Randy Dotinga

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

A version of this article first appeared on Medscape.com.

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

A version of this article first appeared on Medscape.com.

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

A version of this article first appeared on Medscape.com.

CHICAGO—While it’s extremely difficult to link cancer rates to military service, researchers are starting to get some initial inklings of possible connections, a US Department of Veterans Affairs (VA) oncologist told an audience at the 2023 annual meeting of the Association of VA Hematology/Oncology.

One study found surprising levels of abnormal proteins and cancer in the blood of service members, said Christin DeStefano, MD, of David Grant US Air Force Medical Center at Travis Air Force Base in California. Another may have uncovered a link between military trauma and lymphoma. And an analysis of pilots found they have higher rates of certain kinds of cancer— but lower levels of other cancer types.

“It is hard to tell if service-related exposures heighten the risk of cancer. Some aspects of military service might increase cancer risk,” DeStefano said. “But other aspects of military service might decrease cancer risk.”

The VA has been especially focused on the possible link between military service and cancer since the passage of the PACT Act in 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and it’s sparked more than 4.1 million free toxic-exposure screenings for veterans.

VA Under Secretary for Health Shereef Elnahal, MD, MBA, noted in the keynote address at the 2023 AVAHO annual meeting that “Every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts.”

DeStefano noted that there are a variety of challenges to analyzing data regarding connections between military exposure and cancer. For one, “it’s hard to include people from the time they enter the military to postmilitary service. Some are getting their health care in the civilian health care systems.” In addition, “There are a lot of problems with ICD-9 and ICD-10 codes, which can be very erroneous. Maybe somebody came in with a mass, the doctor or the nurse practitioner was busy and they put down ‘suspected cancer,’ and now they have that ICD code in their chart where they never actually had cancer.” This is why more reliable cancer registries are so important, she said.

Another challenge is figuring out when exposures occurred and whether they actually occurred in the military at all. “There are multiple studies suggesting that a first driver event is often acquired 20 to 40 years before a cancer diagnosis, often in one’s 20s and 30s,” she said. “It's hard to quantify an exposure, since there can be exposures before military service and exposures after military service. The amount of exposure and duration of exposure might differ, and individuals might metabolize the exposures differently from each other.”

To make matters more complicated, research is pointing in surprising directions. DeStefano highlighted her not-yet-published study of monoclonal gammopathy (MG), a condition in which abnormal proteins are found in the blood, in 534 service members. MG can be a cancer precursor. Those exposed to burn pits in Iraq had similar risks of MG (6.7%) vs an unexposed, matched control group (5.4%; P = .22), Dr. DeStefano said. Over a mean follow-up of 14 years and 10 years, respectively, 7% of participants in each group developed cancer.

“You might think, ‘this is a negative study. There's no difference.’ However, it is very notable that the prevalence of monoclonal gammopathy was 6.1%. That is 3 times as high as we would expect in somebody in their 40s,” she said. “Also, 7% having a cancer diagnosis is not insignificant.” She added: “It is very possible that many of these service members already have full-blown multiple myeloma or something associated with monoclonal gammopathy that just has not been diagnosed yet.”

In another study, this one published in 2021, Dr. DeStefano and colleagues tracked 8834 injured Iraq/Afghanistan veterans and compared them with matched controls to see if there was a link between severe trauma and cancer. There wasn’t  except for lymphoma (22 vs 7 cases, respectively; odds ratio = 3.1; 95% CI, 1.34-7.37; P = .008). The connection remained after adjustment for confounders.

What’s going on? “It’s possible that blast injury might induce some alterations to the immune system that might set the stage for lymphoma genesis,” she said. “Or maybe that blast injury is a surrogate for a toxic exposure: Maybe carcinogens are released during a blast injury.”

Dr. DeStefano also highlighted a 2022 study that tracked 386,190 Air Force officers. The study found that combat pilots (9.1% of the total) had greater adjusted odds of testicular and prostate cancers and melanoma than the other officers. Why? “Military pilots have exposure to cosmic ionizing radiation as well as ultraviolet radiation,” she said.

But while “these are scary, sobering things,” she noted that combat pilots were less likely to develop several cancers than the general population, including kidney, testicular, colorectal, bladder and thyroid cancer, and they were less likely to die from colorectal cancer.

CHICAGO—While it’s extremely difficult to link cancer rates to military service, researchers are starting to get some initial inklings of possible connections, a US Department of Veterans Affairs (VA) oncologist told an audience at the 2023 annual meeting of the Association of VA Hematology/Oncology.

One study found surprising levels of abnormal proteins and cancer in the blood of service members, said Christin DeStefano, MD, of David Grant US Air Force Medical Center at Travis Air Force Base in California. Another may have uncovered a link between military trauma and lymphoma. And an analysis of pilots found they have higher rates of certain kinds of cancer— but lower levels of other cancer types.

“It is hard to tell if service-related exposures heighten the risk of cancer. Some aspects of military service might increase cancer risk,” DeStefano said. “But other aspects of military service might decrease cancer risk.”

The VA has been especially focused on the possible link between military service and cancer since the passage of the PACT Act in 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and it’s sparked more than 4.1 million free toxic-exposure screenings for veterans.

VA Under Secretary for Health Shereef Elnahal, MD, MBA, noted in the keynote address at the 2023 AVAHO annual meeting that “Every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts.”

DeStefano noted that there are a variety of challenges to analyzing data regarding connections between military exposure and cancer. For one, “it’s hard to include people from the time they enter the military to postmilitary service. Some are getting their health care in the civilian health care systems.” In addition, “There are a lot of problems with ICD-9 and ICD-10 codes, which can be very erroneous. Maybe somebody came in with a mass, the doctor or the nurse practitioner was busy and they put down ‘suspected cancer,’ and now they have that ICD code in their chart where they never actually had cancer.” This is why more reliable cancer registries are so important, she said.

Another challenge is figuring out when exposures occurred and whether they actually occurred in the military at all. “There are multiple studies suggesting that a first driver event is often acquired 20 to 40 years before a cancer diagnosis, often in one’s 20s and 30s,” she said. “It's hard to quantify an exposure, since there can be exposures before military service and exposures after military service. The amount of exposure and duration of exposure might differ, and individuals might metabolize the exposures differently from each other.”

To make matters more complicated, research is pointing in surprising directions. DeStefano highlighted her not-yet-published study of monoclonal gammopathy (MG), a condition in which abnormal proteins are found in the blood, in 534 service members. MG can be a cancer precursor. Those exposed to burn pits in Iraq had similar risks of MG (6.7%) vs an unexposed, matched control group (5.4%; P = .22), Dr. DeStefano said. Over a mean follow-up of 14 years and 10 years, respectively, 7% of participants in each group developed cancer.

“You might think, ‘this is a negative study. There's no difference.’ However, it is very notable that the prevalence of monoclonal gammopathy was 6.1%. That is 3 times as high as we would expect in somebody in their 40s,” she said. “Also, 7% having a cancer diagnosis is not insignificant.” She added: “It is very possible that many of these service members already have full-blown multiple myeloma or something associated with monoclonal gammopathy that just has not been diagnosed yet.”

In another study, this one published in 2021, Dr. DeStefano and colleagues tracked 8834 injured Iraq/Afghanistan veterans and compared them with matched controls to see if there was a link between severe trauma and cancer. There wasn’t  except for lymphoma (22 vs 7 cases, respectively; odds ratio = 3.1; 95% CI, 1.34-7.37; P = .008). The connection remained after adjustment for confounders.

What’s going on? “It’s possible that blast injury might induce some alterations to the immune system that might set the stage for lymphoma genesis,” she said. “Or maybe that blast injury is a surrogate for a toxic exposure: Maybe carcinogens are released during a blast injury.”

Dr. DeStefano also highlighted a 2022 study that tracked 386,190 Air Force officers. The study found that combat pilots (9.1% of the total) had greater adjusted odds of testicular and prostate cancers and melanoma than the other officers. Why? “Military pilots have exposure to cosmic ionizing radiation as well as ultraviolet radiation,” she said.

But while “these are scary, sobering things,” she noted that combat pilots were less likely to develop several cancers than the general population, including kidney, testicular, colorectal, bladder and thyroid cancer, and they were less likely to die from colorectal cancer.

CHICAGO—While it’s extremely difficult to link cancer rates to military service, researchers are starting to get some initial inklings of possible connections, a US Department of Veterans Affairs (VA) oncologist told an audience at the 2023 annual meeting of the Association of VA Hematology/Oncology.

One study found surprising levels of abnormal proteins and cancer in the blood of service members, said Christin DeStefano, MD, of David Grant US Air Force Medical Center at Travis Air Force Base in California. Another may have uncovered a link between military trauma and lymphoma. And an analysis of pilots found they have higher rates of certain kinds of cancer— but lower levels of other cancer types.

“It is hard to tell if service-related exposures heighten the risk of cancer. Some aspects of military service might increase cancer risk,” DeStefano said. “But other aspects of military service might decrease cancer risk.”

The VA has been especially focused on the possible link between military service and cancer since the passage of the PACT Act in 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and it’s sparked more than 4.1 million free toxic-exposure screenings for veterans.

VA Under Secretary for Health Shereef Elnahal, MD, MBA, noted in the keynote address at the 2023 AVAHO annual meeting that “Every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts.”

DeStefano noted that there are a variety of challenges to analyzing data regarding connections between military exposure and cancer. For one, “it’s hard to include people from the time they enter the military to postmilitary service. Some are getting their health care in the civilian health care systems.” In addition, “There are a lot of problems with ICD-9 and ICD-10 codes, which can be very erroneous. Maybe somebody came in with a mass, the doctor or the nurse practitioner was busy and they put down ‘suspected cancer,’ and now they have that ICD code in their chart where they never actually had cancer.” This is why more reliable cancer registries are so important, she said.

Another challenge is figuring out when exposures occurred and whether they actually occurred in the military at all. “There are multiple studies suggesting that a first driver event is often acquired 20 to 40 years before a cancer diagnosis, often in one’s 20s and 30s,” she said. “It's hard to quantify an exposure, since there can be exposures before military service and exposures after military service. The amount of exposure and duration of exposure might differ, and individuals might metabolize the exposures differently from each other.”

To make matters more complicated, research is pointing in surprising directions. DeStefano highlighted her not-yet-published study of monoclonal gammopathy (MG), a condition in which abnormal proteins are found in the blood, in 534 service members. MG can be a cancer precursor. Those exposed to burn pits in Iraq had similar risks of MG (6.7%) vs an unexposed, matched control group (5.4%; P = .22), Dr. DeStefano said. Over a mean follow-up of 14 years and 10 years, respectively, 7% of participants in each group developed cancer.

“You might think, ‘this is a negative study. There's no difference.’ However, it is very notable that the prevalence of monoclonal gammopathy was 6.1%. That is 3 times as high as we would expect in somebody in their 40s,” she said. “Also, 7% having a cancer diagnosis is not insignificant.” She added: “It is very possible that many of these service members already have full-blown multiple myeloma or something associated with monoclonal gammopathy that just has not been diagnosed yet.”

In another study, this one published in 2021, Dr. DeStefano and colleagues tracked 8834 injured Iraq/Afghanistan veterans and compared them with matched controls to see if there was a link between severe trauma and cancer. There wasn’t  except for lymphoma (22 vs 7 cases, respectively; odds ratio = 3.1; 95% CI, 1.34-7.37; P = .008). The connection remained after adjustment for confounders.

What’s going on? “It’s possible that blast injury might induce some alterations to the immune system that might set the stage for lymphoma genesis,” she said. “Or maybe that blast injury is a surrogate for a toxic exposure: Maybe carcinogens are released during a blast injury.”

Dr. DeStefano also highlighted a 2022 study that tracked 386,190 Air Force officers. The study found that combat pilots (9.1% of the total) had greater adjusted odds of testicular and prostate cancers and melanoma than the other officers. Why? “Military pilots have exposure to cosmic ionizing radiation as well as ultraviolet radiation,” she said.

But while “these are scary, sobering things,” she noted that combat pilots were less likely to develop several cancers than the general population, including kidney, testicular, colorectal, bladder and thyroid cancer, and they were less likely to die from colorectal cancer.

MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. Evidence suggests that MS doesn’t disrupt fertility, pregnancy, birth, or lactation. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.

Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.

Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.

While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”

But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”

Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.

The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.

What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”

For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.

Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.

MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. Evidence suggests that MS doesn’t disrupt fertility, pregnancy, birth, or lactation. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.

Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.

Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.

While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”

But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”

Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.

The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.

What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”

For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.

Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.

MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. Evidence suggests that MS doesn’t disrupt fertility, pregnancy, birth, or lactation. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.

Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.

Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.

While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”

But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”

Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.

The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.

What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”

For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.

Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.

MILAN – An analysis of medical records of patients diagnosed with neuromyelitis optica spectrum disorder (NMO) found that many may be misdiagnosed: 47% had diagnoses listed for both NMO and multiple sclerosis (MS), a similar disease that requires different treatment, according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.

“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.

“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.

“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”

As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”

He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”

Exploring the reasons for misdiagnosis

Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”

For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.

ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.

The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.

Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.

Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.

Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”

As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.

What does it all mean?

As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”

Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.” 

In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”

“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”

The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.

MILAN – An analysis of medical records of patients diagnosed with neuromyelitis optica spectrum disorder (NMO) found that many may be misdiagnosed: 47% had diagnoses listed for both NMO and multiple sclerosis (MS), a similar disease that requires different treatment, according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.

“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.

“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.

“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”

As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”

He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”

Exploring the reasons for misdiagnosis

Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”

For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.

ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.

The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.

Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.

Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.

Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”

As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.

What does it all mean?

As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”

Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.” 

In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”

“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”

The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.

MILAN – An analysis of medical records of patients diagnosed with neuromyelitis optica spectrum disorder (NMO) found that many may be misdiagnosed: 47% had diagnoses listed for both NMO and multiple sclerosis (MS), a similar disease that requires different treatment, according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.

“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.

“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.

“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”

As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”

He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”

Exploring the reasons for misdiagnosis

Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”

For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.

ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.

The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.

Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.

Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.

Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”

As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.

What does it all mean?

As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”

Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.” 

In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”

“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”

The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.

MILAN – Two physicians agreed that there’s no doubt that Epstein-Barr virus (EBV) is deeply linked to multiple sclerosis (MS), but they diverged over the extent of its role in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.

Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”

As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
 

A rare complication of EBV infection

In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.

The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”

Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).

Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.

Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.

In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
 

Inadequate evidence for causation

In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”

And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.

He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
 

A missing piece of the puzzle?

In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.

What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
 

MILAN – Two physicians agreed that there’s no doubt that Epstein-Barr virus (EBV) is deeply linked to multiple sclerosis (MS), but they diverged over the extent of its role in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.

Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”

As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
 

A rare complication of EBV infection

In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.

The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”

Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).

Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.

Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.

In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
 

Inadequate evidence for causation

In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”

And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.

He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
 

A missing piece of the puzzle?

In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.

What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
 

MILAN – Two physicians agreed that there’s no doubt that Epstein-Barr virus (EBV) is deeply linked to multiple sclerosis (MS), but they diverged over the extent of its role in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.

Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”

As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
 

A rare complication of EBV infection

In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.

The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”

Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).

Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.

Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.

In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
 

Inadequate evidence for causation

In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”

And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.

He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
 

A missing piece of the puzzle?

In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.

What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
 

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

CHICAGO—The VA could save nearly $10,000 annually per patient in the Mountain West region referral area by administering lower-level hematology/oncology care within the system instead of in the community, according to a new analysis.

The findings reflect that the community care encouraged by the MISSION Act is more expensive than US Department of Veterans Affairs (VA) care, said report lead author Alyson Clough, PharmD, a clinical pharmacy specialist with the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah, in an interview. Clough and colleagues presented the poster at the 2023 annual meeting of the Association of VA Hematology/Oncology.

The 2018 MISSION Act expanded the eligibility for non-VA community services within the VA. “If a veteran requires care that a VA cannot provide in-house, lives in a state/territory without a full-service VAMC, and/or lives further than a certain distance/time from a VA Medical Center, then the veteran may be eligible to receive care in the community,” Clough said.

For the new analysis, the researchers focused on the Salt Lake City VAMC referral area, which spans about 125,000 square miles in Utah, Idaho, and Nevada. “While the MISSION Act helped give those veterans more options for specialty care—including hematology/oncology—many veterans are still driving several hours on a routine basis for chemotherapy treatment and injection therapies, even in the community setting,” Clough explained.

The researchers looked at the costs of “low-risk cancer care,” which Clough said consists of “chemotherapy or immunotherapy that is less likely to cause significant side effects during the infusion, is typically nonhazardous, and/or can be administered via a short infusion [30 minutes or less] or an injection.”

In fiscal year 2022, the VA paid more than $5.7 million for community care services for 380 veterans in the referral area, about $15,060 each, according to the analysis. In contrast, the average cost for 1774 veterans within the VA system was $5424. “By retaining or re-establishing hematology/oncology veteran care within VA, we estimate cost savings of approximately $9636 per unique veteran.”

Specifically, the researchers wrote that the average care costs were $5297 per veteran in the community vs $1143 at the VA, and average drug costs were $9763 per veteran in the community vs $4281 in the VA. These amount to total costs of $15,060 per veteran in the community vs $5424 in the VA.

Low-risk services “are ideal to bring to more isolated regions,” Clough noted. “Traveling and/or finding accommodations for pets can be very difficult for veterans during chemotherapy treatments. Bringing care to the veteran increases veteran convenience, reduces need for transportation, reduces out-of-pocket cost to the veteran, and can improve care coordination.”

It’s not clear why VA care is cheaper than community care, she said, “but it may be related to the [higher] patient volumes we see in our VA facilities.” Lower overhead costs and government pricing contracts for chemotherapies/injectables could also be factors, Clough explained. In an interview, Todd Wagner, PhD, Stanford University Professor in the Department of Surgery and Director of the Health Economics Research Center at the VA, said the analysis needs risk adjustment for cancer severity and other illnesses and comorbidities that could affect cancer treatment. “In our work, sicker veterans get care in VA, and healthier veterans are choosing VA-purchased care [in the community].”

He noted that in the new analysis, the VA care looks much cheaper. “I'm struggling with that result: It flies in the face of our past work,” he said. He added that an analysis should also look at surgery and radiation. “VA has a tradition of providing high-value medications at a lower cost. But VA’s costs of surgery and radiation tend to be more expensive.”

Clough does not plan more research in this area. For now, she said, her site is working to expand to include infusion clinics at local VA community-based outpatient clinics as part of the Close to Me program. The program, launched by the VA in 2022, aims to provide cancer services at community-based outpatient clinics, mobile infusion units, and patient homes.

“As part of this service, we are looking to maximize video-based and phone visits between our existing oncology staff and veterans living in more isolated areas, coordinate labs/imaging locally, and deliver infusion and/or injectable therapies to the veteran,” Clough said.

In addition, she said, “We currently have a dedicated hematology/oncology trained pharmacist and 2 infusion nurses working to expand the service and deliver veteran care in these remote areas.”

There was no funding for this study, and the authors have no disclosures. Wagner discloses grant funding to his institutions from the VA, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, and the Heinz Foundation. 

CHICAGO—The VA could save nearly $10,000 annually per patient in the Mountain West region referral area by administering lower-level hematology/oncology care within the system instead of in the community, according to a new analysis.

The findings reflect that the community care encouraged by the MISSION Act is more expensive than US Department of Veterans Affairs (VA) care, said report lead author Alyson Clough, PharmD, a clinical pharmacy specialist with the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah, in an interview. Clough and colleagues presented the poster at the 2023 annual meeting of the Association of VA Hematology/Oncology.

The 2018 MISSION Act expanded the eligibility for non-VA community services within the VA. “If a veteran requires care that a VA cannot provide in-house, lives in a state/territory without a full-service VAMC, and/or lives further than a certain distance/time from a VA Medical Center, then the veteran may be eligible to receive care in the community,” Clough said.

For the new analysis, the researchers focused on the Salt Lake City VAMC referral area, which spans about 125,000 square miles in Utah, Idaho, and Nevada. “While the MISSION Act helped give those veterans more options for specialty care—including hematology/oncology—many veterans are still driving several hours on a routine basis for chemotherapy treatment and injection therapies, even in the community setting,” Clough explained.

The researchers looked at the costs of “low-risk cancer care,” which Clough said consists of “chemotherapy or immunotherapy that is less likely to cause significant side effects during the infusion, is typically nonhazardous, and/or can be administered via a short infusion [30 minutes or less] or an injection.”

In fiscal year 2022, the VA paid more than $5.7 million for community care services for 380 veterans in the referral area, about $15,060 each, according to the analysis. In contrast, the average cost for 1774 veterans within the VA system was $5424. “By retaining or re-establishing hematology/oncology veteran care within VA, we estimate cost savings of approximately $9636 per unique veteran.”

Specifically, the researchers wrote that the average care costs were $5297 per veteran in the community vs $1143 at the VA, and average drug costs were $9763 per veteran in the community vs $4281 in the VA. These amount to total costs of $15,060 per veteran in the community vs $5424 in the VA.

Low-risk services “are ideal to bring to more isolated regions,” Clough noted. “Traveling and/or finding accommodations for pets can be very difficult for veterans during chemotherapy treatments. Bringing care to the veteran increases veteran convenience, reduces need for transportation, reduces out-of-pocket cost to the veteran, and can improve care coordination.”

It’s not clear why VA care is cheaper than community care, she said, “but it may be related to the [higher] patient volumes we see in our VA facilities.” Lower overhead costs and government pricing contracts for chemotherapies/injectables could also be factors, Clough explained. In an interview, Todd Wagner, PhD, Stanford University Professor in the Department of Surgery and Director of the Health Economics Research Center at the VA, said the analysis needs risk adjustment for cancer severity and other illnesses and comorbidities that could affect cancer treatment. “In our work, sicker veterans get care in VA, and healthier veterans are choosing VA-purchased care [in the community].”

He noted that in the new analysis, the VA care looks much cheaper. “I'm struggling with that result: It flies in the face of our past work,” he said. He added that an analysis should also look at surgery and radiation. “VA has a tradition of providing high-value medications at a lower cost. But VA’s costs of surgery and radiation tend to be more expensive.”

Clough does not plan more research in this area. For now, she said, her site is working to expand to include infusion clinics at local VA community-based outpatient clinics as part of the Close to Me program. The program, launched by the VA in 2022, aims to provide cancer services at community-based outpatient clinics, mobile infusion units, and patient homes.

“As part of this service, we are looking to maximize video-based and phone visits between our existing oncology staff and veterans living in more isolated areas, coordinate labs/imaging locally, and deliver infusion and/or injectable therapies to the veteran,” Clough said.

In addition, she said, “We currently have a dedicated hematology/oncology trained pharmacist and 2 infusion nurses working to expand the service and deliver veteran care in these remote areas.”

There was no funding for this study, and the authors have no disclosures. Wagner discloses grant funding to his institutions from the VA, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, and the Heinz Foundation. 

CHICAGO—The VA could save nearly $10,000 annually per patient in the Mountain West region referral area by administering lower-level hematology/oncology care within the system instead of in the community, according to a new analysis.

The findings reflect that the community care encouraged by the MISSION Act is more expensive than US Department of Veterans Affairs (VA) care, said report lead author Alyson Clough, PharmD, a clinical pharmacy specialist with the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah, in an interview. Clough and colleagues presented the poster at the 2023 annual meeting of the Association of VA Hematology/Oncology.

The 2018 MISSION Act expanded the eligibility for non-VA community services within the VA. “If a veteran requires care that a VA cannot provide in-house, lives in a state/territory without a full-service VAMC, and/or lives further than a certain distance/time from a VA Medical Center, then the veteran may be eligible to receive care in the community,” Clough said.

For the new analysis, the researchers focused on the Salt Lake City VAMC referral area, which spans about 125,000 square miles in Utah, Idaho, and Nevada. “While the MISSION Act helped give those veterans more options for specialty care—including hematology/oncology—many veterans are still driving several hours on a routine basis for chemotherapy treatment and injection therapies, even in the community setting,” Clough explained.

The researchers looked at the costs of “low-risk cancer care,” which Clough said consists of “chemotherapy or immunotherapy that is less likely to cause significant side effects during the infusion, is typically nonhazardous, and/or can be administered via a short infusion [30 minutes or less] or an injection.”

In fiscal year 2022, the VA paid more than $5.7 million for community care services for 380 veterans in the referral area, about $15,060 each, according to the analysis. In contrast, the average cost for 1774 veterans within the VA system was $5424. “By retaining or re-establishing hematology/oncology veteran care within VA, we estimate cost savings of approximately $9636 per unique veteran.”

Specifically, the researchers wrote that the average care costs were $5297 per veteran in the community vs $1143 at the VA, and average drug costs were $9763 per veteran in the community vs $4281 in the VA. These amount to total costs of $15,060 per veteran in the community vs $5424 in the VA.

Low-risk services “are ideal to bring to more isolated regions,” Clough noted. “Traveling and/or finding accommodations for pets can be very difficult for veterans during chemotherapy treatments. Bringing care to the veteran increases veteran convenience, reduces need for transportation, reduces out-of-pocket cost to the veteran, and can improve care coordination.”

It’s not clear why VA care is cheaper than community care, she said, “but it may be related to the [higher] patient volumes we see in our VA facilities.” Lower overhead costs and government pricing contracts for chemotherapies/injectables could also be factors, Clough explained. In an interview, Todd Wagner, PhD, Stanford University Professor in the Department of Surgery and Director of the Health Economics Research Center at the VA, said the analysis needs risk adjustment for cancer severity and other illnesses and comorbidities that could affect cancer treatment. “In our work, sicker veterans get care in VA, and healthier veterans are choosing VA-purchased care [in the community].”

He noted that in the new analysis, the VA care looks much cheaper. “I'm struggling with that result: It flies in the face of our past work,” he said. He added that an analysis should also look at surgery and radiation. “VA has a tradition of providing high-value medications at a lower cost. But VA’s costs of surgery and radiation tend to be more expensive.”

Clough does not plan more research in this area. For now, she said, her site is working to expand to include infusion clinics at local VA community-based outpatient clinics as part of the Close to Me program. The program, launched by the VA in 2022, aims to provide cancer services at community-based outpatient clinics, mobile infusion units, and patient homes.

“As part of this service, we are looking to maximize video-based and phone visits between our existing oncology staff and veterans living in more isolated areas, coordinate labs/imaging locally, and deliver infusion and/or injectable therapies to the veteran,” Clough said.

In addition, she said, “We currently have a dedicated hematology/oncology trained pharmacist and 2 infusion nurses working to expand the service and deliver veteran care in these remote areas.”

There was no funding for this study, and the authors have no disclosures. Wagner discloses grant funding to his institutions from the VA, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, and the Heinz Foundation. 

MILAN – While multiple sclerosis (MS) is “one of two or three great success stories of modern molecular medicine,” we’re still only “halfway home,” University of California, San Francisco, neurology professor Stephen Hauser, MD, told colleagues in a highlighted lecture at the 9th Joint ECTRIMS-ACTRIMS meeting.

Going forward, the MS field should emphasize identifying early biomarkers of MS, Dr. Hauser said.

He noted that many experts had anticipated “that, if we could intervene early in the relapsing phase of the disease, we would stabilize neurodegeneration and patient disability. But one of the big surprises was that that was not the case. Instead, the observed course was that by silencing relapses and focal inflammation, a clinically silent, slow, insidious progression continues during the relapsing phase of disease in patients who are not having ongoing relapses.”

Even as focal activity detected via MRI is silenced, “progression continues” he said. “This remains the great unsolved challenge.”

Dr. Hauser asked colleagues to consider a three-stage model of MS that begins with benign autoimmunity followed by pathogenic autoimmunity with subclinical tissue damage. The third stage is clinical autoimmunity.

How can you determine who’s at risk? Genetics can only fill in part of the picture because they can’t pinpoint exactly who’s likely to develop the disease. “In other autoimmune diseases, serologic autoantibodies have been by far the most effective biomarkers,” he said. “There is real-world support – not only in mice – for the concept that autoimmunity begins as a highly focused immune response that then spreads over time.”

In systemic lupus erythematosus, the cascade toward disease begins about 9 years before clinical presentation, he said. It’s 7 months in type 1 diabetes, and 20 years in rheumatoid arthritis. “These have been enormously powerful in designing both observational and therapeutic studies to try to interrupt autoimmunity at the earliest possible stage.”

What can be done if a MS biomarker is developed and shows that a person is at risk? Dr. Hauser highlighted how the anti-CD3 antibody teplizumab has been developed – and Food and Drug Administration approved – to greatly reduce the risk of type 1 diabetes in high-risk patients. Per a 2021 study, a single-14-day course of the drug was linked to lowering the risk of disease over a median 923 days by more than 50% (hazard ratio, 0.457; P < 0.01). Half of those who received the drug were free of diabetes versus just 22% of those treated by placebo.

“We’ve not yet had those serologic biomarkers in MS. But I’d like to show you that maybe we are getting close to having them,” Dr. Hauser said. He pointed to new research into a U.S. Department of Defense serum repository that’s turned up “a pretty rock-solid prediagnostic biomarker specific to MS.”

Moving on to therapy, Dr. Hauser said it’s clear that “the earlier that we treat, the more likely we are to have a large response. Highly effective therapies delivered as first-line therapies have better long-term outcomes for disability then does a graded approach that doesn’t begin with high-efficacy therapy.”
 

What constitutes a cure?

What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”

He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.

Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”

As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”

Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).

MILAN – While multiple sclerosis (MS) is “one of two or three great success stories of modern molecular medicine,” we’re still only “halfway home,” University of California, San Francisco, neurology professor Stephen Hauser, MD, told colleagues in a highlighted lecture at the 9th Joint ECTRIMS-ACTRIMS meeting.

Going forward, the MS field should emphasize identifying early biomarkers of MS, Dr. Hauser said.

He noted that many experts had anticipated “that, if we could intervene early in the relapsing phase of the disease, we would stabilize neurodegeneration and patient disability. But one of the big surprises was that that was not the case. Instead, the observed course was that by silencing relapses and focal inflammation, a clinically silent, slow, insidious progression continues during the relapsing phase of disease in patients who are not having ongoing relapses.”

Even as focal activity detected via MRI is silenced, “progression continues” he said. “This remains the great unsolved challenge.”

Dr. Hauser asked colleagues to consider a three-stage model of MS that begins with benign autoimmunity followed by pathogenic autoimmunity with subclinical tissue damage. The third stage is clinical autoimmunity.

How can you determine who’s at risk? Genetics can only fill in part of the picture because they can’t pinpoint exactly who’s likely to develop the disease. “In other autoimmune diseases, serologic autoantibodies have been by far the most effective biomarkers,” he said. “There is real-world support – not only in mice – for the concept that autoimmunity begins as a highly focused immune response that then spreads over time.”

In systemic lupus erythematosus, the cascade toward disease begins about 9 years before clinical presentation, he said. It’s 7 months in type 1 diabetes, and 20 years in rheumatoid arthritis. “These have been enormously powerful in designing both observational and therapeutic studies to try to interrupt autoimmunity at the earliest possible stage.”

What can be done if a MS biomarker is developed and shows that a person is at risk? Dr. Hauser highlighted how the anti-CD3 antibody teplizumab has been developed – and Food and Drug Administration approved – to greatly reduce the risk of type 1 diabetes in high-risk patients. Per a 2021 study, a single-14-day course of the drug was linked to lowering the risk of disease over a median 923 days by more than 50% (hazard ratio, 0.457; P < 0.01). Half of those who received the drug were free of diabetes versus just 22% of those treated by placebo.

“We’ve not yet had those serologic biomarkers in MS. But I’d like to show you that maybe we are getting close to having them,” Dr. Hauser said. He pointed to new research into a U.S. Department of Defense serum repository that’s turned up “a pretty rock-solid prediagnostic biomarker specific to MS.”

Moving on to therapy, Dr. Hauser said it’s clear that “the earlier that we treat, the more likely we are to have a large response. Highly effective therapies delivered as first-line therapies have better long-term outcomes for disability then does a graded approach that doesn’t begin with high-efficacy therapy.”
 

What constitutes a cure?

What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”

He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.

Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”

As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”

Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).

MILAN – While multiple sclerosis (MS) is “one of two or three great success stories of modern molecular medicine,” we’re still only “halfway home,” University of California, San Francisco, neurology professor Stephen Hauser, MD, told colleagues in a highlighted lecture at the 9th Joint ECTRIMS-ACTRIMS meeting.

Going forward, the MS field should emphasize identifying early biomarkers of MS, Dr. Hauser said.

He noted that many experts had anticipated “that, if we could intervene early in the relapsing phase of the disease, we would stabilize neurodegeneration and patient disability. But one of the big surprises was that that was not the case. Instead, the observed course was that by silencing relapses and focal inflammation, a clinically silent, slow, insidious progression continues during the relapsing phase of disease in patients who are not having ongoing relapses.”

Even as focal activity detected via MRI is silenced, “progression continues” he said. “This remains the great unsolved challenge.”

Dr. Hauser asked colleagues to consider a three-stage model of MS that begins with benign autoimmunity followed by pathogenic autoimmunity with subclinical tissue damage. The third stage is clinical autoimmunity.

How can you determine who’s at risk? Genetics can only fill in part of the picture because they can’t pinpoint exactly who’s likely to develop the disease. “In other autoimmune diseases, serologic autoantibodies have been by far the most effective biomarkers,” he said. “There is real-world support – not only in mice – for the concept that autoimmunity begins as a highly focused immune response that then spreads over time.”

In systemic lupus erythematosus, the cascade toward disease begins about 9 years before clinical presentation, he said. It’s 7 months in type 1 diabetes, and 20 years in rheumatoid arthritis. “These have been enormously powerful in designing both observational and therapeutic studies to try to interrupt autoimmunity at the earliest possible stage.”

What can be done if a MS biomarker is developed and shows that a person is at risk? Dr. Hauser highlighted how the anti-CD3 antibody teplizumab has been developed – and Food and Drug Administration approved – to greatly reduce the risk of type 1 diabetes in high-risk patients. Per a 2021 study, a single-14-day course of the drug was linked to lowering the risk of disease over a median 923 days by more than 50% (hazard ratio, 0.457; P < 0.01). Half of those who received the drug were free of diabetes versus just 22% of those treated by placebo.

“We’ve not yet had those serologic biomarkers in MS. But I’d like to show you that maybe we are getting close to having them,” Dr. Hauser said. He pointed to new research into a U.S. Department of Defense serum repository that’s turned up “a pretty rock-solid prediagnostic biomarker specific to MS.”

Moving on to therapy, Dr. Hauser said it’s clear that “the earlier that we treat, the more likely we are to have a large response. Highly effective therapies delivered as first-line therapies have better long-term outcomes for disability then does a graded approach that doesn’t begin with high-efficacy therapy.”
 

What constitutes a cure?

What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”

He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.

Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”

As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”

Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).