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Anti-RNPC3 antibody positive status linked to GI dysmotility in systemic sclerosis
in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763
This study represents good work in confirming the association of anti-RNPC3 positivity with severe GI disease first noted by Johns Hopkins investigators in a single-center study (Arthritis Rheumatol. 2017 Jun; 69[6]:1306-12). Now that Dr. McMahan and her associates have confirmed this association in the most severe of GI problems in SSc, it would be very useful to see if there is a lesser degree of GI involvement that also correlates (for example, using the validated UCLA Gastrointestinal Tract Questionnaire 2.0, which gives a continuous graded response).
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also in part-time practice in Los Angeles and Seattle.
This study represents good work in confirming the association of anti-RNPC3 positivity with severe GI disease first noted by Johns Hopkins investigators in a single-center study (Arthritis Rheumatol. 2017 Jun; 69[6]:1306-12). Now that Dr. McMahan and her associates have confirmed this association in the most severe of GI problems in SSc, it would be very useful to see if there is a lesser degree of GI involvement that also correlates (for example, using the validated UCLA Gastrointestinal Tract Questionnaire 2.0, which gives a continuous graded response).
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also in part-time practice in Los Angeles and Seattle.
This study represents good work in confirming the association of anti-RNPC3 positivity with severe GI disease first noted by Johns Hopkins investigators in a single-center study (Arthritis Rheumatol. 2017 Jun; 69[6]:1306-12). Now that Dr. McMahan and her associates have confirmed this association in the most severe of GI problems in SSc, it would be very useful to see if there is a lesser degree of GI involvement that also correlates (for example, using the validated UCLA Gastrointestinal Tract Questionnaire 2.0, which gives a continuous graded response).
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also in part-time practice in Los Angeles and Seattle.
in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763
in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Antibody status may inform GI risk stratification in people with systemic sclerosis.
Major finding: Anti-RNPC3 antibody positive SSc patients are significantly more likely to have moderate to severe GI dysfunction. In a fully adjusted model, patients with moderate to severe GI disease had 3.8-fold higher odds of having anti-RNPC3 antibodies.
Study details: A comparison of anti-RNPC3 antibodies in a discovery cohort of SSc patients with severe GI dysfunction who were on total parenteral nutrition compared with asymptomatic patients from the Johns Hopkins Scleroderma Center. Followed by a case control study to confirm the findings using the Pittsburgh Scleroderma cohort.
Disclosures: The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
Source: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763.
Two distinct subtypes of SLE-linked pulmonary arterial hypertension described
Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.
Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,
In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.
Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.
The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.
Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).
The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.
Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.
“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.
Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.
SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.
Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.
Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,
In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.
Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.
The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.
Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).
The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.
Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.
“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.
Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.
SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.
Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.
Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,
In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.
Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.
The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.
Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).
The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.
Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.
“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.
Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.
SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: A more vasculitic subtype of SLE-PAH is associated with higher mortality.
Major finding: The more severe vasculitic subtype of SLE-PAH shows threefold higher 3-year mortality than a vasculopathic subtype.
Study details: Retrospective cohort study in 195 patients with SLE-PAH
Disclosures: Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.
Source: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.
Decision aid aims to make lupus nephritis treatment decisions more understandable
A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.
Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.
“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”
SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.
“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”
But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”
Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.
“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”
The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”
A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.
The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.
“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”
The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.
In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.
More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.
PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:
• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.
• Track changes in subjective and objective measures of implementation effectiveness.
• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.
The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.
“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”
A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.
Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.
“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”
SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.
“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”
But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”
Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.
“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”
The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”
A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.
The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.
“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”
The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.
In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.
More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.
PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:
• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.
• Track changes in subjective and objective measures of implementation effectiveness.
• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.
The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.
“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”
A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.
Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.
“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”
SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.
“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”
But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”
Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.
“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”
The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”
A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.
The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.
“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”
The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.
In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.
More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.
PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:
• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.
• Track changes in subjective and objective measures of implementation effectiveness.
• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.
The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.
“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”
Pregnancy registries are a valuable resource
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
Guideline-recommended tests’ prognostic ability affirmed in prostanoid-treated PAH
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050
FROM CHEST®
Key clinical point: Survival in patients with pulmonary arterial hypertension (PAH) who are receiving a parenteral prostanoid is closely associated with the results of most guideline-recommended prognostic tests that measure mortality risk.
Major finding:
Study details: A retrospective study of 195 patients with PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016.
Disclosures: Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050.
New insight into celiac disease: What you should know
LAS VEGAS – Mayo Clinic gastroenterologist Joseph A. Murray, MD, has a message for rheumatologists: You might think you know celiac disease, which often mimics rheumatic disorders, but there’s a good chance you don’t.
For one, researchers have discovered only in the past few years that many people with celiac disease (CD) don’t spend their days on the toilet. “It’s really come into the fore in the past 5 years that it can present totally without any GI symptoms,” Dr. Murray said in an interview following his presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
For another, he said, CD “is much more common than we thought,” affecting 1% of whites.
This is all relevant to rheumatologists, Dr. Murray said, because celiac disease can cause rheumatic symptoms and is more likely to affect patients with certain rheumatic conditions.
In the big picture, he said during his presentation, researchers now understand that most people with CD do not suffer from diarrhea, the classic symptom associated with the disorder. A 2014 Italian study of 770 patients with CD found that just one-third had diarrhea (BMC Gastroenterol. 2014;14:194).
Instead of GI symptoms – or in addition to them – CD can cause numerous symptoms that may land patients in a rheumatologist’s office. According to Dr. Murray, these include joint pain (often without joint destruction), peripheral neuropathy, general aches and pains, and chronic fatigue.
“You could have a patient presenting with nondestructive joint problems and general fatigue who has celiac disease as a cause,” he said.
Or patients could have both CD and a rheumatic condition. Patients with lupus and Sjögren’s syndrome, for example, are at higher risk of CD, Dr. Murray said.
In addition, he said, “I will often see overlap between celiac disease and rheumatic arthritis.”
What should you do if you suspect a patient has CD? Dr. Murray suggests referring the patient to a gastroenterologist, although he cautioned physicians to keep in mind that a patient with the condition may not be able to adequately absorb oral medications.
He said it’s crucial to not direct the patient to begin a gluten-free diet. The main way to test a patient for CD is through serology prior to a gluten-free diet, he said.
There’s another hitch regarding a gluten-free diet. As he explained in his presentation, it’s often difficult to convince someone who’s already gone on a gluten-free diet to go off it so they can be challenged with gluten for weeks. In these cases, he said, patients may be afraid of the return of symptoms.
As for treatment, Dr. Murray said “patients can be dramatically improved by a gluten-free diet,” although it’s often difficult for them to tolerate. “Often they’re unhappy,” he said in his presentation. “It’s not an easy diet.”
He noted that patients may go gluten free even if it’s not clear they have to. “If the diet is nutritionally adequate,” he said, “I don’t argue with success.”
Dr. Murray disclosed consulting for various drug makers, receiving royalties from Torax, and receiving grant/contracted research support from drug makers, the Broad Medical Research Program at Crohn’s & Colitis Foundation, and Oberkotter Foundation.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Mayo Clinic gastroenterologist Joseph A. Murray, MD, has a message for rheumatologists: You might think you know celiac disease, which often mimics rheumatic disorders, but there’s a good chance you don’t.
For one, researchers have discovered only in the past few years that many people with celiac disease (CD) don’t spend their days on the toilet. “It’s really come into the fore in the past 5 years that it can present totally without any GI symptoms,” Dr. Murray said in an interview following his presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
For another, he said, CD “is much more common than we thought,” affecting 1% of whites.
This is all relevant to rheumatologists, Dr. Murray said, because celiac disease can cause rheumatic symptoms and is more likely to affect patients with certain rheumatic conditions.
In the big picture, he said during his presentation, researchers now understand that most people with CD do not suffer from diarrhea, the classic symptom associated with the disorder. A 2014 Italian study of 770 patients with CD found that just one-third had diarrhea (BMC Gastroenterol. 2014;14:194).
Instead of GI symptoms – or in addition to them – CD can cause numerous symptoms that may land patients in a rheumatologist’s office. According to Dr. Murray, these include joint pain (often without joint destruction), peripheral neuropathy, general aches and pains, and chronic fatigue.
“You could have a patient presenting with nondestructive joint problems and general fatigue who has celiac disease as a cause,” he said.
Or patients could have both CD and a rheumatic condition. Patients with lupus and Sjögren’s syndrome, for example, are at higher risk of CD, Dr. Murray said.
In addition, he said, “I will often see overlap between celiac disease and rheumatic arthritis.”
What should you do if you suspect a patient has CD? Dr. Murray suggests referring the patient to a gastroenterologist, although he cautioned physicians to keep in mind that a patient with the condition may not be able to adequately absorb oral medications.
He said it’s crucial to not direct the patient to begin a gluten-free diet. The main way to test a patient for CD is through serology prior to a gluten-free diet, he said.
There’s another hitch regarding a gluten-free diet. As he explained in his presentation, it’s often difficult to convince someone who’s already gone on a gluten-free diet to go off it so they can be challenged with gluten for weeks. In these cases, he said, patients may be afraid of the return of symptoms.
As for treatment, Dr. Murray said “patients can be dramatically improved by a gluten-free diet,” although it’s often difficult for them to tolerate. “Often they’re unhappy,” he said in his presentation. “It’s not an easy diet.”
He noted that patients may go gluten free even if it’s not clear they have to. “If the diet is nutritionally adequate,” he said, “I don’t argue with success.”
Dr. Murray disclosed consulting for various drug makers, receiving royalties from Torax, and receiving grant/contracted research support from drug makers, the Broad Medical Research Program at Crohn’s & Colitis Foundation, and Oberkotter Foundation.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Mayo Clinic gastroenterologist Joseph A. Murray, MD, has a message for rheumatologists: You might think you know celiac disease, which often mimics rheumatic disorders, but there’s a good chance you don’t.
For one, researchers have discovered only in the past few years that many people with celiac disease (CD) don’t spend their days on the toilet. “It’s really come into the fore in the past 5 years that it can present totally without any GI symptoms,” Dr. Murray said in an interview following his presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
For another, he said, CD “is much more common than we thought,” affecting 1% of whites.
This is all relevant to rheumatologists, Dr. Murray said, because celiac disease can cause rheumatic symptoms and is more likely to affect patients with certain rheumatic conditions.
In the big picture, he said during his presentation, researchers now understand that most people with CD do not suffer from diarrhea, the classic symptom associated with the disorder. A 2014 Italian study of 770 patients with CD found that just one-third had diarrhea (BMC Gastroenterol. 2014;14:194).
Instead of GI symptoms – or in addition to them – CD can cause numerous symptoms that may land patients in a rheumatologist’s office. According to Dr. Murray, these include joint pain (often without joint destruction), peripheral neuropathy, general aches and pains, and chronic fatigue.
“You could have a patient presenting with nondestructive joint problems and general fatigue who has celiac disease as a cause,” he said.
Or patients could have both CD and a rheumatic condition. Patients with lupus and Sjögren’s syndrome, for example, are at higher risk of CD, Dr. Murray said.
In addition, he said, “I will often see overlap between celiac disease and rheumatic arthritis.”
What should you do if you suspect a patient has CD? Dr. Murray suggests referring the patient to a gastroenterologist, although he cautioned physicians to keep in mind that a patient with the condition may not be able to adequately absorb oral medications.
He said it’s crucial to not direct the patient to begin a gluten-free diet. The main way to test a patient for CD is through serology prior to a gluten-free diet, he said.
There’s another hitch regarding a gluten-free diet. As he explained in his presentation, it’s often difficult to convince someone who’s already gone on a gluten-free diet to go off it so they can be challenged with gluten for weeks. In these cases, he said, patients may be afraid of the return of symptoms.
As for treatment, Dr. Murray said “patients can be dramatically improved by a gluten-free diet,” although it’s often difficult for them to tolerate. “Often they’re unhappy,” he said in his presentation. “It’s not an easy diet.”
He noted that patients may go gluten free even if it’s not clear they have to. “If the diet is nutritionally adequate,” he said, “I don’t argue with success.”
Dr. Murray disclosed consulting for various drug makers, receiving royalties from Torax, and receiving grant/contracted research support from drug makers, the Broad Medical Research Program at Crohn’s & Colitis Foundation, and Oberkotter Foundation.
Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
IgA vasculitis may be more common in adults than assumed
LAS VEGAS – IgA vasculitis has a reputation as an illness of childhood, but rheumatologist Alexandra Villa-Forte, MD, MPH, cautioned colleagues that it can strike adults, too, often in a much more severe form. And, she warned, it’s likely not as rare as physicians assume.
“I believe it’s more common in adults than reported. There’s a huge problem with establishing the right way to make the diagnosis in adults, which is why it is missed,” said Dr. Villa-Forte of the Cleveland Clinic, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
But even if IgA vasculitis (IV) is diagnosed correctly in adults, there are many questions about how to move forward, she said. “Treatment in adults remains a problem since we don’t have data.”
IV is also known as Henoch-Schönlein purpura, or HSP, and “spring fever” because it often appears in children in the spring following an upper respiratory infection.
The condition causes vasculitis, the swelling of small blood vessels in organs such as the skin, joints, kidneys, and intestines. Leaking blood vessels can cause skin rashes known as purpura.
The estimated ranges of disease are high, with the annual incidence in children estimated at 3-26 per 100,000 and in adults at 0.1-1.8 per 100,000. Dr. Villa-Forte noted that the male-to-female ratio is 1.5, and she said the condition is less common in African Americans.
“In children, this is a disease that is frequently self-limited. Most of them don’t need treatment, and most of them do not relapse,” Dr. Villa-Forte said. “In adults, it’s more resistant to treatment, frequently chronic, and frequently relapsing over the years.”
There are other differences in IV between children and adults. “In children, there is a clear seasonal pattern of disease that is not seen in adults,” she said, and it’s linked to preceding infections.
“In adults, there are multiple causes, and most of the time they’re not identified,” she said.
As for diagnosis, she suggests looking at clinical presentation and whether tissue biopsy shows cutaneous leukocytoclastic vasculitis with IgA deposits. She cautioned that increased serum IgA is seen in about 50% of adult patients, making it an unreliable indicator.
Prognosis is much better for children than adults. According to a 2014 study, 80% of children completely recover, compared with 40% of adults. Persistent hematuria or proteinuria occurs in 30% of children and 60% of adults, respectively, while chronic renal failure occurs in 2% of children and 10% of adults (J Korean Med Sci. 2014 Feb;29[2]:198-203).
It’s possible that the latter number may be higher, with as many as 30% of adults developing chronic kidney disease (CKD), Dr. Villa-Forte said.
An estimated 97% of nephritis develops within the first 6 months of disease onset in adults, she said, “and in adults, the active renal disease can persist for over 20 years.”
Guidelines suggest that patients be monitored for CKD for 6 months after disease onset, but Dr. Villa-Forte said it’s better to monitor them for 12 months.
What about treatment? “The major challenge in adults is the real absence between correlation between initial presentation and long-term renal outcome,” she said. “That makes for a difficult choice in terms of treatment selection.”
Fever and cutaneous lesions above the waist may predict renal involvement, she said, although that isn’t confirmed, and increasing proteinuria is a probable factor predicting progression/complications.
According to Dr. Villa-Forte, the value of early treatment hasn’t been proved. Due to the risk of kidney problems, she said, “we don’t feel like we can just watch patients – that we need to do something. But there’s not good data supporting that.”
Various protocols involving steroids, early plasmapheresis, rituximab (Rituxan), and other drug regimens lack evidence, she said, although use of steroids in early nephritis may be beneficial in adults.
Dr. Villa-Forte had no relevant disclosures.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – IgA vasculitis has a reputation as an illness of childhood, but rheumatologist Alexandra Villa-Forte, MD, MPH, cautioned colleagues that it can strike adults, too, often in a much more severe form. And, she warned, it’s likely not as rare as physicians assume.
“I believe it’s more common in adults than reported. There’s a huge problem with establishing the right way to make the diagnosis in adults, which is why it is missed,” said Dr. Villa-Forte of the Cleveland Clinic, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
But even if IgA vasculitis (IV) is diagnosed correctly in adults, there are many questions about how to move forward, she said. “Treatment in adults remains a problem since we don’t have data.”
IV is also known as Henoch-Schönlein purpura, or HSP, and “spring fever” because it often appears in children in the spring following an upper respiratory infection.
The condition causes vasculitis, the swelling of small blood vessels in organs such as the skin, joints, kidneys, and intestines. Leaking blood vessels can cause skin rashes known as purpura.
The estimated ranges of disease are high, with the annual incidence in children estimated at 3-26 per 100,000 and in adults at 0.1-1.8 per 100,000. Dr. Villa-Forte noted that the male-to-female ratio is 1.5, and she said the condition is less common in African Americans.
“In children, this is a disease that is frequently self-limited. Most of them don’t need treatment, and most of them do not relapse,” Dr. Villa-Forte said. “In adults, it’s more resistant to treatment, frequently chronic, and frequently relapsing over the years.”
There are other differences in IV between children and adults. “In children, there is a clear seasonal pattern of disease that is not seen in adults,” she said, and it’s linked to preceding infections.
“In adults, there are multiple causes, and most of the time they’re not identified,” she said.
As for diagnosis, she suggests looking at clinical presentation and whether tissue biopsy shows cutaneous leukocytoclastic vasculitis with IgA deposits. She cautioned that increased serum IgA is seen in about 50% of adult patients, making it an unreliable indicator.
Prognosis is much better for children than adults. According to a 2014 study, 80% of children completely recover, compared with 40% of adults. Persistent hematuria or proteinuria occurs in 30% of children and 60% of adults, respectively, while chronic renal failure occurs in 2% of children and 10% of adults (J Korean Med Sci. 2014 Feb;29[2]:198-203).
It’s possible that the latter number may be higher, with as many as 30% of adults developing chronic kidney disease (CKD), Dr. Villa-Forte said.
An estimated 97% of nephritis develops within the first 6 months of disease onset in adults, she said, “and in adults, the active renal disease can persist for over 20 years.”
Guidelines suggest that patients be monitored for CKD for 6 months after disease onset, but Dr. Villa-Forte said it’s better to monitor them for 12 months.
What about treatment? “The major challenge in adults is the real absence between correlation between initial presentation and long-term renal outcome,” she said. “That makes for a difficult choice in terms of treatment selection.”
Fever and cutaneous lesions above the waist may predict renal involvement, she said, although that isn’t confirmed, and increasing proteinuria is a probable factor predicting progression/complications.
According to Dr. Villa-Forte, the value of early treatment hasn’t been proved. Due to the risk of kidney problems, she said, “we don’t feel like we can just watch patients – that we need to do something. But there’s not good data supporting that.”
Various protocols involving steroids, early plasmapheresis, rituximab (Rituxan), and other drug regimens lack evidence, she said, although use of steroids in early nephritis may be beneficial in adults.
Dr. Villa-Forte had no relevant disclosures.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – IgA vasculitis has a reputation as an illness of childhood, but rheumatologist Alexandra Villa-Forte, MD, MPH, cautioned colleagues that it can strike adults, too, often in a much more severe form. And, she warned, it’s likely not as rare as physicians assume.
“I believe it’s more common in adults than reported. There’s a huge problem with establishing the right way to make the diagnosis in adults, which is why it is missed,” said Dr. Villa-Forte of the Cleveland Clinic, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
But even if IgA vasculitis (IV) is diagnosed correctly in adults, there are many questions about how to move forward, she said. “Treatment in adults remains a problem since we don’t have data.”
IV is also known as Henoch-Schönlein purpura, or HSP, and “spring fever” because it often appears in children in the spring following an upper respiratory infection.
The condition causes vasculitis, the swelling of small blood vessels in organs such as the skin, joints, kidneys, and intestines. Leaking blood vessels can cause skin rashes known as purpura.
The estimated ranges of disease are high, with the annual incidence in children estimated at 3-26 per 100,000 and in adults at 0.1-1.8 per 100,000. Dr. Villa-Forte noted that the male-to-female ratio is 1.5, and she said the condition is less common in African Americans.
“In children, this is a disease that is frequently self-limited. Most of them don’t need treatment, and most of them do not relapse,” Dr. Villa-Forte said. “In adults, it’s more resistant to treatment, frequently chronic, and frequently relapsing over the years.”
There are other differences in IV between children and adults. “In children, there is a clear seasonal pattern of disease that is not seen in adults,” she said, and it’s linked to preceding infections.
“In adults, there are multiple causes, and most of the time they’re not identified,” she said.
As for diagnosis, she suggests looking at clinical presentation and whether tissue biopsy shows cutaneous leukocytoclastic vasculitis with IgA deposits. She cautioned that increased serum IgA is seen in about 50% of adult patients, making it an unreliable indicator.
Prognosis is much better for children than adults. According to a 2014 study, 80% of children completely recover, compared with 40% of adults. Persistent hematuria or proteinuria occurs in 30% of children and 60% of adults, respectively, while chronic renal failure occurs in 2% of children and 10% of adults (J Korean Med Sci. 2014 Feb;29[2]:198-203).
It’s possible that the latter number may be higher, with as many as 30% of adults developing chronic kidney disease (CKD), Dr. Villa-Forte said.
An estimated 97% of nephritis develops within the first 6 months of disease onset in adults, she said, “and in adults, the active renal disease can persist for over 20 years.”
Guidelines suggest that patients be monitored for CKD for 6 months after disease onset, but Dr. Villa-Forte said it’s better to monitor them for 12 months.
What about treatment? “The major challenge in adults is the real absence between correlation between initial presentation and long-term renal outcome,” she said. “That makes for a difficult choice in terms of treatment selection.”
Fever and cutaneous lesions above the waist may predict renal involvement, she said, although that isn’t confirmed, and increasing proteinuria is a probable factor predicting progression/complications.
According to Dr. Villa-Forte, the value of early treatment hasn’t been proved. Due to the risk of kidney problems, she said, “we don’t feel like we can just watch patients – that we need to do something. But there’s not good data supporting that.”
Various protocols involving steroids, early plasmapheresis, rituximab (Rituxan), and other drug regimens lack evidence, she said, although use of steroids in early nephritis may be beneficial in adults.
Dr. Villa-Forte had no relevant disclosures.
Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
Coping with a rheumatology clinic’s ‘worst nightmare’
LAS VEGAS – Cleveland Clinic rheumatologist Alexandra Villa-Forte, MD, MPH, has a vivid way of describing the challenge of maintaining remission in granulomatosis with polyangiitis (GPA): She called it “the worst nightmare in the clinic” in a presentation at the annual Perspectives in Rheumatic Diseases.
Dr. Villa-Forte should know. She’s treated more than 700 patients with GPA, also known as Wegener’s granulomatosis, a rare disorder that causes necrotizing vasculitis of small arteries and veins. She advises close monitoring of patients in remission, caution regarding toxicity, pneumonia prophylaxis, and an understanding of the limitations of existing medications.
An estimated 3 in 100,000 people have GPA, which can be fatal if it’s not treated. “All patients with active GPA should receive prednisone with a second agent,” she said at the conference, held by Global Academy for Medical Education. “We know that increasing the prednisone or using it alone will not result in sustained remission at all.”
According to her, new concepts in therapeutic guidance suggest four criteria should determine the specific agents used: Involvement of critical organ systems, severity of clinical manifestations, rate of change (such as rapidly progressing kidney failure), and individual patient factors such as comorbidities.
Patients facing immediate risk to life or organ function should get higher doses of corticosteroids, a cytotoxic agent, and perhaps plasmapheresis, she said.
Induction therapy should last 3-6 months, followed by maintenance therapy that keeps the condition at bay, Dr. Villa-Forte said. But things do not always go according to plan.
“The main challenge that we encounter is that relapses still occur during treatment. The patient could be on appropriate treatment and appropriate doses and they still relapse,” she said. “The second challenge is that patients who come off treatment have a very high rate of relapse.”
Research suggests that up to 70% of patients off medication relapse by 18 months, and 15%-35% of patients on medication relapse by 12-18 months, Dr. Villa-Forte said.
“Every time a patient relapses, it means induction therapy and high doses of prednisone are started all over again,” she said. “Multiple relapses are associated with a very high rate of complications. That’s what we’re trying to avoid through successful maintenance therapy.”
Which agent is best for maintenance? Research has suggested that there’s little difference in relapse rates between methotrexate and azathioprine, while mycophenolate mofetil was linked to more relapses than was azathioprine. Other research has found that rituximab (Rituxan) is superior to azathioprine at sustaining remission and overall survival (N Engl J Med. 2014 Nov 6;371[19]:1771-80).
Questions about rituximab remain, Dr. Villa-Forte said: Can remission be sustained with fewer infusions? Would higher doses produce long-term benefit after therapy is halted without boosting toxicity?
Regardless of the drug used, relapses from remission are still frequent, suggesting the need to focus on special treatment for patients at higher risk for relapse, she said.
For now, she gave these tips about how to treat patients in remission:
• Reduce treatment toxicity (it’s “significant over time and not better with rituximab”) and focus on disease activity and complications.
• Take regular labs and get a fresh urine sediment analysis with every visit. In some cases, the urine analysis in patients who seem healthy will reveal hematuria, a sign of nephritis. Then, “you have to make a decision about changing the treatment just by looking at the urine.”
• Pay attention to the risk of thrombosis.
• Put patients on Pneumocystis carinii pneumonia prophylaxis even if they’re only on a bit of prednisone.
• Be aware of risk factors for relapse, including a history of at least one relapse and stopping therapy before 48 months.
Dr. Villa-Forte had no relevant disclosures.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Cleveland Clinic rheumatologist Alexandra Villa-Forte, MD, MPH, has a vivid way of describing the challenge of maintaining remission in granulomatosis with polyangiitis (GPA): She called it “the worst nightmare in the clinic” in a presentation at the annual Perspectives in Rheumatic Diseases.
Dr. Villa-Forte should know. She’s treated more than 700 patients with GPA, also known as Wegener’s granulomatosis, a rare disorder that causes necrotizing vasculitis of small arteries and veins. She advises close monitoring of patients in remission, caution regarding toxicity, pneumonia prophylaxis, and an understanding of the limitations of existing medications.
An estimated 3 in 100,000 people have GPA, which can be fatal if it’s not treated. “All patients with active GPA should receive prednisone with a second agent,” she said at the conference, held by Global Academy for Medical Education. “We know that increasing the prednisone or using it alone will not result in sustained remission at all.”
According to her, new concepts in therapeutic guidance suggest four criteria should determine the specific agents used: Involvement of critical organ systems, severity of clinical manifestations, rate of change (such as rapidly progressing kidney failure), and individual patient factors such as comorbidities.
Patients facing immediate risk to life or organ function should get higher doses of corticosteroids, a cytotoxic agent, and perhaps plasmapheresis, she said.
Induction therapy should last 3-6 months, followed by maintenance therapy that keeps the condition at bay, Dr. Villa-Forte said. But things do not always go according to plan.
“The main challenge that we encounter is that relapses still occur during treatment. The patient could be on appropriate treatment and appropriate doses and they still relapse,” she said. “The second challenge is that patients who come off treatment have a very high rate of relapse.”
Research suggests that up to 70% of patients off medication relapse by 18 months, and 15%-35% of patients on medication relapse by 12-18 months, Dr. Villa-Forte said.
“Every time a patient relapses, it means induction therapy and high doses of prednisone are started all over again,” she said. “Multiple relapses are associated with a very high rate of complications. That’s what we’re trying to avoid through successful maintenance therapy.”
Which agent is best for maintenance? Research has suggested that there’s little difference in relapse rates between methotrexate and azathioprine, while mycophenolate mofetil was linked to more relapses than was azathioprine. Other research has found that rituximab (Rituxan) is superior to azathioprine at sustaining remission and overall survival (N Engl J Med. 2014 Nov 6;371[19]:1771-80).
Questions about rituximab remain, Dr. Villa-Forte said: Can remission be sustained with fewer infusions? Would higher doses produce long-term benefit after therapy is halted without boosting toxicity?
Regardless of the drug used, relapses from remission are still frequent, suggesting the need to focus on special treatment for patients at higher risk for relapse, she said.
For now, she gave these tips about how to treat patients in remission:
• Reduce treatment toxicity (it’s “significant over time and not better with rituximab”) and focus on disease activity and complications.
• Take regular labs and get a fresh urine sediment analysis with every visit. In some cases, the urine analysis in patients who seem healthy will reveal hematuria, a sign of nephritis. Then, “you have to make a decision about changing the treatment just by looking at the urine.”
• Pay attention to the risk of thrombosis.
• Put patients on Pneumocystis carinii pneumonia prophylaxis even if they’re only on a bit of prednisone.
• Be aware of risk factors for relapse, including a history of at least one relapse and stopping therapy before 48 months.
Dr. Villa-Forte had no relevant disclosures.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Cleveland Clinic rheumatologist Alexandra Villa-Forte, MD, MPH, has a vivid way of describing the challenge of maintaining remission in granulomatosis with polyangiitis (GPA): She called it “the worst nightmare in the clinic” in a presentation at the annual Perspectives in Rheumatic Diseases.
Dr. Villa-Forte should know. She’s treated more than 700 patients with GPA, also known as Wegener’s granulomatosis, a rare disorder that causes necrotizing vasculitis of small arteries and veins. She advises close monitoring of patients in remission, caution regarding toxicity, pneumonia prophylaxis, and an understanding of the limitations of existing medications.
An estimated 3 in 100,000 people have GPA, which can be fatal if it’s not treated. “All patients with active GPA should receive prednisone with a second agent,” she said at the conference, held by Global Academy for Medical Education. “We know that increasing the prednisone or using it alone will not result in sustained remission at all.”
According to her, new concepts in therapeutic guidance suggest four criteria should determine the specific agents used: Involvement of critical organ systems, severity of clinical manifestations, rate of change (such as rapidly progressing kidney failure), and individual patient factors such as comorbidities.
Patients facing immediate risk to life or organ function should get higher doses of corticosteroids, a cytotoxic agent, and perhaps plasmapheresis, she said.
Induction therapy should last 3-6 months, followed by maintenance therapy that keeps the condition at bay, Dr. Villa-Forte said. But things do not always go according to plan.
“The main challenge that we encounter is that relapses still occur during treatment. The patient could be on appropriate treatment and appropriate doses and they still relapse,” she said. “The second challenge is that patients who come off treatment have a very high rate of relapse.”
Research suggests that up to 70% of patients off medication relapse by 18 months, and 15%-35% of patients on medication relapse by 12-18 months, Dr. Villa-Forte said.
“Every time a patient relapses, it means induction therapy and high doses of prednisone are started all over again,” she said. “Multiple relapses are associated with a very high rate of complications. That’s what we’re trying to avoid through successful maintenance therapy.”
Which agent is best for maintenance? Research has suggested that there’s little difference in relapse rates between methotrexate and azathioprine, while mycophenolate mofetil was linked to more relapses than was azathioprine. Other research has found that rituximab (Rituxan) is superior to azathioprine at sustaining remission and overall survival (N Engl J Med. 2014 Nov 6;371[19]:1771-80).
Questions about rituximab remain, Dr. Villa-Forte said: Can remission be sustained with fewer infusions? Would higher doses produce long-term benefit after therapy is halted without boosting toxicity?
Regardless of the drug used, relapses from remission are still frequent, suggesting the need to focus on special treatment for patients at higher risk for relapse, she said.
For now, she gave these tips about how to treat patients in remission:
• Reduce treatment toxicity (it’s “significant over time and not better with rituximab”) and focus on disease activity and complications.
• Take regular labs and get a fresh urine sediment analysis with every visit. In some cases, the urine analysis in patients who seem healthy will reveal hematuria, a sign of nephritis. Then, “you have to make a decision about changing the treatment just by looking at the urine.”
• Pay attention to the risk of thrombosis.
• Put patients on Pneumocystis carinii pneumonia prophylaxis even if they’re only on a bit of prednisone.
• Be aware of risk factors for relapse, including a history of at least one relapse and stopping therapy before 48 months.
Dr. Villa-Forte had no relevant disclosures.
Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
Two red flags spell trouble ahead in spontaneous coronary artery dissection
MUNICH –
Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.
CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.
SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.
CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.
In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.
Of note, one-third of patients had no cardiovascular risk factors.
The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.
Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.
The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.
Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.
“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.
Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”
“Are you doing that in your practice?” asked Dr. Serruys.
“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”
Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.
“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.
MUNICH –
Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.
CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.
SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.
CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.
In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.
Of note, one-third of patients had no cardiovascular risk factors.
The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.
Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.
The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.
Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.
“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.
Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”
“Are you doing that in your practice?” asked Dr. Serruys.
“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”
Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.
“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.
MUNICH –
Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.
CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.
SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.
CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.
In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.
Of note, one-third of patients had no cardiovascular risk factors.
The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.
Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.
The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.
Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.
“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.
Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”
“Are you doing that in your practice?” asked Dr. Serruys.
“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”
Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.
“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point: SCAD occurring during the peripartum period or in patients with connective tissue disease identifies subgroups at high risk for major adverse cardiovascular events within 30 days.
Major finding: Patients with spontaneous coronary artery dissection and comorbid connective tissue disease were at 8.7-fold increased risk of major adverse cardiovascular events within 30 days.
Study details: CanSCAD is an ongoing, prospective, multicenter, observational study in 750 patients with confirmed spontaneous coronary artery dissection.
Disclosures: CanSCAD is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier.
Idiopathic inflammatory myopathies: Muscle biopsy no longer needed?
A new classification system that incorporates clinical and serologic data may be useful in the classification of idiopathic inflammatory myopathies, results of a recent analysis suggest.
By analyzing the patterns of relationships between 47 variables in this observational, retrospective cohort study, investigators identified 4 clusters of patients that corresponded to known idiopathic inflammatory myopathy subtypes.
Myositis-specific antibodies played a key role in predicting whether a patient belonged in a cluster, according to investigators, who noted that myositis-specific antibodies known to be associated with certain subgroups fell into the corresponding clusters they identified.
“This emphasizes that muscle biopsy may no longer be necessary for diagnosis of idiopathic inflammatory myopathies in patients with [myositis-specific antibodies] and corresponding phenotypes,” said the investigators, led by Kubéraka Mariampillai, PhD, of the Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
The study, described in JAMA Neurology, was based on data for 260 patients in the database of the French Myositis Network. The mean age of the patients was 62 years, and 63% were women.
Investigators conducted a multiple correspondence analysis based on 47 selected variables, including age, race, historical and recent diagnoses, dermatologic changes, creatine kinase levels, myositis-specific antibodies, and pathologic characteristics, among others.
Based on that analysis, they identified four subgroups corresponding to known entities: Dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome.
Using decisional algorithm trees, investigators found that myositis-specific antibodies “played a key role in estimating connection to a cluster,” while by contrast, the pathologic data were “dispensable,” Dr. Mariampillai and her associates said.
The best tree omitted variables related to muscle biopsy and had a 78% correct estimation looking just at antisynthetase antibodies, dermatomyositis rash, and finger flexor scores of 3 or less, investigators said.
“The classification quality of the tree was appreciated on the basis of all classification criteria, with an overall sensitivity of 77.0% and a specificity of 92.0%,” the investigators said.
Patients with polymyositis were present in the study data, but fell mainly in the clusters corresponding to immune-mediated necrotizing myopathy and antisynthetase syndrome.
“This finding indicates that patients with polymyositis do not represent a subgroup of patients, and use of this term should probably be discontinued,” Dr. Mariampillai and coinvestigators said.
The study was supported by Association Française contre les Myopathies, and by CSL Behring, which partly funded the development of electronic case report forms. Dr. Mariampillai and colleagues reported no conflicts of interest related to this work.
SOURCE: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.
A new classification system that incorporates clinical and serologic data may be useful in the classification of idiopathic inflammatory myopathies, results of a recent analysis suggest.
By analyzing the patterns of relationships between 47 variables in this observational, retrospective cohort study, investigators identified 4 clusters of patients that corresponded to known idiopathic inflammatory myopathy subtypes.
Myositis-specific antibodies played a key role in predicting whether a patient belonged in a cluster, according to investigators, who noted that myositis-specific antibodies known to be associated with certain subgroups fell into the corresponding clusters they identified.
“This emphasizes that muscle biopsy may no longer be necessary for diagnosis of idiopathic inflammatory myopathies in patients with [myositis-specific antibodies] and corresponding phenotypes,” said the investigators, led by Kubéraka Mariampillai, PhD, of the Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
The study, described in JAMA Neurology, was based on data for 260 patients in the database of the French Myositis Network. The mean age of the patients was 62 years, and 63% were women.
Investigators conducted a multiple correspondence analysis based on 47 selected variables, including age, race, historical and recent diagnoses, dermatologic changes, creatine kinase levels, myositis-specific antibodies, and pathologic characteristics, among others.
Based on that analysis, they identified four subgroups corresponding to known entities: Dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome.
Using decisional algorithm trees, investigators found that myositis-specific antibodies “played a key role in estimating connection to a cluster,” while by contrast, the pathologic data were “dispensable,” Dr. Mariampillai and her associates said.
The best tree omitted variables related to muscle biopsy and had a 78% correct estimation looking just at antisynthetase antibodies, dermatomyositis rash, and finger flexor scores of 3 or less, investigators said.
“The classification quality of the tree was appreciated on the basis of all classification criteria, with an overall sensitivity of 77.0% and a specificity of 92.0%,” the investigators said.
Patients with polymyositis were present in the study data, but fell mainly in the clusters corresponding to immune-mediated necrotizing myopathy and antisynthetase syndrome.
“This finding indicates that patients with polymyositis do not represent a subgroup of patients, and use of this term should probably be discontinued,” Dr. Mariampillai and coinvestigators said.
The study was supported by Association Française contre les Myopathies, and by CSL Behring, which partly funded the development of electronic case report forms. Dr. Mariampillai and colleagues reported no conflicts of interest related to this work.
SOURCE: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.
A new classification system that incorporates clinical and serologic data may be useful in the classification of idiopathic inflammatory myopathies, results of a recent analysis suggest.
By analyzing the patterns of relationships between 47 variables in this observational, retrospective cohort study, investigators identified 4 clusters of patients that corresponded to known idiopathic inflammatory myopathy subtypes.
Myositis-specific antibodies played a key role in predicting whether a patient belonged in a cluster, according to investigators, who noted that myositis-specific antibodies known to be associated with certain subgroups fell into the corresponding clusters they identified.
“This emphasizes that muscle biopsy may no longer be necessary for diagnosis of idiopathic inflammatory myopathies in patients with [myositis-specific antibodies] and corresponding phenotypes,” said the investigators, led by Kubéraka Mariampillai, PhD, of the Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
The study, described in JAMA Neurology, was based on data for 260 patients in the database of the French Myositis Network. The mean age of the patients was 62 years, and 63% were women.
Investigators conducted a multiple correspondence analysis based on 47 selected variables, including age, race, historical and recent diagnoses, dermatologic changes, creatine kinase levels, myositis-specific antibodies, and pathologic characteristics, among others.
Based on that analysis, they identified four subgroups corresponding to known entities: Dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome.
Using decisional algorithm trees, investigators found that myositis-specific antibodies “played a key role in estimating connection to a cluster,” while by contrast, the pathologic data were “dispensable,” Dr. Mariampillai and her associates said.
The best tree omitted variables related to muscle biopsy and had a 78% correct estimation looking just at antisynthetase antibodies, dermatomyositis rash, and finger flexor scores of 3 or less, investigators said.
“The classification quality of the tree was appreciated on the basis of all classification criteria, with an overall sensitivity of 77.0% and a specificity of 92.0%,” the investigators said.
Patients with polymyositis were present in the study data, but fell mainly in the clusters corresponding to immune-mediated necrotizing myopathy and antisynthetase syndrome.
“This finding indicates that patients with polymyositis do not represent a subgroup of patients, and use of this term should probably be discontinued,” Dr. Mariampillai and coinvestigators said.
The study was supported by Association Française contre les Myopathies, and by CSL Behring, which partly funded the development of electronic case report forms. Dr. Mariampillai and colleagues reported no conflicts of interest related to this work.
SOURCE: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.
FROM JAMA NEUROLOGY
Key clinical point:
Major finding: Myositis-specific antibodies played a key role in predicting whether a patient belonged in a patient cluster.
Study details: An observational, retrospective cohort analysis based on 260 patients in the database of the French Myositis Network.
Disclosures: The study was supported by Association Française contre les Myopathies and CSL Behring. Authors reported no conflicts of interest related to this work.
Source: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.