Multiple Sclerosis

NASHVILLE—For patients with multiple sclerosis (MS) and walking impairments, high-intensity interval exercise is as enjoyable as traditional continuous exercise and does not induce sustained, harmful effects on mood, according to research presented at the 2018 CMSC Annual Meeting. This finding could influence evidence-based prescriptions for exercise that are appropriate for improving physiologic conditioning, according to the researchers.

MS often results in walking dysfunction and physiologic deconditioning. High-intensity interval exercise has induced significant improvements in physiologic conditioning in healthy and clinical populations, including patients with MS. Before integrating high-intensity interval exercise into an exercise prescription, and to increase the likelihood that participants will engage in and adhere to this exercise regimen, investigators thought it important to ascertain whether people with MS and mobility disability enjoy the high-intensity interval exercise and experience mood benefits.

Elizabeth Hubbard, PhD, Assistant Professor of Kinesiology at Berry College in Mount Berry, Georgia, conducted a study to examine the effects of single sessions of high-intensity interval exercise and continuous exercise on mood and enjoyment outcomes in persons with MS and mobility disability. In their study, 20 participants (median Expanded Disability Status Scale score, 5.8) underwent counterbalanced presentations of high-intensity interval exercise and continuous exercise bouts using a recumbent stepper. The high-intensity interval exercise bout was 20 minutes long and included 10 cycles of one-minute intervals at a wattage associated with 90% VO2 peak, followed by one-minute recovery intervals at 15 W. The continuous exercise bout lasted for 20 minutes at a wattage associated with 50% to 60% VO2 peak. The researchers administered the Profile of Mood States (POMS) survey before, immediately after, and 30 minutes after exercise. The Physical Activity Enjoyment Scale (PACES) questionnaire was administered immediately after exercise.

NASHVILLE—For patients with multiple sclerosis (MS) and walking impairments, high-intensity interval exercise is as enjoyable as traditional continuous exercise and does not induce sustained, harmful effects on mood, according to research presented at the 2018 CMSC Annual Meeting. This finding could influence evidence-based prescriptions for exercise that are appropriate for improving physiologic conditioning, according to the researchers.

MS often results in walking dysfunction and physiologic deconditioning. High-intensity interval exercise has induced significant improvements in physiologic conditioning in healthy and clinical populations, including patients with MS. Before integrating high-intensity interval exercise into an exercise prescription, and to increase the likelihood that participants will engage in and adhere to this exercise regimen, investigators thought it important to ascertain whether people with MS and mobility disability enjoy the high-intensity interval exercise and experience mood benefits.

Elizabeth Hubbard, PhD, Assistant Professor of Kinesiology at Berry College in Mount Berry, Georgia, conducted a study to examine the effects of single sessions of high-intensity interval exercise and continuous exercise on mood and enjoyment outcomes in persons with MS and mobility disability. In their study, 20 participants (median Expanded Disability Status Scale score, 5.8) underwent counterbalanced presentations of high-intensity interval exercise and continuous exercise bouts using a recumbent stepper. The high-intensity interval exercise bout was 20 minutes long and included 10 cycles of one-minute intervals at a wattage associated with 90% VO2 peak, followed by one-minute recovery intervals at 15 W. The continuous exercise bout lasted for 20 minutes at a wattage associated with 50% to 60% VO2 peak. The researchers administered the Profile of Mood States (POMS) survey before, immediately after, and 30 minutes after exercise. The Physical Activity Enjoyment Scale (PACES) questionnaire was administered immediately after exercise.

NASHVILLE—For patients with multiple sclerosis (MS) and walking impairments, high-intensity interval exercise is as enjoyable as traditional continuous exercise and does not induce sustained, harmful effects on mood, according to research presented at the 2018 CMSC Annual Meeting. This finding could influence evidence-based prescriptions for exercise that are appropriate for improving physiologic conditioning, according to the researchers.

MS often results in walking dysfunction and physiologic deconditioning. High-intensity interval exercise has induced significant improvements in physiologic conditioning in healthy and clinical populations, including patients with MS. Before integrating high-intensity interval exercise into an exercise prescription, and to increase the likelihood that participants will engage in and adhere to this exercise regimen, investigators thought it important to ascertain whether people with MS and mobility disability enjoy the high-intensity interval exercise and experience mood benefits.

Elizabeth Hubbard, PhD, Assistant Professor of Kinesiology at Berry College in Mount Berry, Georgia, conducted a study to examine the effects of single sessions of high-intensity interval exercise and continuous exercise on mood and enjoyment outcomes in persons with MS and mobility disability. In their study, 20 participants (median Expanded Disability Status Scale score, 5.8) underwent counterbalanced presentations of high-intensity interval exercise and continuous exercise bouts using a recumbent stepper. The high-intensity interval exercise bout was 20 minutes long and included 10 cycles of one-minute intervals at a wattage associated with 90% VO2 peak, followed by one-minute recovery intervals at 15 W. The continuous exercise bout lasted for 20 minutes at a wattage associated with 50% to 60% VO2 peak. The researchers administered the Profile of Mood States (POMS) survey before, immediately after, and 30 minutes after exercise. The Physical Activity Enjoyment Scale (PACES) questionnaire was administered immediately after exercise.

NASHVILLE—For patients with multiple sclerosis (MS) who receive treatment with natalizumab, progressive multifocal leukoencephalopathy (PML) can be avoided, according to research presented at the 2018 CMSC Annual Meeting. “You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Joseph R. Berger, MD, Professor of Neurology at the Hospital of the University of Pennsylvania in Philadelphia.

Long-Term Use of Natalizumab Is Associated With Increased PML Risk

Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger. Instead, it is the medications that introduce the risk, he said, with at least three, and possibly four, drugs posing a risk to patients.

“We know that the risk with natalizumab is incredibly high in the context of John Cunningham virus [JCV] antibody positivity and prolonged therapy,” Dr. Berger said. “You can safely give natalizumab for a short period of time when treating patients with aggressive MS. I will frequently employ that strategy even in the context of JCV antibody positivity.” There is no risk of PML when natalizumab is used for under eight months, Dr. Berger said.“If you leave people on the drug indefinitely, there is a substantial risk of developing PML,” said Dr. Berger. “Individuals who have been on the drug for two years, who have seen prior immunosuppressant therapy, who are JCV antibody positive—that group of individuals develops PML at rates of one in 50 to one in 100.” These levels are “even higher than those in the HIV population before the rise of antiretroviral medications,” he added.

As of November 30, 2017, 177,800 patients have received natalizumab in the postmarketing setting, and 756 cases of PML have been reported as of December 7, 2017. All but three of those cases were in patients with MS, and the overall incidence was 4.19 out of 1,000.

Dr. Berger recommended regular screening MRIs for PML in patients taking natalizumab and advised physicians to be on alert for the appearance of new neurologic symptoms or a new or increasing JCV antibody index.

Drugs With Low and Unknown Risks

Two other MS drugs, fingolimod and dimethyl fumarate, entail a low risk of PML. The numbers of PML cases reported for these drugs are 19 and five, respectively, as of February 2018, said Dr. Berger. Two of the patients receiving fingolimod who developed PML had had earlier exposure to natalizumab.

For JC antibody positive patients receiving dimethyl fumarate, the risk of PML may be eliminated when the treatment is discontinued and their lymphocyte count decreases to a level below 500 per µL Dr. Berger said.

“Unfortunately for fingolimod, we do not have a defined risk-mitigation strategy,” he said. However, researchers have noticed that PML has occurred more often in older people on fingolimod, possibly because of the aging of the immune system.

Alemtuzumab, ocrelizumab (with rituximab as proxy), and teriflunomide (with leflunomide as proxy), entail an unknown risk of PML, according to Dr. Berger. There have been three cases of PML associated with ocrelizumab and one associated with teriflunomide, but all were carry-overs from natalizumab or fingolimod exposure or occurred after natalizumab exposure.

What should a physician do if a patient develops PML? Stopping the drug and restoring the immune system are crucial steps, Dr. Berger said. Although evidence indicates that plasma exchange clears natalizumab, “there is no study that demonstrates that it is in the patient’s best interest,” said Dr. Berger. A retrospective study found no improvement in morbidity or mortality after plasma exchange.

Multiple strategies to treat PML, including immunizations and inhibitors of DNA replication, have failed to make an impact so far, said Dr. Berger. These strategies did not show benefits in clinical trials, and evidence does not support them.

—Randy Dotinga

Suggested Reading

Berger JR. Classifying PML risk with disease modifying therapies. Mult Scler Relat Disord. 2017;12:59-63.

Khatri BO, Man S, Giovannoni G, et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology. 2009;72(5):402-409.

Landi D, De Rossi N, Zagaglia S, et al. No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML. Neurology. 2017;88(12):1144-1152.

NASHVILLE—For patients with multiple sclerosis (MS) who receive treatment with natalizumab, progressive multifocal leukoencephalopathy (PML) can be avoided, according to research presented at the 2018 CMSC Annual Meeting. “You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Joseph R. Berger, MD, Professor of Neurology at the Hospital of the University of Pennsylvania in Philadelphia.

Long-Term Use of Natalizumab Is Associated With Increased PML Risk

Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger. Instead, it is the medications that introduce the risk, he said, with at least three, and possibly four, drugs posing a risk to patients.

“We know that the risk with natalizumab is incredibly high in the context of John Cunningham virus [JCV] antibody positivity and prolonged therapy,” Dr. Berger said. “You can safely give natalizumab for a short period of time when treating patients with aggressive MS. I will frequently employ that strategy even in the context of JCV antibody positivity.” There is no risk of PML when natalizumab is used for under eight months, Dr. Berger said.“If you leave people on the drug indefinitely, there is a substantial risk of developing PML,” said Dr. Berger. “Individuals who have been on the drug for two years, who have seen prior immunosuppressant therapy, who are JCV antibody positive—that group of individuals develops PML at rates of one in 50 to one in 100.” These levels are “even higher than those in the HIV population before the rise of antiretroviral medications,” he added.

As of November 30, 2017, 177,800 patients have received natalizumab in the postmarketing setting, and 756 cases of PML have been reported as of December 7, 2017. All but three of those cases were in patients with MS, and the overall incidence was 4.19 out of 1,000.

Dr. Berger recommended regular screening MRIs for PML in patients taking natalizumab and advised physicians to be on alert for the appearance of new neurologic symptoms or a new or increasing JCV antibody index.

Drugs With Low and Unknown Risks

Two other MS drugs, fingolimod and dimethyl fumarate, entail a low risk of PML. The numbers of PML cases reported for these drugs are 19 and five, respectively, as of February 2018, said Dr. Berger. Two of the patients receiving fingolimod who developed PML had had earlier exposure to natalizumab.

For JC antibody positive patients receiving dimethyl fumarate, the risk of PML may be eliminated when the treatment is discontinued and their lymphocyte count decreases to a level below 500 per µL Dr. Berger said.

“Unfortunately for fingolimod, we do not have a defined risk-mitigation strategy,” he said. However, researchers have noticed that PML has occurred more often in older people on fingolimod, possibly because of the aging of the immune system.

Alemtuzumab, ocrelizumab (with rituximab as proxy), and teriflunomide (with leflunomide as proxy), entail an unknown risk of PML, according to Dr. Berger. There have been three cases of PML associated with ocrelizumab and one associated with teriflunomide, but all were carry-overs from natalizumab or fingolimod exposure or occurred after natalizumab exposure.

What should a physician do if a patient develops PML? Stopping the drug and restoring the immune system are crucial steps, Dr. Berger said. Although evidence indicates that plasma exchange clears natalizumab, “there is no study that demonstrates that it is in the patient’s best interest,” said Dr. Berger. A retrospective study found no improvement in morbidity or mortality after plasma exchange.

Multiple strategies to treat PML, including immunizations and inhibitors of DNA replication, have failed to make an impact so far, said Dr. Berger. These strategies did not show benefits in clinical trials, and evidence does not support them.

—Randy Dotinga

Suggested Reading

Berger JR. Classifying PML risk with disease modifying therapies. Mult Scler Relat Disord. 2017;12:59-63.

Khatri BO, Man S, Giovannoni G, et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology. 2009;72(5):402-409.

Landi D, De Rossi N, Zagaglia S, et al. No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML. Neurology. 2017;88(12):1144-1152.

NASHVILLE—For patients with multiple sclerosis (MS) who receive treatment with natalizumab, progressive multifocal leukoencephalopathy (PML) can be avoided, according to research presented at the 2018 CMSC Annual Meeting. “You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Joseph R. Berger, MD, Professor of Neurology at the Hospital of the University of Pennsylvania in Philadelphia.

Long-Term Use of Natalizumab Is Associated With Increased PML Risk

Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger. Instead, it is the medications that introduce the risk, he said, with at least three, and possibly four, drugs posing a risk to patients.

“We know that the risk with natalizumab is incredibly high in the context of John Cunningham virus [JCV] antibody positivity and prolonged therapy,” Dr. Berger said. “You can safely give natalizumab for a short period of time when treating patients with aggressive MS. I will frequently employ that strategy even in the context of JCV antibody positivity.” There is no risk of PML when natalizumab is used for under eight months, Dr. Berger said.“If you leave people on the drug indefinitely, there is a substantial risk of developing PML,” said Dr. Berger. “Individuals who have been on the drug for two years, who have seen prior immunosuppressant therapy, who are JCV antibody positive—that group of individuals develops PML at rates of one in 50 to one in 100.” These levels are “even higher than those in the HIV population before the rise of antiretroviral medications,” he added.

As of November 30, 2017, 177,800 patients have received natalizumab in the postmarketing setting, and 756 cases of PML have been reported as of December 7, 2017. All but three of those cases were in patients with MS, and the overall incidence was 4.19 out of 1,000.

Dr. Berger recommended regular screening MRIs for PML in patients taking natalizumab and advised physicians to be on alert for the appearance of new neurologic symptoms or a new or increasing JCV antibody index.

Drugs With Low and Unknown Risks

Two other MS drugs, fingolimod and dimethyl fumarate, entail a low risk of PML. The numbers of PML cases reported for these drugs are 19 and five, respectively, as of February 2018, said Dr. Berger. Two of the patients receiving fingolimod who developed PML had had earlier exposure to natalizumab.

For JC antibody positive patients receiving dimethyl fumarate, the risk of PML may be eliminated when the treatment is discontinued and their lymphocyte count decreases to a level below 500 per µL Dr. Berger said.

“Unfortunately for fingolimod, we do not have a defined risk-mitigation strategy,” he said. However, researchers have noticed that PML has occurred more often in older people on fingolimod, possibly because of the aging of the immune system.

Alemtuzumab, ocrelizumab (with rituximab as proxy), and teriflunomide (with leflunomide as proxy), entail an unknown risk of PML, according to Dr. Berger. There have been three cases of PML associated with ocrelizumab and one associated with teriflunomide, but all were carry-overs from natalizumab or fingolimod exposure or occurred after natalizumab exposure.

What should a physician do if a patient develops PML? Stopping the drug and restoring the immune system are crucial steps, Dr. Berger said. Although evidence indicates that plasma exchange clears natalizumab, “there is no study that demonstrates that it is in the patient’s best interest,” said Dr. Berger. A retrospective study found no improvement in morbidity or mortality after plasma exchange.

Multiple strategies to treat PML, including immunizations and inhibitors of DNA replication, have failed to make an impact so far, said Dr. Berger. These strategies did not show benefits in clinical trials, and evidence does not support them.

—Randy Dotinga

Suggested Reading

Berger JR. Classifying PML risk with disease modifying therapies. Mult Scler Relat Disord. 2017;12:59-63.

Khatri BO, Man S, Giovannoni G, et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology. 2009;72(5):402-409.

Landi D, De Rossi N, Zagaglia S, et al. No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML. Neurology. 2017;88(12):1144-1152.

NASHVILLE, TENN. – In a sign of the potential complications that can be spawned by B-cell–depleting therapies, a new report found that 5 of 30 patients with relapsing-remitting multiple sclerosis (RRMS) had to discontinue or interrupt long-term treatment with rituximab (Rituxan) because of serious infections such as pneumonia, septic arthritis, and sinusitis.

The findings are a “big lesson to not just focus on opportunistic infections [with Rituxan use] but also consider nonopportunistic infections that could occur,” lead study author Cindy Darius, a registered nurse with the Johns Hopkins Multiple Sclerosis Center (JHMSC), Baltimore, said in an interview. She presented the research at the annual meeting of the Consortium of Multiple Sclerosis Centers.

copyright Zerbor/Thinkstock

• A woman, aged 30 years, whose rituximab regimen was interrupted after 4 years of treatment when she developed recurrent pneumonia.
• A man, aged 42 years, who took rituximab for a year then stopped after developing ringworm and two bouts of Staphylococcus aureus septic arthritis, and who had previously changed from natalizumab (Tysabri) to rituximab after seroconverting to the John Cunningham virus.
• A woman, aged 65 years, with Sjögren’s syndrome who stopped rituximab at 2 years after developing sinusitis, pneumonia, and herpes simplex virus keratitis.
• A woman, aged 38 years, who discontinued rituximab after 2 years because of recurrent urosepsis, sinusitis, and pyrexia of unknown origin.
• A woman, aged 56 years, who stopped rituximab after 2 years following intractable sinusitis and pneumonia that resulted in empyema and required a thoracotomy.

What might be causing the apparent side effects? Ms. Darius pointed out that the patients were already immunocompromised because of previous treatment with first- and/or second-line medications. She added that the complications “may be due to dosing that may be a little too high for the MS population.”

JHMSC is considering whether to give doses of the drug once a year instead of twice annually, she said. “Other providers are cutting the dose in half: Instead of 1,000 mg, they’re giving 500,” she added. “After the patient has been on the medication for a year or two, and you feel the disease process has stabilized, you may want to consider adjusting the dosage.”

Going forward, the researchers wrote that they “plan to determine the incidence of all serious infectious complications related to rituximab use among MS patients attending the JHMSC, and the influence of different dosing protocols between MS providers in this regard.”

No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.

SOURCE: Darius C et al. CMSC 2018, Abstract DX57.

NASHVILLE, TENN. – In a sign of the potential complications that can be spawned by B-cell–depleting therapies, a new report found that 5 of 30 patients with relapsing-remitting multiple sclerosis (RRMS) had to discontinue or interrupt long-term treatment with rituximab (Rituxan) because of serious infections such as pneumonia, septic arthritis, and sinusitis.

The findings are a “big lesson to not just focus on opportunistic infections [with Rituxan use] but also consider nonopportunistic infections that could occur,” lead study author Cindy Darius, a registered nurse with the Johns Hopkins Multiple Sclerosis Center (JHMSC), Baltimore, said in an interview. She presented the research at the annual meeting of the Consortium of Multiple Sclerosis Centers.

copyright Zerbor/Thinkstock

• A woman, aged 30 years, whose rituximab regimen was interrupted after 4 years of treatment when she developed recurrent pneumonia.
• A man, aged 42 years, who took rituximab for a year then stopped after developing ringworm and two bouts of Staphylococcus aureus septic arthritis, and who had previously changed from natalizumab (Tysabri) to rituximab after seroconverting to the John Cunningham virus.
• A woman, aged 65 years, with Sjögren’s syndrome who stopped rituximab at 2 years after developing sinusitis, pneumonia, and herpes simplex virus keratitis.
• A woman, aged 38 years, who discontinued rituximab after 2 years because of recurrent urosepsis, sinusitis, and pyrexia of unknown origin.
• A woman, aged 56 years, who stopped rituximab after 2 years following intractable sinusitis and pneumonia that resulted in empyema and required a thoracotomy.

What might be causing the apparent side effects? Ms. Darius pointed out that the patients were already immunocompromised because of previous treatment with first- and/or second-line medications. She added that the complications “may be due to dosing that may be a little too high for the MS population.”

JHMSC is considering whether to give doses of the drug once a year instead of twice annually, she said. “Other providers are cutting the dose in half: Instead of 1,000 mg, they’re giving 500,” she added. “After the patient has been on the medication for a year or two, and you feel the disease process has stabilized, you may want to consider adjusting the dosage.”

Going forward, the researchers wrote that they “plan to determine the incidence of all serious infectious complications related to rituximab use among MS patients attending the JHMSC, and the influence of different dosing protocols between MS providers in this regard.”

No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.

SOURCE: Darius C et al. CMSC 2018, Abstract DX57.

NASHVILLE, TENN. – In a sign of the potential complications that can be spawned by B-cell–depleting therapies, a new report found that 5 of 30 patients with relapsing-remitting multiple sclerosis (RRMS) had to discontinue or interrupt long-term treatment with rituximab (Rituxan) because of serious infections such as pneumonia, septic arthritis, and sinusitis.

The findings are a “big lesson to not just focus on opportunistic infections [with Rituxan use] but also consider nonopportunistic infections that could occur,” lead study author Cindy Darius, a registered nurse with the Johns Hopkins Multiple Sclerosis Center (JHMSC), Baltimore, said in an interview. She presented the research at the annual meeting of the Consortium of Multiple Sclerosis Centers.

copyright Zerbor/Thinkstock

• A woman, aged 30 years, whose rituximab regimen was interrupted after 4 years of treatment when she developed recurrent pneumonia.
• A man, aged 42 years, who took rituximab for a year then stopped after developing ringworm and two bouts of Staphylococcus aureus septic arthritis, and who had previously changed from natalizumab (Tysabri) to rituximab after seroconverting to the John Cunningham virus.
• A woman, aged 65 years, with Sjögren’s syndrome who stopped rituximab at 2 years after developing sinusitis, pneumonia, and herpes simplex virus keratitis.
• A woman, aged 38 years, who discontinued rituximab after 2 years because of recurrent urosepsis, sinusitis, and pyrexia of unknown origin.
• A woman, aged 56 years, who stopped rituximab after 2 years following intractable sinusitis and pneumonia that resulted in empyema and required a thoracotomy.

What might be causing the apparent side effects? Ms. Darius pointed out that the patients were already immunocompromised because of previous treatment with first- and/or second-line medications. She added that the complications “may be due to dosing that may be a little too high for the MS population.”

JHMSC is considering whether to give doses of the drug once a year instead of twice annually, she said. “Other providers are cutting the dose in half: Instead of 1,000 mg, they’re giving 500,” she added. “After the patient has been on the medication for a year or two, and you feel the disease process has stabilized, you may want to consider adjusting the dosage.”

Going forward, the researchers wrote that they “plan to determine the incidence of all serious infectious complications related to rituximab use among MS patients attending the JHMSC, and the influence of different dosing protocols between MS providers in this regard.”

No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.

SOURCE: Darius C et al. CMSC 2018, Abstract DX57.

NASHVILLE, TENN. – With much unknown about the risks of cancer and vaccination associated with immunosuppressants used in multiple sclerosis treatment, a neurologist advised colleagues to be aware of the potential dangers and take appropriate precautions.

For example, Eric Williamson, MD, of the University of Pennsylvania and Philadelphia Veterans Administration Hospital, said he goes a step further than recommending that adult female patients with MS who take ocrelizumab (Ocrevus) get regular mammograms. Per policy, he also double-checks to make sure that patients actually get screened.

“I know two women who were diagnosed with breast cancer before they began on their treatment because we asked about mammograms,” said Dr. Williamson, who spoke in a presentation about the risks of immunosuppressants in MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In regard to cancer as a whole, he said, “it’s unclear if there is any true increased risk in MS patients.” But this doesn’t mean there is no danger, he said, since research into immunosuppressants in other contexts show that they can boost the risk of cancer by three times to as much as several hundred times.

In transplant patients, he said, immunosuppressants are linked to higher rates of lymphoproliferative tumors (such as those linked to Epstein-Barr virus), Kaposi sarcoma, and cutaneous, renal, hepatobiliary, and anogenital tumors.

Research is also hazy in regard to specific immunosuppressants used to treat MS. Two reports published about a decade ago raised the possibility that natalizumab (Tysabri) may have sparked a slightly higher risk cancer in patients taking the drug for Crohn’s disease and MS, respectively; the latter report hinted at a higher risk of melanoma specifically. However, Dr. Williamson said postmarketing surveillance has not detected any further sign of trouble (N Engl J Med. 2006;354:899‐910; N Engl J Med. 2008;358;647‐8).

Another drug, ocrelizumab (Ocrevus), has sparked questions about a possible breast cancer risk. As Genentech, its manufacturer, notes: “breast cancer occurred in 6 of 781 females treated with Ocrevus and none of 668 females treated with Rebif [interferon beta-1a] or placebo.”

Guidance on vaccinations

On the vaccination front, Dr. Williamson said vaccines are a good idea for MS patients – as long as they’re “relatively safe” – because some infectious diseases appear to be more severe in this population.

Flu is a special danger, Dr. Williamson said. He recommends the flu vaccine to patients “because people with MS are at higher risk of influenza-related complications or hospitalizations.”

With guidance from a report led by Dr. Williamson, the National Multiple Sclerosis Society offers recommendations about whether patients with MS should use various vaccines (Curr Neurol Neurosci Rep. 2016;16:36).

Dr. Williamson cautioned that patients with MS who take dimethyl fumarate (Tecfidera), ocrelizumab (Ocrevus), and fingolimod (Gilenya) should not use live vaccines. The drugs can pose issues in regard to other vaccines, too, he said (Plos ONE 2013; 8:e78532; Neurol Res 2012;34:730-3; Neurology. 2013;81:552-8).

Autoimmune risk with alemtuzumab

Alemtuzumab (Lemtrada) has been linked to autoimmune thyroid disorders, especially Graves’ disease, Dr. Williamson said. It’s estimated to affect 17%-41% of patients (Front Endocrinol [Lausanne]. 2017;8:254).

Potentially life-threatening idiopathic thrombocytopenic purpura occurs in 2% of patients on Lemtrada, he said, and anti-GMB nephropathy/Goodpasture’s syndrome has been reported in 0.1%.

Dr. Williamson also noted case reports of autoimmune hemolytic anemia and hepatitis. Earlier this year, three reports in Neurology noted acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422, doi: 10.1212/WNL.0000000000005420, doi: 10.1212/WNL.0000000000005417).

Dr. Williamson disclosed past consulting for Bayer, Biogen, Celgene, Genentech, EMD Serono, Teva, and Novartis, and current research support from Actelion and Alexion.

NASHVILLE, TENN. – With much unknown about the risks of cancer and vaccination associated with immunosuppressants used in multiple sclerosis treatment, a neurologist advised colleagues to be aware of the potential dangers and take appropriate precautions.

For example, Eric Williamson, MD, of the University of Pennsylvania and Philadelphia Veterans Administration Hospital, said he goes a step further than recommending that adult female patients with MS who take ocrelizumab (Ocrevus) get regular mammograms. Per policy, he also double-checks to make sure that patients actually get screened.

“I know two women who were diagnosed with breast cancer before they began on their treatment because we asked about mammograms,” said Dr. Williamson, who spoke in a presentation about the risks of immunosuppressants in MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In regard to cancer as a whole, he said, “it’s unclear if there is any true increased risk in MS patients.” But this doesn’t mean there is no danger, he said, since research into immunosuppressants in other contexts show that they can boost the risk of cancer by three times to as much as several hundred times.

In transplant patients, he said, immunosuppressants are linked to higher rates of lymphoproliferative tumors (such as those linked to Epstein-Barr virus), Kaposi sarcoma, and cutaneous, renal, hepatobiliary, and anogenital tumors.

Research is also hazy in regard to specific immunosuppressants used to treat MS. Two reports published about a decade ago raised the possibility that natalizumab (Tysabri) may have sparked a slightly higher risk cancer in patients taking the drug for Crohn’s disease and MS, respectively; the latter report hinted at a higher risk of melanoma specifically. However, Dr. Williamson said postmarketing surveillance has not detected any further sign of trouble (N Engl J Med. 2006;354:899‐910; N Engl J Med. 2008;358;647‐8).

Another drug, ocrelizumab (Ocrevus), has sparked questions about a possible breast cancer risk. As Genentech, its manufacturer, notes: “breast cancer occurred in 6 of 781 females treated with Ocrevus and none of 668 females treated with Rebif [interferon beta-1a] or placebo.”

Guidance on vaccinations

On the vaccination front, Dr. Williamson said vaccines are a good idea for MS patients – as long as they’re “relatively safe” – because some infectious diseases appear to be more severe in this population.

Flu is a special danger, Dr. Williamson said. He recommends the flu vaccine to patients “because people with MS are at higher risk of influenza-related complications or hospitalizations.”

With guidance from a report led by Dr. Williamson, the National Multiple Sclerosis Society offers recommendations about whether patients with MS should use various vaccines (Curr Neurol Neurosci Rep. 2016;16:36).

Dr. Williamson cautioned that patients with MS who take dimethyl fumarate (Tecfidera), ocrelizumab (Ocrevus), and fingolimod (Gilenya) should not use live vaccines. The drugs can pose issues in regard to other vaccines, too, he said (Plos ONE 2013; 8:e78532; Neurol Res 2012;34:730-3; Neurology. 2013;81:552-8).

Autoimmune risk with alemtuzumab

Alemtuzumab (Lemtrada) has been linked to autoimmune thyroid disorders, especially Graves’ disease, Dr. Williamson said. It’s estimated to affect 17%-41% of patients (Front Endocrinol [Lausanne]. 2017;8:254).

Potentially life-threatening idiopathic thrombocytopenic purpura occurs in 2% of patients on Lemtrada, he said, and anti-GMB nephropathy/Goodpasture’s syndrome has been reported in 0.1%.

Dr. Williamson also noted case reports of autoimmune hemolytic anemia and hepatitis. Earlier this year, three reports in Neurology noted acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422, doi: 10.1212/WNL.0000000000005420, doi: 10.1212/WNL.0000000000005417).

Dr. Williamson disclosed past consulting for Bayer, Biogen, Celgene, Genentech, EMD Serono, Teva, and Novartis, and current research support from Actelion and Alexion.

NASHVILLE, TENN. – With much unknown about the risks of cancer and vaccination associated with immunosuppressants used in multiple sclerosis treatment, a neurologist advised colleagues to be aware of the potential dangers and take appropriate precautions.

For example, Eric Williamson, MD, of the University of Pennsylvania and Philadelphia Veterans Administration Hospital, said he goes a step further than recommending that adult female patients with MS who take ocrelizumab (Ocrevus) get regular mammograms. Per policy, he also double-checks to make sure that patients actually get screened.

“I know two women who were diagnosed with breast cancer before they began on their treatment because we asked about mammograms,” said Dr. Williamson, who spoke in a presentation about the risks of immunosuppressants in MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In regard to cancer as a whole, he said, “it’s unclear if there is any true increased risk in MS patients.” But this doesn’t mean there is no danger, he said, since research into immunosuppressants in other contexts show that they can boost the risk of cancer by three times to as much as several hundred times.

In transplant patients, he said, immunosuppressants are linked to higher rates of lymphoproliferative tumors (such as those linked to Epstein-Barr virus), Kaposi sarcoma, and cutaneous, renal, hepatobiliary, and anogenital tumors.

Research is also hazy in regard to specific immunosuppressants used to treat MS. Two reports published about a decade ago raised the possibility that natalizumab (Tysabri) may have sparked a slightly higher risk cancer in patients taking the drug for Crohn’s disease and MS, respectively; the latter report hinted at a higher risk of melanoma specifically. However, Dr. Williamson said postmarketing surveillance has not detected any further sign of trouble (N Engl J Med. 2006;354:899‐910; N Engl J Med. 2008;358;647‐8).

Another drug, ocrelizumab (Ocrevus), has sparked questions about a possible breast cancer risk. As Genentech, its manufacturer, notes: “breast cancer occurred in 6 of 781 females treated with Ocrevus and none of 668 females treated with Rebif [interferon beta-1a] or placebo.”

Guidance on vaccinations

On the vaccination front, Dr. Williamson said vaccines are a good idea for MS patients – as long as they’re “relatively safe” – because some infectious diseases appear to be more severe in this population.

Flu is a special danger, Dr. Williamson said. He recommends the flu vaccine to patients “because people with MS are at higher risk of influenza-related complications or hospitalizations.”

With guidance from a report led by Dr. Williamson, the National Multiple Sclerosis Society offers recommendations about whether patients with MS should use various vaccines (Curr Neurol Neurosci Rep. 2016;16:36).

Dr. Williamson cautioned that patients with MS who take dimethyl fumarate (Tecfidera), ocrelizumab (Ocrevus), and fingolimod (Gilenya) should not use live vaccines. The drugs can pose issues in regard to other vaccines, too, he said (Plos ONE 2013; 8:e78532; Neurol Res 2012;34:730-3; Neurology. 2013;81:552-8).

Autoimmune risk with alemtuzumab

Alemtuzumab (Lemtrada) has been linked to autoimmune thyroid disorders, especially Graves’ disease, Dr. Williamson said. It’s estimated to affect 17%-41% of patients (Front Endocrinol [Lausanne]. 2017;8:254).

Potentially life-threatening idiopathic thrombocytopenic purpura occurs in 2% of patients on Lemtrada, he said, and anti-GMB nephropathy/Goodpasture’s syndrome has been reported in 0.1%.

Dr. Williamson also noted case reports of autoimmune hemolytic anemia and hepatitis. Earlier this year, three reports in Neurology noted acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422, doi: 10.1212/WNL.0000000000005420, doi: 10.1212/WNL.0000000000005417).

Dr. Williamson disclosed past consulting for Bayer, Biogen, Celgene, Genentech, EMD Serono, Teva, and Novartis, and current research support from Actelion and Alexion.

NASHVILLE—Among veterans with multiple sclerosis (MS), excess MS-related mortality is mainly influenced by initial presentation with progressive MS, sensory and cerebellar complaints, and higher levels of disability. Excess mortality also may be influenced by motor complaints and low BMI, according to research presented at the 2018 CMSC Annual Meeting. Main causes of death include MS itself, infection, respiratory disease, and cancer.

These findings suggest a need to pay more attention “to preventive strategies such as yearly influenza immunization, aggressively treating MS-related complications, and comorbidities, especially vascular risk factors,” said the researchers.

Studying mortality in chronic neurologic diseases may help identify treatable risk factors, and population-based studies of English death records have found that about 64% of patients with MS have a neurologic cause of death.

To identify the predictors of mortality in veterans with MS attending outpatient clinics, Meheroz H. Rabadi, MD, Clinical Professor of Neurology at the University of Oklahoma College of Medicine and Medical Director of the Oklahoma City Veterans Affairs Medical Center MS Program, and Christopher E. Aston, PhD, Associate Research Professor of Pediatrics and a biostatistician at the University of Oklahoma Sciences Center, conducted a retrospective study.

Data From a Veterans Affairs Medical Center

The researchers conducted a retrospective electronic chart review of data from 229 veterans with MS diagnosed based on the McDonald criteria who were registered in the MS program at the Oklahoma City Veterans Affairs Medical Center between January 1, 2000, and December 31, 2014. Participants were followed up every four months in the clinic.

Data included age at initial clinic visit, gender, ethnicity and race, age at MS diagnosis, clinical MS subtype (ie, relapsing-remitting, secondary progressive, primary progressive, clinically isolated syndrome, or radiologically isolated syndrome), and initial presenting features (eg, visual complaints, motor weakness, balance disorder, and sensory complaints).

Drs. Rabadi and Aston determined an impairment index based on the presence or absence of motor and nonmotor signs on initial examination. MS severity was measured by initial Expanded Disability Status Scale and total Functional Independence Measure scores.

The researchers recorded the presence of pre-existing and new-onset comorbidities that are commonly encountered in veterans and are the most common causes of disability and death in the United States, such as hypertension, hyperlipidemia, diabetes mellitus, BMI, and history of smoking. They also recorded the presence of MS-related complications such as pressure ulcers, neurogenic bowel, and neurogenic bladder.

Main Causes of Death

A total of 226 participants were included in the analysis; 17% were female. Most participants were white (81%), 13% were black, 1% were Hispanic, and 2% were Native American. The mean age of MS diagnosis was 36, and the mean age of study entry was 49. The mean duration of MS was 21 years, and the mean duration of follow-up was 12 years. In all, 45 (20%) participants had primary progressive MS, 54 (24%) had secondary progressive MS, 96 (43%) had relapsing-remitting MS, and 31 (14%) had another or unknown MS type.

The mortality rate at the end of the 15-year study period was 14%. Among the 33 patients who died, the main causes of death documented were MS disease itself (57% of cases), infection (43%), cancer (18%), and respiratory failure (18%). Cox regression analysis using the whole cohort found that significant predictors of mortality were progressive MS type; older age at entry into the study; the presence of sensory, cerebellar, or motor complaints on presentation; more disability on presentation; lower BMI; diabetes; not having been on disease-modifying therapy; and the presence of pressure ulcers or neurogenic bladder.

Among patients who died during follow up, 36% had primary progressive MS, compared with 17% of patients who were alive; 42% of patients who died had secondary progressive MS, compared with 21% of those who were alive.

In addition, patients who died had an average age of 56 at study entry, compared with an average age of 48 among those who were alive. BMI among those who died was 23.7, compared with 28 among patients who were alive. Thirty-nine percent of patients who died were never on a disease-modifying therapy, compared with 22% of patients who were alive. Thirty-three percent of patients who died had diabetes mellitus, compared with 16% of those who were alive. Finally, 12% of patients who died had pressure ulcers, compared with 2% of patients who were alive, and 82% of patients who died had neurogenic bladder, compared with 53% of patients who were alive.

—Erica Tricarico

NASHVILLE—Among veterans with multiple sclerosis (MS), excess MS-related mortality is mainly influenced by initial presentation with progressive MS, sensory and cerebellar complaints, and higher levels of disability. Excess mortality also may be influenced by motor complaints and low BMI, according to research presented at the 2018 CMSC Annual Meeting. Main causes of death include MS itself, infection, respiratory disease, and cancer.

These findings suggest a need to pay more attention “to preventive strategies such as yearly influenza immunization, aggressively treating MS-related complications, and comorbidities, especially vascular risk factors,” said the researchers.

Studying mortality in chronic neurologic diseases may help identify treatable risk factors, and population-based studies of English death records have found that about 64% of patients with MS have a neurologic cause of death.

To identify the predictors of mortality in veterans with MS attending outpatient clinics, Meheroz H. Rabadi, MD, Clinical Professor of Neurology at the University of Oklahoma College of Medicine and Medical Director of the Oklahoma City Veterans Affairs Medical Center MS Program, and Christopher E. Aston, PhD, Associate Research Professor of Pediatrics and a biostatistician at the University of Oklahoma Sciences Center, conducted a retrospective study.

Data From a Veterans Affairs Medical Center

The researchers conducted a retrospective electronic chart review of data from 229 veterans with MS diagnosed based on the McDonald criteria who were registered in the MS program at the Oklahoma City Veterans Affairs Medical Center between January 1, 2000, and December 31, 2014. Participants were followed up every four months in the clinic.

Data included age at initial clinic visit, gender, ethnicity and race, age at MS diagnosis, clinical MS subtype (ie, relapsing-remitting, secondary progressive, primary progressive, clinically isolated syndrome, or radiologically isolated syndrome), and initial presenting features (eg, visual complaints, motor weakness, balance disorder, and sensory complaints).

Drs. Rabadi and Aston determined an impairment index based on the presence or absence of motor and nonmotor signs on initial examination. MS severity was measured by initial Expanded Disability Status Scale and total Functional Independence Measure scores.

The researchers recorded the presence of pre-existing and new-onset comorbidities that are commonly encountered in veterans and are the most common causes of disability and death in the United States, such as hypertension, hyperlipidemia, diabetes mellitus, BMI, and history of smoking. They also recorded the presence of MS-related complications such as pressure ulcers, neurogenic bowel, and neurogenic bladder.

Main Causes of Death

A total of 226 participants were included in the analysis; 17% were female. Most participants were white (81%), 13% were black, 1% were Hispanic, and 2% were Native American. The mean age of MS diagnosis was 36, and the mean age of study entry was 49. The mean duration of MS was 21 years, and the mean duration of follow-up was 12 years. In all, 45 (20%) participants had primary progressive MS, 54 (24%) had secondary progressive MS, 96 (43%) had relapsing-remitting MS, and 31 (14%) had another or unknown MS type.

The mortality rate at the end of the 15-year study period was 14%. Among the 33 patients who died, the main causes of death documented were MS disease itself (57% of cases), infection (43%), cancer (18%), and respiratory failure (18%). Cox regression analysis using the whole cohort found that significant predictors of mortality were progressive MS type; older age at entry into the study; the presence of sensory, cerebellar, or motor complaints on presentation; more disability on presentation; lower BMI; diabetes; not having been on disease-modifying therapy; and the presence of pressure ulcers or neurogenic bladder.

Among patients who died during follow up, 36% had primary progressive MS, compared with 17% of patients who were alive; 42% of patients who died had secondary progressive MS, compared with 21% of those who were alive.

In addition, patients who died had an average age of 56 at study entry, compared with an average age of 48 among those who were alive. BMI among those who died was 23.7, compared with 28 among patients who were alive. Thirty-nine percent of patients who died were never on a disease-modifying therapy, compared with 22% of patients who were alive. Thirty-three percent of patients who died had diabetes mellitus, compared with 16% of those who were alive. Finally, 12% of patients who died had pressure ulcers, compared with 2% of patients who were alive, and 82% of patients who died had neurogenic bladder, compared with 53% of patients who were alive.

—Erica Tricarico

NASHVILLE—Among veterans with multiple sclerosis (MS), excess MS-related mortality is mainly influenced by initial presentation with progressive MS, sensory and cerebellar complaints, and higher levels of disability. Excess mortality also may be influenced by motor complaints and low BMI, according to research presented at the 2018 CMSC Annual Meeting. Main causes of death include MS itself, infection, respiratory disease, and cancer.

These findings suggest a need to pay more attention “to preventive strategies such as yearly influenza immunization, aggressively treating MS-related complications, and comorbidities, especially vascular risk factors,” said the researchers.

Studying mortality in chronic neurologic diseases may help identify treatable risk factors, and population-based studies of English death records have found that about 64% of patients with MS have a neurologic cause of death.

To identify the predictors of mortality in veterans with MS attending outpatient clinics, Meheroz H. Rabadi, MD, Clinical Professor of Neurology at the University of Oklahoma College of Medicine and Medical Director of the Oklahoma City Veterans Affairs Medical Center MS Program, and Christopher E. Aston, PhD, Associate Research Professor of Pediatrics and a biostatistician at the University of Oklahoma Sciences Center, conducted a retrospective study.

Data From a Veterans Affairs Medical Center

The researchers conducted a retrospective electronic chart review of data from 229 veterans with MS diagnosed based on the McDonald criteria who were registered in the MS program at the Oklahoma City Veterans Affairs Medical Center between January 1, 2000, and December 31, 2014. Participants were followed up every four months in the clinic.

Data included age at initial clinic visit, gender, ethnicity and race, age at MS diagnosis, clinical MS subtype (ie, relapsing-remitting, secondary progressive, primary progressive, clinically isolated syndrome, or radiologically isolated syndrome), and initial presenting features (eg, visual complaints, motor weakness, balance disorder, and sensory complaints).

Drs. Rabadi and Aston determined an impairment index based on the presence or absence of motor and nonmotor signs on initial examination. MS severity was measured by initial Expanded Disability Status Scale and total Functional Independence Measure scores.

The researchers recorded the presence of pre-existing and new-onset comorbidities that are commonly encountered in veterans and are the most common causes of disability and death in the United States, such as hypertension, hyperlipidemia, diabetes mellitus, BMI, and history of smoking. They also recorded the presence of MS-related complications such as pressure ulcers, neurogenic bowel, and neurogenic bladder.

Main Causes of Death

A total of 226 participants were included in the analysis; 17% were female. Most participants were white (81%), 13% were black, 1% were Hispanic, and 2% were Native American. The mean age of MS diagnosis was 36, and the mean age of study entry was 49. The mean duration of MS was 21 years, and the mean duration of follow-up was 12 years. In all, 45 (20%) participants had primary progressive MS, 54 (24%) had secondary progressive MS, 96 (43%) had relapsing-remitting MS, and 31 (14%) had another or unknown MS type.

The mortality rate at the end of the 15-year study period was 14%. Among the 33 patients who died, the main causes of death documented were MS disease itself (57% of cases), infection (43%), cancer (18%), and respiratory failure (18%). Cox regression analysis using the whole cohort found that significant predictors of mortality were progressive MS type; older age at entry into the study; the presence of sensory, cerebellar, or motor complaints on presentation; more disability on presentation; lower BMI; diabetes; not having been on disease-modifying therapy; and the presence of pressure ulcers or neurogenic bladder.

Among patients who died during follow up, 36% had primary progressive MS, compared with 17% of patients who were alive; 42% of patients who died had secondary progressive MS, compared with 21% of those who were alive.

In addition, patients who died had an average age of 56 at study entry, compared with an average age of 48 among those who were alive. BMI among those who died was 23.7, compared with 28 among patients who were alive. Thirty-nine percent of patients who died were never on a disease-modifying therapy, compared with 22% of patients who were alive. Thirty-three percent of patients who died had diabetes mellitus, compared with 16% of those who were alive. Finally, 12% of patients who died had pressure ulcers, compared with 2% of patients who were alive, and 82% of patients who died had neurogenic bladder, compared with 53% of patients who were alive.

—Erica Tricarico

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].

NASHVILLE—In patients with pediatric-onset multiple sclerosis (MS), fingolimod significantly reduces MRI activity and slows brain volume loss for as long as two years, compared with interferon beta-1a, according to data described at the 2018 CMSC Annual Meeting.

Analyzing the PARADIGMS Data

PARADIGMS was a double-blind, double-dummy, active-controlled, parallel-group, multicenter study in which patients participated for as long as two years. The investigators randomized patients with pediatric-onset MS (ages 10 through 17) to oral fingolimod or interferon beta-1a. The dose of fingolimod was adjusted for body weight. MRI was performed at baseline and every six months thereafter until the end of the study core phase. A central reading center analyzed the MRI results. The key MRI outcomes were the number of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions, annual rate of brain volume change, number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume, and number of combined unique active lesions.

The researchers randomized 107 participants to oral fingolimod and 108 to interferon beta-1a. At baseline, mean age was about 15. Most patients were female. Mean disease duration was one to two years. The average number of relapses in the year before screening was approximately 1.5. Participants had 2.6 to 3.1 gadolinium-enhancing T1 lesions.

Data Support Fingolimod’s Efficacy in Pediatric MS

At the end of the study, fingolimod significantly reduced the annualized rate of new or newly enlarged T2 lesions by 52.6% and the number of gadolinium-enhancing T1 lesions per scan by 66.0%, compared with interferon beta-1a. The odds ratio of freedom from new or newly enlarged T2 lesions was 4.51 in the fingolimod arm, compared with the interferon beta-1a arm. The odds ratio of freedom from gadolinium-enhancing lesions was 3.0 in the fingolimod arm, compared with the interferon beta-1a arm.

Compared with interferon beta-1a, treatment with fingolimod for as long as two years significantly reduced the annualized rate of brain volume change (least squares mean: −0.48 vs −0.80). Fingolimod reduced the annualized rate of new T1 hypointense lesions by 62.8% and the number of combined unique active lesions per scan by 60.7%, compared with interferon beta-1a. Fingolimod also reduced T2 hyperintense lesion volume, compared with interferon beta-1a (percentage change from baseline: 18.4% vs 32.4%).

“The rate of T2-related atrophy [in pediatric MS] is concerning, and I am particularly interested in looking at the extension study data as they come out, and we’ll see if there is a decrease during longer-term treatment,” said Dr. Chitnis.

“These results, overall, along with the efficacy demonstrated on the clinical relapse rate, support the overall benefit of fingolimod in pediatric patients with MS,” she concluded.

—Erik Greb

NASHVILLE—In patients with pediatric-onset multiple sclerosis (MS), fingolimod significantly reduces MRI activity and slows brain volume loss for as long as two years, compared with interferon beta-1a, according to data described at the 2018 CMSC Annual Meeting.

Analyzing the PARADIGMS Data

PARADIGMS was a double-blind, double-dummy, active-controlled, parallel-group, multicenter study in which patients participated for as long as two years. The investigators randomized patients with pediatric-onset MS (ages 10 through 17) to oral fingolimod or interferon beta-1a. The dose of fingolimod was adjusted for body weight. MRI was performed at baseline and every six months thereafter until the end of the study core phase. A central reading center analyzed the MRI results. The key MRI outcomes were the number of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions, annual rate of brain volume change, number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume, and number of combined unique active lesions.

The researchers randomized 107 participants to oral fingolimod and 108 to interferon beta-1a. At baseline, mean age was about 15. Most patients were female. Mean disease duration was one to two years. The average number of relapses in the year before screening was approximately 1.5. Participants had 2.6 to 3.1 gadolinium-enhancing T1 lesions.

Data Support Fingolimod’s Efficacy in Pediatric MS

At the end of the study, fingolimod significantly reduced the annualized rate of new or newly enlarged T2 lesions by 52.6% and the number of gadolinium-enhancing T1 lesions per scan by 66.0%, compared with interferon beta-1a. The odds ratio of freedom from new or newly enlarged T2 lesions was 4.51 in the fingolimod arm, compared with the interferon beta-1a arm. The odds ratio of freedom from gadolinium-enhancing lesions was 3.0 in the fingolimod arm, compared with the interferon beta-1a arm.

Compared with interferon beta-1a, treatment with fingolimod for as long as two years significantly reduced the annualized rate of brain volume change (least squares mean: −0.48 vs −0.80). Fingolimod reduced the annualized rate of new T1 hypointense lesions by 62.8% and the number of combined unique active lesions per scan by 60.7%, compared with interferon beta-1a. Fingolimod also reduced T2 hyperintense lesion volume, compared with interferon beta-1a (percentage change from baseline: 18.4% vs 32.4%).

“The rate of T2-related atrophy [in pediatric MS] is concerning, and I am particularly interested in looking at the extension study data as they come out, and we’ll see if there is a decrease during longer-term treatment,” said Dr. Chitnis.

“These results, overall, along with the efficacy demonstrated on the clinical relapse rate, support the overall benefit of fingolimod in pediatric patients with MS,” she concluded.

—Erik Greb

NASHVILLE—In patients with pediatric-onset multiple sclerosis (MS), fingolimod significantly reduces MRI activity and slows brain volume loss for as long as two years, compared with interferon beta-1a, according to data described at the 2018 CMSC Annual Meeting.

Analyzing the PARADIGMS Data

PARADIGMS was a double-blind, double-dummy, active-controlled, parallel-group, multicenter study in which patients participated for as long as two years. The investigators randomized patients with pediatric-onset MS (ages 10 through 17) to oral fingolimod or interferon beta-1a. The dose of fingolimod was adjusted for body weight. MRI was performed at baseline and every six months thereafter until the end of the study core phase. A central reading center analyzed the MRI results. The key MRI outcomes were the number of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions, annual rate of brain volume change, number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume, and number of combined unique active lesions.

The researchers randomized 107 participants to oral fingolimod and 108 to interferon beta-1a. At baseline, mean age was about 15. Most patients were female. Mean disease duration was one to two years. The average number of relapses in the year before screening was approximately 1.5. Participants had 2.6 to 3.1 gadolinium-enhancing T1 lesions.

Data Support Fingolimod’s Efficacy in Pediatric MS

At the end of the study, fingolimod significantly reduced the annualized rate of new or newly enlarged T2 lesions by 52.6% and the number of gadolinium-enhancing T1 lesions per scan by 66.0%, compared with interferon beta-1a. The odds ratio of freedom from new or newly enlarged T2 lesions was 4.51 in the fingolimod arm, compared with the interferon beta-1a arm. The odds ratio of freedom from gadolinium-enhancing lesions was 3.0 in the fingolimod arm, compared with the interferon beta-1a arm.

Compared with interferon beta-1a, treatment with fingolimod for as long as two years significantly reduced the annualized rate of brain volume change (least squares mean: −0.48 vs −0.80). Fingolimod reduced the annualized rate of new T1 hypointense lesions by 62.8% and the number of combined unique active lesions per scan by 60.7%, compared with interferon beta-1a. Fingolimod also reduced T2 hyperintense lesion volume, compared with interferon beta-1a (percentage change from baseline: 18.4% vs 32.4%).

“The rate of T2-related atrophy [in pediatric MS] is concerning, and I am particularly interested in looking at the extension study data as they come out, and we’ll see if there is a decrease during longer-term treatment,” said Dr. Chitnis.

“These results, overall, along with the efficacy demonstrated on the clinical relapse rate, support the overall benefit of fingolimod in pediatric patients with MS,” she concluded.

—Erik Greb

NASHVILLE—Moderate-to-vigorous physical activity is positively associated with retinal nerve fiber layer thickness in children with multiple sclerosis (MS), according to research presented at the 2018 CMSC Annual Meeting. This finding may help to support an intervention targeting moderate-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS.

More than one-third of pediatric patients with MS experience optic neuritis, and most experience visual pathway abnormalities, including reductions in the retinal nerve fiber layer and ganglion cell inner-plexiform layer. Previous studies in adults have shown a positive association between moderate-to-vigorous physical activity and the retinal nerve fiber layer; however, this association has not been evaluated in pediatric patients with MS.

To investigate the associations between mild-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer in pediatric patients with MS, Alexander L. Pearson, a medical student at the University of Ottawa in Ontario, and colleagues conducted a cross-sectional study.

The researchers recruited participants from the Pediatric MS and Demyelinating Disorders Center at the Hospital for Sick Children in Toronto. Eligible participants had a diagnosis of MS (according to the International Pediatric MS Study Group consensus definitions) and were younger than 18. Patients with neuroinflammatory abnormalities associated with underlying systemic or neurologic disorders, recurrent neuroinflammatory disorders other than MS, coexisting ocular pathologies, visual acuity ±6 diopters or worse, were excluded.

Participants received standardized visual evaluations, including ocular coherence tomography. Investigators performed evaluations more than 90 days after an optic neuritis episode using a spectral-domain ocular coherence tomography Cirrus scanner. Participants also completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) more than 30 days after a relapse. This questionnaire was used to calculate the health contribution score.

Generalized linear models were used to assess the associations between moderate-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer when controlling for sex, number of optic neuritis episodes, disease duration at time of ocular coherence tomography, and within-subject correlation between eyes. Bonferroni correction was used to adjust for multiple comparisons.

Thirty patients participated in this study; 23 were female. Ocular coherence tomography was performed at a mean age of 15.7 (range, 10.6–18.0) and a median of 1.9 years from disease onset. The median retinal nerve fiber layer was 90 μm, and the median ganglion cell inner-plexiform layer was 73.5 μm. The median amount of moderate-to-vigorous physical activity was 26.5 metabolic equivalents per week.

The research team found that moderate-to-vigorous physical activity was positively associated with retinal nerve fiber layer thickness. Although the retinal nerve fiber layer and ganglion cell inner-plexiform layer were moderately correlated, moderate-to-vigorous physical activity was not associated with the ganglion cell inner-plexiform layer, said the authors.

“Next steps include a trial using mild-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS,” the researchers concluded.

NASHVILLE—Moderate-to-vigorous physical activity is positively associated with retinal nerve fiber layer thickness in children with multiple sclerosis (MS), according to research presented at the 2018 CMSC Annual Meeting. This finding may help to support an intervention targeting moderate-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS.

More than one-third of pediatric patients with MS experience optic neuritis, and most experience visual pathway abnormalities, including reductions in the retinal nerve fiber layer and ganglion cell inner-plexiform layer. Previous studies in adults have shown a positive association between moderate-to-vigorous physical activity and the retinal nerve fiber layer; however, this association has not been evaluated in pediatric patients with MS.

To investigate the associations between mild-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer in pediatric patients with MS, Alexander L. Pearson, a medical student at the University of Ottawa in Ontario, and colleagues conducted a cross-sectional study.

The researchers recruited participants from the Pediatric MS and Demyelinating Disorders Center at the Hospital for Sick Children in Toronto. Eligible participants had a diagnosis of MS (according to the International Pediatric MS Study Group consensus definitions) and were younger than 18. Patients with neuroinflammatory abnormalities associated with underlying systemic or neurologic disorders, recurrent neuroinflammatory disorders other than MS, coexisting ocular pathologies, visual acuity ±6 diopters or worse, were excluded.

Participants received standardized visual evaluations, including ocular coherence tomography. Investigators performed evaluations more than 90 days after an optic neuritis episode using a spectral-domain ocular coherence tomography Cirrus scanner. Participants also completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) more than 30 days after a relapse. This questionnaire was used to calculate the health contribution score.

Generalized linear models were used to assess the associations between moderate-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer when controlling for sex, number of optic neuritis episodes, disease duration at time of ocular coherence tomography, and within-subject correlation between eyes. Bonferroni correction was used to adjust for multiple comparisons.

Thirty patients participated in this study; 23 were female. Ocular coherence tomography was performed at a mean age of 15.7 (range, 10.6–18.0) and a median of 1.9 years from disease onset. The median retinal nerve fiber layer was 90 μm, and the median ganglion cell inner-plexiform layer was 73.5 μm. The median amount of moderate-to-vigorous physical activity was 26.5 metabolic equivalents per week.

The research team found that moderate-to-vigorous physical activity was positively associated with retinal nerve fiber layer thickness. Although the retinal nerve fiber layer and ganglion cell inner-plexiform layer were moderately correlated, moderate-to-vigorous physical activity was not associated with the ganglion cell inner-plexiform layer, said the authors.

“Next steps include a trial using mild-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS,” the researchers concluded.

NASHVILLE—Moderate-to-vigorous physical activity is positively associated with retinal nerve fiber layer thickness in children with multiple sclerosis (MS), according to research presented at the 2018 CMSC Annual Meeting. This finding may help to support an intervention targeting moderate-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS.

More than one-third of pediatric patients with MS experience optic neuritis, and most experience visual pathway abnormalities, including reductions in the retinal nerve fiber layer and ganglion cell inner-plexiform layer. Previous studies in adults have shown a positive association between moderate-to-vigorous physical activity and the retinal nerve fiber layer; however, this association has not been evaluated in pediatric patients with MS.

To investigate the associations between mild-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer in pediatric patients with MS, Alexander L. Pearson, a medical student at the University of Ottawa in Ontario, and colleagues conducted a cross-sectional study.

The researchers recruited participants from the Pediatric MS and Demyelinating Disorders Center at the Hospital for Sick Children in Toronto. Eligible participants had a diagnosis of MS (according to the International Pediatric MS Study Group consensus definitions) and were younger than 18. Patients with neuroinflammatory abnormalities associated with underlying systemic or neurologic disorders, recurrent neuroinflammatory disorders other than MS, coexisting ocular pathologies, visual acuity ±6 diopters or worse, were excluded.

Participants received standardized visual evaluations, including ocular coherence tomography. Investigators performed evaluations more than 90 days after an optic neuritis episode using a spectral-domain ocular coherence tomography Cirrus scanner. Participants also completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) more than 30 days after a relapse. This questionnaire was used to calculate the health contribution score.

Generalized linear models were used to assess the associations between moderate-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer when controlling for sex, number of optic neuritis episodes, disease duration at time of ocular coherence tomography, and within-subject correlation between eyes. Bonferroni correction was used to adjust for multiple comparisons.

Thirty patients participated in this study; 23 were female. Ocular coherence tomography was performed at a mean age of 15.7 (range, 10.6–18.0) and a median of 1.9 years from disease onset. The median retinal nerve fiber layer was 90 μm, and the median ganglion cell inner-plexiform layer was 73.5 μm. The median amount of moderate-to-vigorous physical activity was 26.5 metabolic equivalents per week.

The research team found that moderate-to-vigorous physical activity was positively associated with retinal nerve fiber layer thickness. Although the retinal nerve fiber layer and ganglion cell inner-plexiform layer were moderately correlated, moderate-to-vigorous physical activity was not associated with the ganglion cell inner-plexiform layer, said the authors.

“Next steps include a trial using mild-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS,” the researchers concluded.

NASHVILLE—Patients with multiple sclerosis (MS) with breakthrough disease may benefit from intramuscular interferon beta 1-a treatment twice per week, according to research described at the 2018 CMSC Annual Meeting. “Advantages to using an intramuscular interferon beta 1-a preparation include no skin reactions and a lower incidence of interferon neutralizing antibodies,” said Robert W. Baumhefner, MD, a neurologist at the Veteran Affairs West Los Angeles Medical Center.

Previous clinical trials have suggested a dose-response effect for interferon beta in MS. The European Interferon Beta-1a Dose Comparison Study, however, found no change in efficacy with just doubling the standard dose of intramuscular interferon beta-1a once per week. This may not be the same as increasing the frequency of intramuscular interferon administration, said Baumhefner. In addition, none of the previous studies have information on patients with breakthrough disease on standard-dose intramuscular interferon beta-1a switched to twice-weekly dosing.

Dr. Baumhefner conducted a retrospective observational study of patients MS with breakthrough disease receiving intramuscular interferon beta 1-a once per week who were switched to intramuscular interferon beta 1-a twice per week.

A total of 107 patients with MS were started on intramuscular interferon beta 1-a from 1995 to 2015 at the MS clinic of the VA West Los Angeles Medical Center. Of these, 59 patients with breakthrough disease were switched to twice-weekly intramuscular interferon beta-1a. There was adequate follow-up for at least two years for 52 of these patients. In addition, participants were followed up an average of every four months.

At each visit, an interval history of any relapse; scores on the Incapacity Status Scale, Functional Systems Scale, and Expanded Disability Status Scale (EDSS); and a proprietary graded neurologic examination were obtained. Annual MRI of the brain using a contrast-enhanced MS protocol was obtained in most patients. Baumhefner defined breakthrough disease as continued clinical relapses, new T2 or enhanced lesions on MRI, or worsening of EDSS or neurologic examination.

Of the 52 patients with adequate follow-up, 26 had no further breakthrough disease for 14 months or longer (range, 14-192 months). Five patients did not tolerate the increase in frequency of administration. Interferon beta neutralizing antibody testing was performed on 25 patients while they were receiving twice-weekly dosing. One patient who failed twice-weekly interferon beta had consistently elevated titers on two determinations (4%). African American patients, those with a higher EDSS score when switching, and patients with a longer duration of stability on weekly dosed treatment may be less likely to respond, the researcher concluded.

NASHVILLE—Patients with multiple sclerosis (MS) with breakthrough disease may benefit from intramuscular interferon beta 1-a treatment twice per week, according to research described at the 2018 CMSC Annual Meeting. “Advantages to using an intramuscular interferon beta 1-a preparation include no skin reactions and a lower incidence of interferon neutralizing antibodies,” said Robert W. Baumhefner, MD, a neurologist at the Veteran Affairs West Los Angeles Medical Center.

Previous clinical trials have suggested a dose-response effect for interferon beta in MS. The European Interferon Beta-1a Dose Comparison Study, however, found no change in efficacy with just doubling the standard dose of intramuscular interferon beta-1a once per week. This may not be the same as increasing the frequency of intramuscular interferon administration, said Baumhefner. In addition, none of the previous studies have information on patients with breakthrough disease on standard-dose intramuscular interferon beta-1a switched to twice-weekly dosing.

Dr. Baumhefner conducted a retrospective observational study of patients MS with breakthrough disease receiving intramuscular interferon beta 1-a once per week who were switched to intramuscular interferon beta 1-a twice per week.

A total of 107 patients with MS were started on intramuscular interferon beta 1-a from 1995 to 2015 at the MS clinic of the VA West Los Angeles Medical Center. Of these, 59 patients with breakthrough disease were switched to twice-weekly intramuscular interferon beta-1a. There was adequate follow-up for at least two years for 52 of these patients. In addition, participants were followed up an average of every four months.

At each visit, an interval history of any relapse; scores on the Incapacity Status Scale, Functional Systems Scale, and Expanded Disability Status Scale (EDSS); and a proprietary graded neurologic examination were obtained. Annual MRI of the brain using a contrast-enhanced MS protocol was obtained in most patients. Baumhefner defined breakthrough disease as continued clinical relapses, new T2 or enhanced lesions on MRI, or worsening of EDSS or neurologic examination.

Of the 52 patients with adequate follow-up, 26 had no further breakthrough disease for 14 months or longer (range, 14-192 months). Five patients did not tolerate the increase in frequency of administration. Interferon beta neutralizing antibody testing was performed on 25 patients while they were receiving twice-weekly dosing. One patient who failed twice-weekly interferon beta had consistently elevated titers on two determinations (4%). African American patients, those with a higher EDSS score when switching, and patients with a longer duration of stability on weekly dosed treatment may be less likely to respond, the researcher concluded.

NASHVILLE—Patients with multiple sclerosis (MS) with breakthrough disease may benefit from intramuscular interferon beta 1-a treatment twice per week, according to research described at the 2018 CMSC Annual Meeting. “Advantages to using an intramuscular interferon beta 1-a preparation include no skin reactions and a lower incidence of interferon neutralizing antibodies,” said Robert W. Baumhefner, MD, a neurologist at the Veteran Affairs West Los Angeles Medical Center.

Previous clinical trials have suggested a dose-response effect for interferon beta in MS. The European Interferon Beta-1a Dose Comparison Study, however, found no change in efficacy with just doubling the standard dose of intramuscular interferon beta-1a once per week. This may not be the same as increasing the frequency of intramuscular interferon administration, said Baumhefner. In addition, none of the previous studies have information on patients with breakthrough disease on standard-dose intramuscular interferon beta-1a switched to twice-weekly dosing.

Dr. Baumhefner conducted a retrospective observational study of patients MS with breakthrough disease receiving intramuscular interferon beta 1-a once per week who were switched to intramuscular interferon beta 1-a twice per week.

A total of 107 patients with MS were started on intramuscular interferon beta 1-a from 1995 to 2015 at the MS clinic of the VA West Los Angeles Medical Center. Of these, 59 patients with breakthrough disease were switched to twice-weekly intramuscular interferon beta-1a. There was adequate follow-up for at least two years for 52 of these patients. In addition, participants were followed up an average of every four months.

At each visit, an interval history of any relapse; scores on the Incapacity Status Scale, Functional Systems Scale, and Expanded Disability Status Scale (EDSS); and a proprietary graded neurologic examination were obtained. Annual MRI of the brain using a contrast-enhanced MS protocol was obtained in most patients. Baumhefner defined breakthrough disease as continued clinical relapses, new T2 or enhanced lesions on MRI, or worsening of EDSS or neurologic examination.

Of the 52 patients with adequate follow-up, 26 had no further breakthrough disease for 14 months or longer (range, 14-192 months). Five patients did not tolerate the increase in frequency of administration. Interferon beta neutralizing antibody testing was performed on 25 patients while they were receiving twice-weekly dosing. One patient who failed twice-weekly interferon beta had consistently elevated titers on two determinations (4%). African American patients, those with a higher EDSS score when switching, and patients with a longer duration of stability on weekly dosed treatment may be less likely to respond, the researcher concluded.