To the Editor:

Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. It has been associated with increased risk for other visceral and hematologic malignancies.¹ Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies. In the United States, a patient’s lifetime risk for CLL is 0.6%. Chronic lymphocytic leukemia often is diagnosed as an incidental finding and typically is not detrimental to a patient’s health. Six cases of MF with antecedent or concomitant CLL were identified in a cohort of patients treated at the University of Minnesota (Minneapolis, Minnesota) from 2005 to 2017 (Table).

All 6 patients were male, with a mean age of 80.5 years. The mean age at CLL diagnosis was 62.5 years, while the mean age at MF diagnosis was 75.3 years. Three patients were younger than 60 years when their CLL was diagnosed: 49, 55, and 57 years. Notably, 4 patients had more aggressive types of MF: 3 with tumor-stage disease, and 1 with folliculotropic MF. Five patients were diagnosed with CLL before their MF was diagnosed (mean, 13.4 years prior; range, 3–31 years), and 1 was diagnosed as part of the initial MF workup.

Given the frequency of both MF and CLL, the co-occurrence of these diseases is not surprising, as other case reports and a larger case series have described the relationship between MF and malignancy.² It is possible that CLL patients are more likely to be diagnosed with MF because of their regular hematology/oncology follow-up; however, none of our patients were referred from hematology/oncology to dermatology. Alternatively, patients with MF may be more likely to be diagnosed with CLL because of repeated bloodwork performed for diagnosis and screening, which occurred in only 1 of 6 cases. Most of the other patients were diagnosed with MF more than a decade after being diagnosed with CLL.

Does having CLL make patients more likely to develop MF? It is known that patients with CLL may experience immunodeficiency secondary to immune dysregulation, making them more susceptible to infection and secondary malignancies.³ Of our 6 cases, 4 had aggressive or advanced forms of MF, which is similar to the findings of Chang et al.² In their report, of 8 patients with MF, 2 had tumor-stage disease and 2 had erythrodermic MF. They determined that these patients had worse overall survival.² Our data corroborate the finding that patients with CLL may develop more severe MF, which leads to the conclusion that patients diagnosed with CLL before, concomitantly, or after their diagnosis of MF should be closely monitored. It is notable that patients with more advanced disease tend to be older at the time of diagnosis and that patients who are diagnosed at 57 years or older have been found to have worse disease-specific survival.^4,5

This report is limited by the small sample size (6 cases), but it serves to draw attention to the phenomenon of co-occurrence of MF and CLL, and the concern that patients with CLL may develop more aggressive MF.

To the Editor:

Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. It has been associated with increased risk for other visceral and hematologic malignancies.¹ Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies. In the United States, a patient’s lifetime risk for CLL is 0.6%. Chronic lymphocytic leukemia often is diagnosed as an incidental finding and typically is not detrimental to a patient’s health. Six cases of MF with antecedent or concomitant CLL were identified in a cohort of patients treated at the University of Minnesota (Minneapolis, Minnesota) from 2005 to 2017 (Table).

All 6 patients were male, with a mean age of 80.5 years. The mean age at CLL diagnosis was 62.5 years, while the mean age at MF diagnosis was 75.3 years. Three patients were younger than 60 years when their CLL was diagnosed: 49, 55, and 57 years. Notably, 4 patients had more aggressive types of MF: 3 with tumor-stage disease, and 1 with folliculotropic MF. Five patients were diagnosed with CLL before their MF was diagnosed (mean, 13.4 years prior; range, 3–31 years), and 1 was diagnosed as part of the initial MF workup.

Given the frequency of both MF and CLL, the co-occurrence of these diseases is not surprising, as other case reports and a larger case series have described the relationship between MF and malignancy.² It is possible that CLL patients are more likely to be diagnosed with MF because of their regular hematology/oncology follow-up; however, none of our patients were referred from hematology/oncology to dermatology. Alternatively, patients with MF may be more likely to be diagnosed with CLL because of repeated bloodwork performed for diagnosis and screening, which occurred in only 1 of 6 cases. Most of the other patients were diagnosed with MF more than a decade after being diagnosed with CLL.

Does having CLL make patients more likely to develop MF? It is known that patients with CLL may experience immunodeficiency secondary to immune dysregulation, making them more susceptible to infection and secondary malignancies.³ Of our 6 cases, 4 had aggressive or advanced forms of MF, which is similar to the findings of Chang et al.² In their report, of 8 patients with MF, 2 had tumor-stage disease and 2 had erythrodermic MF. They determined that these patients had worse overall survival.² Our data corroborate the finding that patients with CLL may develop more severe MF, which leads to the conclusion that patients diagnosed with CLL before, concomitantly, or after their diagnosis of MF should be closely monitored. It is notable that patients with more advanced disease tend to be older at the time of diagnosis and that patients who are diagnosed at 57 years or older have been found to have worse disease-specific survival.^4,5

This report is limited by the small sample size (6 cases), but it serves to draw attention to the phenomenon of co-occurrence of MF and CLL, and the concern that patients with CLL may develop more aggressive MF.

To the Editor:

Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. It has been associated with increased risk for other visceral and hematologic malignancies.¹ Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies. In the United States, a patient’s lifetime risk for CLL is 0.6%. Chronic lymphocytic leukemia often is diagnosed as an incidental finding and typically is not detrimental to a patient’s health. Six cases of MF with antecedent or concomitant CLL were identified in a cohort of patients treated at the University of Minnesota (Minneapolis, Minnesota) from 2005 to 2017 (Table).

All 6 patients were male, with a mean age of 80.5 years. The mean age at CLL diagnosis was 62.5 years, while the mean age at MF diagnosis was 75.3 years. Three patients were younger than 60 years when their CLL was diagnosed: 49, 55, and 57 years. Notably, 4 patients had more aggressive types of MF: 3 with tumor-stage disease, and 1 with folliculotropic MF. Five patients were diagnosed with CLL before their MF was diagnosed (mean, 13.4 years prior; range, 3–31 years), and 1 was diagnosed as part of the initial MF workup.

Given the frequency of both MF and CLL, the co-occurrence of these diseases is not surprising, as other case reports and a larger case series have described the relationship between MF and malignancy.² It is possible that CLL patients are more likely to be diagnosed with MF because of their regular hematology/oncology follow-up; however, none of our patients were referred from hematology/oncology to dermatology. Alternatively, patients with MF may be more likely to be diagnosed with CLL because of repeated bloodwork performed for diagnosis and screening, which occurred in only 1 of 6 cases. Most of the other patients were diagnosed with MF more than a decade after being diagnosed with CLL.

Does having CLL make patients more likely to develop MF? It is known that patients with CLL may experience immunodeficiency secondary to immune dysregulation, making them more susceptible to infection and secondary malignancies.³ Of our 6 cases, 4 had aggressive or advanced forms of MF, which is similar to the findings of Chang et al.² In their report, of 8 patients with MF, 2 had tumor-stage disease and 2 had erythrodermic MF. They determined that these patients had worse overall survival.² Our data corroborate the finding that patients with CLL may develop more severe MF, which leads to the conclusion that patients diagnosed with CLL before, concomitantly, or after their diagnosis of MF should be closely monitored. It is notable that patients with more advanced disease tend to be older at the time of diagnosis and that patients who are diagnosed at 57 years or older have been found to have worse disease-specific survival.^4,5

This report is limited by the small sample size (6 cases), but it serves to draw attention to the phenomenon of co-occurrence of MF and CLL, and the concern that patients with CLL may develop more aggressive MF.

BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.

Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.

“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.

The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.

Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).

While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.

Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.

During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.

“This is wonderful data that shows surgery is very effective,” one attendee said.

“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”

The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.

*This story was updated on November 15, 2019.

SOURCE: Pais R et al. The Liver Meeting 2019, Abstract 66.

BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.

Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.

“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.

The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.

Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).

While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.

Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.

During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.

“This is wonderful data that shows surgery is very effective,” one attendee said.

“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”

The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.

*This story was updated on November 15, 2019.

SOURCE: Pais R et al. The Liver Meeting 2019, Abstract 66.

BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.

Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.

“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.

The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.

Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).

While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.

Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.

During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.

“This is wonderful data that shows surgery is very effective,” one attendee said.

“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”

The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.

*This story was updated on November 15, 2019.

SOURCE: Pais R et al. The Liver Meeting 2019, Abstract 66.

ATLANTA – The benefits of tocilizumab for giant cell arteritis (GCA), as demonstrated in the pivotal phase 3 GiACTA trial, proved durable in nearly half of the patients treated weekly during the trial, according to findings from a 2-year long-term extension period.

Of 250 patients treated in the double-blind portion of the trial, 215 entered the extension period (part 2 of the trial), and 197 (92%) completed all 3 years of the trial. A total of 38 of 81 (47%) extension participants in clinical remission (CR) at week 52 after receiving tocilizumab (Actemra) weekly maintained it throughout the extension, and 13 of 36 (36%) treated every other week maintained it, John Stone, MD, reported at the annual meeting of the American College of Rheumatology.

Notably, more of those 51 patients treated with tocilizumab who maintained CR throughout the extension were treatment free at the end of the extension, compared with those originally assigned to the placebo groups (65% vs. 45%), and their median time to first flare after stopping treatment was longer, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital and associate professor of medicine in the division of rheumatology at Harvard Medical School, both in Boston.

For example, times to first flare were 575 and 428 days for the weekly and biweekly tocilizumab dosing groups – which each had 26-week prednisone tapering – but they were only 162 days in a placebo group with 26-week prednisone tapering and 295 days for patients in another placebo group with 52-week prednisone tapering, Dr. Stone explained. Retreatment with tocilizumab restored CR in patients who experienced flares after discontinuing treatment, he added.

Importantly, cumulative glucocorticoid doses over the 3 years were also lower in the tocilizumab groups (2,647 and 3,782 mg/day with weekly and biweekly tocilizumab and 5,248, and 5,323 mg/day in the placebo groups, respectively), Dr. Stone said.

No new safety signals were observed during the extension. Rates of serious adverse events (SAEs) and serious infections per 100 patient-years during the entire 3 years of the study were comparable among those who never received tocilizumab and those who received at least 1 dose (23.2 and 25.4 for SAEs and 4.6 and 3.5 for serious infections).
 

Detailed results of the extension period

GiACTA enrolled patients with GCA and randomized them to receive weekly or biweekly treatment with the interleukin-6 receptor–alpha inhibitor tocilizumab at doses of 162 mg delivered subcutaneously with a 26-week prednisone taper, or to the placebo groups with a 26- or 52-week prednisone taper. The results, reported in 2017, demonstrated the superiority of tocilizumab over placebo for providing sustained glucocorticoid-free remission and ultimately led to approval from Food and Drug Administration of the biologic agent for the treatment of GCA.

The current analysis was carried out to determine long-term safety, to explore maintenance of efficacy after discontinuation, and to “gain insight into the long-term glucocorticoid-sparing effects of tocilizumab,” Dr. Stone said.

He noted that the extension period was not randomized because of the way that patients in the “original four randomized groups had sorted themselves out into very different groups by virtue of their response in part 1 [of the trial],” which made randomization impossible because of the varying categories of patients.

Patients in the extension were also treated at investigators’ discretion to prevent “catastrophic GCA flares, vision loss, and other problems” that could potentially occur with discontinuation of the blinded injections in part 1, he said.

Nevertheless, the analysis “provides some incredibly important information about the management of GCA now,” he said, adding that the dramatic effect of the original randomization was still profound at 3 years “despite the fact that investigators could treat the patients as they wished.”

“Even at 3 years there was still a profound difference in the cumulative glucocorticoid [use], compared to those patients who were randomized to one of the placebo versus prednisone groups,” he explained.

However, the most important question from this study relates to what happened when weekly tocilizumab was stopped: Of the 81 patients in part 2 who were in CR on tocilizumab after part 1 of the study, 59 (73%) were not started on any treatment by their investigator, and of those, 25 (42%) maintained treatment-free remission for 2 full years following discontinuation of tocilizumab, he said.
 

What happened when prednisone was stopped?

In the absence of a direct comparison group (since the extension wasn’t a randomized, controlled part of the trial), the best comparison to that is what happens when prednisone is stopped, he noted.

“And we did that experiment in part 1” of the trial, he said. Overall, 68% of patients in the prednisone/placebo groups flared in 1-year of follow-up, and most of those did so even before they stopped prednisone. In the group that received placebo plus a 52-week prednisone taper, 49% of patients flared and “every single one of those patients flared before they got off prednisone,” he said.

“So in that context, 2 years of treatment-free remission following weekly tocilizumab discontinuation seems very good,” he added.

Of the patients who flared in part 2 of the trial, 11 whose investigator elected to treat them with only tocilizumab reentered remission in a median of 15.8 days, 13 treated with tocilizumab and glucocorticoids reentered remission in a median of 8.5 days (1 didn’t reenter remission at all), and 15 treated with only glucocorticoids reentered remission in a median of 38 days.

“There are a number of biases in these data, but they do point out the fact that some patients can be treated with tocilizumab alone,” Dr. Stone said. “I would be very careful doing that.”

The trial was not powered for the comparison of weekly versus biweekly dosing, he said. However, “multiple lines of investigation and analysis support the idea that weekly tocilizumab is more effective at controlling disease,” he added. But “if you want to be assured that you are doing everything you can to control the disease, weekly tocilizumab would be better than every-other-week tocilizumab,” he said.

GiACTA was funded by Roche. Dr. Stone reported research grants from Roche/Genentech and consulting fees from Chugal, Roche/Genentech, and Xencor.

[email protected]

SOURCE: Stone J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 808.

ATLANTA – The benefits of tocilizumab for giant cell arteritis (GCA), as demonstrated in the pivotal phase 3 GiACTA trial, proved durable in nearly half of the patients treated weekly during the trial, according to findings from a 2-year long-term extension period.

Of 250 patients treated in the double-blind portion of the trial, 215 entered the extension period (part 2 of the trial), and 197 (92%) completed all 3 years of the trial. A total of 38 of 81 (47%) extension participants in clinical remission (CR) at week 52 after receiving tocilizumab (Actemra) weekly maintained it throughout the extension, and 13 of 36 (36%) treated every other week maintained it, John Stone, MD, reported at the annual meeting of the American College of Rheumatology.

Notably, more of those 51 patients treated with tocilizumab who maintained CR throughout the extension were treatment free at the end of the extension, compared with those originally assigned to the placebo groups (65% vs. 45%), and their median time to first flare after stopping treatment was longer, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital and associate professor of medicine in the division of rheumatology at Harvard Medical School, both in Boston.

For example, times to first flare were 575 and 428 days for the weekly and biweekly tocilizumab dosing groups – which each had 26-week prednisone tapering – but they were only 162 days in a placebo group with 26-week prednisone tapering and 295 days for patients in another placebo group with 52-week prednisone tapering, Dr. Stone explained. Retreatment with tocilizumab restored CR in patients who experienced flares after discontinuing treatment, he added.

Importantly, cumulative glucocorticoid doses over the 3 years were also lower in the tocilizumab groups (2,647 and 3,782 mg/day with weekly and biweekly tocilizumab and 5,248, and 5,323 mg/day in the placebo groups, respectively), Dr. Stone said.

No new safety signals were observed during the extension. Rates of serious adverse events (SAEs) and serious infections per 100 patient-years during the entire 3 years of the study were comparable among those who never received tocilizumab and those who received at least 1 dose (23.2 and 25.4 for SAEs and 4.6 and 3.5 for serious infections).
 

Detailed results of the extension period

GiACTA enrolled patients with GCA and randomized them to receive weekly or biweekly treatment with the interleukin-6 receptor–alpha inhibitor tocilizumab at doses of 162 mg delivered subcutaneously with a 26-week prednisone taper, or to the placebo groups with a 26- or 52-week prednisone taper. The results, reported in 2017, demonstrated the superiority of tocilizumab over placebo for providing sustained glucocorticoid-free remission and ultimately led to approval from Food and Drug Administration of the biologic agent for the treatment of GCA.

The current analysis was carried out to determine long-term safety, to explore maintenance of efficacy after discontinuation, and to “gain insight into the long-term glucocorticoid-sparing effects of tocilizumab,” Dr. Stone said.

He noted that the extension period was not randomized because of the way that patients in the “original four randomized groups had sorted themselves out into very different groups by virtue of their response in part 1 [of the trial],” which made randomization impossible because of the varying categories of patients.

Patients in the extension were also treated at investigators’ discretion to prevent “catastrophic GCA flares, vision loss, and other problems” that could potentially occur with discontinuation of the blinded injections in part 1, he said.

Nevertheless, the analysis “provides some incredibly important information about the management of GCA now,” he said, adding that the dramatic effect of the original randomization was still profound at 3 years “despite the fact that investigators could treat the patients as they wished.”

“Even at 3 years there was still a profound difference in the cumulative glucocorticoid [use], compared to those patients who were randomized to one of the placebo versus prednisone groups,” he explained.

However, the most important question from this study relates to what happened when weekly tocilizumab was stopped: Of the 81 patients in part 2 who were in CR on tocilizumab after part 1 of the study, 59 (73%) were not started on any treatment by their investigator, and of those, 25 (42%) maintained treatment-free remission for 2 full years following discontinuation of tocilizumab, he said.
 

What happened when prednisone was stopped?

In the absence of a direct comparison group (since the extension wasn’t a randomized, controlled part of the trial), the best comparison to that is what happens when prednisone is stopped, he noted.

“And we did that experiment in part 1” of the trial, he said. Overall, 68% of patients in the prednisone/placebo groups flared in 1-year of follow-up, and most of those did so even before they stopped prednisone. In the group that received placebo plus a 52-week prednisone taper, 49% of patients flared and “every single one of those patients flared before they got off prednisone,” he said.

“So in that context, 2 years of treatment-free remission following weekly tocilizumab discontinuation seems very good,” he added.

Of the patients who flared in part 2 of the trial, 11 whose investigator elected to treat them with only tocilizumab reentered remission in a median of 15.8 days, 13 treated with tocilizumab and glucocorticoids reentered remission in a median of 8.5 days (1 didn’t reenter remission at all), and 15 treated with only glucocorticoids reentered remission in a median of 38 days.

“There are a number of biases in these data, but they do point out the fact that some patients can be treated with tocilizumab alone,” Dr. Stone said. “I would be very careful doing that.”

The trial was not powered for the comparison of weekly versus biweekly dosing, he said. However, “multiple lines of investigation and analysis support the idea that weekly tocilizumab is more effective at controlling disease,” he added. But “if you want to be assured that you are doing everything you can to control the disease, weekly tocilizumab would be better than every-other-week tocilizumab,” he said.

GiACTA was funded by Roche. Dr. Stone reported research grants from Roche/Genentech and consulting fees from Chugal, Roche/Genentech, and Xencor.

[email protected]

SOURCE: Stone J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 808.

ATLANTA – The benefits of tocilizumab for giant cell arteritis (GCA), as demonstrated in the pivotal phase 3 GiACTA trial, proved durable in nearly half of the patients treated weekly during the trial, according to findings from a 2-year long-term extension period.

Of 250 patients treated in the double-blind portion of the trial, 215 entered the extension period (part 2 of the trial), and 197 (92%) completed all 3 years of the trial. A total of 38 of 81 (47%) extension participants in clinical remission (CR) at week 52 after receiving tocilizumab (Actemra) weekly maintained it throughout the extension, and 13 of 36 (36%) treated every other week maintained it, John Stone, MD, reported at the annual meeting of the American College of Rheumatology.

Notably, more of those 51 patients treated with tocilizumab who maintained CR throughout the extension were treatment free at the end of the extension, compared with those originally assigned to the placebo groups (65% vs. 45%), and their median time to first flare after stopping treatment was longer, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital and associate professor of medicine in the division of rheumatology at Harvard Medical School, both in Boston.

For example, times to first flare were 575 and 428 days for the weekly and biweekly tocilizumab dosing groups – which each had 26-week prednisone tapering – but they were only 162 days in a placebo group with 26-week prednisone tapering and 295 days for patients in another placebo group with 52-week prednisone tapering, Dr. Stone explained. Retreatment with tocilizumab restored CR in patients who experienced flares after discontinuing treatment, he added.

Importantly, cumulative glucocorticoid doses over the 3 years were also lower in the tocilizumab groups (2,647 and 3,782 mg/day with weekly and biweekly tocilizumab and 5,248, and 5,323 mg/day in the placebo groups, respectively), Dr. Stone said.

No new safety signals were observed during the extension. Rates of serious adverse events (SAEs) and serious infections per 100 patient-years during the entire 3 years of the study were comparable among those who never received tocilizumab and those who received at least 1 dose (23.2 and 25.4 for SAEs and 4.6 and 3.5 for serious infections).
 

Detailed results of the extension period

GiACTA enrolled patients with GCA and randomized them to receive weekly or biweekly treatment with the interleukin-6 receptor–alpha inhibitor tocilizumab at doses of 162 mg delivered subcutaneously with a 26-week prednisone taper, or to the placebo groups with a 26- or 52-week prednisone taper. The results, reported in 2017, demonstrated the superiority of tocilizumab over placebo for providing sustained glucocorticoid-free remission and ultimately led to approval from Food and Drug Administration of the biologic agent for the treatment of GCA.

The current analysis was carried out to determine long-term safety, to explore maintenance of efficacy after discontinuation, and to “gain insight into the long-term glucocorticoid-sparing effects of tocilizumab,” Dr. Stone said.

He noted that the extension period was not randomized because of the way that patients in the “original four randomized groups had sorted themselves out into very different groups by virtue of their response in part 1 [of the trial],” which made randomization impossible because of the varying categories of patients.

Patients in the extension were also treated at investigators’ discretion to prevent “catastrophic GCA flares, vision loss, and other problems” that could potentially occur with discontinuation of the blinded injections in part 1, he said.

Nevertheless, the analysis “provides some incredibly important information about the management of GCA now,” he said, adding that the dramatic effect of the original randomization was still profound at 3 years “despite the fact that investigators could treat the patients as they wished.”

“Even at 3 years there was still a profound difference in the cumulative glucocorticoid [use], compared to those patients who were randomized to one of the placebo versus prednisone groups,” he explained.

However, the most important question from this study relates to what happened when weekly tocilizumab was stopped: Of the 81 patients in part 2 who were in CR on tocilizumab after part 1 of the study, 59 (73%) were not started on any treatment by their investigator, and of those, 25 (42%) maintained treatment-free remission for 2 full years following discontinuation of tocilizumab, he said.
 

What happened when prednisone was stopped?

In the absence of a direct comparison group (since the extension wasn’t a randomized, controlled part of the trial), the best comparison to that is what happens when prednisone is stopped, he noted.

“And we did that experiment in part 1” of the trial, he said. Overall, 68% of patients in the prednisone/placebo groups flared in 1-year of follow-up, and most of those did so even before they stopped prednisone. In the group that received placebo plus a 52-week prednisone taper, 49% of patients flared and “every single one of those patients flared before they got off prednisone,” he said.

“So in that context, 2 years of treatment-free remission following weekly tocilizumab discontinuation seems very good,” he added.

Of the patients who flared in part 2 of the trial, 11 whose investigator elected to treat them with only tocilizumab reentered remission in a median of 15.8 days, 13 treated with tocilizumab and glucocorticoids reentered remission in a median of 8.5 days (1 didn’t reenter remission at all), and 15 treated with only glucocorticoids reentered remission in a median of 38 days.

“There are a number of biases in these data, but they do point out the fact that some patients can be treated with tocilizumab alone,” Dr. Stone said. “I would be very careful doing that.”

The trial was not powered for the comparison of weekly versus biweekly dosing, he said. However, “multiple lines of investigation and analysis support the idea that weekly tocilizumab is more effective at controlling disease,” he added. But “if you want to be assured that you are doing everything you can to control the disease, weekly tocilizumab would be better than every-other-week tocilizumab,” he said.

GiACTA was funded by Roche. Dr. Stone reported research grants from Roche/Genentech and consulting fees from Chugal, Roche/Genentech, and Xencor.

[email protected]

SOURCE: Stone J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 808.

Amneal Pharmaceuticals has announced a voluntary recall for both ranitidine tablets and ranitidine syrup because of potential N-nitrosodimethylamine (NDMA) levels above Food and Drug Administration–allowed cutoffs, according to an FDA MedWatch alert.

NDMA, a probable human carcinogen, has been found in several different ranitidine products since an initial FDA announcement in September 2019. Ranitidine, a histamine₂ receptor blocker, is indicated for multiple conditions, including treatment and prevention of ulcers of the stomach and intestines and treatment of gastroesophageal reflux disease.

The affected ranitidine products being recalled by Amneal include 60-, 100-, 180-, 500-, and 1,000-count 150-mg tablets; 30-, 100-, 250-, and 1,000-count 300-mg tablets, and a 15-mg/mL syrup. The manufacturer has not received any reports of adverse events confirmed to be directly related to the recall.

Consumers should contact their physicians or health care providers if they have experienced any problems that may be related to the use of this drug product, the FDA said. Adverse reactions or quality problems can be reported to Amneal Drug Safety by phone at 1-877-835-5472.

[email protected]

Amneal Pharmaceuticals has announced a voluntary recall for both ranitidine tablets and ranitidine syrup because of potential N-nitrosodimethylamine (NDMA) levels above Food and Drug Administration–allowed cutoffs, according to an FDA MedWatch alert.

NDMA, a probable human carcinogen, has been found in several different ranitidine products since an initial FDA announcement in September 2019. Ranitidine, a histamine₂ receptor blocker, is indicated for multiple conditions, including treatment and prevention of ulcers of the stomach and intestines and treatment of gastroesophageal reflux disease.

The affected ranitidine products being recalled by Amneal include 60-, 100-, 180-, 500-, and 1,000-count 150-mg tablets; 30-, 100-, 250-, and 1,000-count 300-mg tablets, and a 15-mg/mL syrup. The manufacturer has not received any reports of adverse events confirmed to be directly related to the recall.

Consumers should contact their physicians or health care providers if they have experienced any problems that may be related to the use of this drug product, the FDA said. Adverse reactions or quality problems can be reported to Amneal Drug Safety by phone at 1-877-835-5472.

[email protected]

Amneal Pharmaceuticals has announced a voluntary recall for both ranitidine tablets and ranitidine syrup because of potential N-nitrosodimethylamine (NDMA) levels above Food and Drug Administration–allowed cutoffs, according to an FDA MedWatch alert.

NDMA, a probable human carcinogen, has been found in several different ranitidine products since an initial FDA announcement in September 2019. Ranitidine, a histamine₂ receptor blocker, is indicated for multiple conditions, including treatment and prevention of ulcers of the stomach and intestines and treatment of gastroesophageal reflux disease.

The affected ranitidine products being recalled by Amneal include 60-, 100-, 180-, 500-, and 1,000-count 150-mg tablets; 30-, 100-, 250-, and 1,000-count 300-mg tablets, and a 15-mg/mL syrup. The manufacturer has not received any reports of adverse events confirmed to be directly related to the recall.

Consumers should contact their physicians or health care providers if they have experienced any problems that may be related to the use of this drug product, the FDA said. Adverse reactions or quality problems can be reported to Amneal Drug Safety by phone at 1-877-835-5472.

[email protected]

The tyrosine kinase inhibitor (TKI) lorlatinib showed deep responses and intracranial activity in both TKI-pretreated and TKI-naive patients with advanced ROS1-positive non–small cell lung cancer (NSCLC), according to results from a phase 1-2 trial.

“We investigated the antitumour activity and safety of lorlatinib in advanced, ROS1-positive NSCLC,” wrote Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center, Boston, and colleagues. Their report is in The Lancet Oncology.

The single-arm, open-label study included 69 patients with advanced ROS1-positive disease with or without CNS involvement. The effects of lorlatinib were evaluated across 28 institutions in 12 different countries around the globe.

At baseline, the median age of study participants was 54 years (range, 44-61 years), and 57% were positive for brain metastases.

Study participants received 100 mg of oral lorlatinib once daily in repeated 21-day cycles. Drug therapy was continued until death, disease progression, unacceptable toxicity, or withdrawal of consent.

The primary outcome measured was intracranial and overall response. Activity outcomes were evaluated in subjects given a minimum of one dose of lorlatinib.

A total of 58% of patients were previously treated with crizotinib, while 30% of patients were TKI-naive. Among 40 crizotinib-pretreated patients, 14 patients (35%) had an objective response, with a median duration of response and PFS of 13.8 and 8.5 months, respectively.

Among 21 TKI-naive patients, 13 patients (62%) had an objective response, with a median duration of response and PFS of 25.3 and 21 months, respectively.

“Intracranial responses were achieved in seven (64%) of 11 TKI-naive patients and 12 (50%) of 24 previous crizotinib-only patients,” they reported.

With respect to safety, serious lorlatinib-related adverse events were observed in 7% of patients, with no therapy-related deaths reported. The most frequently seen grade 3-4 TEAEs were hypertriglyceridemia (19%) and hypercholesterolemia (14%).

The researchers noted a key limitation of the study was the small sample size; however, due to the rare nature of ROS1 rearrangements in patients with NSCLC, increasing enrollment for future studies could be challenging.

“Because crizotinib-refractory patients have few treatment options, lorlatinib could represent an important next-line targeted agent,” they concluded.

Pfizer funded the study. The authors reported financial affiliations with Ariad, Blueprint Medicines, Chugai Pharmaceutical, Daiichi Sankyo, EMD Serono, Pfizer, KSQ Therapeutics, Servier, TP Therapeutics, and other companies.

SOURCE: Shaw AT et al. Lancet Oncol. 2019 Oct 25. doi: 10.1016/S1470-2045(19)30655-2.

The tyrosine kinase inhibitor (TKI) lorlatinib showed deep responses and intracranial activity in both TKI-pretreated and TKI-naive patients with advanced ROS1-positive non–small cell lung cancer (NSCLC), according to results from a phase 1-2 trial.

“We investigated the antitumour activity and safety of lorlatinib in advanced, ROS1-positive NSCLC,” wrote Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center, Boston, and colleagues. Their report is in The Lancet Oncology.

The single-arm, open-label study included 69 patients with advanced ROS1-positive disease with or without CNS involvement. The effects of lorlatinib were evaluated across 28 institutions in 12 different countries around the globe.

At baseline, the median age of study participants was 54 years (range, 44-61 years), and 57% were positive for brain metastases.

Study participants received 100 mg of oral lorlatinib once daily in repeated 21-day cycles. Drug therapy was continued until death, disease progression, unacceptable toxicity, or withdrawal of consent.

The primary outcome measured was intracranial and overall response. Activity outcomes were evaluated in subjects given a minimum of one dose of lorlatinib.

A total of 58% of patients were previously treated with crizotinib, while 30% of patients were TKI-naive. Among 40 crizotinib-pretreated patients, 14 patients (35%) had an objective response, with a median duration of response and PFS of 13.8 and 8.5 months, respectively.

Among 21 TKI-naive patients, 13 patients (62%) had an objective response, with a median duration of response and PFS of 25.3 and 21 months, respectively.

“Intracranial responses were achieved in seven (64%) of 11 TKI-naive patients and 12 (50%) of 24 previous crizotinib-only patients,” they reported.

With respect to safety, serious lorlatinib-related adverse events were observed in 7% of patients, with no therapy-related deaths reported. The most frequently seen grade 3-4 TEAEs were hypertriglyceridemia (19%) and hypercholesterolemia (14%).

The researchers noted a key limitation of the study was the small sample size; however, due to the rare nature of ROS1 rearrangements in patients with NSCLC, increasing enrollment for future studies could be challenging.

“Because crizotinib-refractory patients have few treatment options, lorlatinib could represent an important next-line targeted agent,” they concluded.

Pfizer funded the study. The authors reported financial affiliations with Ariad, Blueprint Medicines, Chugai Pharmaceutical, Daiichi Sankyo, EMD Serono, Pfizer, KSQ Therapeutics, Servier, TP Therapeutics, and other companies.

SOURCE: Shaw AT et al. Lancet Oncol. 2019 Oct 25. doi: 10.1016/S1470-2045(19)30655-2.

The tyrosine kinase inhibitor (TKI) lorlatinib showed deep responses and intracranial activity in both TKI-pretreated and TKI-naive patients with advanced ROS1-positive non–small cell lung cancer (NSCLC), according to results from a phase 1-2 trial.

“We investigated the antitumour activity and safety of lorlatinib in advanced, ROS1-positive NSCLC,” wrote Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center, Boston, and colleagues. Their report is in The Lancet Oncology.

The single-arm, open-label study included 69 patients with advanced ROS1-positive disease with or without CNS involvement. The effects of lorlatinib were evaluated across 28 institutions in 12 different countries around the globe.

At baseline, the median age of study participants was 54 years (range, 44-61 years), and 57% were positive for brain metastases.

Study participants received 100 mg of oral lorlatinib once daily in repeated 21-day cycles. Drug therapy was continued until death, disease progression, unacceptable toxicity, or withdrawal of consent.

The primary outcome measured was intracranial and overall response. Activity outcomes were evaluated in subjects given a minimum of one dose of lorlatinib.

A total of 58% of patients were previously treated with crizotinib, while 30% of patients were TKI-naive. Among 40 crizotinib-pretreated patients, 14 patients (35%) had an objective response, with a median duration of response and PFS of 13.8 and 8.5 months, respectively.

Among 21 TKI-naive patients, 13 patients (62%) had an objective response, with a median duration of response and PFS of 25.3 and 21 months, respectively.

“Intracranial responses were achieved in seven (64%) of 11 TKI-naive patients and 12 (50%) of 24 previous crizotinib-only patients,” they reported.

With respect to safety, serious lorlatinib-related adverse events were observed in 7% of patients, with no therapy-related deaths reported. The most frequently seen grade 3-4 TEAEs were hypertriglyceridemia (19%) and hypercholesterolemia (14%).

The researchers noted a key limitation of the study was the small sample size; however, due to the rare nature of ROS1 rearrangements in patients with NSCLC, increasing enrollment for future studies could be challenging.

“Because crizotinib-refractory patients have few treatment options, lorlatinib could represent an important next-line targeted agent,” they concluded.

Pfizer funded the study. The authors reported financial affiliations with Ariad, Blueprint Medicines, Chugai Pharmaceutical, Daiichi Sankyo, EMD Serono, Pfizer, KSQ Therapeutics, Servier, TP Therapeutics, and other companies.

SOURCE: Shaw AT et al. Lancet Oncol. 2019 Oct 25. doi: 10.1016/S1470-2045(19)30655-2.

A 19-year-old man was diagnosed with relapsing multiple sclerosis (MS) at age 7 and is currently being treated with an infusible monoclonal antibody (mAb) therapy. Early in the day, he receives an infusion at an outpatient clinic. That night, he begins to experience numbness and tingling in his right upper extremity, which prompts a visit to an urgent care clinic. There, the clinician administers IV fluids to the patient. After his symptoms improve, the patient is discharged home.

The next morning, he has a new onset of left-side shoulder and neck pain with a pulsating headache. The patient reports his symptoms to his primary care provider (PCP), who instructs him to visit the emergency department (ED) for evaluation and treatment of a possible infection.

EXAMINATION

The patient arrives at the ED with a 102.4°F fever, vomiting, cough, mild congestion, diaphoresis, generalized myalgias, and chills. He also reports depression and anxiety, saying that for the past 7 days, “I haven’t felt like my normal self.”

Medical history includes moderate persistent asthma that is not well controlled, status asthmaticus, and use of an electronic vaporizing device for inhaling nicotine and marijuana/tetrahydrocannabinol (THC). Besides mAb infusions, his medications include hydrocodone/acetaminophen, prochlorperazine, gabapentin, hydroxyzine, trazodone, albuterol, and montelukast.

Examination reveals vital signs within normal limits. Lab work confirms elevated white blood cell count and absolute neutrophil count. Chest x-ray shows diffuse bilateral interstitial and patchy airspace opacities. He is diagnosed with bilateral pneumonia and is admitted and started on an IV antibiotic.

Within 24 hours, a new chest x-ray shows worsening symptoms. CT of the chest with contrast reveals diffuse bilateral ground-glass and airspace opacities suggestive of acute respiratory distress syndrome; bilateral thickening of the pulmonary interstitium; trace bilateral pleural effusions; increased caliber of the main pulmonary artery; and mediastinal and right hilar lymphadenopathy.

Subsequently, the patient developed sepsis and went into acute hypoxemic respiratory failure. He is transferred to the ICU, and pulmonology is consulted. A bronchoscopy with bronchoalveolar lavage (BAL) reveals neutrophil predominance; fungal, bacterial, and viral cultures are negative. The patient is started on broad-spectrum IV antibiotics and high-dose IV steroids. After 4 days, he begins to improve and is transferred out of the ICU. He is discharged with oral steroids and antibiotics.

Continue to: DISCUSSION

Fortunately, the PCP and the ED provider identified risk factors that contributed to the patient’s pneumonia and its subsequent worsening to sepsis and acute hypoxemic respiratory failure. The immunosuppressive/immunomodulatory effect of mAb therapy increased the patient’s risk for infection and the severity of infection, which is why vigilant safety monitoring and surveillance is essential with mAb treatment.¹ Bloodwork should be performed at least every 6 months and include a complete blood count, complete metabolic panel with differential, and JC virus antibody test. Additionally, urinalysis should be performed prior to every mAb infusion. All testing recommended in the package insert for the patient’s prescribed therapy should be performed.

The patient’s history of asthma and his chronic vaping predisposed him to respiratory infections. In mice studies, exposure to e-cigarette vapor has been shown to be cytotoxic to airway cells and to decrease macrophage and neutrophil antimicrobial function.² Exposure also alters immunomodulating cytokines in the airway, increases inflammatory markers seen in BAL and serum samples, and increases the virulence of Staphylococcus aureus.²

TREATMENT AND PATIENT EDUCATION

The PCP’s treatment plan included patient education about the importance of infection control measures when receiving a mAb; this includes practicing good hand and environmental hygiene, maintaining vaccinations, avoiding or reducing exposure to individuals who have infections or colds, avoiding large crowds (especially during flu season), and following recommendations for nutrition and hydration. The PCP also discussed how to recognize the early signs and symptoms of an infection—and the need for vigilant safety monitoring. The PCP described available options for smoking cessation, including nicotine replacement products, prescription non-nicotine medications, behavioral therapy, and/or counseling (individual, group or telephone) and discussed the risks associated with consuming nicotine and/or marijuana/THC and using electronic vaporizing devices.

The PCP emphasized the importance of completing the entire course of the oral antibiotics prescribed at discharge. The patient and the PCP agreed to the following plan of care: appointments with a pulmonologist and a neurologist within the next 2 weeks, and follow-up visits with the PCP every 6 months (or more frequently, as needed) and with a neurologist at least every 6 months (or as indicated by his medication’s prescribing recommendations).

A 19-year-old man was diagnosed with relapsing multiple sclerosis (MS) at age 7 and is currently being treated with an infusible monoclonal antibody (mAb) therapy. Early in the day, he receives an infusion at an outpatient clinic. That night, he begins to experience numbness and tingling in his right upper extremity, which prompts a visit to an urgent care clinic. There, the clinician administers IV fluids to the patient. After his symptoms improve, the patient is discharged home.

The next morning, he has a new onset of left-side shoulder and neck pain with a pulsating headache. The patient reports his symptoms to his primary care provider (PCP), who instructs him to visit the emergency department (ED) for evaluation and treatment of a possible infection.

EXAMINATION

The patient arrives at the ED with a 102.4°F fever, vomiting, cough, mild congestion, diaphoresis, generalized myalgias, and chills. He also reports depression and anxiety, saying that for the past 7 days, “I haven’t felt like my normal self.”

Medical history includes moderate persistent asthma that is not well controlled, status asthmaticus, and use of an electronic vaporizing device for inhaling nicotine and marijuana/tetrahydrocannabinol (THC). Besides mAb infusions, his medications include hydrocodone/acetaminophen, prochlorperazine, gabapentin, hydroxyzine, trazodone, albuterol, and montelukast.

Examination reveals vital signs within normal limits. Lab work confirms elevated white blood cell count and absolute neutrophil count. Chest x-ray shows diffuse bilateral interstitial and patchy airspace opacities. He is diagnosed with bilateral pneumonia and is admitted and started on an IV antibiotic.

Within 24 hours, a new chest x-ray shows worsening symptoms. CT of the chest with contrast reveals diffuse bilateral ground-glass and airspace opacities suggestive of acute respiratory distress syndrome; bilateral thickening of the pulmonary interstitium; trace bilateral pleural effusions; increased caliber of the main pulmonary artery; and mediastinal and right hilar lymphadenopathy.

Subsequently, the patient developed sepsis and went into acute hypoxemic respiratory failure. He is transferred to the ICU, and pulmonology is consulted. A bronchoscopy with bronchoalveolar lavage (BAL) reveals neutrophil predominance; fungal, bacterial, and viral cultures are negative. The patient is started on broad-spectrum IV antibiotics and high-dose IV steroids. After 4 days, he begins to improve and is transferred out of the ICU. He is discharged with oral steroids and antibiotics.

Continue to: DISCUSSION

Fortunately, the PCP and the ED provider identified risk factors that contributed to the patient’s pneumonia and its subsequent worsening to sepsis and acute hypoxemic respiratory failure. The immunosuppressive/immunomodulatory effect of mAb therapy increased the patient’s risk for infection and the severity of infection, which is why vigilant safety monitoring and surveillance is essential with mAb treatment.¹ Bloodwork should be performed at least every 6 months and include a complete blood count, complete metabolic panel with differential, and JC virus antibody test. Additionally, urinalysis should be performed prior to every mAb infusion. All testing recommended in the package insert for the patient’s prescribed therapy should be performed.

The patient’s history of asthma and his chronic vaping predisposed him to respiratory infections. In mice studies, exposure to e-cigarette vapor has been shown to be cytotoxic to airway cells and to decrease macrophage and neutrophil antimicrobial function.² Exposure also alters immunomodulating cytokines in the airway, increases inflammatory markers seen in BAL and serum samples, and increases the virulence of Staphylococcus aureus.²

TREATMENT AND PATIENT EDUCATION

The PCP’s treatment plan included patient education about the importance of infection control measures when receiving a mAb; this includes practicing good hand and environmental hygiene, maintaining vaccinations, avoiding or reducing exposure to individuals who have infections or colds, avoiding large crowds (especially during flu season), and following recommendations for nutrition and hydration. The PCP also discussed how to recognize the early signs and symptoms of an infection—and the need for vigilant safety monitoring. The PCP described available options for smoking cessation, including nicotine replacement products, prescription non-nicotine medications, behavioral therapy, and/or counseling (individual, group or telephone) and discussed the risks associated with consuming nicotine and/or marijuana/THC and using electronic vaporizing devices.

The PCP emphasized the importance of completing the entire course of the oral antibiotics prescribed at discharge. The patient and the PCP agreed to the following plan of care: appointments with a pulmonologist and a neurologist within the next 2 weeks, and follow-up visits with the PCP every 6 months (or more frequently, as needed) and with a neurologist at least every 6 months (or as indicated by his medication’s prescribing recommendations).

A 19-year-old man was diagnosed with relapsing multiple sclerosis (MS) at age 7 and is currently being treated with an infusible monoclonal antibody (mAb) therapy. Early in the day, he receives an infusion at an outpatient clinic. That night, he begins to experience numbness and tingling in his right upper extremity, which prompts a visit to an urgent care clinic. There, the clinician administers IV fluids to the patient. After his symptoms improve, the patient is discharged home.

The next morning, he has a new onset of left-side shoulder and neck pain with a pulsating headache. The patient reports his symptoms to his primary care provider (PCP), who instructs him to visit the emergency department (ED) for evaluation and treatment of a possible infection.

EXAMINATION

The patient arrives at the ED with a 102.4°F fever, vomiting, cough, mild congestion, diaphoresis, generalized myalgias, and chills. He also reports depression and anxiety, saying that for the past 7 days, “I haven’t felt like my normal self.”

Medical history includes moderate persistent asthma that is not well controlled, status asthmaticus, and use of an electronic vaporizing device for inhaling nicotine and marijuana/tetrahydrocannabinol (THC). Besides mAb infusions, his medications include hydrocodone/acetaminophen, prochlorperazine, gabapentin, hydroxyzine, trazodone, albuterol, and montelukast.

Examination reveals vital signs within normal limits. Lab work confirms elevated white blood cell count and absolute neutrophil count. Chest x-ray shows diffuse bilateral interstitial and patchy airspace opacities. He is diagnosed with bilateral pneumonia and is admitted and started on an IV antibiotic.

Within 24 hours, a new chest x-ray shows worsening symptoms. CT of the chest with contrast reveals diffuse bilateral ground-glass and airspace opacities suggestive of acute respiratory distress syndrome; bilateral thickening of the pulmonary interstitium; trace bilateral pleural effusions; increased caliber of the main pulmonary artery; and mediastinal and right hilar lymphadenopathy.

Subsequently, the patient developed sepsis and went into acute hypoxemic respiratory failure. He is transferred to the ICU, and pulmonology is consulted. A bronchoscopy with bronchoalveolar lavage (BAL) reveals neutrophil predominance; fungal, bacterial, and viral cultures are negative. The patient is started on broad-spectrum IV antibiotics and high-dose IV steroids. After 4 days, he begins to improve and is transferred out of the ICU. He is discharged with oral steroids and antibiotics.

Continue to: DISCUSSION

Fortunately, the PCP and the ED provider identified risk factors that contributed to the patient’s pneumonia and its subsequent worsening to sepsis and acute hypoxemic respiratory failure. The immunosuppressive/immunomodulatory effect of mAb therapy increased the patient’s risk for infection and the severity of infection, which is why vigilant safety monitoring and surveillance is essential with mAb treatment.¹ Bloodwork should be performed at least every 6 months and include a complete blood count, complete metabolic panel with differential, and JC virus antibody test. Additionally, urinalysis should be performed prior to every mAb infusion. All testing recommended in the package insert for the patient’s prescribed therapy should be performed.

The patient’s history of asthma and his chronic vaping predisposed him to respiratory infections. In mice studies, exposure to e-cigarette vapor has been shown to be cytotoxic to airway cells and to decrease macrophage and neutrophil antimicrobial function.² Exposure also alters immunomodulating cytokines in the airway, increases inflammatory markers seen in BAL and serum samples, and increases the virulence of Staphylococcus aureus.²

TREATMENT AND PATIENT EDUCATION

The PCP’s treatment plan included patient education about the importance of infection control measures when receiving a mAb; this includes practicing good hand and environmental hygiene, maintaining vaccinations, avoiding or reducing exposure to individuals who have infections or colds, avoiding large crowds (especially during flu season), and following recommendations for nutrition and hydration. The PCP also discussed how to recognize the early signs and symptoms of an infection—and the need for vigilant safety monitoring. The PCP described available options for smoking cessation, including nicotine replacement products, prescription non-nicotine medications, behavioral therapy, and/or counseling (individual, group or telephone) and discussed the risks associated with consuming nicotine and/or marijuana/THC and using electronic vaporizing devices.

The PCP emphasized the importance of completing the entire course of the oral antibiotics prescribed at discharge. The patient and the PCP agreed to the following plan of care: appointments with a pulmonologist and a neurologist within the next 2 weeks, and follow-up visits with the PCP every 6 months (or more frequently, as needed) and with a neurologist at least every 6 months (or as indicated by his medication’s prescribing recommendations).

The last time I saw her she was coiled up like a garter snake resting comfortable in the old toiletries travel case that was my “black bag” for more than 40 years. Joining her in peaceful solitude were a couple of ear curettes, an insufflator, and a dead pocket flashlight. The Kermit the Frog sticker on her diaphragm was faded to a barely recognizable blur. The chest piece was frozen in the diaphragm position as it had been for several decades. I never felt comfortable using the bell side.

Hiraman/Getty Images

She was the gift from a drug company back when medical students were more interested in freebies than making a statement about conflicts of interest. I have had to change her tubing several times when cracks at the bifurcation would allow me to hear my own breath sounds better than the patient’s. The ear pieces were the originals that I modified to fit my auditory canals more comfortably.

I suspect that many of you have developed a close relationship with your stethoscope, as I did. We were always close. She was either her coiled up in my pants’ pocket or clasped around my neck where she wore through collars at a costly clip. Her chest piece was kept tucked in my shirt to keep it warm for the patients. I never hung her over my shoulders the way physicians do in publicity photos. I always found that practice pretentious and impractical.

If I decided tomorrow to leave the challenges of retirement behind and reopen my practice would it make any sense to go down to the basement and roust out my old stethoscope from her slumber? There are better ways evaluate hearts and lungs and many of them will fit in my pocket just as well as that old stethoscope. Paul Wallach, MD, an executive associate dean at the Indiana University, Indianapolis, predicts that within a decade hand-held ultrasound devices with become part of a routine part of the physical exam (Lindsey Tanner. “Is the stethoscope dying? High-tech rivals pose a challenge.” Associated Press. 2019 Oct 23). Instruction in the use of these devices has already become part of the curriculum in some medical schools.

There have been several studies demonstrating that chest auscultation is a skill that some of us have lost and many others never successfully mastered. As much as I treasure my old stethoscope, is it time to get rid of those albatrosses hanging around our necks? They do bang against desks with a deafening ring. Cute infants and toddlers yank on them while we are trying to listen to their chests. If there are better ways to auscultate chests that will fit in our pockets shouldn’t we be using them?

Well, there is the cost for one thing. But, inevitably the price will come down and portability will go up. If we allow our stethoscopes to become nothing more than nostalgic museum pieces to sit along with the head mirror, what will replace them as tangible symbols of our identity as physicians? What will photographers drape over our shoulders? With very few of us in office practice wearing white coats or scrub suits, we run the risk of losing our identity.

Sadly, I fear we will have to accept the disappearance of the stethoscope as a natural consequence of the technological march. But, it also is an unfortunate reflection of the fact that the art of doing a physical exam is fading. With auscultation and palpation disappearing from our diagnostic tool kit we must be careful to preserve and improve the one skill that is indispensable to the practice of medicine.

And, that is listening to what the patient has to tell us.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

The last time I saw her she was coiled up like a garter snake resting comfortable in the old toiletries travel case that was my “black bag” for more than 40 years. Joining her in peaceful solitude were a couple of ear curettes, an insufflator, and a dead pocket flashlight. The Kermit the Frog sticker on her diaphragm was faded to a barely recognizable blur. The chest piece was frozen in the diaphragm position as it had been for several decades. I never felt comfortable using the bell side.

Hiraman/Getty Images

She was the gift from a drug company back when medical students were more interested in freebies than making a statement about conflicts of interest. I have had to change her tubing several times when cracks at the bifurcation would allow me to hear my own breath sounds better than the patient’s. The ear pieces were the originals that I modified to fit my auditory canals more comfortably.

I suspect that many of you have developed a close relationship with your stethoscope, as I did. We were always close. She was either her coiled up in my pants’ pocket or clasped around my neck where she wore through collars at a costly clip. Her chest piece was kept tucked in my shirt to keep it warm for the patients. I never hung her over my shoulders the way physicians do in publicity photos. I always found that practice pretentious and impractical.

If I decided tomorrow to leave the challenges of retirement behind and reopen my practice would it make any sense to go down to the basement and roust out my old stethoscope from her slumber? There are better ways evaluate hearts and lungs and many of them will fit in my pocket just as well as that old stethoscope. Paul Wallach, MD, an executive associate dean at the Indiana University, Indianapolis, predicts that within a decade hand-held ultrasound devices with become part of a routine part of the physical exam (Lindsey Tanner. “Is the stethoscope dying? High-tech rivals pose a challenge.” Associated Press. 2019 Oct 23). Instruction in the use of these devices has already become part of the curriculum in some medical schools.

There have been several studies demonstrating that chest auscultation is a skill that some of us have lost and many others never successfully mastered. As much as I treasure my old stethoscope, is it time to get rid of those albatrosses hanging around our necks? They do bang against desks with a deafening ring. Cute infants and toddlers yank on them while we are trying to listen to their chests. If there are better ways to auscultate chests that will fit in our pockets shouldn’t we be using them?

Well, there is the cost for one thing. But, inevitably the price will come down and portability will go up. If we allow our stethoscopes to become nothing more than nostalgic museum pieces to sit along with the head mirror, what will replace them as tangible symbols of our identity as physicians? What will photographers drape over our shoulders? With very few of us in office practice wearing white coats or scrub suits, we run the risk of losing our identity.

Sadly, I fear we will have to accept the disappearance of the stethoscope as a natural consequence of the technological march. But, it also is an unfortunate reflection of the fact that the art of doing a physical exam is fading. With auscultation and palpation disappearing from our diagnostic tool kit we must be careful to preserve and improve the one skill that is indispensable to the practice of medicine.

And, that is listening to what the patient has to tell us.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

The last time I saw her she was coiled up like a garter snake resting comfortable in the old toiletries travel case that was my “black bag” for more than 40 years. Joining her in peaceful solitude were a couple of ear curettes, an insufflator, and a dead pocket flashlight. The Kermit the Frog sticker on her diaphragm was faded to a barely recognizable blur. The chest piece was frozen in the diaphragm position as it had been for several decades. I never felt comfortable using the bell side.

Hiraman/Getty Images

She was the gift from a drug company back when medical students were more interested in freebies than making a statement about conflicts of interest. I have had to change her tubing several times when cracks at the bifurcation would allow me to hear my own breath sounds better than the patient’s. The ear pieces were the originals that I modified to fit my auditory canals more comfortably.

I suspect that many of you have developed a close relationship with your stethoscope, as I did. We were always close. She was either her coiled up in my pants’ pocket or clasped around my neck where she wore through collars at a costly clip. Her chest piece was kept tucked in my shirt to keep it warm for the patients. I never hung her over my shoulders the way physicians do in publicity photos. I always found that practice pretentious and impractical.

If I decided tomorrow to leave the challenges of retirement behind and reopen my practice would it make any sense to go down to the basement and roust out my old stethoscope from her slumber? There are better ways evaluate hearts and lungs and many of them will fit in my pocket just as well as that old stethoscope. Paul Wallach, MD, an executive associate dean at the Indiana University, Indianapolis, predicts that within a decade hand-held ultrasound devices with become part of a routine part of the physical exam (Lindsey Tanner. “Is the stethoscope dying? High-tech rivals pose a challenge.” Associated Press. 2019 Oct 23). Instruction in the use of these devices has already become part of the curriculum in some medical schools.

There have been several studies demonstrating that chest auscultation is a skill that some of us have lost and many others never successfully mastered. As much as I treasure my old stethoscope, is it time to get rid of those albatrosses hanging around our necks? They do bang against desks with a deafening ring. Cute infants and toddlers yank on them while we are trying to listen to their chests. If there are better ways to auscultate chests that will fit in our pockets shouldn’t we be using them?

Well, there is the cost for one thing. But, inevitably the price will come down and portability will go up. If we allow our stethoscopes to become nothing more than nostalgic museum pieces to sit along with the head mirror, what will replace them as tangible symbols of our identity as physicians? What will photographers drape over our shoulders? With very few of us in office practice wearing white coats or scrub suits, we run the risk of losing our identity.

Sadly, I fear we will have to accept the disappearance of the stethoscope as a natural consequence of the technological march. But, it also is an unfortunate reflection of the fact that the art of doing a physical exam is fading. With auscultation and palpation disappearing from our diagnostic tool kit we must be careful to preserve and improve the one skill that is indispensable to the practice of medicine.

And, that is listening to what the patient has to tell us.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

My final appointment for the day was very late, with only 10 minutes left in the session. I was closing my office door when my patient, a middle-aged woman, rushed up and said: “I am sorry to be so late, but traffic was terrible. I am out of my meds. Will you still see me?” I agreed. She was touched and thanked me.

As she sat down, still breathless, she said: “I have had a lot on my mind. After we work out the meds, could we please talk about them? One thing is the climate problem, but there is really no point in worrying about something you cannot do anything about.”

I refilled her meds, then I responded to her offhand comment about climate by saying, “I, too, have been concerned about climate change. Tell me your concerns.” She opened up and, to my surprise, burst into tears, saying, “how terrible it is, what we’re doing to the earth, and how bad it will be for those to come. How could we leave the earth in such a mess?” She was clearly grieving. I agreed and said: “There is a lot to be done, and we can do many things to help. Have you heard about the Green New Deal?” We talked about this for a few minutes, and she was very interested.

At first, she disavowed the problem, saying that, while it bothered her, nothing could be done about it, so why talk about it? Disavowal is a common defense that shields us from our real feelings about disturbing problems. Once I invited her to talk about it, she opened up with grief and near paralyzing sadness. This was my opportunity to let her know that there is a realistic plan for dealing with climate change. If she were to get politically active or involved with like-minded groups, hope could be possible. (As young Greta Thunberg, the Swedish youth climate action leader, teaches us, “Where there is no action, there is no hope, but where there is action, hope is everywhere.”)

My patient was comforted by verbalizing her despair and heartened by my suggestions, especially some thoughts about the Green New Deal. So, what does a psychiatrist need to know about the Green New Deal?

It is essentially a broad legislative conceptual agenda with wide-ranging implications. The resolution has growing support in Congress. Its scope has been compared to the 1960s moon landing or the New Deal that helped this nation come out of the Great Depression. The primary goal is to bring the United States to 100% sustainable clean energy by 2030. It also proposes to help those most vulnerable to the stresses of climate change, such as “indigenous communities, communities of color, migrant communities, deinstitutionalized communities, depopulated communities, the poor, lower income workers, women, the elderly, the unhoused, people with disabilities, and youth.” Our patient population reflects many of those cohorts and will likely be helped directly by this ambitious agenda.

Specifically, the Green New Deal would transition the United States from fossil fuel dependence to clean energy sources, such as solar and wind power, upgrade the power grid, refurbish and retrofit buildings to become sustainable and energy efficient, overhaul transportation systems, and promote the transition to electric vehicles and high-speed rail. This transition of the infrastructure and economy will, in turn, create millions of good jobs, including meaningful and rewarding work for workers and communities transitioning away from fossil fuel industry–related activities.

The Green New Deal is intended to address the reality and risks of climate change. The World Health Organization has deemed climate change the greatest public health threat of the 21st century. Consider the following ominous developments:

The current atmospheric CO₂ level is 415 parts per million and rising, an increase from preindustrial levels of 278 ppm. Earthworms have now expanded their territory to include boreal forests near the Arctic, munching the foot-thick organic forest floor, potentially releasing much more CO₂. Permafrost is melting near the Arctic, as is sea ice, reducing the amount of solar radiation reflected back to space. Perversely and ironically, the loss of sea ice is touted by some climate deniers as an opportunity for expanded oil and gas exploration in the Arctic.

Extreme weather events are increasing in frequency and duration. Record-setting hurricanes, floods, tornadoes, heat waves, and wildfires are becoming the “new normal,” except for the fact that they are expected to continue worsening.

If the United States continues business as usual without addressing our climate trajectory, there will be dire consequences for all future generations. Without serious efforts to combat global warming, a 4- to 5-degree Celsius increase by the end of the century is likely. This would be catastrophic, leading to the collapse of the ice sheets, massive coastal inundation, unrelenting heat waves, wildfires beyond imagination, severe droughts, starvation, immense storms, and vast areas of the earth becoming uninhabitable.

It is time for the United States to join the rest of the world in dealing with global warming. The nations of the earth need to unite for the common good and to save our planet. The Green New Deal would represent a major step in that direction and would certainly help our patients to have more meaningful, hopeful, and healthier lives.
 

Dr. Peterson is assistant clinical professor in the department of psychiatry at Georgetown University in Washington. He is an active member of the Climate Psychiatry Alliance and the Caucus on Climate Change and Mental Health at the American Psychiatric Association. Dr. Peterson changed key facts about the patient’s story to protect her confidentiality.

My final appointment for the day was very late, with only 10 minutes left in the session. I was closing my office door when my patient, a middle-aged woman, rushed up and said: “I am sorry to be so late, but traffic was terrible. I am out of my meds. Will you still see me?” I agreed. She was touched and thanked me.

As she sat down, still breathless, she said: “I have had a lot on my mind. After we work out the meds, could we please talk about them? One thing is the climate problem, but there is really no point in worrying about something you cannot do anything about.”

I refilled her meds, then I responded to her offhand comment about climate by saying, “I, too, have been concerned about climate change. Tell me your concerns.” She opened up and, to my surprise, burst into tears, saying, “how terrible it is, what we’re doing to the earth, and how bad it will be for those to come. How could we leave the earth in such a mess?” She was clearly grieving. I agreed and said: “There is a lot to be done, and we can do many things to help. Have you heard about the Green New Deal?” We talked about this for a few minutes, and she was very interested.

At first, she disavowed the problem, saying that, while it bothered her, nothing could be done about it, so why talk about it? Disavowal is a common defense that shields us from our real feelings about disturbing problems. Once I invited her to talk about it, she opened up with grief and near paralyzing sadness. This was my opportunity to let her know that there is a realistic plan for dealing with climate change. If she were to get politically active or involved with like-minded groups, hope could be possible. (As young Greta Thunberg, the Swedish youth climate action leader, teaches us, “Where there is no action, there is no hope, but where there is action, hope is everywhere.”)

My patient was comforted by verbalizing her despair and heartened by my suggestions, especially some thoughts about the Green New Deal. So, what does a psychiatrist need to know about the Green New Deal?

It is essentially a broad legislative conceptual agenda with wide-ranging implications. The resolution has growing support in Congress. Its scope has been compared to the 1960s moon landing or the New Deal that helped this nation come out of the Great Depression. The primary goal is to bring the United States to 100% sustainable clean energy by 2030. It also proposes to help those most vulnerable to the stresses of climate change, such as “indigenous communities, communities of color, migrant communities, deinstitutionalized communities, depopulated communities, the poor, lower income workers, women, the elderly, the unhoused, people with disabilities, and youth.” Our patient population reflects many of those cohorts and will likely be helped directly by this ambitious agenda.

Specifically, the Green New Deal would transition the United States from fossil fuel dependence to clean energy sources, such as solar and wind power, upgrade the power grid, refurbish and retrofit buildings to become sustainable and energy efficient, overhaul transportation systems, and promote the transition to electric vehicles and high-speed rail. This transition of the infrastructure and economy will, in turn, create millions of good jobs, including meaningful and rewarding work for workers and communities transitioning away from fossil fuel industry–related activities.

The Green New Deal is intended to address the reality and risks of climate change. The World Health Organization has deemed climate change the greatest public health threat of the 21st century. Consider the following ominous developments:

The current atmospheric CO₂ level is 415 parts per million and rising, an increase from preindustrial levels of 278 ppm. Earthworms have now expanded their territory to include boreal forests near the Arctic, munching the foot-thick organic forest floor, potentially releasing much more CO₂. Permafrost is melting near the Arctic, as is sea ice, reducing the amount of solar radiation reflected back to space. Perversely and ironically, the loss of sea ice is touted by some climate deniers as an opportunity for expanded oil and gas exploration in the Arctic.

Extreme weather events are increasing in frequency and duration. Record-setting hurricanes, floods, tornadoes, heat waves, and wildfires are becoming the “new normal,” except for the fact that they are expected to continue worsening.

If the United States continues business as usual without addressing our climate trajectory, there will be dire consequences for all future generations. Without serious efforts to combat global warming, a 4- to 5-degree Celsius increase by the end of the century is likely. This would be catastrophic, leading to the collapse of the ice sheets, massive coastal inundation, unrelenting heat waves, wildfires beyond imagination, severe droughts, starvation, immense storms, and vast areas of the earth becoming uninhabitable.

It is time for the United States to join the rest of the world in dealing with global warming. The nations of the earth need to unite for the common good and to save our planet. The Green New Deal would represent a major step in that direction and would certainly help our patients to have more meaningful, hopeful, and healthier lives.
 

Dr. Peterson is assistant clinical professor in the department of psychiatry at Georgetown University in Washington. He is an active member of the Climate Psychiatry Alliance and the Caucus on Climate Change and Mental Health at the American Psychiatric Association. Dr. Peterson changed key facts about the patient’s story to protect her confidentiality.

My final appointment for the day was very late, with only 10 minutes left in the session. I was closing my office door when my patient, a middle-aged woman, rushed up and said: “I am sorry to be so late, but traffic was terrible. I am out of my meds. Will you still see me?” I agreed. She was touched and thanked me.

As she sat down, still breathless, she said: “I have had a lot on my mind. After we work out the meds, could we please talk about them? One thing is the climate problem, but there is really no point in worrying about something you cannot do anything about.”

I refilled her meds, then I responded to her offhand comment about climate by saying, “I, too, have been concerned about climate change. Tell me your concerns.” She opened up and, to my surprise, burst into tears, saying, “how terrible it is, what we’re doing to the earth, and how bad it will be for those to come. How could we leave the earth in such a mess?” She was clearly grieving. I agreed and said: “There is a lot to be done, and we can do many things to help. Have you heard about the Green New Deal?” We talked about this for a few minutes, and she was very interested.

At first, she disavowed the problem, saying that, while it bothered her, nothing could be done about it, so why talk about it? Disavowal is a common defense that shields us from our real feelings about disturbing problems. Once I invited her to talk about it, she opened up with grief and near paralyzing sadness. This was my opportunity to let her know that there is a realistic plan for dealing with climate change. If she were to get politically active or involved with like-minded groups, hope could be possible. (As young Greta Thunberg, the Swedish youth climate action leader, teaches us, “Where there is no action, there is no hope, but where there is action, hope is everywhere.”)

My patient was comforted by verbalizing her despair and heartened by my suggestions, especially some thoughts about the Green New Deal. So, what does a psychiatrist need to know about the Green New Deal?

It is essentially a broad legislative conceptual agenda with wide-ranging implications. The resolution has growing support in Congress. Its scope has been compared to the 1960s moon landing or the New Deal that helped this nation come out of the Great Depression. The primary goal is to bring the United States to 100% sustainable clean energy by 2030. It also proposes to help those most vulnerable to the stresses of climate change, such as “indigenous communities, communities of color, migrant communities, deinstitutionalized communities, depopulated communities, the poor, lower income workers, women, the elderly, the unhoused, people with disabilities, and youth.” Our patient population reflects many of those cohorts and will likely be helped directly by this ambitious agenda.

Specifically, the Green New Deal would transition the United States from fossil fuel dependence to clean energy sources, such as solar and wind power, upgrade the power grid, refurbish and retrofit buildings to become sustainable and energy efficient, overhaul transportation systems, and promote the transition to electric vehicles and high-speed rail. This transition of the infrastructure and economy will, in turn, create millions of good jobs, including meaningful and rewarding work for workers and communities transitioning away from fossil fuel industry–related activities.

The Green New Deal is intended to address the reality and risks of climate change. The World Health Organization has deemed climate change the greatest public health threat of the 21st century. Consider the following ominous developments:

The current atmospheric CO₂ level is 415 parts per million and rising, an increase from preindustrial levels of 278 ppm. Earthworms have now expanded their territory to include boreal forests near the Arctic, munching the foot-thick organic forest floor, potentially releasing much more CO₂. Permafrost is melting near the Arctic, as is sea ice, reducing the amount of solar radiation reflected back to space. Perversely and ironically, the loss of sea ice is touted by some climate deniers as an opportunity for expanded oil and gas exploration in the Arctic.

Extreme weather events are increasing in frequency and duration. Record-setting hurricanes, floods, tornadoes, heat waves, and wildfires are becoming the “new normal,” except for the fact that they are expected to continue worsening.

If the United States continues business as usual without addressing our climate trajectory, there will be dire consequences for all future generations. Without serious efforts to combat global warming, a 4- to 5-degree Celsius increase by the end of the century is likely. This would be catastrophic, leading to the collapse of the ice sheets, massive coastal inundation, unrelenting heat waves, wildfires beyond imagination, severe droughts, starvation, immense storms, and vast areas of the earth becoming uninhabitable.

It is time for the United States to join the rest of the world in dealing with global warming. The nations of the earth need to unite for the common good and to save our planet. The Green New Deal would represent a major step in that direction and would certainly help our patients to have more meaningful, hopeful, and healthier lives.
 

Dr. Peterson is assistant clinical professor in the department of psychiatry at Georgetown University in Washington. He is an active member of the Climate Psychiatry Alliance and the Caucus on Climate Change and Mental Health at the American Psychiatric Association. Dr. Peterson changed key facts about the patient’s story to protect her confidentiality.

Medicare beneficiaries charged the standard premium for Medicare Part B coverage will be paying $144.60 each month in 2020, up $9.10 from 2019.

anttohoho/Thinkstock

Deductibles also will increase to $198 next year, up $13 from the current year.

The Centers for Medicare & Medicaid Services said in a statement announcing the hikes that the increases are “largely due to rising spending on physician administered drugs. These higher costs have a ripple effect and result in higher Part B premiums and deductibles.”

The formal details on the premium and deductible increases have been posted online and are scheduled for publication in the Federal Register on Nov. 13.

The CMS and Congress are looking into a number of options to help contain the spending on drugs, including the use of an international pricing index to put U.S. spending more in line with the lower prices offered in foreign countries, automatic rebates when drug prices rise faster than the rate of inflation, and a modern take on the failed competitive acquisition program.

The agency also announced increases in the inpatient hospital deductible that will be paid under Medicare Part A when beneficiaries are admitted into a hospital in 2020. The deductible increases to $1,408 next year, up from $1,364 this year. The daily coinsurance for the 61st-90th day increases to $352 from $341, while the daily coinsurance for lifetime reserve days increases to $704 from $682.

Skilled nursing facility coinsurance also rises during this same time period to $176 from $170.50.

More information on Part A deductibles can be found here, while information on Part A premiums can be found here.

[email protected]

Medicare beneficiaries charged the standard premium for Medicare Part B coverage will be paying $144.60 each month in 2020, up $9.10 from 2019.

anttohoho/Thinkstock

Deductibles also will increase to $198 next year, up $13 from the current year.

The Centers for Medicare & Medicaid Services said in a statement announcing the hikes that the increases are “largely due to rising spending on physician administered drugs. These higher costs have a ripple effect and result in higher Part B premiums and deductibles.”

The formal details on the premium and deductible increases have been posted online and are scheduled for publication in the Federal Register on Nov. 13.

The CMS and Congress are looking into a number of options to help contain the spending on drugs, including the use of an international pricing index to put U.S. spending more in line with the lower prices offered in foreign countries, automatic rebates when drug prices rise faster than the rate of inflation, and a modern take on the failed competitive acquisition program.

The agency also announced increases in the inpatient hospital deductible that will be paid under Medicare Part A when beneficiaries are admitted into a hospital in 2020. The deductible increases to $1,408 next year, up from $1,364 this year. The daily coinsurance for the 61st-90th day increases to $352 from $341, while the daily coinsurance for lifetime reserve days increases to $704 from $682.

Skilled nursing facility coinsurance also rises during this same time period to $176 from $170.50.

More information on Part A deductibles can be found here, while information on Part A premiums can be found here.

[email protected]

Medicare beneficiaries charged the standard premium for Medicare Part B coverage will be paying $144.60 each month in 2020, up $9.10 from 2019.

anttohoho/Thinkstock

Deductibles also will increase to $198 next year, up $13 from the current year.

The Centers for Medicare & Medicaid Services said in a statement announcing the hikes that the increases are “largely due to rising spending on physician administered drugs. These higher costs have a ripple effect and result in higher Part B premiums and deductibles.”

The formal details on the premium and deductible increases have been posted online and are scheduled for publication in the Federal Register on Nov. 13.

The CMS and Congress are looking into a number of options to help contain the spending on drugs, including the use of an international pricing index to put U.S. spending more in line with the lower prices offered in foreign countries, automatic rebates when drug prices rise faster than the rate of inflation, and a modern take on the failed competitive acquisition program.

The agency also announced increases in the inpatient hospital deductible that will be paid under Medicare Part A when beneficiaries are admitted into a hospital in 2020. The deductible increases to $1,408 next year, up from $1,364 this year. The daily coinsurance for the 61st-90th day increases to $352 from $341, while the daily coinsurance for lifetime reserve days increases to $704 from $682.

Skilled nursing facility coinsurance also rises during this same time period to $176 from $170.50.

More information on Part A deductibles can be found here, while information on Part A premiums can be found here.

[email protected]

ATLANTA – Tumor necrosis factor inhibitors almost quadrupled the risk of psoriasis in children with inflammatory bowel disease, juvenile idiopathic arthritis, or chronic nonbacterial osteomyelitis in a review of 4,111 patients at the Children’s Hospital of Philadelphia.

The finding confirms a clinical suspicion that biologics can cause psoriasis in children, just as has been shown in adults, said lead investigator Lisa Buckley, MD, a rheumatology fellow at the hospital when she conducted the study, but now a pediatric rheumatologist at Vanderbilt University, Nashville, Tenn. The study was recently published in Arthritis Care & Research.

“I don’t think this will change my prescribing habits” because tumor necrosis factor inhibitors (TNFi) are so useful, but “what this will change is how much information I give to families about the risk of psoriasis, especially in kids with a family history,” which also predisposed children in the study to psoriasis, Dr. Buckley said . “Anecdotally, psoriasis has not been part of the traditional risk-benefit conversation with families. This has added that to my” discussion, he added.

TNFi “psoriasis can be a really big deal for these children, especially in adolescence. They don’t want to go to school and things like that. Children and parents often prioritize [it] over the underlying disease,” she said.

For now, how to best manage TNFi psoriasis is uncertain. Children often are in remission when it starts, and a decision has to be made whether to discontinue treatment, reduce the dose, or add something for the psoriasis. There are no clear answers at the moment. “This is the beginning of the beginning of studies looking at this. It just proves that there actually is a problem,” Dr. Buckley said at the annual meeting of the American College of Rheumatology.

About three-quarters of the children had inflammatory bowel disease, and most of the rest had juvenile idiopathic arthritis. Just 2% had chronic nonbacterial osteomyelitis. Billing codes were used to confirm diagnosis, new-onset psoriasis, and incident TNFi exposure, defined as at least one prescription for adalimumab, etanercept, or infliximab.

Overall, 1,614 children (39%) were treated with a TNFi and 2,497 (61%) were not. There were 58 cases of psoriasis in the TNFi group for an incidence ratio of 12.3 cases per 1,000 person-years, and a standard IR – observed psoriasis cases over expected cases in the general pediatrics population – of 30.

There were 25 cases among children not treated with a TNFi, for an IR of 3.8 per 1,000 person-years and SIR of 9.3.

In the end, TNFi exposure was associated with a marked increase in psoriasis risk (hazard ratio, 3.84; 95% confidence interval, 2.28-6.47; P less than .001). Family history was positive in 8% of subjects and was a known risk factor; it was the only other independent predictor (HR, 3.11; 95% CI, 1.79-5.41; P less than .001).

Obesity, which was linked in previous studies to psoriasis and was higher in the non-TNFI group, did not influence risk, nor did methotrexate, which was also used more commonly in the TNFi group. “We thought that including patients on methotrexate, which is a treatment for psoriasis, might have altered the outcomes, but it didn’t seem to make any difference in developing psoriasis,” Dr. Buckley said.

It’s possible that children on a TNFi had higher disease activity, and that in itself increased the risk of psoriasis, but there isn’t an association in the literature between high disease activity and psoriasis, she said. In past reports, TNFi-induced psoriasis was most likely to occur in adults who were in disease remission.

Subjects were aged about 11 years on average and about equally split between boys and girls; three-quarters were white. Children previously diagnosed with psoriasis were excluded. Average follow up was about 2 years.

The National Institutes of Health funded the work. The investigators didn’t report any relevant disclosures.

[email protected]

SOURCE: Buckley L et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1816.

ATLANTA – Tumor necrosis factor inhibitors almost quadrupled the risk of psoriasis in children with inflammatory bowel disease, juvenile idiopathic arthritis, or chronic nonbacterial osteomyelitis in a review of 4,111 patients at the Children’s Hospital of Philadelphia.

The finding confirms a clinical suspicion that biologics can cause psoriasis in children, just as has been shown in adults, said lead investigator Lisa Buckley, MD, a rheumatology fellow at the hospital when she conducted the study, but now a pediatric rheumatologist at Vanderbilt University, Nashville, Tenn. The study was recently published in Arthritis Care & Research.

“I don’t think this will change my prescribing habits” because tumor necrosis factor inhibitors (TNFi) are so useful, but “what this will change is how much information I give to families about the risk of psoriasis, especially in kids with a family history,” which also predisposed children in the study to psoriasis, Dr. Buckley said . “Anecdotally, psoriasis has not been part of the traditional risk-benefit conversation with families. This has added that to my” discussion, he added.

TNFi “psoriasis can be a really big deal for these children, especially in adolescence. They don’t want to go to school and things like that. Children and parents often prioritize [it] over the underlying disease,” she said.

For now, how to best manage TNFi psoriasis is uncertain. Children often are in remission when it starts, and a decision has to be made whether to discontinue treatment, reduce the dose, or add something for the psoriasis. There are no clear answers at the moment. “This is the beginning of the beginning of studies looking at this. It just proves that there actually is a problem,” Dr. Buckley said at the annual meeting of the American College of Rheumatology.

About three-quarters of the children had inflammatory bowel disease, and most of the rest had juvenile idiopathic arthritis. Just 2% had chronic nonbacterial osteomyelitis. Billing codes were used to confirm diagnosis, new-onset psoriasis, and incident TNFi exposure, defined as at least one prescription for adalimumab, etanercept, or infliximab.

Overall, 1,614 children (39%) were treated with a TNFi and 2,497 (61%) were not. There were 58 cases of psoriasis in the TNFi group for an incidence ratio of 12.3 cases per 1,000 person-years, and a standard IR – observed psoriasis cases over expected cases in the general pediatrics population – of 30.

There were 25 cases among children not treated with a TNFi, for an IR of 3.8 per 1,000 person-years and SIR of 9.3.

In the end, TNFi exposure was associated with a marked increase in psoriasis risk (hazard ratio, 3.84; 95% confidence interval, 2.28-6.47; P less than .001). Family history was positive in 8% of subjects and was a known risk factor; it was the only other independent predictor (HR, 3.11; 95% CI, 1.79-5.41; P less than .001).

Obesity, which was linked in previous studies to psoriasis and was higher in the non-TNFI group, did not influence risk, nor did methotrexate, which was also used more commonly in the TNFi group. “We thought that including patients on methotrexate, which is a treatment for psoriasis, might have altered the outcomes, but it didn’t seem to make any difference in developing psoriasis,” Dr. Buckley said.

It’s possible that children on a TNFi had higher disease activity, and that in itself increased the risk of psoriasis, but there isn’t an association in the literature between high disease activity and psoriasis, she said. In past reports, TNFi-induced psoriasis was most likely to occur in adults who were in disease remission.

Subjects were aged about 11 years on average and about equally split between boys and girls; three-quarters were white. Children previously diagnosed with psoriasis were excluded. Average follow up was about 2 years.

The National Institutes of Health funded the work. The investigators didn’t report any relevant disclosures.

[email protected]

SOURCE: Buckley L et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1816.

ATLANTA – Tumor necrosis factor inhibitors almost quadrupled the risk of psoriasis in children with inflammatory bowel disease, juvenile idiopathic arthritis, or chronic nonbacterial osteomyelitis in a review of 4,111 patients at the Children’s Hospital of Philadelphia.

The finding confirms a clinical suspicion that biologics can cause psoriasis in children, just as has been shown in adults, said lead investigator Lisa Buckley, MD, a rheumatology fellow at the hospital when she conducted the study, but now a pediatric rheumatologist at Vanderbilt University, Nashville, Tenn. The study was recently published in Arthritis Care & Research.

“I don’t think this will change my prescribing habits” because tumor necrosis factor inhibitors (TNFi) are so useful, but “what this will change is how much information I give to families about the risk of psoriasis, especially in kids with a family history,” which also predisposed children in the study to psoriasis, Dr. Buckley said . “Anecdotally, psoriasis has not been part of the traditional risk-benefit conversation with families. This has added that to my” discussion, he added.

TNFi “psoriasis can be a really big deal for these children, especially in adolescence. They don’t want to go to school and things like that. Children and parents often prioritize [it] over the underlying disease,” she said.

For now, how to best manage TNFi psoriasis is uncertain. Children often are in remission when it starts, and a decision has to be made whether to discontinue treatment, reduce the dose, or add something for the psoriasis. There are no clear answers at the moment. “This is the beginning of the beginning of studies looking at this. It just proves that there actually is a problem,” Dr. Buckley said at the annual meeting of the American College of Rheumatology.

About three-quarters of the children had inflammatory bowel disease, and most of the rest had juvenile idiopathic arthritis. Just 2% had chronic nonbacterial osteomyelitis. Billing codes were used to confirm diagnosis, new-onset psoriasis, and incident TNFi exposure, defined as at least one prescription for adalimumab, etanercept, or infliximab.

Overall, 1,614 children (39%) were treated with a TNFi and 2,497 (61%) were not. There were 58 cases of psoriasis in the TNFi group for an incidence ratio of 12.3 cases per 1,000 person-years, and a standard IR – observed psoriasis cases over expected cases in the general pediatrics population – of 30.

There were 25 cases among children not treated with a TNFi, for an IR of 3.8 per 1,000 person-years and SIR of 9.3.

In the end, TNFi exposure was associated with a marked increase in psoriasis risk (hazard ratio, 3.84; 95% confidence interval, 2.28-6.47; P less than .001). Family history was positive in 8% of subjects and was a known risk factor; it was the only other independent predictor (HR, 3.11; 95% CI, 1.79-5.41; P less than .001).

Obesity, which was linked in previous studies to psoriasis and was higher in the non-TNFI group, did not influence risk, nor did methotrexate, which was also used more commonly in the TNFi group. “We thought that including patients on methotrexate, which is a treatment for psoriasis, might have altered the outcomes, but it didn’t seem to make any difference in developing psoriasis,” Dr. Buckley said.

It’s possible that children on a TNFi had higher disease activity, and that in itself increased the risk of psoriasis, but there isn’t an association in the literature between high disease activity and psoriasis, she said. In past reports, TNFi-induced psoriasis was most likely to occur in adults who were in disease remission.

Subjects were aged about 11 years on average and about equally split between boys and girls; three-quarters were white. Children previously diagnosed with psoriasis were excluded. Average follow up was about 2 years.

The National Institutes of Health funded the work. The investigators didn’t report any relevant disclosures.

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SOURCE: Buckley L et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1816.