actually may get a higher serum level,” he said, explaining that that may negate the benefits with respect to nausea.
His preferred approach, he said, is to either split dosing – for example, splitting a 20-mg dose into two 10-mg doses followed 10 hours later with Leucovorin (folinic acid) – or to give the full methotrexate dose at bedtime followed 10 hours later with Leucovorin.
“I use a lot of Leucovorin – a lot,” he noted.
For those patients who get nauseated at the mere mention of methotrexate, though, it’s probably best to try a different drug, he said.
Another approach, suggested by Vivian Bykerk, MD, of the Hospital for Special Surgery in New York, is to give Zofran (ondansetron) with methotrexate. Other suggestions included lowering the methotrexate dose and injecting the drug.
For fatigue, there has been some suggestion of a benefit with B-12 supplementation, panel members said. Dr. Bykerk noted some ongoing work that is demonstrating a benefit with sublingual B-12 for methotrexate intolerance in general, and it appears to allow for much higher methotrexate dosing, she said.
Early reports regarding those as-yet-unpublished data are, indeed, promising, Dr. Weinblatt said, noting that in his practice he has been using subcutaneous B-12 given at about 1,000 mcg 2 days before methotrexate and then on the day of methotrexate for patients with fatigue who are “failing Leucovorin, failing caffeine.”
Addressing fatigue and nausea in patients on methotrexate is important because, in his experience in appropriately monitored patients, it’s not serious adverse events, but rather fatigue and nausea, that most often lead to stopping methotrexate.
Dr. Weinblatt reported financial relationships with nearly 20 pharmaceutical companies. Dr. Bykerk reported financial relationships with Amgen, Brainstorm, Bristol-Myers Squibb, Pfizer, and Regeneron. Dr. Veale reported financial relationships with AbbVie, Janssen, Pfizer, Roche, and UCB. Dr. Ritchlin reported financial relationships with AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and UCB.
Methotrexate-related nausea and fatigue are an issue for many rheumatology patients who otherwise benefit from the treatment, but
Subcutaneous dosing is one option suggested by panel members Christopher Ritchlin, MD, of the University of Rochester (N.Y.) and Douglas Veale, MD, of St. Vincent’s University Hospital, Dublin, who along with several other colleagues fielded questions during a discussion session at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“I like sub-Q,” agreed discussion moderator Michael E. Weinblatt, MD, of Brigham and Women’s Hospital, Boston. “But I actually would lower the dose sub-Q before I gave it because you actually may get a higher serum level,” he said, explaining that that may negate the benefits with respect to nausea.
His preferred approach, he said, is to either split dosing – for example, splitting a 20-mg dose into two 10-mg doses followed 10 hours later with Leucovorin (folinic acid) – or to give the full methotrexate dose at bedtime followed 10 hours later with Leucovorin.
“I use a lot of Leucovorin – a lot,” he noted.
For those patients who get nauseated at the mere mention of methotrexate, though, it’s probably best to try a different drug, he said.
Another approach, suggested by Vivian Bykerk, MD, of the Hospital for Special Surgery in New York, is to give Zofran (ondansetron) with methotrexate. Other suggestions included lowering the methotrexate dose and injecting the drug.
For fatigue, there has been some suggestion of a benefit with B-12 supplementation, panel members said. Dr. Bykerk noted some ongoing work that is demonstrating a benefit with sublingual B-12 for methotrexate intolerance in general, and it appears to allow for much higher methotrexate dosing, she said.
Early reports regarding those as-yet-unpublished data are, indeed, promising, Dr. Weinblatt said, noting that in his practice he has been using subcutaneous B-12 given at about 1,000 mcg 2 days before methotrexate and then on the day of methotrexate for patients with fatigue who are “failing Leucovorin, failing caffeine.”
Addressing fatigue and nausea in patients on methotrexate is important because, in his experience in appropriately monitored patients, it’s not serious adverse events, but rather fatigue and nausea, that most often lead to stopping methotrexate.
Dr. Weinblatt reported financial relationships with nearly 20 pharmaceutical companies. Dr. Bykerk reported financial relationships with Amgen, Brainstorm, Bristol-Myers Squibb, Pfizer, and Regeneron. Dr. Veale reported financial relationships with AbbVie, Janssen, Pfizer, Roche, and UCB. Dr. Ritchlin reported financial relationships with AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and UCB.
Methotrexate-related nausea and fatigue are an issue for many rheumatology patients who otherwise benefit from the treatment, but
Subcutaneous dosing is one option suggested by panel members Christopher Ritchlin, MD, of the University of Rochester (N.Y.) and Douglas Veale, MD, of St. Vincent’s University Hospital, Dublin, who along with several other colleagues fielded questions during a discussion session at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“I like sub-Q,” agreed discussion moderator Michael E. Weinblatt, MD, of Brigham and Women’s Hospital, Boston. “But I actually would lower the dose sub-Q before I gave it because you actually may get a higher serum level,” he said, explaining that that may negate the benefits with respect to nausea.
His preferred approach, he said, is to either split dosing – for example, splitting a 20-mg dose into two 10-mg doses followed 10 hours later with Leucovorin (folinic acid) – or to give the full methotrexate dose at bedtime followed 10 hours later with Leucovorin.
“I use a lot of Leucovorin – a lot,” he noted.
For those patients who get nauseated at the mere mention of methotrexate, though, it’s probably best to try a different drug, he said.
Another approach, suggested by Vivian Bykerk, MD, of the Hospital for Special Surgery in New York, is to give Zofran (ondansetron) with methotrexate. Other suggestions included lowering the methotrexate dose and injecting the drug.
For fatigue, there has been some suggestion of a benefit with B-12 supplementation, panel members said. Dr. Bykerk noted some ongoing work that is demonstrating a benefit with sublingual B-12 for methotrexate intolerance in general, and it appears to allow for much higher methotrexate dosing, she said.
Early reports regarding those as-yet-unpublished data are, indeed, promising, Dr. Weinblatt said, noting that in his practice he has been using subcutaneous B-12 given at about 1,000 mcg 2 days before methotrexate and then on the day of methotrexate for patients with fatigue who are “failing Leucovorin, failing caffeine.”
Addressing fatigue and nausea in patients on methotrexate is important because, in his experience in appropriately monitored patients, it’s not serious adverse events, but rather fatigue and nausea, that most often lead to stopping methotrexate.
Dr. Weinblatt reported financial relationships with nearly 20 pharmaceutical companies. Dr. Bykerk reported financial relationships with Amgen, Brainstorm, Bristol-Myers Squibb, Pfizer, and Regeneron. Dr. Veale reported financial relationships with AbbVie, Janssen, Pfizer, Roche, and UCB. Dr. Ritchlin reported financial relationships with AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and UCB.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM
Stopping TNF inhibitors before 20 weeks’ gestation not linked to worsening RA, JIA
In pregnant women with arthritis, discontinuing tumor necrosis factor inhibitors prior to gestational week 20 seems feasible without an increased risk of disease worsening, particularly in those with well-controlled disease, according to authors of a recent analysis of a prospective cohort study.
Stopping tumor necrosis factor inhibitor (TNFi) treatment at that point in the second trimester was not linked to any clinically important worsening of patient-reported outcomes later in pregnancy for women with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA), the researchers said.
However, continuing a TNFi past gestational week 20 may also be warranted for some patients, according to the researchers, led by Frauke Förger, MD, of the University of Bern (Switzerland).
“In case of active disease, the continuation of TNF inhibitors beyond gestational week 20 seems reasonable from the standpoint of improved disease activity in the third trimester, which may in turn lead to improved pregnancy outcomes,” Dr. Förger and her coinvestigators wrote in Arthritis & Rheumatology.
These findings stand in contrast to those of another recent study, in which stopping a TNF inhibitor after a positive pregnancy test was linked to disease flares in women with RA, according to the authors.
“The timing of drug discontinuation during pregnancy may be of importance,” they said in their report.
Beyond these studies, there are very limited data on the effects of discontinuing TNF inhibitors in pregnant women with rheumatoid arthritis, and “a lack of any data” in pregnant women with JIA, they said.
The current investigation by Dr. Förger and her colleagues included 490 pregnant women in the United States or Canada who were enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project, a prospective cohort study. Of those women, 397 had RA and 93 had JIA.
About one-quarter of the women (122, or 24.9%) discontinued TNF inhibitor therapy prior to gestational week 20, while 41% continued on TNF inhibitors beyond that point, and 34.1% did not use a TNF inhibitor in pregnancy.
For those women who discontinued TNF inhibitors before gestational week 20, scores on the Patient Activity Scale (PAS) were stable over time, Dr. Förger and her colleagues reported.
Women who continued TNF inhibitor treatment past gestational week 20 had improved PAS scores in the third trimester, according to results of a univariate analysis (P = .02). However, the improvement appeared to be attenuated after adjustment for factors including race, smoking, use of prednisone or disease-modifying antirheumatic drugs, and gestational age, the investigators said.
They were unable to analyze the effects of ongoing TNFi treatment or discontinuation on patients with JIA separately because of the limited number of such patients in each group.
Another limitation of the study is that a high proportion of women – nearly three-quarters – had low disease activity at the start of pregnancy, according to the investigators, who said that group of women might expect some degree of improvement in the third trimester with or without TNF inhibitor discontinuation.
“In this context, the ameliorating effect of pregnancy on RA and JIA, which is most pronounced in the third trimester, may play a role,” they explained.
A certain proportion of women choose to discontinue certain arthritis treatments during pregnancy because of concerns that the medication may lead to fetal harm, but that may be changing, the investigators noted in their report.
“In recent years, more patients requiring treatment have been continuing on effective TNF inhibitors beyond conception as the available data on the safety of TNF inhibitors during pregnancy has increased,” they wrote.
Dr. Förger and her coauthors reported no financial disclosures or conflicts of interest. Financial support for the OTIS Collaborative Research Group comes from industry sources including AbbVie, Bristol-Myers Squibb, Celgene, Hoffman La Roche-Genentech, Janssen, Pfizer, Regeneron, Sandoz, and UCB, among others.
SOURCE: Förger F et al. Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40821
In pregnant women with arthritis, discontinuing tumor necrosis factor inhibitors prior to gestational week 20 seems feasible without an increased risk of disease worsening, particularly in those with well-controlled disease, according to authors of a recent analysis of a prospective cohort study.
Stopping tumor necrosis factor inhibitor (TNFi) treatment at that point in the second trimester was not linked to any clinically important worsening of patient-reported outcomes later in pregnancy for women with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA), the researchers said.
However, continuing a TNFi past gestational week 20 may also be warranted for some patients, according to the researchers, led by Frauke Förger, MD, of the University of Bern (Switzerland).
“In case of active disease, the continuation of TNF inhibitors beyond gestational week 20 seems reasonable from the standpoint of improved disease activity in the third trimester, which may in turn lead to improved pregnancy outcomes,” Dr. Förger and her coinvestigators wrote in Arthritis & Rheumatology.
These findings stand in contrast to those of another recent study, in which stopping a TNF inhibitor after a positive pregnancy test was linked to disease flares in women with RA, according to the authors.
“The timing of drug discontinuation during pregnancy may be of importance,” they said in their report.
Beyond these studies, there are very limited data on the effects of discontinuing TNF inhibitors in pregnant women with rheumatoid arthritis, and “a lack of any data” in pregnant women with JIA, they said.
The current investigation by Dr. Förger and her colleagues included 490 pregnant women in the United States or Canada who were enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project, a prospective cohort study. Of those women, 397 had RA and 93 had JIA.
About one-quarter of the women (122, or 24.9%) discontinued TNF inhibitor therapy prior to gestational week 20, while 41% continued on TNF inhibitors beyond that point, and 34.1% did not use a TNF inhibitor in pregnancy.
For those women who discontinued TNF inhibitors before gestational week 20, scores on the Patient Activity Scale (PAS) were stable over time, Dr. Förger and her colleagues reported.
Women who continued TNF inhibitor treatment past gestational week 20 had improved PAS scores in the third trimester, according to results of a univariate analysis (P = .02). However, the improvement appeared to be attenuated after adjustment for factors including race, smoking, use of prednisone or disease-modifying antirheumatic drugs, and gestational age, the investigators said.
They were unable to analyze the effects of ongoing TNFi treatment or discontinuation on patients with JIA separately because of the limited number of such patients in each group.
Another limitation of the study is that a high proportion of women – nearly three-quarters – had low disease activity at the start of pregnancy, according to the investigators, who said that group of women might expect some degree of improvement in the third trimester with or without TNF inhibitor discontinuation.
“In this context, the ameliorating effect of pregnancy on RA and JIA, which is most pronounced in the third trimester, may play a role,” they explained.
A certain proportion of women choose to discontinue certain arthritis treatments during pregnancy because of concerns that the medication may lead to fetal harm, but that may be changing, the investigators noted in their report.
“In recent years, more patients requiring treatment have been continuing on effective TNF inhibitors beyond conception as the available data on the safety of TNF inhibitors during pregnancy has increased,” they wrote.
Dr. Förger and her coauthors reported no financial disclosures or conflicts of interest. Financial support for the OTIS Collaborative Research Group comes from industry sources including AbbVie, Bristol-Myers Squibb, Celgene, Hoffman La Roche-Genentech, Janssen, Pfizer, Regeneron, Sandoz, and UCB, among others.
SOURCE: Förger F et al. Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40821
In pregnant women with arthritis, discontinuing tumor necrosis factor inhibitors prior to gestational week 20 seems feasible without an increased risk of disease worsening, particularly in those with well-controlled disease, according to authors of a recent analysis of a prospective cohort study.
Stopping tumor necrosis factor inhibitor (TNFi) treatment at that point in the second trimester was not linked to any clinically important worsening of patient-reported outcomes later in pregnancy for women with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA), the researchers said.
However, continuing a TNFi past gestational week 20 may also be warranted for some patients, according to the researchers, led by Frauke Förger, MD, of the University of Bern (Switzerland).
“In case of active disease, the continuation of TNF inhibitors beyond gestational week 20 seems reasonable from the standpoint of improved disease activity in the third trimester, which may in turn lead to improved pregnancy outcomes,” Dr. Förger and her coinvestigators wrote in Arthritis & Rheumatology.
These findings stand in contrast to those of another recent study, in which stopping a TNF inhibitor after a positive pregnancy test was linked to disease flares in women with RA, according to the authors.
“The timing of drug discontinuation during pregnancy may be of importance,” they said in their report.
Beyond these studies, there are very limited data on the effects of discontinuing TNF inhibitors in pregnant women with rheumatoid arthritis, and “a lack of any data” in pregnant women with JIA, they said.
The current investigation by Dr. Förger and her colleagues included 490 pregnant women in the United States or Canada who were enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project, a prospective cohort study. Of those women, 397 had RA and 93 had JIA.
About one-quarter of the women (122, or 24.9%) discontinued TNF inhibitor therapy prior to gestational week 20, while 41% continued on TNF inhibitors beyond that point, and 34.1% did not use a TNF inhibitor in pregnancy.
For those women who discontinued TNF inhibitors before gestational week 20, scores on the Patient Activity Scale (PAS) were stable over time, Dr. Förger and her colleagues reported.
Women who continued TNF inhibitor treatment past gestational week 20 had improved PAS scores in the third trimester, according to results of a univariate analysis (P = .02). However, the improvement appeared to be attenuated after adjustment for factors including race, smoking, use of prednisone or disease-modifying antirheumatic drugs, and gestational age, the investigators said.
They were unable to analyze the effects of ongoing TNFi treatment or discontinuation on patients with JIA separately because of the limited number of such patients in each group.
Another limitation of the study is that a high proportion of women – nearly three-quarters – had low disease activity at the start of pregnancy, according to the investigators, who said that group of women might expect some degree of improvement in the third trimester with or without TNF inhibitor discontinuation.
“In this context, the ameliorating effect of pregnancy on RA and JIA, which is most pronounced in the third trimester, may play a role,” they explained.
A certain proportion of women choose to discontinue certain arthritis treatments during pregnancy because of concerns that the medication may lead to fetal harm, but that may be changing, the investigators noted in their report.
“In recent years, more patients requiring treatment have been continuing on effective TNF inhibitors beyond conception as the available data on the safety of TNF inhibitors during pregnancy has increased,” they wrote.
Dr. Förger and her coauthors reported no financial disclosures or conflicts of interest. Financial support for the OTIS Collaborative Research Group comes from industry sources including AbbVie, Bristol-Myers Squibb, Celgene, Hoffman La Roche-Genentech, Janssen, Pfizer, Regeneron, Sandoz, and UCB, among others.
SOURCE: Förger F et al. Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40821
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: In contrast to a previous report,
Major finding: Patient Activity Scale (PAS) scores were stable over time in women who discontinued TNF inhibitors before gestational week 20. Those who continued past week 20 had improved PAS scores in the third trimester (univariate analysis; P = .02).
Study details: Analysis including 490 pregnant women in the United States or Canada who enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project, a prospective cohort study.
Disclosures: Dr. Förger and her coauthors reported no financial disclosures or conflicts of interest. Financial support for the OTIS Collaborative Research Group comes from industry sources including AbbVie, Bristol-Myers Squibb, Celgene, Hoffman La Roche-Genentech, Janssen, Pfizer, Regeneron, Sandoz, and UCB, among others.
Source: Förger F et al. Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40821.
Women with RA have reduced chance of live birth after assisted reproduction treatment
Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.
The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.
Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.
However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.
The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.
Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.
Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.
Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.
“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.
Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.
Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.
SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.
Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.
The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.
Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.
However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.
The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.
Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.
Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.
Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.
“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.
Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.
Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.
SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.
Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.
The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.
Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.
However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.
The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.
Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.
Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.
Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.
“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.
Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.
Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.
SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: Women with rheumatoid arthritis (RA) who undergo assisted reproduction treatment have decreased chances of live births, compared with women without RA.
Major finding: The odds ratio for live births per embryo transfer in women with RA, as compared to women without RA, was 0.78 (95% confidence interval, 0.65-0.92).
Study details: A nationwide cohort study including 1,149 embryo transfers in women with rheumatoid arthritis and 198,941 without rheumatoid arthritis
Disclosures: Study authors had no disclosures. Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense (Denmark) University Hospital.
Source: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.
Treat-to-target approach for CVD risk factors decreased atherosclerosis in RA patients
Researchers from the Netherlands found that a treat-to-target approach for cardiovascular risk factors in patients with rheumatoid arthritis was effective in reducing clinical and subclinical atherosclerosis; however, the researchers noted there was a “considerable” dropout in the study that could have limited the results, according to data recently published in Annals of the Rheumatic Diseases.
Benjamin Burggraaf, MD, and his associates at Franciscus Gasthuis & Vlietland Hospital in Rotterdam, the Netherlands, performed an open-label, randomized, controlled trial of 320 patients with rheumatoid arthritis (RA) who were younger than 70 years old (mean age, 52.4 years) without a prior history of cardiovascular disease (CVD) and diabetes mellitus. The patients received either usual care for traditional CVD risk factors or a treat-to-target approach using a prespecified protocol for treating hypertension, hyperlipidemia and hypertriglyceridemia, as well hemoglobin A1c greater than 48 mmol/mol. A total of 219 patients (68.4%) finished the study after 5 years. The two groups were similar at baseline, but the treat-to-target group had significantly more women (77.2%) compared with the usual care group (62.0%).
The researchers compared the progression of carotid intima media thickness (cIMT) at baseline and 5 years, with secondary outcomes of nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass grafting, percutaneous coronary intervention, peripheral atherosclerotic arterial disease–related amputation, peripheral atherosclerotic arterial disease revascularization, and death due to cardiovascular causes.
“To account for the high dropout, all missing cIMT values after 5 years of follow-up were imputed with all available cIMT values (baseline, years 1-4) and treatment group as covariate,” the researchers said. “Assuming that unobserved cIMT values were missing at random, missing data were imputed with multiple imputation using the fully conditional specification method for seven cycles.”
Dr. Burggraaf and his colleagues found the treat-to-target group had lower mean cIMT progression (0.023 mm; 95% confidence interval, 0.011-0.036) at 5-year follow-up than did the group that received usual care for CVD risk factors (0.045 mm; 95% CI, 0.030-0.059; P = .028). At 5 years, there were no significant differences between treat-to-target and usual care groups regarding mean systolic blood pressure (124.6 mm Hg vs. 124.7 mm Hg, respectively; P = .97), treat-to-target treatment targets for blood pressure (72.4% for usual care vs. 75.9% for treat-to-target; P = .56) and mean HbA1c (37.6 mmol/mol for treat-to-target vs. 37.0 mmol/mol for usual care; P = .39). The treat-to-target group also had fewer cardiovascular events (two events, 1.3%) compared with the usual care group (seven events, 4.7%; P = .048). There were five patients in the treat-to-target group who died during the study (4.7%), compared with seven patients (3.2%) in the usual care group (P = .51).
“Although the difference in cIMT progression between the groups was relatively small in absolute terms, the relative reduction in progression was almost 50% in favor of the treat-to-target group,” they noted. “In light of the reduction of cardiovascular events, these effects are, in our opinion, clinically relevant.”
Other limitations of the study included the use of cIMT as a “soft endpoint” for modern cardiovascular trials and the use of unblinded cIMT progression measurement. In addition, the researchers noted the study was underpowered, and they used data from a type 2 diabetes mellitus cohort to perform the power calculation, which carried a 50% reduction in CVD risk factors. “We had doubts whether this high risk would apply to patients with RA and therefore used a more conservative target of 20% reduction for cIMT progression,” the researchers said.
This study was funded by the Franciscus Gasthuis & Vlietland Hospital, the Foundation for Research and Development of the Department of Internal Medicine, and the Coolsingel Foundation, Rotterdam. One author reported being a consultant for and receiving lecture honoraria from Merck.
SOURCE: Burggraaf B et al. Ann Rheum Dis. 2019 Jan 4. doi: 10.1136/annrheumdis-2018-214075.
It is well recognized that traditional cardiovascular disease (CVD) risk factors contribute to atherogenesis and CVD events in rheumatoid arthritis (RA) patients at least as much as inflammatory risk factors, and traditional risk factors and inflammatory risk factors may interact (i.e. inflammatory risk factors have a greater impact in the setting of higher number of traditional risk factors).
There is documented reluctance among many rheumatologists to take on the additional burden of screening and managing hyperlipidemia, hypertension, diabetes, weight management, diet, and so on in addition to all the other aspects of managing these patients that take a lot of time. Research is needed on how to efficiently streamline measurement and management of CVD risk in these patients to optimize outcomes.
Jon T. Giles, MD , is a rheumatologist in the division of rheumatology at Columbia University in New York. He was not involved in the study by Burggraaf et al. and reported no relevant conflicts of interest.
It is well recognized that traditional cardiovascular disease (CVD) risk factors contribute to atherogenesis and CVD events in rheumatoid arthritis (RA) patients at least as much as inflammatory risk factors, and traditional risk factors and inflammatory risk factors may interact (i.e. inflammatory risk factors have a greater impact in the setting of higher number of traditional risk factors).
There is documented reluctance among many rheumatologists to take on the additional burden of screening and managing hyperlipidemia, hypertension, diabetes, weight management, diet, and so on in addition to all the other aspects of managing these patients that take a lot of time. Research is needed on how to efficiently streamline measurement and management of CVD risk in these patients to optimize outcomes.
Jon T. Giles, MD , is a rheumatologist in the division of rheumatology at Columbia University in New York. He was not involved in the study by Burggraaf et al. and reported no relevant conflicts of interest.
It is well recognized that traditional cardiovascular disease (CVD) risk factors contribute to atherogenesis and CVD events in rheumatoid arthritis (RA) patients at least as much as inflammatory risk factors, and traditional risk factors and inflammatory risk factors may interact (i.e. inflammatory risk factors have a greater impact in the setting of higher number of traditional risk factors).
There is documented reluctance among many rheumatologists to take on the additional burden of screening and managing hyperlipidemia, hypertension, diabetes, weight management, diet, and so on in addition to all the other aspects of managing these patients that take a lot of time. Research is needed on how to efficiently streamline measurement and management of CVD risk in these patients to optimize outcomes.
Jon T. Giles, MD , is a rheumatologist in the division of rheumatology at Columbia University in New York. He was not involved in the study by Burggraaf et al. and reported no relevant conflicts of interest.
Researchers from the Netherlands found that a treat-to-target approach for cardiovascular risk factors in patients with rheumatoid arthritis was effective in reducing clinical and subclinical atherosclerosis; however, the researchers noted there was a “considerable” dropout in the study that could have limited the results, according to data recently published in Annals of the Rheumatic Diseases.
Benjamin Burggraaf, MD, and his associates at Franciscus Gasthuis & Vlietland Hospital in Rotterdam, the Netherlands, performed an open-label, randomized, controlled trial of 320 patients with rheumatoid arthritis (RA) who were younger than 70 years old (mean age, 52.4 years) without a prior history of cardiovascular disease (CVD) and diabetes mellitus. The patients received either usual care for traditional CVD risk factors or a treat-to-target approach using a prespecified protocol for treating hypertension, hyperlipidemia and hypertriglyceridemia, as well hemoglobin A1c greater than 48 mmol/mol. A total of 219 patients (68.4%) finished the study after 5 years. The two groups were similar at baseline, but the treat-to-target group had significantly more women (77.2%) compared with the usual care group (62.0%).
The researchers compared the progression of carotid intima media thickness (cIMT) at baseline and 5 years, with secondary outcomes of nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass grafting, percutaneous coronary intervention, peripheral atherosclerotic arterial disease–related amputation, peripheral atherosclerotic arterial disease revascularization, and death due to cardiovascular causes.
“To account for the high dropout, all missing cIMT values after 5 years of follow-up were imputed with all available cIMT values (baseline, years 1-4) and treatment group as covariate,” the researchers said. “Assuming that unobserved cIMT values were missing at random, missing data were imputed with multiple imputation using the fully conditional specification method for seven cycles.”
Dr. Burggraaf and his colleagues found the treat-to-target group had lower mean cIMT progression (0.023 mm; 95% confidence interval, 0.011-0.036) at 5-year follow-up than did the group that received usual care for CVD risk factors (0.045 mm; 95% CI, 0.030-0.059; P = .028). At 5 years, there were no significant differences between treat-to-target and usual care groups regarding mean systolic blood pressure (124.6 mm Hg vs. 124.7 mm Hg, respectively; P = .97), treat-to-target treatment targets for blood pressure (72.4% for usual care vs. 75.9% for treat-to-target; P = .56) and mean HbA1c (37.6 mmol/mol for treat-to-target vs. 37.0 mmol/mol for usual care; P = .39). The treat-to-target group also had fewer cardiovascular events (two events, 1.3%) compared with the usual care group (seven events, 4.7%; P = .048). There were five patients in the treat-to-target group who died during the study (4.7%), compared with seven patients (3.2%) in the usual care group (P = .51).
“Although the difference in cIMT progression between the groups was relatively small in absolute terms, the relative reduction in progression was almost 50% in favor of the treat-to-target group,” they noted. “In light of the reduction of cardiovascular events, these effects are, in our opinion, clinically relevant.”
Other limitations of the study included the use of cIMT as a “soft endpoint” for modern cardiovascular trials and the use of unblinded cIMT progression measurement. In addition, the researchers noted the study was underpowered, and they used data from a type 2 diabetes mellitus cohort to perform the power calculation, which carried a 50% reduction in CVD risk factors. “We had doubts whether this high risk would apply to patients with RA and therefore used a more conservative target of 20% reduction for cIMT progression,” the researchers said.
This study was funded by the Franciscus Gasthuis & Vlietland Hospital, the Foundation for Research and Development of the Department of Internal Medicine, and the Coolsingel Foundation, Rotterdam. One author reported being a consultant for and receiving lecture honoraria from Merck.
SOURCE: Burggraaf B et al. Ann Rheum Dis. 2019 Jan 4. doi: 10.1136/annrheumdis-2018-214075.
Researchers from the Netherlands found that a treat-to-target approach for cardiovascular risk factors in patients with rheumatoid arthritis was effective in reducing clinical and subclinical atherosclerosis; however, the researchers noted there was a “considerable” dropout in the study that could have limited the results, according to data recently published in Annals of the Rheumatic Diseases.
Benjamin Burggraaf, MD, and his associates at Franciscus Gasthuis & Vlietland Hospital in Rotterdam, the Netherlands, performed an open-label, randomized, controlled trial of 320 patients with rheumatoid arthritis (RA) who were younger than 70 years old (mean age, 52.4 years) without a prior history of cardiovascular disease (CVD) and diabetes mellitus. The patients received either usual care for traditional CVD risk factors or a treat-to-target approach using a prespecified protocol for treating hypertension, hyperlipidemia and hypertriglyceridemia, as well hemoglobin A1c greater than 48 mmol/mol. A total of 219 patients (68.4%) finished the study after 5 years. The two groups were similar at baseline, but the treat-to-target group had significantly more women (77.2%) compared with the usual care group (62.0%).
The researchers compared the progression of carotid intima media thickness (cIMT) at baseline and 5 years, with secondary outcomes of nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass grafting, percutaneous coronary intervention, peripheral atherosclerotic arterial disease–related amputation, peripheral atherosclerotic arterial disease revascularization, and death due to cardiovascular causes.
“To account for the high dropout, all missing cIMT values after 5 years of follow-up were imputed with all available cIMT values (baseline, years 1-4) and treatment group as covariate,” the researchers said. “Assuming that unobserved cIMT values were missing at random, missing data were imputed with multiple imputation using the fully conditional specification method for seven cycles.”
Dr. Burggraaf and his colleagues found the treat-to-target group had lower mean cIMT progression (0.023 mm; 95% confidence interval, 0.011-0.036) at 5-year follow-up than did the group that received usual care for CVD risk factors (0.045 mm; 95% CI, 0.030-0.059; P = .028). At 5 years, there were no significant differences between treat-to-target and usual care groups regarding mean systolic blood pressure (124.6 mm Hg vs. 124.7 mm Hg, respectively; P = .97), treat-to-target treatment targets for blood pressure (72.4% for usual care vs. 75.9% for treat-to-target; P = .56) and mean HbA1c (37.6 mmol/mol for treat-to-target vs. 37.0 mmol/mol for usual care; P = .39). The treat-to-target group also had fewer cardiovascular events (two events, 1.3%) compared with the usual care group (seven events, 4.7%; P = .048). There were five patients in the treat-to-target group who died during the study (4.7%), compared with seven patients (3.2%) in the usual care group (P = .51).
“Although the difference in cIMT progression between the groups was relatively small in absolute terms, the relative reduction in progression was almost 50% in favor of the treat-to-target group,” they noted. “In light of the reduction of cardiovascular events, these effects are, in our opinion, clinically relevant.”
Other limitations of the study included the use of cIMT as a “soft endpoint” for modern cardiovascular trials and the use of unblinded cIMT progression measurement. In addition, the researchers noted the study was underpowered, and they used data from a type 2 diabetes mellitus cohort to perform the power calculation, which carried a 50% reduction in CVD risk factors. “We had doubts whether this high risk would apply to patients with RA and therefore used a more conservative target of 20% reduction for cIMT progression,” the researchers said.
This study was funded by the Franciscus Gasthuis & Vlietland Hospital, the Foundation for Research and Development of the Department of Internal Medicine, and the Coolsingel Foundation, Rotterdam. One author reported being a consultant for and receiving lecture honoraria from Merck.
SOURCE: Burggraaf B et al. Ann Rheum Dis. 2019 Jan 4. doi: 10.1136/annrheumdis-2018-214075.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: The treat-to-target group had greater mean carotid intima media thickness progression (0.023 mm; 95% confidence interval, 0.011-0.036) at 5-year follow-up compared with the group that received usual care for cardiovascular disease risk factors (0.045 mm; 95% CI, 0.030-0.059; P = .028).
Study details: An open-label, randomized, controlled trial of 320 RA patients who received a treat-to-target intervention or usual care for cardiovascular disease risk factors.
Disclosures: This study was funded by the Franciscus Gasthuis & Vlietland Hospital, the Foundation for Research and Development of the Department of Internal Medicine, and the Coolsingel Foundation, Rotterdam. One author reported being a consultant for and receiving lecture honoraria from Merck.
Source: Burggraaf B et al. Ann Rheum Dis. 2019 Jan 4. doi: 10.1136/annrheumdis-2018-214075.
Blood test shows potential as an early biomarker of methotrexate inefficacy
A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.
“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.
The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.
Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10-25) and 4 weeks (P = 4.9 x 10-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).
The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”
The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.
The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.
“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.
The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.
Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10-25) and 4 weeks (P = 4.9 x 10-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).
The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”
The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.
The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.
“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.
The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.
Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10-25) and 4 weeks (P = 4.9 x 10-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).
The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”
The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.
The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: A blood test that uses a gene expression ratio between 4 weeks and pretreatment yielded a ROC AUC of 0.78 for predicting methotrexate inefficacy at 6 months.
Study details: An analysis of blood samples from 85 participants in a U.K.-based longitudinal observational study of RA patients starting methotrexate for the first time.
Disclosures: The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
Source: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
Abatacept reduced infections in RA patients
Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.
“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.
In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.
Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.
The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.
The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.
SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.
Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.
“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.
In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.
Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.
The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.
The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.
SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.
Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.
“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.
In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.
Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.
The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.
The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.
SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Abatacept was associated with a lower risk of hospitalized infection in RA patients, compared with a tumor necrosis factor inhibitor.
Major finding: The incidence of hospitalized infections in RA patients was significantly lower with abatacept versus a tumor necrosis factor inhibitor (hazard ratio, 0.78).
Study details: The data come from 11,248 matched pairs of patients.
Disclosures: The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.
Source: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.
Jakinib explosion for RA: Where do they fit in clinical practice?
CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.
The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
Upadacitinib
SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.
Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.
“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.
The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.
“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”
The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.
Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.
As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.
The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”
Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.
“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.
Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.
SELECT-EARLY: This trial involved 947 methotrexate-naive patients with moderately to severely active RA deemed at baseline to be at high risk for disease progression. They were randomized to upadacitinib at 15 or 30 mg once daily or to methotrexate monotherapy. The markers utilized for high-risk disease were positive serology, an elevated CRP, and/or erosions at baseline, explained Ronald van Vollenhoven, MD, PhD, professor of rheumatology at the University of Amsterdam.
The coprimary endpoints were the week 12 ACR 50 and DAS28-CRP-less-than-2.6 response rates. ACR 50 was achieved in 28.3% of patients on methotrexate, 52.1% on the lower dose of upadacitinib, and 56.4% on upadacitinib 30 mg. The corresponding week 24 rates were 33.4%, 60.3%, and 65.6%.
The week 12 DAS28-CRP-less-than-2.6 rates were 13.7%, 35.6%, and 40.8%. By week 24, the rates had improved to 18.5%, 48.3%, and 50%.
Other functional, clinical, and quality-of-life endpoints followed suit. There was no radiographic progression over the course of 24 weeks in 77.7% of patients on methotrexate, 87.5% on upadacitinib 15 mg, and 89.3% on the JAKi at 30 mg.
The safety profile of upadacitinib was generally similar to that of methotrexate. Decreases in hemoglobin and neutrophils were more common in the high-dose upadacitinib group, while increased transaminase levels and reduced lymphocytes occurred more often with methotrexate.
Asked if the SELECT-EARLY results will lead to a change in the major guidelines for treatment of early RA, Dr. van Vollenhoven replied: “The advent of JAKis is changing the treatment of RA. Right now the positioning of JAKis is a big point of discussion: Should they be second or third or even fourth line? But it’s clear that methotrexate stands undisputed as the first-line treatment for RA in clinical practice. That has to do in part with lots and lots of experience, the fact that some patients do well with methotrexate, the convenience, but also the pricing.”
The goal in SELECT-EARLY was to test an individualized approach in which JAKis, which are clearly more effective than methotrexate, might be reserved as first-line therapy for the subgroup of patients with compelling markers for worse prognosis, and who are therefore less likely to turn out to be methotrexate responders.
“The markers we used aren’t good enough yet to engage in individualized treatment with a very specific drug, but we’re all trying very hard to find out who needs which treatment at which point in time,” the rheumatologist said.
SELECT-MONOTHERAPY: This trial randomized 648 patients with active RA and insufficient response to methotrexate to double-blind monotherapy with once-daily upadacitinib at 15 or 30 mg or to continued methotrexate.
Once again, upadacitinib achieved all of its primary and secondary endpoints. The week 14 ACR 20 rates for methotrexate and low- and high-dose upadacitinib were 41.2%, 67.7%, and 71.2%, respectively, with DAS28-CRP-less-than-or-equal-to-3.2 rates of 19.4%, 44.7%, and 53%. Remission as defined by a Clinical Disease Activity Index (CDAI) score of 2.8 or less was achieved in 1% of patients on methotrexate, 15% on upadacitinib 15 mg, and nearly 20% with upadacitinib 30 mg, reported Josef S. Smolen, MD, professor of medicine and chairman of rheumatology at the Medical University of Vienna.
Peficitinib
Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.
Which oral JAKi to use?
Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.
“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”
Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”
If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.
Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.
“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.
Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”
The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.
CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.
The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
Upadacitinib
SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.
Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.
“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.
The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.
“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”
The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.
Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.
As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.
The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”
Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.
“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.
Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.
SELECT-EARLY: This trial involved 947 methotrexate-naive patients with moderately to severely active RA deemed at baseline to be at high risk for disease progression. They were randomized to upadacitinib at 15 or 30 mg once daily or to methotrexate monotherapy. The markers utilized for high-risk disease were positive serology, an elevated CRP, and/or erosions at baseline, explained Ronald van Vollenhoven, MD, PhD, professor of rheumatology at the University of Amsterdam.
The coprimary endpoints were the week 12 ACR 50 and DAS28-CRP-less-than-2.6 response rates. ACR 50 was achieved in 28.3% of patients on methotrexate, 52.1% on the lower dose of upadacitinib, and 56.4% on upadacitinib 30 mg. The corresponding week 24 rates were 33.4%, 60.3%, and 65.6%.
The week 12 DAS28-CRP-less-than-2.6 rates were 13.7%, 35.6%, and 40.8%. By week 24, the rates had improved to 18.5%, 48.3%, and 50%.
Other functional, clinical, and quality-of-life endpoints followed suit. There was no radiographic progression over the course of 24 weeks in 77.7% of patients on methotrexate, 87.5% on upadacitinib 15 mg, and 89.3% on the JAKi at 30 mg.
The safety profile of upadacitinib was generally similar to that of methotrexate. Decreases in hemoglobin and neutrophils were more common in the high-dose upadacitinib group, while increased transaminase levels and reduced lymphocytes occurred more often with methotrexate.
Asked if the SELECT-EARLY results will lead to a change in the major guidelines for treatment of early RA, Dr. van Vollenhoven replied: “The advent of JAKis is changing the treatment of RA. Right now the positioning of JAKis is a big point of discussion: Should they be second or third or even fourth line? But it’s clear that methotrexate stands undisputed as the first-line treatment for RA in clinical practice. That has to do in part with lots and lots of experience, the fact that some patients do well with methotrexate, the convenience, but also the pricing.”
The goal in SELECT-EARLY was to test an individualized approach in which JAKis, which are clearly more effective than methotrexate, might be reserved as first-line therapy for the subgroup of patients with compelling markers for worse prognosis, and who are therefore less likely to turn out to be methotrexate responders.
“The markers we used aren’t good enough yet to engage in individualized treatment with a very specific drug, but we’re all trying very hard to find out who needs which treatment at which point in time,” the rheumatologist said.
SELECT-MONOTHERAPY: This trial randomized 648 patients with active RA and insufficient response to methotrexate to double-blind monotherapy with once-daily upadacitinib at 15 or 30 mg or to continued methotrexate.
Once again, upadacitinib achieved all of its primary and secondary endpoints. The week 14 ACR 20 rates for methotrexate and low- and high-dose upadacitinib were 41.2%, 67.7%, and 71.2%, respectively, with DAS28-CRP-less-than-or-equal-to-3.2 rates of 19.4%, 44.7%, and 53%. Remission as defined by a Clinical Disease Activity Index (CDAI) score of 2.8 or less was achieved in 1% of patients on methotrexate, 15% on upadacitinib 15 mg, and nearly 20% with upadacitinib 30 mg, reported Josef S. Smolen, MD, professor of medicine and chairman of rheumatology at the Medical University of Vienna.
Peficitinib
Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.
Which oral JAKi to use?
Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.
“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”
Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”
If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.
Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.
“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.
Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”
The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.
CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.
The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
Upadacitinib
SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.
Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.
“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.
The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.
“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”
The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.
Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.
As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.
The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”
Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.
“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.
Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.
SELECT-EARLY: This trial involved 947 methotrexate-naive patients with moderately to severely active RA deemed at baseline to be at high risk for disease progression. They were randomized to upadacitinib at 15 or 30 mg once daily or to methotrexate monotherapy. The markers utilized for high-risk disease were positive serology, an elevated CRP, and/or erosions at baseline, explained Ronald van Vollenhoven, MD, PhD, professor of rheumatology at the University of Amsterdam.
The coprimary endpoints were the week 12 ACR 50 and DAS28-CRP-less-than-2.6 response rates. ACR 50 was achieved in 28.3% of patients on methotrexate, 52.1% on the lower dose of upadacitinib, and 56.4% on upadacitinib 30 mg. The corresponding week 24 rates were 33.4%, 60.3%, and 65.6%.
The week 12 DAS28-CRP-less-than-2.6 rates were 13.7%, 35.6%, and 40.8%. By week 24, the rates had improved to 18.5%, 48.3%, and 50%.
Other functional, clinical, and quality-of-life endpoints followed suit. There was no radiographic progression over the course of 24 weeks in 77.7% of patients on methotrexate, 87.5% on upadacitinib 15 mg, and 89.3% on the JAKi at 30 mg.
The safety profile of upadacitinib was generally similar to that of methotrexate. Decreases in hemoglobin and neutrophils were more common in the high-dose upadacitinib group, while increased transaminase levels and reduced lymphocytes occurred more often with methotrexate.
Asked if the SELECT-EARLY results will lead to a change in the major guidelines for treatment of early RA, Dr. van Vollenhoven replied: “The advent of JAKis is changing the treatment of RA. Right now the positioning of JAKis is a big point of discussion: Should they be second or third or even fourth line? But it’s clear that methotrexate stands undisputed as the first-line treatment for RA in clinical practice. That has to do in part with lots and lots of experience, the fact that some patients do well with methotrexate, the convenience, but also the pricing.”
The goal in SELECT-EARLY was to test an individualized approach in which JAKis, which are clearly more effective than methotrexate, might be reserved as first-line therapy for the subgroup of patients with compelling markers for worse prognosis, and who are therefore less likely to turn out to be methotrexate responders.
“The markers we used aren’t good enough yet to engage in individualized treatment with a very specific drug, but we’re all trying very hard to find out who needs which treatment at which point in time,” the rheumatologist said.
SELECT-MONOTHERAPY: This trial randomized 648 patients with active RA and insufficient response to methotrexate to double-blind monotherapy with once-daily upadacitinib at 15 or 30 mg or to continued methotrexate.
Once again, upadacitinib achieved all of its primary and secondary endpoints. The week 14 ACR 20 rates for methotrexate and low- and high-dose upadacitinib were 41.2%, 67.7%, and 71.2%, respectively, with DAS28-CRP-less-than-or-equal-to-3.2 rates of 19.4%, 44.7%, and 53%. Remission as defined by a Clinical Disease Activity Index (CDAI) score of 2.8 or less was achieved in 1% of patients on methotrexate, 15% on upadacitinib 15 mg, and nearly 20% with upadacitinib 30 mg, reported Josef S. Smolen, MD, professor of medicine and chairman of rheumatology at the Medical University of Vienna.
Peficitinib
Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.
Which oral JAKi to use?
Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.
“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”
Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”
If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.
Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.
“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.
Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”
The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.
REPORTING FROM THE ACR ANNUAL MEETING
New insight gained into natural history of interstitial pneumonia with autoimmune features
CHICAGO – than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.
“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.
Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.
The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).
The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.
During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.
In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.
In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.
Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.
SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.
CHICAGO – than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.
“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.
Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.
The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).
The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.
During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.
In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.
In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.
Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.
SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.
CHICAGO – than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.
“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.
Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.
The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).
The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.
During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.
In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.
In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.
Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.
SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.
REPORTING FROM the ACR ANNUAL MEETING
Key clinical point: The adjusted risk of progression to a systemic autoimmune rheumatic disease is 14.1 times greater in interstitial pneumonia with autoimmune features than in idiopathic interstitial lung disease without such features.
Major finding: A total of 16% of patients with interstitial pneumonia with autoimmune features progressed to a systemic autoimmune rheumatic disease during follow-up, compared with 1.6% of patients with idiopathic interstitial lung disease without such features.
Study details: This retrospective, single-center study included 174 patients with idiopathic interstitial lung disease followed for a median of 5.2 years.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was conducted free of commercial support.
Source: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.
Drug-drug interactions in rheumatology patients on PPIs: An underappreciated problem?
CHICAGO – posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.
Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.
Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.
Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.
Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.
Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.
Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.
Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.
Genentech sponsored the study.
SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228
CHICAGO – posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.
Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.
Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.
Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.
Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.
Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.
Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.
Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.
Genentech sponsored the study.
SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228
CHICAGO – posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.
Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.
Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.
Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.
Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.
Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.
Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.
Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.
Genentech sponsored the study.
SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228
REPORTING FROM the ACR ANNUAL MEETING
Key clinical point: Ask your RA and SLE patients about concomitant chronic use of PPIs to avoid drug-drug interactions.
Major finding: More than one-third of RA and SLE patients are chronic users of PPIs, which raises potential drug-drug interaction issues for many commonly prescribed oral antirheumatic drugs.
Study details: This retrospective study utilized national claims data to examine chronic use of PPIs among more than 77,000 patients with RA and 2,224 with SLE.
Disclosures: The presenter is employed at Genentech, which sponsored the study.
Source: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 228
Rheumatologist prescribing rates predict chronic opioid use in RA patients
CHICAGO – A physician’s baseline opioid prescribing rate strongly predicts future chronic opioid use in rheumatoid arthritis patients, an analysis of data from the Consortium of Rheumatology Researchers of North America (Corrona) Rheumatoid Arthritis Registry suggests.
The baseline 12-month opioid prescribing rate of 148 physicians in the initial cohort varied widely from 0% to 70% (median, 27%), and among 9,337 patients in the registry beyond the baseline 12 months, physician opioid prescribing rates during the baseline period were significantly associated with risk for chronic opioid use, Yvonne C. Lee, MD, reported at the annual meeting of the American College of Rheumatology. She and her colleagues defined chronic opioid use as any opioid use during at least two consecutive study visits.
“It is important to understand the relative contributions of patient vs. physician characteristics on chronic opioid use,” said Dr. Lee of Northwestern University, Chicago. She that the goals of the current study were to identify the extent to which rheumatologists in the United States varied in baseline opioid prescribing rates and to determine the implications of baseline prescribing rates with respect to future chronic opioid use.
Compared with the lowest quartile of baseline opioid prescribing (rate of 18% or less), the second, third, and fourth quartiles of prescribing were associated with increasing odds of chronic opioid use (odds ratios of 1.16, 1.89, and 2.01 for the quartiles, respectively) during the study period, she said.
The researchers saw similar relationships when they used a stricter definition of opioid use and when they extended the cutoff between the baseline and study periods to 18 months. The relationships persisted after adjusting for numerous patient characteristics, such as age, sex, race, insurance status, RA duration, and treatments used, she said.
Subgroup analyses were also conducted to examine heterogeneity across clinical characteristics, including Clinical Disease Activity Index score (10 or less vs. greater than 10), pain intensity (scores of 40 or less, greater than 40 to 60, and greater than 60 out of 100), and use vs. nonuse of antidepressant medication. The relationships between physician baseline prescribing and chronic opioid use were similar across subgroups, she noted.
The findings help to characterize the role of rheumatologists’ prescribing rates in the ongoing opioid crisis even though the conclusions that can be reached are limited by the fact that some patients may receive opioid prescriptions from physicians outside the registry, by a lack of data on specific opioid types and doses, and by a lack of detailed information about physician characteristics, Dr. Lee said.
Physicians were included in the analysis only if they had contributed at least 10 RA patients to the registry within their first year of participation, and patients were included if they were patients of those physicians, if they had at least 12 months of follow-up data available, and if they were not prevalent opioid users at study entry.
A long-term goal is to target interventions to appropriate subgroups, she said, noting that 21%-29% of patients who are prescribed opioids for chronic pain misuse them, and more than 33,000 Americans die of opioid overdoses each year.
“Implications [of the findings] are that, in addition to targeting patients, we may also really want to consider interventions that target high-intensity prescribers. This may be useful for helping to decrease chronic opioid use in patients,” she concluded.
Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.
SOURCE: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917
CHICAGO – A physician’s baseline opioid prescribing rate strongly predicts future chronic opioid use in rheumatoid arthritis patients, an analysis of data from the Consortium of Rheumatology Researchers of North America (Corrona) Rheumatoid Arthritis Registry suggests.
The baseline 12-month opioid prescribing rate of 148 physicians in the initial cohort varied widely from 0% to 70% (median, 27%), and among 9,337 patients in the registry beyond the baseline 12 months, physician opioid prescribing rates during the baseline period were significantly associated with risk for chronic opioid use, Yvonne C. Lee, MD, reported at the annual meeting of the American College of Rheumatology. She and her colleagues defined chronic opioid use as any opioid use during at least two consecutive study visits.
“It is important to understand the relative contributions of patient vs. physician characteristics on chronic opioid use,” said Dr. Lee of Northwestern University, Chicago. She that the goals of the current study were to identify the extent to which rheumatologists in the United States varied in baseline opioid prescribing rates and to determine the implications of baseline prescribing rates with respect to future chronic opioid use.
Compared with the lowest quartile of baseline opioid prescribing (rate of 18% or less), the second, third, and fourth quartiles of prescribing were associated with increasing odds of chronic opioid use (odds ratios of 1.16, 1.89, and 2.01 for the quartiles, respectively) during the study period, she said.
The researchers saw similar relationships when they used a stricter definition of opioid use and when they extended the cutoff between the baseline and study periods to 18 months. The relationships persisted after adjusting for numerous patient characteristics, such as age, sex, race, insurance status, RA duration, and treatments used, she said.
Subgroup analyses were also conducted to examine heterogeneity across clinical characteristics, including Clinical Disease Activity Index score (10 or less vs. greater than 10), pain intensity (scores of 40 or less, greater than 40 to 60, and greater than 60 out of 100), and use vs. nonuse of antidepressant medication. The relationships between physician baseline prescribing and chronic opioid use were similar across subgroups, she noted.
The findings help to characterize the role of rheumatologists’ prescribing rates in the ongoing opioid crisis even though the conclusions that can be reached are limited by the fact that some patients may receive opioid prescriptions from physicians outside the registry, by a lack of data on specific opioid types and doses, and by a lack of detailed information about physician characteristics, Dr. Lee said.
Physicians were included in the analysis only if they had contributed at least 10 RA patients to the registry within their first year of participation, and patients were included if they were patients of those physicians, if they had at least 12 months of follow-up data available, and if they were not prevalent opioid users at study entry.
A long-term goal is to target interventions to appropriate subgroups, she said, noting that 21%-29% of patients who are prescribed opioids for chronic pain misuse them, and more than 33,000 Americans die of opioid overdoses each year.
“Implications [of the findings] are that, in addition to targeting patients, we may also really want to consider interventions that target high-intensity prescribers. This may be useful for helping to decrease chronic opioid use in patients,” she concluded.
Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.
SOURCE: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917
CHICAGO – A physician’s baseline opioid prescribing rate strongly predicts future chronic opioid use in rheumatoid arthritis patients, an analysis of data from the Consortium of Rheumatology Researchers of North America (Corrona) Rheumatoid Arthritis Registry suggests.
The baseline 12-month opioid prescribing rate of 148 physicians in the initial cohort varied widely from 0% to 70% (median, 27%), and among 9,337 patients in the registry beyond the baseline 12 months, physician opioid prescribing rates during the baseline period were significantly associated with risk for chronic opioid use, Yvonne C. Lee, MD, reported at the annual meeting of the American College of Rheumatology. She and her colleagues defined chronic opioid use as any opioid use during at least two consecutive study visits.
“It is important to understand the relative contributions of patient vs. physician characteristics on chronic opioid use,” said Dr. Lee of Northwestern University, Chicago. She that the goals of the current study were to identify the extent to which rheumatologists in the United States varied in baseline opioid prescribing rates and to determine the implications of baseline prescribing rates with respect to future chronic opioid use.
Compared with the lowest quartile of baseline opioid prescribing (rate of 18% or less), the second, third, and fourth quartiles of prescribing were associated with increasing odds of chronic opioid use (odds ratios of 1.16, 1.89, and 2.01 for the quartiles, respectively) during the study period, she said.
The researchers saw similar relationships when they used a stricter definition of opioid use and when they extended the cutoff between the baseline and study periods to 18 months. The relationships persisted after adjusting for numerous patient characteristics, such as age, sex, race, insurance status, RA duration, and treatments used, she said.
Subgroup analyses were also conducted to examine heterogeneity across clinical characteristics, including Clinical Disease Activity Index score (10 or less vs. greater than 10), pain intensity (scores of 40 or less, greater than 40 to 60, and greater than 60 out of 100), and use vs. nonuse of antidepressant medication. The relationships between physician baseline prescribing and chronic opioid use were similar across subgroups, she noted.
The findings help to characterize the role of rheumatologists’ prescribing rates in the ongoing opioid crisis even though the conclusions that can be reached are limited by the fact that some patients may receive opioid prescriptions from physicians outside the registry, by a lack of data on specific opioid types and doses, and by a lack of detailed information about physician characteristics, Dr. Lee said.
Physicians were included in the analysis only if they had contributed at least 10 RA patients to the registry within their first year of participation, and patients were included if they were patients of those physicians, if they had at least 12 months of follow-up data available, and if they were not prevalent opioid users at study entry.
A long-term goal is to target interventions to appropriate subgroups, she said, noting that 21%-29% of patients who are prescribed opioids for chronic pain misuse them, and more than 33,000 Americans die of opioid overdoses each year.
“Implications [of the findings] are that, in addition to targeting patients, we may also really want to consider interventions that target high-intensity prescribers. This may be useful for helping to decrease chronic opioid use in patients,” she concluded.
Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.
SOURCE: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The odds of chronic opioid use increased with rising baseline prescribing rates (odds ratios, 1.16, 1.89, and 2.01 for 2nd, 3rd, and 4th quartiles vs. 1st quartile of prescribing, respectively).
Study details: An analysis of data from 148 physicians and 9,337 Corrona RA Registry patients.
Disclosures: Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.
Source: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917