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Add-on aripiprazole shows modest improvement over bupropion in depression
In men with major depressive disorder (MMD) who were not responding well to an antidepressant treatment, adding aripiprazole resulted in a modest increase in the likelihood of remission, compared with switching to bupropion monotherapy, according to results from a new randomized study.
The findings, published online July 11 in JAMA, come from a randomized, single-blinded trial enrolling more than 1,500 Veterans Health Administration patients (85% men; mean age, 54) with persistent MDD symptoms despite a trial of at least 1 antidepressant drug (JAMA. 2017;318[2]:132-45.).
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, led by Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, Conn., and carried out at 35 Veterans Health Administration treatment centers, was designed to help answer some of the lingering questions about augmentation strategies that the landmark, federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, from 2006, could not answer.
While the STAR*D investigators found bupropion to be an effective switching and augmentation agent in people who had failed citalopram monotherapy, the study was not powered to compare results for switching and augmentation. Nor did STAR*D include augmentation with atypical antipsychotics such as aripiprazole, a treatment strategy that was not yet in wide use.
The VAST-D study also differed from most depression trials in that most of the patients were men. The main outcome was clinical remission within 12 weeks of initiating one of the three treatment strategies. Subjects were randomized to augmentation of current treatment with aripiprazole 2-15 mg (n = 505) or bupropion 150-400 mg (n = 506) or were switched from current treatment to bupropion monotherapy (n = 511).
Remission rates during the first 12 weeks were 22% for patients switched from their current drug to bupropion, 27% for those who augmented treatment with bupropion, and 29% for those who augmented treatment with aripiprazole, though the difference in remission reached statistical significance only for the adjunctive aripiprazole group vs. the bupropion monotherapy group (relative risk, 1.30; 95% confidence interval, 1.05-1.60; P = .02).
Clinical response, as measured using two validated scoring systems, was higher (74%) in the aripiprazole group at 12 weeks, compared with the bupropion only (62%) or bupropion augmentation (66%) groups, a difference that reached statistical significance. Anxiety was more commonly reported among patients in the bupropion groups, while somnolence, akathisia, and weight gain were more frequently reported among patients treated with aripiprazole.
Though aripiprazole augmentation was seen associated with a higher rate of remission and greater response, Dr. Mohamed and her colleagues cautioned that, “given the small effect size and adverse effects” associated with the atypical antipsychotic drug, “further analysis, including cost-effectiveness, is needed to understand the net utility of this approach.”
The Department of Veterans Affairs sponsored the study. Bristol-Myers Squibb provided aripiprazole to investigators. Of the study’s 16 listed coauthors, 5 reported financial relationships with Bristol-Myers Squibb or other manufacturers.
“The modest advantage of aripiprazole augmentation over the two other treatment options in the VAST-D study suggests that this approach should be considered earlier by clinicians for patients with MDD who have an inadequate response to antidepressant therapies,” Maurizio Fava, MD, wrote in an editorial accompanying the study published by JAMA.
He also pointed out that the demographic makeup of the patients study was largely male, which is significantly different “from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D.”
Dr. Fava cited the differences in the proportion of patients with posttraumatic stress disorder in the VAST-D and STAR*D study. In VAST-D, 44%-48% had PTSD, compared with a rate of 17% in the STAR*D cohort. “Did such enrichment potentially favor one of the treatment options of VAST-D? Although a placebo-controlled study of bupropion in chronic PTSD showed no benefit of this therapy, a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials of atypical antipsychotics for the treatment of PTSD found that these agents may be superior to placebo,” Dr. Fava wrote.
Finally, he cited the differences in mean age of onset of MDD in the two studies. In the VAST-D study, the mean age of onset ranged from 36 to 38 years and compared with a mean age of onset of 25 in STAR*D. “The older age of onset of MDD in the VAST-D study suggests that, in many cases, the MDD may have been secondary to other psychiatric conditions, such as PTSD. Therefore, there might be some significant neurobiological differences between the two populations,” Dr. Fava wrote (JAMA. 2017;318[2]:126-8).
Dr. Fava is affiliated with the division of clinical research at Massachusetts General Hospital, Boston. He reported financial relationships with numerous pharmaceutical companies.
“The modest advantage of aripiprazole augmentation over the two other treatment options in the VAST-D study suggests that this approach should be considered earlier by clinicians for patients with MDD who have an inadequate response to antidepressant therapies,” Maurizio Fava, MD, wrote in an editorial accompanying the study published by JAMA.
He also pointed out that the demographic makeup of the patients study was largely male, which is significantly different “from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D.”
Dr. Fava cited the differences in the proportion of patients with posttraumatic stress disorder in the VAST-D and STAR*D study. In VAST-D, 44%-48% had PTSD, compared with a rate of 17% in the STAR*D cohort. “Did such enrichment potentially favor one of the treatment options of VAST-D? Although a placebo-controlled study of bupropion in chronic PTSD showed no benefit of this therapy, a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials of atypical antipsychotics for the treatment of PTSD found that these agents may be superior to placebo,” Dr. Fava wrote.
Finally, he cited the differences in mean age of onset of MDD in the two studies. In the VAST-D study, the mean age of onset ranged from 36 to 38 years and compared with a mean age of onset of 25 in STAR*D. “The older age of onset of MDD in the VAST-D study suggests that, in many cases, the MDD may have been secondary to other psychiatric conditions, such as PTSD. Therefore, there might be some significant neurobiological differences between the two populations,” Dr. Fava wrote (JAMA. 2017;318[2]:126-8).
Dr. Fava is affiliated with the division of clinical research at Massachusetts General Hospital, Boston. He reported financial relationships with numerous pharmaceutical companies.
“The modest advantage of aripiprazole augmentation over the two other treatment options in the VAST-D study suggests that this approach should be considered earlier by clinicians for patients with MDD who have an inadequate response to antidepressant therapies,” Maurizio Fava, MD, wrote in an editorial accompanying the study published by JAMA.
He also pointed out that the demographic makeup of the patients study was largely male, which is significantly different “from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D.”
Dr. Fava cited the differences in the proportion of patients with posttraumatic stress disorder in the VAST-D and STAR*D study. In VAST-D, 44%-48% had PTSD, compared with a rate of 17% in the STAR*D cohort. “Did such enrichment potentially favor one of the treatment options of VAST-D? Although a placebo-controlled study of bupropion in chronic PTSD showed no benefit of this therapy, a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials of atypical antipsychotics for the treatment of PTSD found that these agents may be superior to placebo,” Dr. Fava wrote.
Finally, he cited the differences in mean age of onset of MDD in the two studies. In the VAST-D study, the mean age of onset ranged from 36 to 38 years and compared with a mean age of onset of 25 in STAR*D. “The older age of onset of MDD in the VAST-D study suggests that, in many cases, the MDD may have been secondary to other psychiatric conditions, such as PTSD. Therefore, there might be some significant neurobiological differences between the two populations,” Dr. Fava wrote (JAMA. 2017;318[2]:126-8).
Dr. Fava is affiliated with the division of clinical research at Massachusetts General Hospital, Boston. He reported financial relationships with numerous pharmaceutical companies.
In men with major depressive disorder (MMD) who were not responding well to an antidepressant treatment, adding aripiprazole resulted in a modest increase in the likelihood of remission, compared with switching to bupropion monotherapy, according to results from a new randomized study.
The findings, published online July 11 in JAMA, come from a randomized, single-blinded trial enrolling more than 1,500 Veterans Health Administration patients (85% men; mean age, 54) with persistent MDD symptoms despite a trial of at least 1 antidepressant drug (JAMA. 2017;318[2]:132-45.).
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, led by Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, Conn., and carried out at 35 Veterans Health Administration treatment centers, was designed to help answer some of the lingering questions about augmentation strategies that the landmark, federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, from 2006, could not answer.
While the STAR*D investigators found bupropion to be an effective switching and augmentation agent in people who had failed citalopram monotherapy, the study was not powered to compare results for switching and augmentation. Nor did STAR*D include augmentation with atypical antipsychotics such as aripiprazole, a treatment strategy that was not yet in wide use.
The VAST-D study also differed from most depression trials in that most of the patients were men. The main outcome was clinical remission within 12 weeks of initiating one of the three treatment strategies. Subjects were randomized to augmentation of current treatment with aripiprazole 2-15 mg (n = 505) or bupropion 150-400 mg (n = 506) or were switched from current treatment to bupropion monotherapy (n = 511).
Remission rates during the first 12 weeks were 22% for patients switched from their current drug to bupropion, 27% for those who augmented treatment with bupropion, and 29% for those who augmented treatment with aripiprazole, though the difference in remission reached statistical significance only for the adjunctive aripiprazole group vs. the bupropion monotherapy group (relative risk, 1.30; 95% confidence interval, 1.05-1.60; P = .02).
Clinical response, as measured using two validated scoring systems, was higher (74%) in the aripiprazole group at 12 weeks, compared with the bupropion only (62%) or bupropion augmentation (66%) groups, a difference that reached statistical significance. Anxiety was more commonly reported among patients in the bupropion groups, while somnolence, akathisia, and weight gain were more frequently reported among patients treated with aripiprazole.
Though aripiprazole augmentation was seen associated with a higher rate of remission and greater response, Dr. Mohamed and her colleagues cautioned that, “given the small effect size and adverse effects” associated with the atypical antipsychotic drug, “further analysis, including cost-effectiveness, is needed to understand the net utility of this approach.”
The Department of Veterans Affairs sponsored the study. Bristol-Myers Squibb provided aripiprazole to investigators. Of the study’s 16 listed coauthors, 5 reported financial relationships with Bristol-Myers Squibb or other manufacturers.
In men with major depressive disorder (MMD) who were not responding well to an antidepressant treatment, adding aripiprazole resulted in a modest increase in the likelihood of remission, compared with switching to bupropion monotherapy, according to results from a new randomized study.
The findings, published online July 11 in JAMA, come from a randomized, single-blinded trial enrolling more than 1,500 Veterans Health Administration patients (85% men; mean age, 54) with persistent MDD symptoms despite a trial of at least 1 antidepressant drug (JAMA. 2017;318[2]:132-45.).
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, led by Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, Conn., and carried out at 35 Veterans Health Administration treatment centers, was designed to help answer some of the lingering questions about augmentation strategies that the landmark, federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, from 2006, could not answer.
While the STAR*D investigators found bupropion to be an effective switching and augmentation agent in people who had failed citalopram monotherapy, the study was not powered to compare results for switching and augmentation. Nor did STAR*D include augmentation with atypical antipsychotics such as aripiprazole, a treatment strategy that was not yet in wide use.
The VAST-D study also differed from most depression trials in that most of the patients were men. The main outcome was clinical remission within 12 weeks of initiating one of the three treatment strategies. Subjects were randomized to augmentation of current treatment with aripiprazole 2-15 mg (n = 505) or bupropion 150-400 mg (n = 506) or were switched from current treatment to bupropion monotherapy (n = 511).
Remission rates during the first 12 weeks were 22% for patients switched from their current drug to bupropion, 27% for those who augmented treatment with bupropion, and 29% for those who augmented treatment with aripiprazole, though the difference in remission reached statistical significance only for the adjunctive aripiprazole group vs. the bupropion monotherapy group (relative risk, 1.30; 95% confidence interval, 1.05-1.60; P = .02).
Clinical response, as measured using two validated scoring systems, was higher (74%) in the aripiprazole group at 12 weeks, compared with the bupropion only (62%) or bupropion augmentation (66%) groups, a difference that reached statistical significance. Anxiety was more commonly reported among patients in the bupropion groups, while somnolence, akathisia, and weight gain were more frequently reported among patients treated with aripiprazole.
Though aripiprazole augmentation was seen associated with a higher rate of remission and greater response, Dr. Mohamed and her colleagues cautioned that, “given the small effect size and adverse effects” associated with the atypical antipsychotic drug, “further analysis, including cost-effectiveness, is needed to understand the net utility of this approach.”
The Department of Veterans Affairs sponsored the study. Bristol-Myers Squibb provided aripiprazole to investigators. Of the study’s 16 listed coauthors, 5 reported financial relationships with Bristol-Myers Squibb or other manufacturers.
FROM JAMA
Key clinical point: Aripiprazole added to a current antidepressant was associated with a modestly higher remission rate among men with MDD than was switching to bupropion monotherapy.
Major finding: Remission by 12 weeks was 28.9% among patients receiving add-on aripiprazole, vs. 22.3% for bupropion alone (RR, 1.30; 95% CI, 1.05-1.60; P = 0.02).
Data source: A randomized, single-blinded multicenter trial enrolling more than 1,500 patients (85% men) with persistent MDD despite treatment.
Disclosures: The Veterans Health Administration sponsored the study. One of the study drugs was donated by a manufacturer, and 5 of 16 coauthors disclosed financial conflicts of interest.
Common malaria diagnostic test also can predict treatment-related anemia
While the drug artesunate remains the gold standard for patients with severe Plasmodium falciparum malaria, it also can induce anemia within days or weeks of starting treatment.
In research published online in Science Translational Medicine, a team of researchers led by Papa Alioune Ndour, PhD, of the Université Paris Descartes, presented findings on how a cheap, widely available diagnostic test for malaria infection can be used, under a modified protocol, to predict a form of anemia known as postartesunate delayed hemolysis (PADH) (Sci Transl Med. 2017 Jul 5;9[397]. pii: eaaf9377).
Dr. Ndour and his colleagues discovered, studying prospective cohorts of 95 artesunate-treated malaria patients in Bangladesh and 53 in France, that, if they administered an HRP2 test on day 3 of treatment, a positive result predicted PADH with 89% sensitivity and 73% specificity. However, while the diagnostic test uses a whole blood sample, blood must be diluted 1:500 for the same test to predict PADH. The investigators also studied a comparison cohort of 49 quinine-treated patients in France, in whom HRP2 persistence was much lower.
Using the HRP2-based tests for PADH prediction is more complex than using it for malaria diagnosis, as blood samples must be diluted and because assessment “involves a quantitative element” to determine whether once-infected red blood cells have reached a concentration associated with a high risk of hemolysis, Dr. Ndour and his colleagues cautioned.
“Future large prospective studies will more precisely determine the robustness of prediction in different geographic and logistical settings,” the researchers wrote in their analysis.
The study was funded by the Bill & Melinda Gates Foundation, the French National Research Agency, and the Wellcome Trust. Five investigators, including Dr. Ndour, disclosed research grants from pharmaceutical firms for artesunate studies, two disclosed advisory board relationships with a Sigma Tau Laboratories, and another reported industry funding for anemia research related to artesunate.
While the drug artesunate remains the gold standard for patients with severe Plasmodium falciparum malaria, it also can induce anemia within days or weeks of starting treatment.
In research published online in Science Translational Medicine, a team of researchers led by Papa Alioune Ndour, PhD, of the Université Paris Descartes, presented findings on how a cheap, widely available diagnostic test for malaria infection can be used, under a modified protocol, to predict a form of anemia known as postartesunate delayed hemolysis (PADH) (Sci Transl Med. 2017 Jul 5;9[397]. pii: eaaf9377).
Dr. Ndour and his colleagues discovered, studying prospective cohorts of 95 artesunate-treated malaria patients in Bangladesh and 53 in France, that, if they administered an HRP2 test on day 3 of treatment, a positive result predicted PADH with 89% sensitivity and 73% specificity. However, while the diagnostic test uses a whole blood sample, blood must be diluted 1:500 for the same test to predict PADH. The investigators also studied a comparison cohort of 49 quinine-treated patients in France, in whom HRP2 persistence was much lower.
Using the HRP2-based tests for PADH prediction is more complex than using it for malaria diagnosis, as blood samples must be diluted and because assessment “involves a quantitative element” to determine whether once-infected red blood cells have reached a concentration associated with a high risk of hemolysis, Dr. Ndour and his colleagues cautioned.
“Future large prospective studies will more precisely determine the robustness of prediction in different geographic and logistical settings,” the researchers wrote in their analysis.
The study was funded by the Bill & Melinda Gates Foundation, the French National Research Agency, and the Wellcome Trust. Five investigators, including Dr. Ndour, disclosed research grants from pharmaceutical firms for artesunate studies, two disclosed advisory board relationships with a Sigma Tau Laboratories, and another reported industry funding for anemia research related to artesunate.
While the drug artesunate remains the gold standard for patients with severe Plasmodium falciparum malaria, it also can induce anemia within days or weeks of starting treatment.
In research published online in Science Translational Medicine, a team of researchers led by Papa Alioune Ndour, PhD, of the Université Paris Descartes, presented findings on how a cheap, widely available diagnostic test for malaria infection can be used, under a modified protocol, to predict a form of anemia known as postartesunate delayed hemolysis (PADH) (Sci Transl Med. 2017 Jul 5;9[397]. pii: eaaf9377).
Dr. Ndour and his colleagues discovered, studying prospective cohorts of 95 artesunate-treated malaria patients in Bangladesh and 53 in France, that, if they administered an HRP2 test on day 3 of treatment, a positive result predicted PADH with 89% sensitivity and 73% specificity. However, while the diagnostic test uses a whole blood sample, blood must be diluted 1:500 for the same test to predict PADH. The investigators also studied a comparison cohort of 49 quinine-treated patients in France, in whom HRP2 persistence was much lower.
Using the HRP2-based tests for PADH prediction is more complex than using it for malaria diagnosis, as blood samples must be diluted and because assessment “involves a quantitative element” to determine whether once-infected red blood cells have reached a concentration associated with a high risk of hemolysis, Dr. Ndour and his colleagues cautioned.
“Future large prospective studies will more precisely determine the robustness of prediction in different geographic and logistical settings,” the researchers wrote in their analysis.
The study was funded by the Bill & Melinda Gates Foundation, the French National Research Agency, and the Wellcome Trust. Five investigators, including Dr. Ndour, disclosed research grants from pharmaceutical firms for artesunate studies, two disclosed advisory board relationships with a Sigma Tau Laboratories, and another reported industry funding for anemia research related to artesunate.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point:
Major finding: A positive result on an HRP2 test with diluted blood was 89% sensitive and 73% specific in predicting treatment-related anemia.
Data source: Two prospective cohorts of 95 artesunate-treated malaria patients in Bangladesh and 53 in France, plus a comparison cohort of 49 quinine-treated patients in France.
Disclosures: International foundations sponsored the study. Six of the investigators disclosed research support or other financial conflicts.
Daily 150-mg aspirin dose slashes preterm preeclampsia risk
While low-dose aspirin has been shown for decades to decrease the risk of preterm preeclampsia, yet to be established are the optimal dose and time of day to administer aspirin; how preeclampsia risk is best assessed; and at what gestational week it is best to start aspirin.
New findings from a randomized, double-blind, placebo-controlled trial show that a daily 150-mg dose of aspirin, taken at night, significantly reduced incidence of preterm preeclampsia in women identified as being at high risk in the first trimester (N Engl J Med. 2017 June 28. doi: 10.1056/NEJMoa1704559).
After 156 women dropped out of the study or were lost to follow-up, investigators had results from 798 women in the aspirin group and 822 in the placebo group, with about 80% of subjects having taken aspirin or placebo as directed. The study’s primary outcome was delivery with preeclampsia before 37 weeks, seen in 13 women (1.6%) in the aspirin group, compared with 35 (4.3%) in the placebo group (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P = .004).
Other decisions incorporated into the study design, including those about aspirin dosage (higher than the currently recommended 60-80 mg for this population), taking aspirin at night, and the gestational age at which to start aspirin, were based on results from prior trials, studies, and meta-analyses, the researchers said.
Screening at 11-13 weeks’ gestation identifies less than 40% of term preeclampsia, studies have shown, and aspirin did not reduce term preeclampsia in this study, the investigators said.
The European Union Seventh Framework Program and the Fetal Medicine Foundation (UK) sponsored the study. None of the investigators had any relevant financial disclosures.
While low-dose aspirin has been shown for decades to decrease the risk of preterm preeclampsia, yet to be established are the optimal dose and time of day to administer aspirin; how preeclampsia risk is best assessed; and at what gestational week it is best to start aspirin.
New findings from a randomized, double-blind, placebo-controlled trial show that a daily 150-mg dose of aspirin, taken at night, significantly reduced incidence of preterm preeclampsia in women identified as being at high risk in the first trimester (N Engl J Med. 2017 June 28. doi: 10.1056/NEJMoa1704559).
After 156 women dropped out of the study or were lost to follow-up, investigators had results from 798 women in the aspirin group and 822 in the placebo group, with about 80% of subjects having taken aspirin or placebo as directed. The study’s primary outcome was delivery with preeclampsia before 37 weeks, seen in 13 women (1.6%) in the aspirin group, compared with 35 (4.3%) in the placebo group (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P = .004).
Other decisions incorporated into the study design, including those about aspirin dosage (higher than the currently recommended 60-80 mg for this population), taking aspirin at night, and the gestational age at which to start aspirin, were based on results from prior trials, studies, and meta-analyses, the researchers said.
Screening at 11-13 weeks’ gestation identifies less than 40% of term preeclampsia, studies have shown, and aspirin did not reduce term preeclampsia in this study, the investigators said.
The European Union Seventh Framework Program and the Fetal Medicine Foundation (UK) sponsored the study. None of the investigators had any relevant financial disclosures.
While low-dose aspirin has been shown for decades to decrease the risk of preterm preeclampsia, yet to be established are the optimal dose and time of day to administer aspirin; how preeclampsia risk is best assessed; and at what gestational week it is best to start aspirin.
New findings from a randomized, double-blind, placebo-controlled trial show that a daily 150-mg dose of aspirin, taken at night, significantly reduced incidence of preterm preeclampsia in women identified as being at high risk in the first trimester (N Engl J Med. 2017 June 28. doi: 10.1056/NEJMoa1704559).
After 156 women dropped out of the study or were lost to follow-up, investigators had results from 798 women in the aspirin group and 822 in the placebo group, with about 80% of subjects having taken aspirin or placebo as directed. The study’s primary outcome was delivery with preeclampsia before 37 weeks, seen in 13 women (1.6%) in the aspirin group, compared with 35 (4.3%) in the placebo group (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P = .004).
Other decisions incorporated into the study design, including those about aspirin dosage (higher than the currently recommended 60-80 mg for this population), taking aspirin at night, and the gestational age at which to start aspirin, were based on results from prior trials, studies, and meta-analyses, the researchers said.
Screening at 11-13 weeks’ gestation identifies less than 40% of term preeclampsia, studies have shown, and aspirin did not reduce term preeclampsia in this study, the investigators said.
The European Union Seventh Framework Program and the Fetal Medicine Foundation (UK) sponsored the study. None of the investigators had any relevant financial disclosures.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Among patients taking aspirin, 1.6% developed preterm preeclampsia, compared with 4.3% of those taking placebo (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P = .004).
Data source: A randomized, international, multicenter trial enrolling nearly 1,800 women identified through screening as being at high risk of preeclampsia.
Disclosures: The European Union Seventh Framework Program and the Fetal Medicine Foundation (UK) sponsored the study. None of the investigators had any relevant financial disclosures.
VIDEO: Adding ultrasound to treat to target doesn’t improve RA remission outcomes
MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.
In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.
“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”
Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.
Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.
Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.
To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.
As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.
In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.
The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.
Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”
But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.
“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”
Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.
Dr. Sepriano and his associates had no conflicts of interest to declare.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.
In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.
“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”
Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.
Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.
Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.
To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.
As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.
In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.
The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.
Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”
But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.
“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”
Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.
Dr. Sepriano and his associates had no conflicts of interest to declare.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.
In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.
“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”
Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.
Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.
Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.
To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.
As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.
In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.
The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.
Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”
But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.
“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”
Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.
Dr. Sepriano and his associates had no conflicts of interest to declare.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Adding ultrasound to the treatment protocol actually reduced the likelihood of patients achieving remission by up to 66%, depending on the remission assessment used.
Data source: The observational study comprised 130 patients and more than 1,000 clinical visits.
Disclosures: Dr. Sepriano had no financial disclosures.
Pain often persists despite biologic treatment in PsA
MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.
At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.
In an interview. Dr. Conaghan said that it’s important for clinicians not to assume that pain in a PsA patient on a biologic means that the drug is not working.
“The main limitation of our study is that we haven’t worked out how well-controlled patients’ psoriatic arthritis is, so, although we know they’re on a biologic for more than 3 months, we don’t know if they were responding well to it.” But, even in the absence of systemic inflammation, he said, there are other potential causes for pain that should not be overlooked.
“There’s no reason why PsA patients wouldn’t have pain due to tendinitis, enthesitis, and osteoarthritis – the same mechanical-type joint pain that we see in the whole community of people over 40,” Dr. Conaghan said. “I am concerned that, once we give someone a label of inflammatory arthritis, we stop looking at all the other things that can happen to their musculoskeletal system.”
Moreover, he said, “people who’ve had arthritis severe enough to need a biologic treatment will have muscle deconditioning and weakness. It’s very common that PsA patients have trouble opening jars and getting out of chairs.”
Such weakness “can lead to mechanical joint pain, which fortunately can be improved – along with the pain – through muscle strengthening and rehabilitation.”
For their study, Dr. Conaghan and his colleagues collected information from clinicians on treatment and from patients. The questionnaires incorporated several measures of disability, pain, functional impairment, and health-related quality of life that have been validated for use in PsA patients.
Severe pain was significantly associated with increased use of prescription nonsteroidal anti-inflammatory drugs and opioids, as well as nonprescription pain medication. Patients 65 years and older had a significantly greater likelihood of being unemployed or retired because of PsA if they reported severe pain, compared with those reporting mild or moderate pain.
A number of quality of life and work-related measures were also associated with pain severity. Dr. Conaghan and his colleagues found that the risk of disability increased with bodily pain, and more severe pain was associated with greater activity impairment, worse social functioning, more work impairment, and work time missed, among other measures (P less than .0001 for all).
“What we saw is that, the more pain you have, the more your world shrinks in,” Dr. Conaghan said.
Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.
At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.
In an interview. Dr. Conaghan said that it’s important for clinicians not to assume that pain in a PsA patient on a biologic means that the drug is not working.
“The main limitation of our study is that we haven’t worked out how well-controlled patients’ psoriatic arthritis is, so, although we know they’re on a biologic for more than 3 months, we don’t know if they were responding well to it.” But, even in the absence of systemic inflammation, he said, there are other potential causes for pain that should not be overlooked.
“There’s no reason why PsA patients wouldn’t have pain due to tendinitis, enthesitis, and osteoarthritis – the same mechanical-type joint pain that we see in the whole community of people over 40,” Dr. Conaghan said. “I am concerned that, once we give someone a label of inflammatory arthritis, we stop looking at all the other things that can happen to their musculoskeletal system.”
Moreover, he said, “people who’ve had arthritis severe enough to need a biologic treatment will have muscle deconditioning and weakness. It’s very common that PsA patients have trouble opening jars and getting out of chairs.”
Such weakness “can lead to mechanical joint pain, which fortunately can be improved – along with the pain – through muscle strengthening and rehabilitation.”
For their study, Dr. Conaghan and his colleagues collected information from clinicians on treatment and from patients. The questionnaires incorporated several measures of disability, pain, functional impairment, and health-related quality of life that have been validated for use in PsA patients.
Severe pain was significantly associated with increased use of prescription nonsteroidal anti-inflammatory drugs and opioids, as well as nonprescription pain medication. Patients 65 years and older had a significantly greater likelihood of being unemployed or retired because of PsA if they reported severe pain, compared with those reporting mild or moderate pain.
A number of quality of life and work-related measures were also associated with pain severity. Dr. Conaghan and his colleagues found that the risk of disability increased with bodily pain, and more severe pain was associated with greater activity impairment, worse social functioning, more work impairment, and work time missed, among other measures (P less than .0001 for all).
“What we saw is that, the more pain you have, the more your world shrinks in,” Dr. Conaghan said.
Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.
At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.
In an interview. Dr. Conaghan said that it’s important for clinicians not to assume that pain in a PsA patient on a biologic means that the drug is not working.
“The main limitation of our study is that we haven’t worked out how well-controlled patients’ psoriatic arthritis is, so, although we know they’re on a biologic for more than 3 months, we don’t know if they were responding well to it.” But, even in the absence of systemic inflammation, he said, there are other potential causes for pain that should not be overlooked.
“There’s no reason why PsA patients wouldn’t have pain due to tendinitis, enthesitis, and osteoarthritis – the same mechanical-type joint pain that we see in the whole community of people over 40,” Dr. Conaghan said. “I am concerned that, once we give someone a label of inflammatory arthritis, we stop looking at all the other things that can happen to their musculoskeletal system.”
Moreover, he said, “people who’ve had arthritis severe enough to need a biologic treatment will have muscle deconditioning and weakness. It’s very common that PsA patients have trouble opening jars and getting out of chairs.”
Such weakness “can lead to mechanical joint pain, which fortunately can be improved – along with the pain – through muscle strengthening and rehabilitation.”
For their study, Dr. Conaghan and his colleagues collected information from clinicians on treatment and from patients. The questionnaires incorporated several measures of disability, pain, functional impairment, and health-related quality of life that have been validated for use in PsA patients.
Severe pain was significantly associated with increased use of prescription nonsteroidal anti-inflammatory drugs and opioids, as well as nonprescription pain medication. Patients 65 years and older had a significantly greater likelihood of being unemployed or retired because of PsA if they reported severe pain, compared with those reporting mild or moderate pain.
A number of quality of life and work-related measures were also associated with pain severity. Dr. Conaghan and his colleagues found that the risk of disability increased with bodily pain, and more severe pain was associated with greater activity impairment, worse social functioning, more work impairment, and work time missed, among other measures (P less than .0001 for all).
“What we saw is that, the more pain you have, the more your world shrinks in,” Dr. Conaghan said.
Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Overall, 37% of PsA patients reported severe pain despite treatment with biologic agents.
Data source: A multinational survey of 782 consecutive PsA patients on biologic agents.
Disclosures: Dr. Conaghan reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Roche. Some of his study coauthors have similar disclosures. Four coauthors are employees of Novartis.
Studies provide insight into link between cancer immunotherapy and autoimmune disease
MADRID – Rheumatologists all over the world are beginning to find that the new class of anticancer immune checkpoint inhibitor therapies have the potential to elicit symptoms of rheumatoid arthritis (RA) and other rheumatic diseases in patients with no previous history of them, and two reports from the European Congress of Rheumatology provide typical examples.
These immune checkpoint inhibitor (ICI) agents, which include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), target regulatory pathways in T cells to boost antitumor immune responses, leading to improved survival for many cancer patients, but the induction of rheumatic disease can sometimes lead to the suspension of the agents, according to investigators.
“This phenomenon was unknown to me and my group before [February 2016], when we started noting referrals of patients from oncology,” Dr. Calabrese said. “We were seeing symptoms of everything from Sjögren’s syndrome to inflammatory arthritis and myositis in patients being treated with these drugs for their cancer.” The same year, Dr. Calabrese and her team began coordinating an ongoing study to assess these patients.
Dr. Calabrese said that the cohort has shown so far that patients who develop autoimmune disease after immune checkpoint inhibitors “require much higher doses – of steroids in particular – to treat their symptoms,” and this can all too often result in being taken out of a clinical trial or having to stop cancer treatment.
Most of the patients in the cohort were treated with steroids only, while three patients received biologic agents, and four received methotrexate or antimalarials.
Dr. Calabrese said that the serology results were available for all the patients in the cohort and “were largely unremarkable.”
She noted that the rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment. “We have some patients that have been off their checkpoint inhibitors for over a year and still have symptoms, so it’s looking like it might be a more long-term effect,” she said.
“In my unit, we also manage patients with myeloma, and I developed a weekly consultation with a cancer center,” Dr. Belkhir said. In 2015, she saw her first patient with RA and no previous history who had been treated with checkpoint inhibitors. That patient’s symptoms resolved after treatment with nonsteroidal anti-inflammatory drugs alone.
Dr. Belkhir is sharing results from this and five other patients presenting with symptoms of RA after their cancer treatment with immune checkpoint inhibitors, taken from a larger cohort of patients (n = 13) with a spectrum of rheumatic disease–like adverse effects. None of the six patients in this study had a previous clinical history of RA. They manifested their RA symptoms after a median of 1 month on cancer immunotherapy.
Some were able to continue their checkpoint inhibitors and be treated simultaneously for RA with steroids, antimalarials, methotrexate, and NSAIDs, Dr. Belkhir said. None received biologic agents, and each medication strategy, she said, was arrived at in consultation with the treating oncologist.
Dr. Belkhir’s team also looked closely at serology and found all six patients to be at least weakly, and mostly strongly, seropositive for RA. Three patients underwent testing for anticyclic citrullinated protein antibodies prior to starting cancer immunotherapy and two of these three were anti-CCP positive. Now, she said, the oncologists she’s working with are testing for anticyclic citrullinated peptides and rheumatoid factor prior to initiating cancer immunotherapy, so that this relationship is better understood.
“It is possible that antibodies were already present and that the anti-PD1 immunotherapy,” one type of immune checkpoint inhibitor, “acted as a trigger for the disease.” Animal studies have suggested a role for PD1 in the development of autoimmune disease, “but it’s not well investigated,” Dr. Belkhir said.
Dr. Belkhir and Dr. Calabrese both acknowledged that the understanding of checkpoint inhibitor–induced autoimmune disease is in its infancy. Clinical trials largely missed the phenomenon, the researchers said, because the trials were not designed to capture musculoskeletal adverse effects with the same granularity as other serious adverse events.
“This will be a long discussion in the months and the years ahead with oncologists,” Dr. Belkhir said.
Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
MADRID – Rheumatologists all over the world are beginning to find that the new class of anticancer immune checkpoint inhibitor therapies have the potential to elicit symptoms of rheumatoid arthritis (RA) and other rheumatic diseases in patients with no previous history of them, and two reports from the European Congress of Rheumatology provide typical examples.
These immune checkpoint inhibitor (ICI) agents, which include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), target regulatory pathways in T cells to boost antitumor immune responses, leading to improved survival for many cancer patients, but the induction of rheumatic disease can sometimes lead to the suspension of the agents, according to investigators.
“This phenomenon was unknown to me and my group before [February 2016], when we started noting referrals of patients from oncology,” Dr. Calabrese said. “We were seeing symptoms of everything from Sjögren’s syndrome to inflammatory arthritis and myositis in patients being treated with these drugs for their cancer.” The same year, Dr. Calabrese and her team began coordinating an ongoing study to assess these patients.
Dr. Calabrese said that the cohort has shown so far that patients who develop autoimmune disease after immune checkpoint inhibitors “require much higher doses – of steroids in particular – to treat their symptoms,” and this can all too often result in being taken out of a clinical trial or having to stop cancer treatment.
Most of the patients in the cohort were treated with steroids only, while three patients received biologic agents, and four received methotrexate or antimalarials.
Dr. Calabrese said that the serology results were available for all the patients in the cohort and “were largely unremarkable.”
She noted that the rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment. “We have some patients that have been off their checkpoint inhibitors for over a year and still have symptoms, so it’s looking like it might be a more long-term effect,” she said.
“In my unit, we also manage patients with myeloma, and I developed a weekly consultation with a cancer center,” Dr. Belkhir said. In 2015, she saw her first patient with RA and no previous history who had been treated with checkpoint inhibitors. That patient’s symptoms resolved after treatment with nonsteroidal anti-inflammatory drugs alone.
Dr. Belkhir is sharing results from this and five other patients presenting with symptoms of RA after their cancer treatment with immune checkpoint inhibitors, taken from a larger cohort of patients (n = 13) with a spectrum of rheumatic disease–like adverse effects. None of the six patients in this study had a previous clinical history of RA. They manifested their RA symptoms after a median of 1 month on cancer immunotherapy.
Some were able to continue their checkpoint inhibitors and be treated simultaneously for RA with steroids, antimalarials, methotrexate, and NSAIDs, Dr. Belkhir said. None received biologic agents, and each medication strategy, she said, was arrived at in consultation with the treating oncologist.
Dr. Belkhir’s team also looked closely at serology and found all six patients to be at least weakly, and mostly strongly, seropositive for RA. Three patients underwent testing for anticyclic citrullinated protein antibodies prior to starting cancer immunotherapy and two of these three were anti-CCP positive. Now, she said, the oncologists she’s working with are testing for anticyclic citrullinated peptides and rheumatoid factor prior to initiating cancer immunotherapy, so that this relationship is better understood.
“It is possible that antibodies were already present and that the anti-PD1 immunotherapy,” one type of immune checkpoint inhibitor, “acted as a trigger for the disease.” Animal studies have suggested a role for PD1 in the development of autoimmune disease, “but it’s not well investigated,” Dr. Belkhir said.
Dr. Belkhir and Dr. Calabrese both acknowledged that the understanding of checkpoint inhibitor–induced autoimmune disease is in its infancy. Clinical trials largely missed the phenomenon, the researchers said, because the trials were not designed to capture musculoskeletal adverse effects with the same granularity as other serious adverse events.
“This will be a long discussion in the months and the years ahead with oncologists,” Dr. Belkhir said.
Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
MADRID – Rheumatologists all over the world are beginning to find that the new class of anticancer immune checkpoint inhibitor therapies have the potential to elicit symptoms of rheumatoid arthritis (RA) and other rheumatic diseases in patients with no previous history of them, and two reports from the European Congress of Rheumatology provide typical examples.
These immune checkpoint inhibitor (ICI) agents, which include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), target regulatory pathways in T cells to boost antitumor immune responses, leading to improved survival for many cancer patients, but the induction of rheumatic disease can sometimes lead to the suspension of the agents, according to investigators.
“This phenomenon was unknown to me and my group before [February 2016], when we started noting referrals of patients from oncology,” Dr. Calabrese said. “We were seeing symptoms of everything from Sjögren’s syndrome to inflammatory arthritis and myositis in patients being treated with these drugs for their cancer.” The same year, Dr. Calabrese and her team began coordinating an ongoing study to assess these patients.
Dr. Calabrese said that the cohort has shown so far that patients who develop autoimmune disease after immune checkpoint inhibitors “require much higher doses – of steroids in particular – to treat their symptoms,” and this can all too often result in being taken out of a clinical trial or having to stop cancer treatment.
Most of the patients in the cohort were treated with steroids only, while three patients received biologic agents, and four received methotrexate or antimalarials.
Dr. Calabrese said that the serology results were available for all the patients in the cohort and “were largely unremarkable.”
She noted that the rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment. “We have some patients that have been off their checkpoint inhibitors for over a year and still have symptoms, so it’s looking like it might be a more long-term effect,” she said.
“In my unit, we also manage patients with myeloma, and I developed a weekly consultation with a cancer center,” Dr. Belkhir said. In 2015, she saw her first patient with RA and no previous history who had been treated with checkpoint inhibitors. That patient’s symptoms resolved after treatment with nonsteroidal anti-inflammatory drugs alone.
Dr. Belkhir is sharing results from this and five other patients presenting with symptoms of RA after their cancer treatment with immune checkpoint inhibitors, taken from a larger cohort of patients (n = 13) with a spectrum of rheumatic disease–like adverse effects. None of the six patients in this study had a previous clinical history of RA. They manifested their RA symptoms after a median of 1 month on cancer immunotherapy.
Some were able to continue their checkpoint inhibitors and be treated simultaneously for RA with steroids, antimalarials, methotrexate, and NSAIDs, Dr. Belkhir said. None received biologic agents, and each medication strategy, she said, was arrived at in consultation with the treating oncologist.
Dr. Belkhir’s team also looked closely at serology and found all six patients to be at least weakly, and mostly strongly, seropositive for RA. Three patients underwent testing for anticyclic citrullinated protein antibodies prior to starting cancer immunotherapy and two of these three were anti-CCP positive. Now, she said, the oncologists she’s working with are testing for anticyclic citrullinated peptides and rheumatoid factor prior to initiating cancer immunotherapy, so that this relationship is better understood.
“It is possible that antibodies were already present and that the anti-PD1 immunotherapy,” one type of immune checkpoint inhibitor, “acted as a trigger for the disease.” Animal studies have suggested a role for PD1 in the development of autoimmune disease, “but it’s not well investigated,” Dr. Belkhir said.
Dr. Belkhir and Dr. Calabrese both acknowledged that the understanding of checkpoint inhibitor–induced autoimmune disease is in its infancy. Clinical trials largely missed the phenomenon, the researchers said, because the trials were not designed to capture musculoskeletal adverse effects with the same granularity as other serious adverse events.
“This will be a long discussion in the months and the years ahead with oncologists,” Dr. Belkhir said.
Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Rheumatic symptoms did not always resolve after pausing or stopping the cancer treatment, and some were able to continue their checkpoint inhibitors and be treated simultaneously for RA.
Data source: Two retrospective cohort reviews of patients on immune checkpoint inhibitors.
Disclosures: Neither Dr. Calabrese nor Dr. Belkhir reported having any relevant conflicts of interest.
Algorithm aims to tackle clozapine resistance
SAN DIEGO – The atypical antipsychotic drug clozapine is the standard of care for patients with treatment-resistant schizophrenia, but about half do not see an adequate response.
At the annual meeting of the American Psychiatric Association, Randall F. White, MD, presented an algorithm for clozapine-resistant patients intended to simplify and clarify a path forward. He also presented outcome data from a cohort of patients managed using this approach.
The algorithm recommends electroconvulsive therapy if there is inadequate response to clozapine alone or with fluvoxamine, which sometimes is used to boost clozapine serum level, especially in patients who are heavy smokers. If ECT fails to reduce symptoms or the patient refuses it, topiramate, aripiprazole, or sulpiride may be added to clozapine treatment, said Dr. White of the University of British Columbia, Vancouver.
And finally, if psychosis persists, certain patients should be offered cognitive-behavioral therapy with a psychologist trained in helping people with psychosis, Dr. White and his colleagues advise.
Dr. White said in an interview that the idea for a systematic approach to clozapine resistance came from clinical experience of the British Columbia Psychosis Program, which specializes in patients with severe schizophrenia and treatment resistance.
“About half of our patients come to us already on clozapine and aren’t getting better, so we needed to figure out a coherent approach to help them,” he said, noting that there is no current standard of care and that many “come to us already on four or five medications, and it can seem a bit random.”
When these patients are admitted, “we try to simplify their treatment and figure out what’s going on, and then offer ECT if appropriate,” he said.
Dr. White presented data from a cohort of patients assessed at the program between 2012 and 2017, of which 114 were taking clozapine at admission and had a diagnosis of schizophrenia or schizoaffective disorder.
To be considered clozapine-resistant, patients had to be taking 500 mg or more for at least 60 days, yet have persistent positive symptoms and moderate to severe impairment. Dr. White and his colleagues identified 20 patients with clozapine resistance. Of these, eight were offered ECT, and three accepted. At the time of discharge, 16 patients remained on clozapine with or without fluvoxamine. Four patients were treated with the recommended adjunctive agents aripiprazole or sulpiride and five with other agents.
Dr. White said the three agents recommended in the algorithm were determined by literature reviews, including meta-analyses of randomized trials. Several commonly used adjunctive agents to clozapine, including risperidone, were ruled out, for lack of evidence in this patient group.
Sulpiride, one of the drugs recommended in the algorithm, is not marketed in North America, and in Canada is accessible only by special arrangement. The evidence for aripiprazole, meanwhile, “is not stupendous,” Dr. White said, “but there’s a signal.”
The topiramate recommendation is based on results from a 2016 meta-analysis of randomized controlled trials. “Topiramate has a possible advantage of ameliorating metabolic problems,” Dr. White said, and the meta-analysis showed a significant effect size in improving positive and negative symptoms. However, he noted, on rare occasions, it has been seen to exacerbate psychosis.
Dr. White said few of the treatment-resistant patients seen in his program have had a course of ECT despite evidence of benefit. “Instead of ECT, they usually are put on multiple medications,” he said. “Admittedly, getting some of these patients to accept ECT isn’t easy.”
Because the program is designed to keep patients for 6 or more months as needed, “we have the luxury of time,” Dr. White said, to allow for the discontinuation of extraneous medicines and for an ECT trial if indicated.
“I know that in other hospitals, and other health care settings, they don’t have that – they have to figure out what to do quickly. And ECT is not the quickest treatment.”
Offering cognitive-behavioral therapy to people with psychosis is possible, he stressed, and supported by evidence from at least one study. “In this population, it’s challenging,” he acknowledged. “I don’t think I’d do it concurrently with ECT but as an alternative to or after ECT.”
Dr. White disclosed no conflicts of interest related to his research.
SAN DIEGO – The atypical antipsychotic drug clozapine is the standard of care for patients with treatment-resistant schizophrenia, but about half do not see an adequate response.
At the annual meeting of the American Psychiatric Association, Randall F. White, MD, presented an algorithm for clozapine-resistant patients intended to simplify and clarify a path forward. He also presented outcome data from a cohort of patients managed using this approach.
The algorithm recommends electroconvulsive therapy if there is inadequate response to clozapine alone or with fluvoxamine, which sometimes is used to boost clozapine serum level, especially in patients who are heavy smokers. If ECT fails to reduce symptoms or the patient refuses it, topiramate, aripiprazole, or sulpiride may be added to clozapine treatment, said Dr. White of the University of British Columbia, Vancouver.
And finally, if psychosis persists, certain patients should be offered cognitive-behavioral therapy with a psychologist trained in helping people with psychosis, Dr. White and his colleagues advise.
Dr. White said in an interview that the idea for a systematic approach to clozapine resistance came from clinical experience of the British Columbia Psychosis Program, which specializes in patients with severe schizophrenia and treatment resistance.
“About half of our patients come to us already on clozapine and aren’t getting better, so we needed to figure out a coherent approach to help them,” he said, noting that there is no current standard of care and that many “come to us already on four or five medications, and it can seem a bit random.”
When these patients are admitted, “we try to simplify their treatment and figure out what’s going on, and then offer ECT if appropriate,” he said.
Dr. White presented data from a cohort of patients assessed at the program between 2012 and 2017, of which 114 were taking clozapine at admission and had a diagnosis of schizophrenia or schizoaffective disorder.
To be considered clozapine-resistant, patients had to be taking 500 mg or more for at least 60 days, yet have persistent positive symptoms and moderate to severe impairment. Dr. White and his colleagues identified 20 patients with clozapine resistance. Of these, eight were offered ECT, and three accepted. At the time of discharge, 16 patients remained on clozapine with or without fluvoxamine. Four patients were treated with the recommended adjunctive agents aripiprazole or sulpiride and five with other agents.
Dr. White said the three agents recommended in the algorithm were determined by literature reviews, including meta-analyses of randomized trials. Several commonly used adjunctive agents to clozapine, including risperidone, were ruled out, for lack of evidence in this patient group.
Sulpiride, one of the drugs recommended in the algorithm, is not marketed in North America, and in Canada is accessible only by special arrangement. The evidence for aripiprazole, meanwhile, “is not stupendous,” Dr. White said, “but there’s a signal.”
The topiramate recommendation is based on results from a 2016 meta-analysis of randomized controlled trials. “Topiramate has a possible advantage of ameliorating metabolic problems,” Dr. White said, and the meta-analysis showed a significant effect size in improving positive and negative symptoms. However, he noted, on rare occasions, it has been seen to exacerbate psychosis.
Dr. White said few of the treatment-resistant patients seen in his program have had a course of ECT despite evidence of benefit. “Instead of ECT, they usually are put on multiple medications,” he said. “Admittedly, getting some of these patients to accept ECT isn’t easy.”
Because the program is designed to keep patients for 6 or more months as needed, “we have the luxury of time,” Dr. White said, to allow for the discontinuation of extraneous medicines and for an ECT trial if indicated.
“I know that in other hospitals, and other health care settings, they don’t have that – they have to figure out what to do quickly. And ECT is not the quickest treatment.”
Offering cognitive-behavioral therapy to people with psychosis is possible, he stressed, and supported by evidence from at least one study. “In this population, it’s challenging,” he acknowledged. “I don’t think I’d do it concurrently with ECT but as an alternative to or after ECT.”
Dr. White disclosed no conflicts of interest related to his research.
SAN DIEGO – The atypical antipsychotic drug clozapine is the standard of care for patients with treatment-resistant schizophrenia, but about half do not see an adequate response.
At the annual meeting of the American Psychiatric Association, Randall F. White, MD, presented an algorithm for clozapine-resistant patients intended to simplify and clarify a path forward. He also presented outcome data from a cohort of patients managed using this approach.
The algorithm recommends electroconvulsive therapy if there is inadequate response to clozapine alone or with fluvoxamine, which sometimes is used to boost clozapine serum level, especially in patients who are heavy smokers. If ECT fails to reduce symptoms or the patient refuses it, topiramate, aripiprazole, or sulpiride may be added to clozapine treatment, said Dr. White of the University of British Columbia, Vancouver.
And finally, if psychosis persists, certain patients should be offered cognitive-behavioral therapy with a psychologist trained in helping people with psychosis, Dr. White and his colleagues advise.
Dr. White said in an interview that the idea for a systematic approach to clozapine resistance came from clinical experience of the British Columbia Psychosis Program, which specializes in patients with severe schizophrenia and treatment resistance.
“About half of our patients come to us already on clozapine and aren’t getting better, so we needed to figure out a coherent approach to help them,” he said, noting that there is no current standard of care and that many “come to us already on four or five medications, and it can seem a bit random.”
When these patients are admitted, “we try to simplify their treatment and figure out what’s going on, and then offer ECT if appropriate,” he said.
Dr. White presented data from a cohort of patients assessed at the program between 2012 and 2017, of which 114 were taking clozapine at admission and had a diagnosis of schizophrenia or schizoaffective disorder.
To be considered clozapine-resistant, patients had to be taking 500 mg or more for at least 60 days, yet have persistent positive symptoms and moderate to severe impairment. Dr. White and his colleagues identified 20 patients with clozapine resistance. Of these, eight were offered ECT, and three accepted. At the time of discharge, 16 patients remained on clozapine with or without fluvoxamine. Four patients were treated with the recommended adjunctive agents aripiprazole or sulpiride and five with other agents.
Dr. White said the three agents recommended in the algorithm were determined by literature reviews, including meta-analyses of randomized trials. Several commonly used adjunctive agents to clozapine, including risperidone, were ruled out, for lack of evidence in this patient group.
Sulpiride, one of the drugs recommended in the algorithm, is not marketed in North America, and in Canada is accessible only by special arrangement. The evidence for aripiprazole, meanwhile, “is not stupendous,” Dr. White said, “but there’s a signal.”
The topiramate recommendation is based on results from a 2016 meta-analysis of randomized controlled trials. “Topiramate has a possible advantage of ameliorating metabolic problems,” Dr. White said, and the meta-analysis showed a significant effect size in improving positive and negative symptoms. However, he noted, on rare occasions, it has been seen to exacerbate psychosis.
Dr. White said few of the treatment-resistant patients seen in his program have had a course of ECT despite evidence of benefit. “Instead of ECT, they usually are put on multiple medications,” he said. “Admittedly, getting some of these patients to accept ECT isn’t easy.”
Because the program is designed to keep patients for 6 or more months as needed, “we have the luxury of time,” Dr. White said, to allow for the discontinuation of extraneous medicines and for an ECT trial if indicated.
“I know that in other hospitals, and other health care settings, they don’t have that – they have to figure out what to do quickly. And ECT is not the quickest treatment.”
Offering cognitive-behavioral therapy to people with psychosis is possible, he stressed, and supported by evidence from at least one study. “In this population, it’s challenging,” he acknowledged. “I don’t think I’d do it concurrently with ECT but as an alternative to or after ECT.”
Dr. White disclosed no conflicts of interest related to his research.
EXPERT ANALYSIS FROM APA
Impairment persists despite treatment in adult ADHD
SAN DIEGO – Despite treatment with short- or long-acting medications, adults with attention-deficit/hyperactivity disorder report more impairment than do non-ADHD adults across several domains of daily life, and at certain times of day.
The findings, from a study presented at the annual meeting of the American Psychiatric Association, suggest that adults with ADHD have burdens that may persist despite medication.
The studies compared a cohort of 616 adults with a self-reported ADHD diagnosis and at least 6 months on medication, including short-acting stimulants, long-acting agents, or a combination of these. The researchers also recruited a comparison cohort of 200 non-ADHD adults.
“Interestingly, there was not only a difference between ADHD and non-ADHD groups, but there was also significant impairment reported among patients who are currently being treated for ADHD,” Alexandra Khachatryan, MPH, of Shire Pharmaceuticals, the study’s senior author, said in an interview. Ms. Khachatryan and her colleagues presented the findings at the APA.
For example, 44% of the ADHD respondents reported that the afternoon was the most challenging time of day, compared with 29% of non-ADHD participants (P less than .001). Mid-morning also was significantly more challenging for the ADHD group, with 26% reporting difficulties, compared with 17% of the non-ADHD cohort (P less than .01).
Other statistically significant between-group differences were seen related to managing affect and emotions, sustaining effort, working memory and recall, and interpersonal relationships.
“In addition to the burden patients report across the day, they also expressed significant challenges with psychosocial functioning and managing the demands of work, social, and family life despite treatment,” said Norman Atkins, PhD, of Shire, a coauthor of the study.
A separate poster by the same research group, using the same study data from the cohort of 616 currently treated adult ADHD patients (mean age 39, 70% female) looked at self-reported impairment across daily life domains by patients under different medication regimens.
Patients in the cohort were treated with short-acting stimulants (n = 166), long-acting stimulants (n = 201), or augmentation strategies (n = 249). The researchers found that afternoons and evenings were most difficult for patients regardless of treatment approach.
Ms. Khachatryan said the study was intended to help clinicians “understand what we’re offering patients and if we’re adequately meeting the needs of patients across the day. And we found that adults experience burden across the day despite being treated, and what they report as the most challenging times of day are the afternoon and evening hours,” when work, family, and household obligations are likely to be present.
Dr. Atkins added: “From an ADHD management perspective, the key takeaway is that these impairments occur across multiple settings and are most problematic at certain times of the day. It’s important for providers to have a meaningful conversation with their patients about their day-to-day challenges to fully appreciate how ADHD impacts their functioning so they can best optimize care.”
The researchers acknowledged as limitations of their study its high number of women participants, potentially reducing the generalizability of its findings; the reliance on self-reported outcomes; and between-group differences for the ADHD and non-ADHD groups that included differences in mean age (39 vs. 43, respectively) and full-time employment status (57% vs. 42%).
The study was sponsored by Shire Pharmaceuticals, with three of its five coauthors employed by the company.
SAN DIEGO – Despite treatment with short- or long-acting medications, adults with attention-deficit/hyperactivity disorder report more impairment than do non-ADHD adults across several domains of daily life, and at certain times of day.
The findings, from a study presented at the annual meeting of the American Psychiatric Association, suggest that adults with ADHD have burdens that may persist despite medication.
The studies compared a cohort of 616 adults with a self-reported ADHD diagnosis and at least 6 months on medication, including short-acting stimulants, long-acting agents, or a combination of these. The researchers also recruited a comparison cohort of 200 non-ADHD adults.
“Interestingly, there was not only a difference between ADHD and non-ADHD groups, but there was also significant impairment reported among patients who are currently being treated for ADHD,” Alexandra Khachatryan, MPH, of Shire Pharmaceuticals, the study’s senior author, said in an interview. Ms. Khachatryan and her colleagues presented the findings at the APA.
For example, 44% of the ADHD respondents reported that the afternoon was the most challenging time of day, compared with 29% of non-ADHD participants (P less than .001). Mid-morning also was significantly more challenging for the ADHD group, with 26% reporting difficulties, compared with 17% of the non-ADHD cohort (P less than .01).
Other statistically significant between-group differences were seen related to managing affect and emotions, sustaining effort, working memory and recall, and interpersonal relationships.
“In addition to the burden patients report across the day, they also expressed significant challenges with psychosocial functioning and managing the demands of work, social, and family life despite treatment,” said Norman Atkins, PhD, of Shire, a coauthor of the study.
A separate poster by the same research group, using the same study data from the cohort of 616 currently treated adult ADHD patients (mean age 39, 70% female) looked at self-reported impairment across daily life domains by patients under different medication regimens.
Patients in the cohort were treated with short-acting stimulants (n = 166), long-acting stimulants (n = 201), or augmentation strategies (n = 249). The researchers found that afternoons and evenings were most difficult for patients regardless of treatment approach.
Ms. Khachatryan said the study was intended to help clinicians “understand what we’re offering patients and if we’re adequately meeting the needs of patients across the day. And we found that adults experience burden across the day despite being treated, and what they report as the most challenging times of day are the afternoon and evening hours,” when work, family, and household obligations are likely to be present.
Dr. Atkins added: “From an ADHD management perspective, the key takeaway is that these impairments occur across multiple settings and are most problematic at certain times of the day. It’s important for providers to have a meaningful conversation with their patients about their day-to-day challenges to fully appreciate how ADHD impacts their functioning so they can best optimize care.”
The researchers acknowledged as limitations of their study its high number of women participants, potentially reducing the generalizability of its findings; the reliance on self-reported outcomes; and between-group differences for the ADHD and non-ADHD groups that included differences in mean age (39 vs. 43, respectively) and full-time employment status (57% vs. 42%).
The study was sponsored by Shire Pharmaceuticals, with three of its five coauthors employed by the company.
SAN DIEGO – Despite treatment with short- or long-acting medications, adults with attention-deficit/hyperactivity disorder report more impairment than do non-ADHD adults across several domains of daily life, and at certain times of day.
The findings, from a study presented at the annual meeting of the American Psychiatric Association, suggest that adults with ADHD have burdens that may persist despite medication.
The studies compared a cohort of 616 adults with a self-reported ADHD diagnosis and at least 6 months on medication, including short-acting stimulants, long-acting agents, or a combination of these. The researchers also recruited a comparison cohort of 200 non-ADHD adults.
“Interestingly, there was not only a difference between ADHD and non-ADHD groups, but there was also significant impairment reported among patients who are currently being treated for ADHD,” Alexandra Khachatryan, MPH, of Shire Pharmaceuticals, the study’s senior author, said in an interview. Ms. Khachatryan and her colleagues presented the findings at the APA.
For example, 44% of the ADHD respondents reported that the afternoon was the most challenging time of day, compared with 29% of non-ADHD participants (P less than .001). Mid-morning also was significantly more challenging for the ADHD group, with 26% reporting difficulties, compared with 17% of the non-ADHD cohort (P less than .01).
Other statistically significant between-group differences were seen related to managing affect and emotions, sustaining effort, working memory and recall, and interpersonal relationships.
“In addition to the burden patients report across the day, they also expressed significant challenges with psychosocial functioning and managing the demands of work, social, and family life despite treatment,” said Norman Atkins, PhD, of Shire, a coauthor of the study.
A separate poster by the same research group, using the same study data from the cohort of 616 currently treated adult ADHD patients (mean age 39, 70% female) looked at self-reported impairment across daily life domains by patients under different medication regimens.
Patients in the cohort were treated with short-acting stimulants (n = 166), long-acting stimulants (n = 201), or augmentation strategies (n = 249). The researchers found that afternoons and evenings were most difficult for patients regardless of treatment approach.
Ms. Khachatryan said the study was intended to help clinicians “understand what we’re offering patients and if we’re adequately meeting the needs of patients across the day. And we found that adults experience burden across the day despite being treated, and what they report as the most challenging times of day are the afternoon and evening hours,” when work, family, and household obligations are likely to be present.
Dr. Atkins added: “From an ADHD management perspective, the key takeaway is that these impairments occur across multiple settings and are most problematic at certain times of the day. It’s important for providers to have a meaningful conversation with their patients about their day-to-day challenges to fully appreciate how ADHD impacts their functioning so they can best optimize care.”
The researchers acknowledged as limitations of their study its high number of women participants, potentially reducing the generalizability of its findings; the reliance on self-reported outcomes; and between-group differences for the ADHD and non-ADHD groups that included differences in mean age (39 vs. 43, respectively) and full-time employment status (57% vs. 42%).
The study was sponsored by Shire Pharmaceuticals, with three of its five coauthors employed by the company.
AT APA
Hidden burdens, limited follow-up complicate refugee mental health
SAN DIEGO – Psychiatrists may encounter refugee patients from war-torn countries in virtually every part of the United States with complex mental health needs, including high rates of posttraumatic stress disorder, chronic pain, and somatic symptoms, according to two presenters at the annual meeting of the American Psychiatric Association.
Over the past decade, refugees from Middle Eastern counties – particularly Iraq, Syria, and Afghanistan – have increased fourfold as a percentage of all refugees in the United States, while those from Sub-Saharan Africa continue to make up a large share. Despite heated political wrangling, the U.S. Department of State recently increased limits on the number of refugees that can be accepted. California, Texas, New York, Michigan, Ohio, and Washington are the states resettling the most new arrivals.
Refugees with trauma exposure have high rates of posttraumatic stress disorder, chronic pain, and somatic symptoms. In addition, recent research suggests, these refugees may have poorly understood stressors related to migration and adjustment that also may be significant contributors to mental illness risk. Despite this, refugees generally have less access to mental health care than does the general population.
The presenters shared their perspectives on refugee mental health with findings that could inform the timing and nature of interventions in these potentially vulnerable populations.
Cynthia L. Arfken, PhD, of Wayne State University in Detroit, presented results from an ongoing cohort study of Syrian families presenting to a primary care clinic as part of their State Department–mandated health check upon resettlement. Arash Javanbakht, MD, also of the university, led the research.
The investigators recruited families at a primary care clinic in southeastern Michigan, where refugees receive health assessments within the first month of arrival in the United States.
The researchers consecutively enrolled and evaluated 297 individuals, including 59 children aged 6 and older (mean age, 11.3) from Syria. These families represented 95% of refugees seen at the clinic during the study period, from June to December 2016.
The researchers also collected hair and saliva samples from consenting families for a separate study looking at biomarkers and mental health outcomes.
Adults were screened for PTSD using the PTSD checklist for adults, and children for anxiety using the Screen for Child Anxiety Related Emotional Disorders, or SCARED, measure. Psychiatric nurses and bilingual health care workers helped the team obtain consent and conduct assessments.
The researchers found that 61% of the children had a probable anxiety diagnosis, and nearly 85% had probable separation anxiety. Higher child anxiety scores were associated with higher PTSD scores in mothers (P = .05).
Dr. Arfken said in an interview that she and her team were “shocked” at the high prevalence of probable anxiety disorders in the cohort, in part because they’d conducted an earlier study enrolling adult Iraqi refugees and “found hardly any psychiatric symptoms at all.”
The high levels of anxiety seen among the Syrian refugees may be related to the severity of the ongoing conflict, Dr. Arfken said. The children’s results were sufficiently jarring to the team that “we changed our whole plan,” she said, “to concentrate on following up both the children who showed distress and those who did not.” They also attempted some nonmedical interventions, such as dance and mindfulness groups.
Also at the conference, Christopher Morrow, MD, of the University of Maryland in Baltimore, presented findings from a case study that illuminates some of the potential mental health risks for resettled refugees.
Dr. Morrow described a 31-year-old man from Afghanistan who had worked for the U.S. Special Forces in Afghanistan as a translator and subsequently entered the United States as a refugee. About a year later he was admitted to an inpatient psychiatric unit after a violent suicide attempt and was treated for depression.
The researchers noted that the patient had no previous history of depression or other mental illness prior to arriving in the United States. “His symptoms developed over the course of the first year of resettlement,” Dr. Morrow said in an interview.
This patient, Dr. Morrow said, was single and was not religious, leaving him not inclined to join a mosque or other Islamic community group. He was placed in an unskilled work assignment, despite his well-developed skills as a translator. Over the course of a year, he became increasingly isolated and “decompensated to the point where there was a really violent suicide attempt.
“We think that some kind of programmed follow-up – be it a community resource or through primary care – could have helped stabilize him before he got to a point of real hopelessness,” Dr. Morrow said.
Dr. Morrow and his colleagues proposed two interventions as adjustments to current health policy for refugees: adding universal mental health screening to each refugee’s health check in the first month after arrival, and scheduling follow-up later in the resettlement process.
“If there is active follow-up, a way that you could check in with these individuals as they’re acclimating, that’s probably the point where you could intervene best,” he said.
Dr. Morrow and Dr. Arfken disclosed no conflicts of interest related to their research.
SAN DIEGO – Psychiatrists may encounter refugee patients from war-torn countries in virtually every part of the United States with complex mental health needs, including high rates of posttraumatic stress disorder, chronic pain, and somatic symptoms, according to two presenters at the annual meeting of the American Psychiatric Association.
Over the past decade, refugees from Middle Eastern counties – particularly Iraq, Syria, and Afghanistan – have increased fourfold as a percentage of all refugees in the United States, while those from Sub-Saharan Africa continue to make up a large share. Despite heated political wrangling, the U.S. Department of State recently increased limits on the number of refugees that can be accepted. California, Texas, New York, Michigan, Ohio, and Washington are the states resettling the most new arrivals.
Refugees with trauma exposure have high rates of posttraumatic stress disorder, chronic pain, and somatic symptoms. In addition, recent research suggests, these refugees may have poorly understood stressors related to migration and adjustment that also may be significant contributors to mental illness risk. Despite this, refugees generally have less access to mental health care than does the general population.
The presenters shared their perspectives on refugee mental health with findings that could inform the timing and nature of interventions in these potentially vulnerable populations.
Cynthia L. Arfken, PhD, of Wayne State University in Detroit, presented results from an ongoing cohort study of Syrian families presenting to a primary care clinic as part of their State Department–mandated health check upon resettlement. Arash Javanbakht, MD, also of the university, led the research.
The investigators recruited families at a primary care clinic in southeastern Michigan, where refugees receive health assessments within the first month of arrival in the United States.
The researchers consecutively enrolled and evaluated 297 individuals, including 59 children aged 6 and older (mean age, 11.3) from Syria. These families represented 95% of refugees seen at the clinic during the study period, from June to December 2016.
The researchers also collected hair and saliva samples from consenting families for a separate study looking at biomarkers and mental health outcomes.
Adults were screened for PTSD using the PTSD checklist for adults, and children for anxiety using the Screen for Child Anxiety Related Emotional Disorders, or SCARED, measure. Psychiatric nurses and bilingual health care workers helped the team obtain consent and conduct assessments.
The researchers found that 61% of the children had a probable anxiety diagnosis, and nearly 85% had probable separation anxiety. Higher child anxiety scores were associated with higher PTSD scores in mothers (P = .05).
Dr. Arfken said in an interview that she and her team were “shocked” at the high prevalence of probable anxiety disorders in the cohort, in part because they’d conducted an earlier study enrolling adult Iraqi refugees and “found hardly any psychiatric symptoms at all.”
The high levels of anxiety seen among the Syrian refugees may be related to the severity of the ongoing conflict, Dr. Arfken said. The children’s results were sufficiently jarring to the team that “we changed our whole plan,” she said, “to concentrate on following up both the children who showed distress and those who did not.” They also attempted some nonmedical interventions, such as dance and mindfulness groups.
Also at the conference, Christopher Morrow, MD, of the University of Maryland in Baltimore, presented findings from a case study that illuminates some of the potential mental health risks for resettled refugees.
Dr. Morrow described a 31-year-old man from Afghanistan who had worked for the U.S. Special Forces in Afghanistan as a translator and subsequently entered the United States as a refugee. About a year later he was admitted to an inpatient psychiatric unit after a violent suicide attempt and was treated for depression.
The researchers noted that the patient had no previous history of depression or other mental illness prior to arriving in the United States. “His symptoms developed over the course of the first year of resettlement,” Dr. Morrow said in an interview.
This patient, Dr. Morrow said, was single and was not religious, leaving him not inclined to join a mosque or other Islamic community group. He was placed in an unskilled work assignment, despite his well-developed skills as a translator. Over the course of a year, he became increasingly isolated and “decompensated to the point where there was a really violent suicide attempt.
“We think that some kind of programmed follow-up – be it a community resource or through primary care – could have helped stabilize him before he got to a point of real hopelessness,” Dr. Morrow said.
Dr. Morrow and his colleagues proposed two interventions as adjustments to current health policy for refugees: adding universal mental health screening to each refugee’s health check in the first month after arrival, and scheduling follow-up later in the resettlement process.
“If there is active follow-up, a way that you could check in with these individuals as they’re acclimating, that’s probably the point where you could intervene best,” he said.
Dr. Morrow and Dr. Arfken disclosed no conflicts of interest related to their research.
SAN DIEGO – Psychiatrists may encounter refugee patients from war-torn countries in virtually every part of the United States with complex mental health needs, including high rates of posttraumatic stress disorder, chronic pain, and somatic symptoms, according to two presenters at the annual meeting of the American Psychiatric Association.
Over the past decade, refugees from Middle Eastern counties – particularly Iraq, Syria, and Afghanistan – have increased fourfold as a percentage of all refugees in the United States, while those from Sub-Saharan Africa continue to make up a large share. Despite heated political wrangling, the U.S. Department of State recently increased limits on the number of refugees that can be accepted. California, Texas, New York, Michigan, Ohio, and Washington are the states resettling the most new arrivals.
Refugees with trauma exposure have high rates of posttraumatic stress disorder, chronic pain, and somatic symptoms. In addition, recent research suggests, these refugees may have poorly understood stressors related to migration and adjustment that also may be significant contributors to mental illness risk. Despite this, refugees generally have less access to mental health care than does the general population.
The presenters shared their perspectives on refugee mental health with findings that could inform the timing and nature of interventions in these potentially vulnerable populations.
Cynthia L. Arfken, PhD, of Wayne State University in Detroit, presented results from an ongoing cohort study of Syrian families presenting to a primary care clinic as part of their State Department–mandated health check upon resettlement. Arash Javanbakht, MD, also of the university, led the research.
The investigators recruited families at a primary care clinic in southeastern Michigan, where refugees receive health assessments within the first month of arrival in the United States.
The researchers consecutively enrolled and evaluated 297 individuals, including 59 children aged 6 and older (mean age, 11.3) from Syria. These families represented 95% of refugees seen at the clinic during the study period, from June to December 2016.
The researchers also collected hair and saliva samples from consenting families for a separate study looking at biomarkers and mental health outcomes.
Adults were screened for PTSD using the PTSD checklist for adults, and children for anxiety using the Screen for Child Anxiety Related Emotional Disorders, or SCARED, measure. Psychiatric nurses and bilingual health care workers helped the team obtain consent and conduct assessments.
The researchers found that 61% of the children had a probable anxiety diagnosis, and nearly 85% had probable separation anxiety. Higher child anxiety scores were associated with higher PTSD scores in mothers (P = .05).
Dr. Arfken said in an interview that she and her team were “shocked” at the high prevalence of probable anxiety disorders in the cohort, in part because they’d conducted an earlier study enrolling adult Iraqi refugees and “found hardly any psychiatric symptoms at all.”
The high levels of anxiety seen among the Syrian refugees may be related to the severity of the ongoing conflict, Dr. Arfken said. The children’s results were sufficiently jarring to the team that “we changed our whole plan,” she said, “to concentrate on following up both the children who showed distress and those who did not.” They also attempted some nonmedical interventions, such as dance and mindfulness groups.
Also at the conference, Christopher Morrow, MD, of the University of Maryland in Baltimore, presented findings from a case study that illuminates some of the potential mental health risks for resettled refugees.
Dr. Morrow described a 31-year-old man from Afghanistan who had worked for the U.S. Special Forces in Afghanistan as a translator and subsequently entered the United States as a refugee. About a year later he was admitted to an inpatient psychiatric unit after a violent suicide attempt and was treated for depression.
The researchers noted that the patient had no previous history of depression or other mental illness prior to arriving in the United States. “His symptoms developed over the course of the first year of resettlement,” Dr. Morrow said in an interview.
This patient, Dr. Morrow said, was single and was not religious, leaving him not inclined to join a mosque or other Islamic community group. He was placed in an unskilled work assignment, despite his well-developed skills as a translator. Over the course of a year, he became increasingly isolated and “decompensated to the point where there was a really violent suicide attempt.
“We think that some kind of programmed follow-up – be it a community resource or through primary care – could have helped stabilize him before he got to a point of real hopelessness,” Dr. Morrow said.
Dr. Morrow and his colleagues proposed two interventions as adjustments to current health policy for refugees: adding universal mental health screening to each refugee’s health check in the first month after arrival, and scheduling follow-up later in the resettlement process.
“If there is active follow-up, a way that you could check in with these individuals as they’re acclimating, that’s probably the point where you could intervene best,” he said.
Dr. Morrow and Dr. Arfken disclosed no conflicts of interest related to their research.
EXPERT ANALYSIS FROM APA
Seeing a doctor reduces readmission risk in schizophrenia patients
SAN DIEGO – Readmission rates after discharge for patients with schizophrenia are notoriously high, with approximately a quarter of U.S. schizophrenia patients readmitted within 3 months, according to Paul A. Kurdyak, MD, PhD.
In Ontario, Canada, readmission rates for people with schizophrenia are 12.5% within 30 days of discharge. Paradoxically, however, these same patients receive less follow-up than people hospitalized for other psychiatric disorders, Dr. Kurdyak of the Institute for Clinical Evaluative Sciences in Toronto reported at the annual meeting of the American Psychiatric Association.
To explore the relationship between discharge, follow-up, and subsequent readmission in this population, he assessed the impact of physician follow-up in the month after discharge on readmission rates for schizophrenia patients, noting a lack of published evidence on whether or how it helps. “We try and use readmission as a general performance indicator, and we try and use postdischarge follow-up as a general indicator, but there was no evidence to determine whether seeing a physician following discharge has an impact on anything,” Dr. Kurdyak said.
He and his colleagues tracked primary care and outpatient psychiatric visits in the first 30 days after discharge for about 20,000 people who had been hospitalized with schizophrenia in Ontario. “We chose 30 days because we knew the rate of follow-up within 7 days was just so low,” he said.
He said more than one in three of these patients went more than 30 days without seeing any physician at all.
Schizophrenia patients “are individuals with really high needs, whose average length of stay is about 2 weeks,” he said. “It’s hard to stabilize somebody in 2 weeks, so to have so many of them drop off a cliff [after discharge] is not great.”
Another finding was that the patients who saw any doctor – whether their primary care physician or psychiatrist – saw reduced rates of readmission at 30-210 days after discharge.
Where the benefit of seeing a physician was seen in sharpest relief was among the patients deemed, by use of a validated scoring system, to be at highest risk for readmission. These patients, who made up two-thirds of the cohort, saw a 15% reduction in readmission if they’d had a visit with either a primary care physician or psychiatrist and a 19% reduction if they’d seen both types of physician relative to patients who had no physician follow-up post discharge.
“In the high-risk group, you see a very clear separation between those who saw no physician and those who saw any physician,” Dr. Kurdyak said.
Some of the limitations of the study included the fact that little was known about the quality of the follow-up physician visits or about clinical collaboration, the causes for lack of follow-up were not clear, and follow-up by nonphysician health personnel was not captured.
Nonetheless, Dr. Kurdyak said, “the moral of the story is [that] seeing a physician really differentiates from seeing no physician statistically and clinically.”
In Canada, he noted, “we like to feel comfortable with the idea of universal health care, but, when we take a closer look, we often see real inequities and disparities despite universal health care. I think this is one of these situations where, if readmission is an indicator of need, our ability to provide services to those in the greatest need falls short of the ideal.”
Dr. Kurdyak disclosed no conflicts of interest relevant to his research.
SAN DIEGO – Readmission rates after discharge for patients with schizophrenia are notoriously high, with approximately a quarter of U.S. schizophrenia patients readmitted within 3 months, according to Paul A. Kurdyak, MD, PhD.
In Ontario, Canada, readmission rates for people with schizophrenia are 12.5% within 30 days of discharge. Paradoxically, however, these same patients receive less follow-up than people hospitalized for other psychiatric disorders, Dr. Kurdyak of the Institute for Clinical Evaluative Sciences in Toronto reported at the annual meeting of the American Psychiatric Association.
To explore the relationship between discharge, follow-up, and subsequent readmission in this population, he assessed the impact of physician follow-up in the month after discharge on readmission rates for schizophrenia patients, noting a lack of published evidence on whether or how it helps. “We try and use readmission as a general performance indicator, and we try and use postdischarge follow-up as a general indicator, but there was no evidence to determine whether seeing a physician following discharge has an impact on anything,” Dr. Kurdyak said.
He and his colleagues tracked primary care and outpatient psychiatric visits in the first 30 days after discharge for about 20,000 people who had been hospitalized with schizophrenia in Ontario. “We chose 30 days because we knew the rate of follow-up within 7 days was just so low,” he said.
He said more than one in three of these patients went more than 30 days without seeing any physician at all.
Schizophrenia patients “are individuals with really high needs, whose average length of stay is about 2 weeks,” he said. “It’s hard to stabilize somebody in 2 weeks, so to have so many of them drop off a cliff [after discharge] is not great.”
Another finding was that the patients who saw any doctor – whether their primary care physician or psychiatrist – saw reduced rates of readmission at 30-210 days after discharge.
Where the benefit of seeing a physician was seen in sharpest relief was among the patients deemed, by use of a validated scoring system, to be at highest risk for readmission. These patients, who made up two-thirds of the cohort, saw a 15% reduction in readmission if they’d had a visit with either a primary care physician or psychiatrist and a 19% reduction if they’d seen both types of physician relative to patients who had no physician follow-up post discharge.
“In the high-risk group, you see a very clear separation between those who saw no physician and those who saw any physician,” Dr. Kurdyak said.
Some of the limitations of the study included the fact that little was known about the quality of the follow-up physician visits or about clinical collaboration, the causes for lack of follow-up were not clear, and follow-up by nonphysician health personnel was not captured.
Nonetheless, Dr. Kurdyak said, “the moral of the story is [that] seeing a physician really differentiates from seeing no physician statistically and clinically.”
In Canada, he noted, “we like to feel comfortable with the idea of universal health care, but, when we take a closer look, we often see real inequities and disparities despite universal health care. I think this is one of these situations where, if readmission is an indicator of need, our ability to provide services to those in the greatest need falls short of the ideal.”
Dr. Kurdyak disclosed no conflicts of interest relevant to his research.
SAN DIEGO – Readmission rates after discharge for patients with schizophrenia are notoriously high, with approximately a quarter of U.S. schizophrenia patients readmitted within 3 months, according to Paul A. Kurdyak, MD, PhD.
In Ontario, Canada, readmission rates for people with schizophrenia are 12.5% within 30 days of discharge. Paradoxically, however, these same patients receive less follow-up than people hospitalized for other psychiatric disorders, Dr. Kurdyak of the Institute for Clinical Evaluative Sciences in Toronto reported at the annual meeting of the American Psychiatric Association.
To explore the relationship between discharge, follow-up, and subsequent readmission in this population, he assessed the impact of physician follow-up in the month after discharge on readmission rates for schizophrenia patients, noting a lack of published evidence on whether or how it helps. “We try and use readmission as a general performance indicator, and we try and use postdischarge follow-up as a general indicator, but there was no evidence to determine whether seeing a physician following discharge has an impact on anything,” Dr. Kurdyak said.
He and his colleagues tracked primary care and outpatient psychiatric visits in the first 30 days after discharge for about 20,000 people who had been hospitalized with schizophrenia in Ontario. “We chose 30 days because we knew the rate of follow-up within 7 days was just so low,” he said.
He said more than one in three of these patients went more than 30 days without seeing any physician at all.
Schizophrenia patients “are individuals with really high needs, whose average length of stay is about 2 weeks,” he said. “It’s hard to stabilize somebody in 2 weeks, so to have so many of them drop off a cliff [after discharge] is not great.”
Another finding was that the patients who saw any doctor – whether their primary care physician or psychiatrist – saw reduced rates of readmission at 30-210 days after discharge.
Where the benefit of seeing a physician was seen in sharpest relief was among the patients deemed, by use of a validated scoring system, to be at highest risk for readmission. These patients, who made up two-thirds of the cohort, saw a 15% reduction in readmission if they’d had a visit with either a primary care physician or psychiatrist and a 19% reduction if they’d seen both types of physician relative to patients who had no physician follow-up post discharge.
“In the high-risk group, you see a very clear separation between those who saw no physician and those who saw any physician,” Dr. Kurdyak said.
Some of the limitations of the study included the fact that little was known about the quality of the follow-up physician visits or about clinical collaboration, the causes for lack of follow-up were not clear, and follow-up by nonphysician health personnel was not captured.
Nonetheless, Dr. Kurdyak said, “the moral of the story is [that] seeing a physician really differentiates from seeing no physician statistically and clinically.”
In Canada, he noted, “we like to feel comfortable with the idea of universal health care, but, when we take a closer look, we often see real inequities and disparities despite universal health care. I think this is one of these situations where, if readmission is an indicator of need, our ability to provide services to those in the greatest need falls short of the ideal.”
Dr. Kurdyak disclosed no conflicts of interest relevant to his research.
AT APA
Key clinical point:
Major finding: Patients at highest risk of readmission saw a 15% reduction in readmission after 30 days if they’d seen a primary care doctor or psychiatrist, compared with those who’d seen neither.
Data source: Records from about 20,000 schizophrenia patients hospitalized in Ontario in 2012, identified in government databases.
Disclosures: The study was conducted at an institute receiving most of its support from the Ontario government.