Multiple Sclerosis

Established risk factors for multiple sclerosis (MS) do not appear to impact risk of transverse myelitis (TM) or neuromyelitis optica (NMO), according to a case-control study of participants in the Accelerated Cure Project for Multiple Sclerosis.

Researchers analyzed 1,237 MS cases, 98 NMO cases, 133 TM cases, and 488 healthy controls for MS risk factors including smoking history, a history of infectious mononucleosis, anti-EBNA1 Ab titers, and HLA-DR15, and found:

• Risk factors and odds of MS were as expected.

• There was little evidence of an association between the risk factors for MS and increased odds of NMO or TM.

Citation: Simon KC, Schmidt H, Loud S, Ascherio A. Risk factors for multiple sclerosis, neuromyelitis optica and transverse myelitis. Mult Scler. 2015;21(6):703-709. doi:10.1177/1352458514551780.

Established risk factors for multiple sclerosis (MS) do not appear to impact risk of transverse myelitis (TM) or neuromyelitis optica (NMO), according to a case-control study of participants in the Accelerated Cure Project for Multiple Sclerosis.

Researchers analyzed 1,237 MS cases, 98 NMO cases, 133 TM cases, and 488 healthy controls for MS risk factors including smoking history, a history of infectious mononucleosis, anti-EBNA1 Ab titers, and HLA-DR15, and found:

• Risk factors and odds of MS were as expected.

• There was little evidence of an association between the risk factors for MS and increased odds of NMO or TM.

Citation: Simon KC, Schmidt H, Loud S, Ascherio A. Risk factors for multiple sclerosis, neuromyelitis optica and transverse myelitis. Mult Scler. 2015;21(6):703-709. doi:10.1177/1352458514551780.

Established risk factors for multiple sclerosis (MS) do not appear to impact risk of transverse myelitis (TM) or neuromyelitis optica (NMO), according to a case-control study of participants in the Accelerated Cure Project for Multiple Sclerosis.

Researchers analyzed 1,237 MS cases, 98 NMO cases, 133 TM cases, and 488 healthy controls for MS risk factors including smoking history, a history of infectious mononucleosis, anti-EBNA1 Ab titers, and HLA-DR15, and found:

• Risk factors and odds of MS were as expected.

• There was little evidence of an association between the risk factors for MS and increased odds of NMO or TM.

Citation: Simon KC, Schmidt H, Loud S, Ascherio A. Risk factors for multiple sclerosis, neuromyelitis optica and transverse myelitis. Mult Scler. 2015;21(6):703-709. doi:10.1177/1352458514551780.

The stress of being a caregiver to a patient with multiple sclerosis can result in substantial physical and psychological health concerns, and have a negative impact on employment, according to a survey of 1,446 care partners from the North American Research Committee on Multiple Sclerosis (NARCOMS).

Researchers analyzed data from an online questionnaire, including demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact on employment. They found:

• The average Zarit score was 24.6, which is in the mild caregiver burden range.

• Female caregivers reported higher levels of burden and stress than their male counterparts, and were more likely to use medication for stress, anxiety, and mood disorders.

• Male caregivers had higher rates of physical complaints than females.

• Care partners of patients with primary progressive MS reported greater perceived burden than those with secondary progressive MS and relapsing-remitting MS.

• In the past year, more than 40% of care partners had missed work due to caregiving responsibilities.   

Citation: McKenzie T, Quig ME, Tyry T, et al. Care partners and multiple sclerosis: differential impact on men and women. Int J MS Care. 2015. doi:10.7224/1537-2073.2014-083 [epub ahead of print].

The stress of being a caregiver to a patient with multiple sclerosis can result in substantial physical and psychological health concerns, and have a negative impact on employment, according to a survey of 1,446 care partners from the North American Research Committee on Multiple Sclerosis (NARCOMS).

Researchers analyzed data from an online questionnaire, including demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact on employment. They found:

• The average Zarit score was 24.6, which is in the mild caregiver burden range.

• Female caregivers reported higher levels of burden and stress than their male counterparts, and were more likely to use medication for stress, anxiety, and mood disorders.

• Male caregivers had higher rates of physical complaints than females.

• Care partners of patients with primary progressive MS reported greater perceived burden than those with secondary progressive MS and relapsing-remitting MS.

• In the past year, more than 40% of care partners had missed work due to caregiving responsibilities.   

Citation: McKenzie T, Quig ME, Tyry T, et al. Care partners and multiple sclerosis: differential impact on men and women. Int J MS Care. 2015. doi:10.7224/1537-2073.2014-083 [epub ahead of print].

The stress of being a caregiver to a patient with multiple sclerosis can result in substantial physical and psychological health concerns, and have a negative impact on employment, according to a survey of 1,446 care partners from the North American Research Committee on Multiple Sclerosis (NARCOMS).

Researchers analyzed data from an online questionnaire, including demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact on employment. They found:

• The average Zarit score was 24.6, which is in the mild caregiver burden range.

• Female caregivers reported higher levels of burden and stress than their male counterparts, and were more likely to use medication for stress, anxiety, and mood disorders.

• Male caregivers had higher rates of physical complaints than females.

• Care partners of patients with primary progressive MS reported greater perceived burden than those with secondary progressive MS and relapsing-remitting MS.

• In the past year, more than 40% of care partners had missed work due to caregiving responsibilities.   

Citation: McKenzie T, Quig ME, Tyry T, et al. Care partners and multiple sclerosis: differential impact on men and women. Int J MS Care. 2015. doi:10.7224/1537-2073.2014-083 [epub ahead of print].

A purported multiple sclerosis cure widely known as the “liberation” procedure — venoplasty to treat chronic cerebrospinal venous insufficiency — has patients traveling abroad against doctor advice to receive the unregulated procedure.

An analysis of data from the Canadian Survey of Health Lifestyle and Aging with MS, which included 753 patients over the age of 55 years old with 20 years or more of MS symptoms, found 13% underwent the alternative treatment. Researchers determined the following odds ratio for 5 factors:

• Living alone, 0.24

• Diagnosis of anxiety, 0.29

• Rating of neurologist’s helpfulness, 0.56

• Body mass index, 0.93

• Perceived physical impact of MS, 1.02

The study authors recommend physicians provide information on the risks and benefits of unregulated procedures to patients and their families who are dissatisfied with their neurologists.

Citation: Ploughman M, Manning OJ, Beaulieu S, et al.  Predictors of chronic cerebrospinal venous insufficiency procedure use among older people with multiple sclerosis: a national case-control study. BMC Health Serv Res. 2015. 15:161. doi:10.1186/s12913-015-835-y.

A purported multiple sclerosis cure widely known as the “liberation” procedure — venoplasty to treat chronic cerebrospinal venous insufficiency — has patients traveling abroad against doctor advice to receive the unregulated procedure.

An analysis of data from the Canadian Survey of Health Lifestyle and Aging with MS, which included 753 patients over the age of 55 years old with 20 years or more of MS symptoms, found 13% underwent the alternative treatment. Researchers determined the following odds ratio for 5 factors:

• Living alone, 0.24

• Diagnosis of anxiety, 0.29

• Rating of neurologist’s helpfulness, 0.56

• Body mass index, 0.93

• Perceived physical impact of MS, 1.02

The study authors recommend physicians provide information on the risks and benefits of unregulated procedures to patients and their families who are dissatisfied with their neurologists.

Citation: Ploughman M, Manning OJ, Beaulieu S, et al.  Predictors of chronic cerebrospinal venous insufficiency procedure use among older people with multiple sclerosis: a national case-control study. BMC Health Serv Res. 2015. 15:161. doi:10.1186/s12913-015-835-y.

A purported multiple sclerosis cure widely known as the “liberation” procedure — venoplasty to treat chronic cerebrospinal venous insufficiency — has patients traveling abroad against doctor advice to receive the unregulated procedure.

An analysis of data from the Canadian Survey of Health Lifestyle and Aging with MS, which included 753 patients over the age of 55 years old with 20 years or more of MS symptoms, found 13% underwent the alternative treatment. Researchers determined the following odds ratio for 5 factors:

• Living alone, 0.24

• Diagnosis of anxiety, 0.29

• Rating of neurologist’s helpfulness, 0.56

• Body mass index, 0.93

• Perceived physical impact of MS, 1.02

The study authors recommend physicians provide information on the risks and benefits of unregulated procedures to patients and their families who are dissatisfied with their neurologists.

Citation: Ploughman M, Manning OJ, Beaulieu S, et al.  Predictors of chronic cerebrospinal venous insufficiency procedure use among older people with multiple sclerosis: a national case-control study. BMC Health Serv Res. 2015. 15:161. doi:10.1186/s12913-015-835-y.

WASHINGTON – An analysis of long-term safety data of fingolimod in patients with relapsing multiple sclerosis treated for as long as 7 years has not identified new safety issues or increases in any known adverse events identified in the core studies conducted before approval, Dr. Jeffrey Cohen reported at the annual meeting of the American Academy of Neurology.

The results, based on data from the ongoing LONGTERMS open-label extension study following the safety and tolerability of fingolimod in patients enrolled in phase II and III trials, confirm that the treatment is “suitable” for long-term therapy for patients with relapsing MS, said Dr. Cohen, director of the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

Fingolimod, a sphingosine 1-phosphate receptor modulator marketed as Gilenya, was approved by the Food and Drug Administration in 2010 for relapsing forms of MS at a dose of 0.5 mg taken orally once a day. As of November 2014, more than 114,000 people worldwide have been treated with fingolimod, representing more than 195,000 patient-years of exposure, according to Dr. Cohen, who cited data from Novartis, the manufacturer.

He presented the results of the analysis of adverse events (AEs), serious adverse events (SAEs), and AEs of “special interest,” among 1,655 people with relapsing-remitting MS enrolled in LONGTERMS who were treated with fingolimod (0.5 mg a day) for a mean of 4 years (839 were on treatment for at least 7 years). They included 1,212 people treated with fingolimod in the core studies, as well as people in those studies who were on placebo or a comparator treatment and were rerandomized to treatment with fingolimod. At enrollment in the original study, the mean age was 38 years, and 70% of the patients were females. The patients had had MS for a mean of 5 years, and had a mean score of 2.31 on the Expanded Disability Status Scale (EDSS).

The analysis compared the safety profile in the extension and core studies by calculating the incidence rate (IR) for the events in each database, and calculating the incidence rate ratio (IRR) by dividing the IR for the longterm study cohort by the IR for the core cohort. (The IRs were expressed as the number of AEs “per 100 patient-years of the at-risk population.”) AEs of special interest were infections, hypertension, respiratory conditions, lymphopenia, macular edema, bradyarrhythmia after the first dose, reproductive toxicity, liver transaminase elevation, skin cancer, other malignant neoplasms, and thromboembolic events.

The only SAE with an IRR that exceeded 1 was herpes zoster infections, but the odds ratio was broad and overlapped one, Dr. Cohen said. The results for other SAEs included an IRR of 0.47 for bradyarrhythmia after the first dose, and an IRR of 0.45 for macular edema.

In the analysis of AEs, leucopenia and lymphopenia “seem to be increased” with more time on fingolimod, he noted. In the long-term cohort, the IR for this adverse event was 6.2, compared with 4.6 for the core cohort, for an IRR of 1.36. However, this could have been a result of increased reporting resulting from investigators’ awareness of lymphocyte counts, since it is an open-label study, he said, pointing out that in the core studies, lymphocyte counts were unblinded only if they reached 0.2 x 10⁹/L. There was no evidence of a progressive decline in lymphocyte counts, with no significant differences in trends over time with mean lymphocyte counts between those in the core and extension studies, although “we can’t eliminate” this possibility, he added.

The overall rate of infections did not appear to increase over time, with an IRR of 0.72.

There were more serious infections with longer treatment among patients with sustained low levels of peripheral lymphocyte counts, defined as absolute lymphocyte counts below 0.4 x 10⁹/L for at least 60% of the records during the corresponding time interval. There were 28 cases of serious infection among those on treatment for more than 2 years and 14 cases among those on treatment for 2 years or less. The occurrence rate for the number of serious infections, which could be more than once for an individual patient, was 1.4 among those treated for more than 2 years vs. 1.0 for those treated for 2 years or less, for an occurrence rate ratio of 1.47.

Pointing out that the number of cases was small and the confidence intervals for this finding were wide, Dr. Cohen concluded that the LONGTERMS data do not support “an overall increased risk of infections with long-term exposure or with sustained low peripheral lymphocyte counts.”

Dr. Cohen disclosed ties with Novartis, which funded the study.

emechcatie@frontlinemedcom.com

WASHINGTON – An analysis of long-term safety data of fingolimod in patients with relapsing multiple sclerosis treated for as long as 7 years has not identified new safety issues or increases in any known adverse events identified in the core studies conducted before approval, Dr. Jeffrey Cohen reported at the annual meeting of the American Academy of Neurology.

The results, based on data from the ongoing LONGTERMS open-label extension study following the safety and tolerability of fingolimod in patients enrolled in phase II and III trials, confirm that the treatment is “suitable” for long-term therapy for patients with relapsing MS, said Dr. Cohen, director of the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

Fingolimod, a sphingosine 1-phosphate receptor modulator marketed as Gilenya, was approved by the Food and Drug Administration in 2010 for relapsing forms of MS at a dose of 0.5 mg taken orally once a day. As of November 2014, more than 114,000 people worldwide have been treated with fingolimod, representing more than 195,000 patient-years of exposure, according to Dr. Cohen, who cited data from Novartis, the manufacturer.

He presented the results of the analysis of adverse events (AEs), serious adverse events (SAEs), and AEs of “special interest,” among 1,655 people with relapsing-remitting MS enrolled in LONGTERMS who were treated with fingolimod (0.5 mg a day) for a mean of 4 years (839 were on treatment for at least 7 years). They included 1,212 people treated with fingolimod in the core studies, as well as people in those studies who were on placebo or a comparator treatment and were rerandomized to treatment with fingolimod. At enrollment in the original study, the mean age was 38 years, and 70% of the patients were females. The patients had had MS for a mean of 5 years, and had a mean score of 2.31 on the Expanded Disability Status Scale (EDSS).

The analysis compared the safety profile in the extension and core studies by calculating the incidence rate (IR) for the events in each database, and calculating the incidence rate ratio (IRR) by dividing the IR for the longterm study cohort by the IR for the core cohort. (The IRs were expressed as the number of AEs “per 100 patient-years of the at-risk population.”) AEs of special interest were infections, hypertension, respiratory conditions, lymphopenia, macular edema, bradyarrhythmia after the first dose, reproductive toxicity, liver transaminase elevation, skin cancer, other malignant neoplasms, and thromboembolic events.

The only SAE with an IRR that exceeded 1 was herpes zoster infections, but the odds ratio was broad and overlapped one, Dr. Cohen said. The results for other SAEs included an IRR of 0.47 for bradyarrhythmia after the first dose, and an IRR of 0.45 for macular edema.

In the analysis of AEs, leucopenia and lymphopenia “seem to be increased” with more time on fingolimod, he noted. In the long-term cohort, the IR for this adverse event was 6.2, compared with 4.6 for the core cohort, for an IRR of 1.36. However, this could have been a result of increased reporting resulting from investigators’ awareness of lymphocyte counts, since it is an open-label study, he said, pointing out that in the core studies, lymphocyte counts were unblinded only if they reached 0.2 x 10⁹/L. There was no evidence of a progressive decline in lymphocyte counts, with no significant differences in trends over time with mean lymphocyte counts between those in the core and extension studies, although “we can’t eliminate” this possibility, he added.

The overall rate of infections did not appear to increase over time, with an IRR of 0.72.

There were more serious infections with longer treatment among patients with sustained low levels of peripheral lymphocyte counts, defined as absolute lymphocyte counts below 0.4 x 10⁹/L for at least 60% of the records during the corresponding time interval. There were 28 cases of serious infection among those on treatment for more than 2 years and 14 cases among those on treatment for 2 years or less. The occurrence rate for the number of serious infections, which could be more than once for an individual patient, was 1.4 among those treated for more than 2 years vs. 1.0 for those treated for 2 years or less, for an occurrence rate ratio of 1.47.

Pointing out that the number of cases was small and the confidence intervals for this finding were wide, Dr. Cohen concluded that the LONGTERMS data do not support “an overall increased risk of infections with long-term exposure or with sustained low peripheral lymphocyte counts.”

Dr. Cohen disclosed ties with Novartis, which funded the study.

emechcatie@frontlinemedcom.com

WASHINGTON – An analysis of long-term safety data of fingolimod in patients with relapsing multiple sclerosis treated for as long as 7 years has not identified new safety issues or increases in any known adverse events identified in the core studies conducted before approval, Dr. Jeffrey Cohen reported at the annual meeting of the American Academy of Neurology.

The results, based on data from the ongoing LONGTERMS open-label extension study following the safety and tolerability of fingolimod in patients enrolled in phase II and III trials, confirm that the treatment is “suitable” for long-term therapy for patients with relapsing MS, said Dr. Cohen, director of the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

Fingolimod, a sphingosine 1-phosphate receptor modulator marketed as Gilenya, was approved by the Food and Drug Administration in 2010 for relapsing forms of MS at a dose of 0.5 mg taken orally once a day. As of November 2014, more than 114,000 people worldwide have been treated with fingolimod, representing more than 195,000 patient-years of exposure, according to Dr. Cohen, who cited data from Novartis, the manufacturer.

He presented the results of the analysis of adverse events (AEs), serious adverse events (SAEs), and AEs of “special interest,” among 1,655 people with relapsing-remitting MS enrolled in LONGTERMS who were treated with fingolimod (0.5 mg a day) for a mean of 4 years (839 were on treatment for at least 7 years). They included 1,212 people treated with fingolimod in the core studies, as well as people in those studies who were on placebo or a comparator treatment and were rerandomized to treatment with fingolimod. At enrollment in the original study, the mean age was 38 years, and 70% of the patients were females. The patients had had MS for a mean of 5 years, and had a mean score of 2.31 on the Expanded Disability Status Scale (EDSS).

The analysis compared the safety profile in the extension and core studies by calculating the incidence rate (IR) for the events in each database, and calculating the incidence rate ratio (IRR) by dividing the IR for the longterm study cohort by the IR for the core cohort. (The IRs were expressed as the number of AEs “per 100 patient-years of the at-risk population.”) AEs of special interest were infections, hypertension, respiratory conditions, lymphopenia, macular edema, bradyarrhythmia after the first dose, reproductive toxicity, liver transaminase elevation, skin cancer, other malignant neoplasms, and thromboembolic events.

The only SAE with an IRR that exceeded 1 was herpes zoster infections, but the odds ratio was broad and overlapped one, Dr. Cohen said. The results for other SAEs included an IRR of 0.47 for bradyarrhythmia after the first dose, and an IRR of 0.45 for macular edema.

In the analysis of AEs, leucopenia and lymphopenia “seem to be increased” with more time on fingolimod, he noted. In the long-term cohort, the IR for this adverse event was 6.2, compared with 4.6 for the core cohort, for an IRR of 1.36. However, this could have been a result of increased reporting resulting from investigators’ awareness of lymphocyte counts, since it is an open-label study, he said, pointing out that in the core studies, lymphocyte counts were unblinded only if they reached 0.2 x 10⁹/L. There was no evidence of a progressive decline in lymphocyte counts, with no significant differences in trends over time with mean lymphocyte counts between those in the core and extension studies, although “we can’t eliminate” this possibility, he added.

The overall rate of infections did not appear to increase over time, with an IRR of 0.72.

There were more serious infections with longer treatment among patients with sustained low levels of peripheral lymphocyte counts, defined as absolute lymphocyte counts below 0.4 x 10⁹/L for at least 60% of the records during the corresponding time interval. There were 28 cases of serious infection among those on treatment for more than 2 years and 14 cases among those on treatment for 2 years or less. The occurrence rate for the number of serious infections, which could be more than once for an individual patient, was 1.4 among those treated for more than 2 years vs. 1.0 for those treated for 2 years or less, for an occurrence rate ratio of 1.47.

Pointing out that the number of cases was small and the confidence intervals for this finding were wide, Dr. Cohen concluded that the LONGTERMS data do not support “an overall increased risk of infections with long-term exposure or with sustained low peripheral lymphocyte counts.”

Dr. Cohen disclosed ties with Novartis, which funded the study.

emechcatie@frontlinemedcom.com

WASHINGTON – Beneficial effects of peginterferon beta-1a administered every 2 weeks were evident as early as 12 weeks after starting treatment, in the pivotal phase III study comparing peginterferon beta-1a to placebo in patients with relapsing remitting multiple sclerosis, Dr. Scott Newsome, said at the annual meeting of the American Academy of Neurology.

At 12 weeks, treatment with peginterferon beta-1a was associated with a 37% reduction in the adjusted annualized relapse rate (ARR) compared with placebo, in the ADVANCE study, said Dr. Newsome of the department of neurology at Johns Hopkins University, Baltimore.

ADVANCE compared 125 mcg of peginterferon beta-1a administered every 2 or 4 weeks to placebo in patients with relapsing remitting MS. The efficacy of peginterferon beta-1a was maintained over 2 years. Greater efficacy was seen with administration every 2 weeks (Lancet Neurol. 2014;13:657-65). In August 2014, the Food and Drug Administration approved peginterferon beta-1a, at a dose of 125 mcg administered subcutaneously every 14 days, for relapsing forms of multiple sclerosis; it is marketed as Plegridy by Biogen Idec.

Interim results of the follow-up study of patients enrolled in ADVANCE – the ATTAIN trial – have shown that over 3 years of treatment, no new safety issues or concerns have emerged, and the clinical effects of treatment are maintained, according to Dr. Marcelo Kremenchutzky of Western University, London, Ont., who presented those results at the meeting.

Dr. Newsome presented the 12-week data among 512 patients randomized to treatment every 2 weeks and 500 randomized to placebo in the ADVANCE study; their mean age was 36-37 years, almost two-thirds were female, and 81%-82% were white. They were enrolled for a mean of 6-7 years from their first MS symptoms and had had a mean of 2.6 relapses within the previous 3 years. Their mean Expanded Disability Status Scale (EDSS) scores were 2.44-2.47.

At 12 weeks, the ARR, the primary endpoint, among those on peginterferon beta-1a was 0.259 vs. 0.414 among those on placebo, a 37.4% reduction over placebo (P = .045), Dr. Newsome said. The ARR was adjusted for baseline EDSS, relapse rate, and age. (At 48 weeks, the ARR among those on peginterferon beta-1a every 2 weeks was 0.26, compared with 0.40 among those on placebo, a significantly reduced risk of 36%, with a P value of .0007.)

The proportion of patients who relapsed at 12 weeks – 6% of those on peginterferon beta-1a vs. 9.5% of those on placebo – was reduced by 36.8% (P = .041), with a “clear separation” between the treatment and control arms at 12 weeks, he noted.

In addition, the estimated proportion of patients with an onset of 24-week confirmed disability progression (CDP) was 0 among those on peginterferon beta-1a versus 1.0% among those on placebo (P = .026). This result was not as robust as the relapse results, but there was a clear separation between the arms with statistical significance, said Dr. Newsome, director of outpatient neurology services at Johns Hopkins.

In the ADVANCE study, PEG administered every 2 or 4 weeks was well tolerated with a favorable safety profile in the first year, and a similar safety profile between the two dosing regimens, he added.

Dr. Kremenchutzky, director of the Multiple Sclerosis Clinic in London, Ont., presented the 1-year data in the ongoing extension study that is evaluating long-term MS outcomes, safety, and tolerability of peginterferon beta-1a among patients enrolled in ADVANCE, including those treated with peginterferon beta-1a every 2 weeks (376) or every 4 weeks (354).

Also included are 344 patients who were on placebo but were rerandomized to peginterferon beta-1a every 2 or 4 weeks (the delayed treatment group) after 1 year in the ADVANCE study; they were included in the analyses after they had been on treatment for 2 years.

After 1 year in the ATTAIN study, injection-site reactions and flu-like symptoms remained the most frequent adverse events associated with peginterferon beta-1a, and most were mild to moderate. Treatment has also been associated with “low levels” of laboratory abnormalities and immunogenicity, and clinical efficacy has been maintained for 3 years, Dr. Kremenchutzky said at the meeting.

Adverse events were “very similar” in the 4-week and 2-week treatment groups. Over 3 years, 96% of patients in both groups had experienced an adverse event, and the rates of treatment-related adverse events (91%), and severe adverse events (24%) were the same in both groups. The rates of treatment discontinuations due to an adverse event (7%-8%) and withdrawal from the study due to an adverse event (8%-9%) were similar.

The rates of flu-like symptoms over 3 years were also similar (62%-64%) in the two groups, and influenza-like illness was reported in 55% of those dosed every 2 weeks and in 45% of those dosed every 4 weeks. In addition to influenza-like illness, pyrexia was the most common flu-like symptom reported over 3 years (43%-45%).

About 65%-69% of those in the two groups reported injection-site reactions, with erythema the most common (62%-64%), followed by pain (17%-18%) and pruritus (12%-16%).

Lab abnormalities were comparable with both dosing schedules: Over 3 years, white blood cell counts were reduced in 6% of those on the 2-week schedule, compared with 8% among those on the 4-week schedule. Lymphocyte counts were reduced in 12% and 9% of those on the 2-week and 4-week schedules, respectively. In addition, 8% of those on the 2-week dose and 6% of those on the 4-week dose had low hemoglobin (100 g/L or less) over the 3 years.

Rates of anti-IFN and anti-PEG antibodies associated with both schedules were low, Dr. Kremenchutzkysaid. Over 3 years, 7%-9% tested positive for IFN binding antibody at least once, and 4%-6% of the total were “persistent positive.” Another 9% of those on the 4-week schedule and 6% of those on the 2-week schedule were anti-PEG antibody positive at least once, and 3%-5% of the patients in total had persistent levels. Titers were high in less than 1% of the total.

In ATTAIN, efficacy endpoints were secondary, and included ARR, which was reduced by 25.1% over 3 years among those receiving the dose every 2 weeks, compared with every 4 weeks (P = .0199). By 144 weeks, 30.5% of those on the 2-week schedule and 41.1% of those on the 4-week schedule had experienced a relapse, a significant difference (P = .0070), Dr. Kremenchutzky said.

The proportion of those with CDP by 144 weeks was 15.5% among those on the 4-week schedule, vs. 9.2% among those on the 2-week schedule (P = .0098), he added.

The studies were funded by Biogen Idec. Dr. Newsome and Dr. Kremenchutzky both disclosed having been compensated for activities with Biogen Idec and other companies that market MS drugs.

emechcatie@frontlinemedcom.com

WASHINGTON – Beneficial effects of peginterferon beta-1a administered every 2 weeks were evident as early as 12 weeks after starting treatment, in the pivotal phase III study comparing peginterferon beta-1a to placebo in patients with relapsing remitting multiple sclerosis, Dr. Scott Newsome, said at the annual meeting of the American Academy of Neurology.

At 12 weeks, treatment with peginterferon beta-1a was associated with a 37% reduction in the adjusted annualized relapse rate (ARR) compared with placebo, in the ADVANCE study, said Dr. Newsome of the department of neurology at Johns Hopkins University, Baltimore.

ADVANCE compared 125 mcg of peginterferon beta-1a administered every 2 or 4 weeks to placebo in patients with relapsing remitting MS. The efficacy of peginterferon beta-1a was maintained over 2 years. Greater efficacy was seen with administration every 2 weeks (Lancet Neurol. 2014;13:657-65). In August 2014, the Food and Drug Administration approved peginterferon beta-1a, at a dose of 125 mcg administered subcutaneously every 14 days, for relapsing forms of multiple sclerosis; it is marketed as Plegridy by Biogen Idec.

Interim results of the follow-up study of patients enrolled in ADVANCE – the ATTAIN trial – have shown that over 3 years of treatment, no new safety issues or concerns have emerged, and the clinical effects of treatment are maintained, according to Dr. Marcelo Kremenchutzky of Western University, London, Ont., who presented those results at the meeting.

Dr. Newsome presented the 12-week data among 512 patients randomized to treatment every 2 weeks and 500 randomized to placebo in the ADVANCE study; their mean age was 36-37 years, almost two-thirds were female, and 81%-82% were white. They were enrolled for a mean of 6-7 years from their first MS symptoms and had had a mean of 2.6 relapses within the previous 3 years. Their mean Expanded Disability Status Scale (EDSS) scores were 2.44-2.47.

At 12 weeks, the ARR, the primary endpoint, among those on peginterferon beta-1a was 0.259 vs. 0.414 among those on placebo, a 37.4% reduction over placebo (P = .045), Dr. Newsome said. The ARR was adjusted for baseline EDSS, relapse rate, and age. (At 48 weeks, the ARR among those on peginterferon beta-1a every 2 weeks was 0.26, compared with 0.40 among those on placebo, a significantly reduced risk of 36%, with a P value of .0007.)

The proportion of patients who relapsed at 12 weeks – 6% of those on peginterferon beta-1a vs. 9.5% of those on placebo – was reduced by 36.8% (P = .041), with a “clear separation” between the treatment and control arms at 12 weeks, he noted.

In addition, the estimated proportion of patients with an onset of 24-week confirmed disability progression (CDP) was 0 among those on peginterferon beta-1a versus 1.0% among those on placebo (P = .026). This result was not as robust as the relapse results, but there was a clear separation between the arms with statistical significance, said Dr. Newsome, director of outpatient neurology services at Johns Hopkins.

In the ADVANCE study, PEG administered every 2 or 4 weeks was well tolerated with a favorable safety profile in the first year, and a similar safety profile between the two dosing regimens, he added.

Dr. Kremenchutzky, director of the Multiple Sclerosis Clinic in London, Ont., presented the 1-year data in the ongoing extension study that is evaluating long-term MS outcomes, safety, and tolerability of peginterferon beta-1a among patients enrolled in ADVANCE, including those treated with peginterferon beta-1a every 2 weeks (376) or every 4 weeks (354).

Also included are 344 patients who were on placebo but were rerandomized to peginterferon beta-1a every 2 or 4 weeks (the delayed treatment group) after 1 year in the ADVANCE study; they were included in the analyses after they had been on treatment for 2 years.

After 1 year in the ATTAIN study, injection-site reactions and flu-like symptoms remained the most frequent adverse events associated with peginterferon beta-1a, and most were mild to moderate. Treatment has also been associated with “low levels” of laboratory abnormalities and immunogenicity, and clinical efficacy has been maintained for 3 years, Dr. Kremenchutzky said at the meeting.

Adverse events were “very similar” in the 4-week and 2-week treatment groups. Over 3 years, 96% of patients in both groups had experienced an adverse event, and the rates of treatment-related adverse events (91%), and severe adverse events (24%) were the same in both groups. The rates of treatment discontinuations due to an adverse event (7%-8%) and withdrawal from the study due to an adverse event (8%-9%) were similar.

The rates of flu-like symptoms over 3 years were also similar (62%-64%) in the two groups, and influenza-like illness was reported in 55% of those dosed every 2 weeks and in 45% of those dosed every 4 weeks. In addition to influenza-like illness, pyrexia was the most common flu-like symptom reported over 3 years (43%-45%).

About 65%-69% of those in the two groups reported injection-site reactions, with erythema the most common (62%-64%), followed by pain (17%-18%) and pruritus (12%-16%).

Lab abnormalities were comparable with both dosing schedules: Over 3 years, white blood cell counts were reduced in 6% of those on the 2-week schedule, compared with 8% among those on the 4-week schedule. Lymphocyte counts were reduced in 12% and 9% of those on the 2-week and 4-week schedules, respectively. In addition, 8% of those on the 2-week dose and 6% of those on the 4-week dose had low hemoglobin (100 g/L or less) over the 3 years.

Rates of anti-IFN and anti-PEG antibodies associated with both schedules were low, Dr. Kremenchutzkysaid. Over 3 years, 7%-9% tested positive for IFN binding antibody at least once, and 4%-6% of the total were “persistent positive.” Another 9% of those on the 4-week schedule and 6% of those on the 2-week schedule were anti-PEG antibody positive at least once, and 3%-5% of the patients in total had persistent levels. Titers were high in less than 1% of the total.

In ATTAIN, efficacy endpoints were secondary, and included ARR, which was reduced by 25.1% over 3 years among those receiving the dose every 2 weeks, compared with every 4 weeks (P = .0199). By 144 weeks, 30.5% of those on the 2-week schedule and 41.1% of those on the 4-week schedule had experienced a relapse, a significant difference (P = .0070), Dr. Kremenchutzky said.

The proportion of those with CDP by 144 weeks was 15.5% among those on the 4-week schedule, vs. 9.2% among those on the 2-week schedule (P = .0098), he added.

The studies were funded by Biogen Idec. Dr. Newsome and Dr. Kremenchutzky both disclosed having been compensated for activities with Biogen Idec and other companies that market MS drugs.

emechcatie@frontlinemedcom.com

WASHINGTON – Beneficial effects of peginterferon beta-1a administered every 2 weeks were evident as early as 12 weeks after starting treatment, in the pivotal phase III study comparing peginterferon beta-1a to placebo in patients with relapsing remitting multiple sclerosis, Dr. Scott Newsome, said at the annual meeting of the American Academy of Neurology.

At 12 weeks, treatment with peginterferon beta-1a was associated with a 37% reduction in the adjusted annualized relapse rate (ARR) compared with placebo, in the ADVANCE study, said Dr. Newsome of the department of neurology at Johns Hopkins University, Baltimore.

ADVANCE compared 125 mcg of peginterferon beta-1a administered every 2 or 4 weeks to placebo in patients with relapsing remitting MS. The efficacy of peginterferon beta-1a was maintained over 2 years. Greater efficacy was seen with administration every 2 weeks (Lancet Neurol. 2014;13:657-65). In August 2014, the Food and Drug Administration approved peginterferon beta-1a, at a dose of 125 mcg administered subcutaneously every 14 days, for relapsing forms of multiple sclerosis; it is marketed as Plegridy by Biogen Idec.

Interim results of the follow-up study of patients enrolled in ADVANCE – the ATTAIN trial – have shown that over 3 years of treatment, no new safety issues or concerns have emerged, and the clinical effects of treatment are maintained, according to Dr. Marcelo Kremenchutzky of Western University, London, Ont., who presented those results at the meeting.

Dr. Newsome presented the 12-week data among 512 patients randomized to treatment every 2 weeks and 500 randomized to placebo in the ADVANCE study; their mean age was 36-37 years, almost two-thirds were female, and 81%-82% were white. They were enrolled for a mean of 6-7 years from their first MS symptoms and had had a mean of 2.6 relapses within the previous 3 years. Their mean Expanded Disability Status Scale (EDSS) scores were 2.44-2.47.

At 12 weeks, the ARR, the primary endpoint, among those on peginterferon beta-1a was 0.259 vs. 0.414 among those on placebo, a 37.4% reduction over placebo (P = .045), Dr. Newsome said. The ARR was adjusted for baseline EDSS, relapse rate, and age. (At 48 weeks, the ARR among those on peginterferon beta-1a every 2 weeks was 0.26, compared with 0.40 among those on placebo, a significantly reduced risk of 36%, with a P value of .0007.)

The proportion of patients who relapsed at 12 weeks – 6% of those on peginterferon beta-1a vs. 9.5% of those on placebo – was reduced by 36.8% (P = .041), with a “clear separation” between the treatment and control arms at 12 weeks, he noted.

In addition, the estimated proportion of patients with an onset of 24-week confirmed disability progression (CDP) was 0 among those on peginterferon beta-1a versus 1.0% among those on placebo (P = .026). This result was not as robust as the relapse results, but there was a clear separation between the arms with statistical significance, said Dr. Newsome, director of outpatient neurology services at Johns Hopkins.

In the ADVANCE study, PEG administered every 2 or 4 weeks was well tolerated with a favorable safety profile in the first year, and a similar safety profile between the two dosing regimens, he added.

Dr. Kremenchutzky, director of the Multiple Sclerosis Clinic in London, Ont., presented the 1-year data in the ongoing extension study that is evaluating long-term MS outcomes, safety, and tolerability of peginterferon beta-1a among patients enrolled in ADVANCE, including those treated with peginterferon beta-1a every 2 weeks (376) or every 4 weeks (354).

Also included are 344 patients who were on placebo but were rerandomized to peginterferon beta-1a every 2 or 4 weeks (the delayed treatment group) after 1 year in the ADVANCE study; they were included in the analyses after they had been on treatment for 2 years.

After 1 year in the ATTAIN study, injection-site reactions and flu-like symptoms remained the most frequent adverse events associated with peginterferon beta-1a, and most were mild to moderate. Treatment has also been associated with “low levels” of laboratory abnormalities and immunogenicity, and clinical efficacy has been maintained for 3 years, Dr. Kremenchutzky said at the meeting.

Adverse events were “very similar” in the 4-week and 2-week treatment groups. Over 3 years, 96% of patients in both groups had experienced an adverse event, and the rates of treatment-related adverse events (91%), and severe adverse events (24%) were the same in both groups. The rates of treatment discontinuations due to an adverse event (7%-8%) and withdrawal from the study due to an adverse event (8%-9%) were similar.

The rates of flu-like symptoms over 3 years were also similar (62%-64%) in the two groups, and influenza-like illness was reported in 55% of those dosed every 2 weeks and in 45% of those dosed every 4 weeks. In addition to influenza-like illness, pyrexia was the most common flu-like symptom reported over 3 years (43%-45%).

About 65%-69% of those in the two groups reported injection-site reactions, with erythema the most common (62%-64%), followed by pain (17%-18%) and pruritus (12%-16%).

Lab abnormalities were comparable with both dosing schedules: Over 3 years, white blood cell counts were reduced in 6% of those on the 2-week schedule, compared with 8% among those on the 4-week schedule. Lymphocyte counts were reduced in 12% and 9% of those on the 2-week and 4-week schedules, respectively. In addition, 8% of those on the 2-week dose and 6% of those on the 4-week dose had low hemoglobin (100 g/L or less) over the 3 years.

Rates of anti-IFN and anti-PEG antibodies associated with both schedules were low, Dr. Kremenchutzkysaid. Over 3 years, 7%-9% tested positive for IFN binding antibody at least once, and 4%-6% of the total were “persistent positive.” Another 9% of those on the 4-week schedule and 6% of those on the 2-week schedule were anti-PEG antibody positive at least once, and 3%-5% of the patients in total had persistent levels. Titers were high in less than 1% of the total.

In ATTAIN, efficacy endpoints were secondary, and included ARR, which was reduced by 25.1% over 3 years among those receiving the dose every 2 weeks, compared with every 4 weeks (P = .0199). By 144 weeks, 30.5% of those on the 2-week schedule and 41.1% of those on the 4-week schedule had experienced a relapse, a significant difference (P = .0070), Dr. Kremenchutzky said.

The proportion of those with CDP by 144 weeks was 15.5% among those on the 4-week schedule, vs. 9.2% among those on the 2-week schedule (P = .0098), he added.

The studies were funded by Biogen Idec. Dr. Newsome and Dr. Kremenchutzky both disclosed having been compensated for activities with Biogen Idec and other companies that market MS drugs.

emechcatie@frontlinemedcom.com

The Multiple Sclerosis Coalition’s consensus paper on the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) includes the following recommendations:

• Treatment with an FDA-approved DMT should be initiated as soon as possible following a diagnosis of relapsing disease; after a first clinical event with MRI features consistent with MS in which other causes have been ruled out; and in patients with progressive MS with clinical relapses and/or inflammatory activity.

• Treatment with DMTs should continue indefinitely unless there are intolerable side effects, inadequate adherence, sub-optimal treatment response, or a more appropriate option becomes available.

• When additional clinical or MRI activity occurs while on treatment, consider an alternate regimen with a different mechanism of action.

• Absence of relapse while on DMT should not be considered a reason to discontinue treatment.

The full report is available here.

Citation: Costello K, Halper J, Kalb R, Skutnik L, Rapp R. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. A consensus paper by the Multiple Sclerosis Coalition. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Updated March 2015. Accessed April 30, 2015.

Commentary: Multiple Sclerosis is a disease with no cure but treatment options that have evolved and expanded over the past 25 years. The need to treat early, treat effectively, and to monitor for disease activity not apparent clinically but identified on MRI and by other metrics has become more critical due to the multiplicity of treatment options. The complexity and nuances of mechanism of action, route, frequency, efficacy, sequencing, and monitoring for disease modifying therapy has also become more involved, and keeping abreast of the ever expanding and important information required to effectively treat this illness has become more than a full time job. 

This article is an extremely important review of many of the ins and outs, risks and benefits, and options of treatment. More importantly, it is a comprehensive resource with background information regarding the impact of this disease related to cognition, fatigue, mood, and incidence of these less commonly recognized but ever-present burdens that add to disease-related disability that should be identified and treated along with disease activity. To provide anything less than effective and comprehensive care is no longer justified. This review provides an overview of care needs and treatment options for MS clinicians and for our patients. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

The Multiple Sclerosis Coalition’s consensus paper on the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) includes the following recommendations:

• Treatment with an FDA-approved DMT should be initiated as soon as possible following a diagnosis of relapsing disease; after a first clinical event with MRI features consistent with MS in which other causes have been ruled out; and in patients with progressive MS with clinical relapses and/or inflammatory activity.

• Treatment with DMTs should continue indefinitely unless there are intolerable side effects, inadequate adherence, sub-optimal treatment response, or a more appropriate option becomes available.

• When additional clinical or MRI activity occurs while on treatment, consider an alternate regimen with a different mechanism of action.

• Absence of relapse while on DMT should not be considered a reason to discontinue treatment.

The full report is available here.

Citation: Costello K, Halper J, Kalb R, Skutnik L, Rapp R. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. A consensus paper by the Multiple Sclerosis Coalition. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Updated March 2015. Accessed April 30, 2015.

Commentary: Multiple Sclerosis is a disease with no cure but treatment options that have evolved and expanded over the past 25 years. The need to treat early, treat effectively, and to monitor for disease activity not apparent clinically but identified on MRI and by other metrics has become more critical due to the multiplicity of treatment options. The complexity and nuances of mechanism of action, route, frequency, efficacy, sequencing, and monitoring for disease modifying therapy has also become more involved, and keeping abreast of the ever expanding and important information required to effectively treat this illness has become more than a full time job. 

This article is an extremely important review of many of the ins and outs, risks and benefits, and options of treatment. More importantly, it is a comprehensive resource with background information regarding the impact of this disease related to cognition, fatigue, mood, and incidence of these less commonly recognized but ever-present burdens that add to disease-related disability that should be identified and treated along with disease activity. To provide anything less than effective and comprehensive care is no longer justified. This review provides an overview of care needs and treatment options for MS clinicians and for our patients. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

The Multiple Sclerosis Coalition’s consensus paper on the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) includes the following recommendations:

• Treatment with an FDA-approved DMT should be initiated as soon as possible following a diagnosis of relapsing disease; after a first clinical event with MRI features consistent with MS in which other causes have been ruled out; and in patients with progressive MS with clinical relapses and/or inflammatory activity.

• Treatment with DMTs should continue indefinitely unless there are intolerable side effects, inadequate adherence, sub-optimal treatment response, or a more appropriate option becomes available.

• When additional clinical or MRI activity occurs while on treatment, consider an alternate regimen with a different mechanism of action.

• Absence of relapse while on DMT should not be considered a reason to discontinue treatment.

The full report is available here.

Citation: Costello K, Halper J, Kalb R, Skutnik L, Rapp R. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. A consensus paper by the Multiple Sclerosis Coalition. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Updated March 2015. Accessed April 30, 2015.

Commentary: Multiple Sclerosis is a disease with no cure but treatment options that have evolved and expanded over the past 25 years. The need to treat early, treat effectively, and to monitor for disease activity not apparent clinically but identified on MRI and by other metrics has become more critical due to the multiplicity of treatment options. The complexity and nuances of mechanism of action, route, frequency, efficacy, sequencing, and monitoring for disease modifying therapy has also become more involved, and keeping abreast of the ever expanding and important information required to effectively treat this illness has become more than a full time job. 

This article is an extremely important review of many of the ins and outs, risks and benefits, and options of treatment. More importantly, it is a comprehensive resource with background information regarding the impact of this disease related to cognition, fatigue, mood, and incidence of these less commonly recognized but ever-present burdens that add to disease-related disability that should be identified and treated along with disease activity. To provide anything less than effective and comprehensive care is no longer justified. This review provides an overview of care needs and treatment options for MS clinicians and for our patients. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY