Here, you can read about the latest research into new drugs for MS and it's symptoms.
A new comprehensive report on the safety of MS drugs may have doctors rethinking their recommendations.
The results are in, and according to a recent report comparing the safety records of all multiple sclerosis (MS) drugs on the market, Tecfidera took the top safety prize. The report reveals that newer MS drugs received high marks for safety, while older interferon drugs had more reported side effects.
California-based health informatics company AdverseEvents analyzed side effects data from the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) database. The FDA asks that doctors, consumers, and drugmakers report any serious negative health events they or their patients experience while taking an FDA-approved drug.
Using a formula called the “reporting odds ratio” (ROR), analysts compare how often an adverse event (AE) has been reported, regardless of drug, to how often the event has been reported for a specific drug in the FAERS database. This helps safety professionals identify AE and drug pairs with a higher than usual occurrence of a particular side effect, sending up a red flag.
Because the ROR is a ratio that is not affected by length of time a drug has been on the market, the analysts at AdverseEvents were able to compare the oldest MS drugs with the newest and compile accurate results, giving each drug an “RxScore.”
So, comparing the AEs reported for all MS drugs only during the time period since Tecfidera won approval did not affect the outcome, said Keith Hoffman, Vice President of Scientific Affairs at AdverseEvents, in an interview with Healthline. “We have completed that time comparison with other drug classes many times and the overall results stayed the same.”
A Few Bad Apples
The RxScore scale ranges from 0 to 100, with higher numbers indicating a greater risk of adverse events. Avonex, Rebif and Betaseron, all interferons, had the worst safety records, with scores between 53 and 55. Copaxone had the fourth highest score at 47.4.
Betaseron had the highest ratio for reports of disability or death, while Avonex users were hospitalized due to AEs the most often.
People taking Avonex reported more malignant tumors, breast cancer diagnoses, and flu-like symptoms than those taking other drugs, while Betaseron users reported more heart attacks, bacterial infections, and liver problems.
Rebif received the worst RxScore, with a higher proportion of negative events including suicidal behavior, optic nerve inflammation, and cancers of the female reproductive system.
Copaxone fared worst for life-threatening allergic reactions and psychiatric symptoms. But Copaxone, FDA-approved in 1996, scored best on measures of several side effects, including cognitive disorders and flu-like symptoms, making it the safest of the older first-line MS drugs.
The Best of the Bunch Tecfidera attained the lowest RxScore of 33 and the lowest ROR of life-threatening events, hospitalizations, disability, or death. It also scored lowest for everything from bacterial infections to optic nerve disorders and liver problems. Overall, Tecfidera had the lowest ROR for 24 out of the 58 side effects the researchers studied.
Gilenya scored second best at 39.4, but users had more cardiac-related AEs, including lowered heart rate, and the drug also scored the worst for vision disorders and skin cancers. Gilenya, FDA-approved in 2010, did not hold the lowest score for any reported AEs.
Aubagio, with the same RxScore as Gilenya, had the highest number of reports of diarrhea, but that’s the only side effect for which it scored the highest, making it among the safest of the MS therapies.
Tysabri scored relatively well but had the highest ROR for cognitive disorders, JC virus positive tests, and secondary progressive MS. The report also concluded that the relationship between Tysabri and primary multifocaleukoencephalothopy, or PML, a rare and deadly brain infection, was confirmed.
Extavia had the worst safety score of any of the new MS drugs at 44.9, and users suffered the most depression, falls, headaches, and injection site reactions.
What Does It All Mean?
The FAERS database only examines side effects, not effectiveness. And it cannot predict side effects that may emerge over time.
“We are limited by what is recorded into FAERS,” Hoffman points out. “If a safety concern takes years to manifest after a drug’s approval we will not see those reports until they are filed.”
Although this report is an effective tool for neurologists recommending drugs to their patients, doctors must also consider each drug's effectiveness. Does it have a track record for reducing relapses, preventing disability, or protecting neurons?
Weighing the risks and benefits is a crucial process when selecting a drug for an MS patient. And everyone’s MS experience is different. Nobody will have all of the reported side effects—or all of the benefits.
Source: Healthline Copyright © 2005 - 2014 Healthline Networks, Inc (03/07/14)
Brain volume changes in patients with relapsing-remitting MS treated with Interferon Beta-1a(03/06/14)
The reductions in brain volume often seen in patients with chronic relapsing–remitting multiple sclerosis may be reduced by treatment with interferon beta-1a, though treatment may be affected by the patient’s immunologic status, according to data presented by Michael G. Dwyer, PhD, at the 2014 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Sixth Cooperative Meeting with Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Dwyer is an assistant professor of neurology in the Department of Neurology at the University of Buffalo School of Medicine and Biomedical Sciences, and the technical imaging director of the Buffalo Neuroimaging Analysis Center, Buffalo, NY.
According to Dwyer, chronic relapsing-remitting multiple sclerosis (RRMS) progression is often associated with decreased brain volume. “We know there are volume changes, but we don’t have a ‘smoking gun,’” he said.
In the study write-up, the authors noted that “Over the short term, brain volume may change, via inflammation-related hydrodynamic changes, which subside following anti-inflammatory therapy,” known as pseudoatrophy.
Dwyer presented data from a study, titled “Relapsing-Remitting Multiple Sclerosis Treated with Interferon Beta-1a: Immunologic and Short-term Volume Changes,” that compared percent brain volume change between 23 patients with relapsing-remitting multiple sclerosis who were treated for 24 weeks with subcutaneous injections of interferon beta-1a three times per week, and 15 healthy controls.
Patients were evaluated via magnetic resonance imaging (MRI) at baseline, and at months 3 and 6. Researchers also assessed immunologic markers (CD4+ T cells producing interleukin (IL)-17F) at baseline and again at 6 months.
Researchers assessed percent brain volume change from baseline to month 3, from month 3 to month 6, and from baseline to month 6 and compared differences both within and between groups. The study found that the percent brain volume change between baseline and 3 months was -0.95% (SD= 1.712%) among patients with relapsing-remitting multiple sclerosis (P=0.03) and 0.24% (SD 1.068%) among healthy controls (P=0.36).
The difference was significant between groups (P=0.02).
However, the researchers found no significant difference in percent brain volume change within or between either group from months 3 to 6, or from baseline to month 6.
The authors reported that decreased percentage of CD4+ T cells producing IL-17F from baseline to month 6 “was significantly correlated with reduced brain volume over months 0 to 6 (r = 0.51, P=0.02)” in patients with relapsing-remitting multiple sclerosis.
Treatment with subcutaneous interferon beta-1a was associated with reduced brain volume over the first 3 months of treatment, but there were no differences in brain volume seen in treated patients from month 3 to month 6, or from baseline to month 6.
The authors noted “the correlation between decreased percentage of CD4+ T cells producing inflammatory IL-17F and volume reduction is supportive of an early anti-inflammatory effect” of treatment with subcutaneous interferon beta-1a.
Source: HCPLive Copyright HCPLive 2006-2014 Intellisphere, LLC (03/06/14)
Doctors urged to consider newer agents to gain maximal efficacy in initiating treatment for MS(02/05/14)
Although there are a host of options available for treating multiple sclerosis (MS), the practicing clinician will find relatively little guidance to help optimise treatment for individual patients, according to the University of California-San Francisco’s Bruce Cree, MD, PhD. He presented a review of treatment choices and strategies at the American Academy of Neurology annual conference on April 30, 2014, in Philadelphia, PA
In framing choices for clinicians, Cree noted that strategies for initiating treatment may vary; further, there is a dearth of good “switch” studies, which would give guidance about changing MS treatment when a patient is not tolerating a medication or not responding to treatment. However, a thorough understanding of the efficacy and safety profiles of some of the newer choices among MS drugs can help with logical and patient-centered decision making.
Cree began the discussion by proposing that initial treatment planning could be guided by one of two strategies. The first would involve a tiered strategy, beginning with medications generally accepted as safer, but which may be less efficacious. Treatment response can be assessed by relapse incidence, disability progression, and changes in imaging findings. An alternate strategy, reviewed below, would try for maximal efficacy from the initial time of treatment forward.
Medications generally considered to be “first-tier” would be the interferons, along with glatiramer acetate (Copaxone), according to Cree. Some clinicians might also place fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) in the first-line category. The common side effects associated with interferon therapy are significant but well known, and clinicians can be vigilant for worsening or serious effects. Similarly, glatiramer acetate can cause post-injection site reactions, flushing, and chest pain, all of which can be anticipated and monitored.
For some clinicians and some patients, fingolimod’s safety profile might place it in the second-line column. Mitoxantrone (Novantrone) and natalizumab (Tysabri), also generally considered less safe, would similarly be considered second-line therapy. This tiered approach has the advantage of being easily understood by patients and families, and uses proven agents with well-known safety and side effect profiles. On the other hand, Cree said this tiered treatment strategy does not take individual patient needs into account. For many patients, natalizumab will be considered: it has been proven effective, with a 68-70% reduction in relative risk (RR) of relapse and a 42-54% reduction in hazard ratio (HR) for disability progression. However, individuals who are positive for the John Cunningham virus (JCV) antibody are at increased risk for progressive multifocal leukoencephalopathy (PML), a potentially devastating complication. About 50% of individuals carry the JCV antibody, and their risk for PML may be particularly high if they have had prior immunosuppression.
Fingolimod, another effective treatment, yields an overall 54% reduction in RR of relapse and a 30% reduced HR for disability progression. There is no clear risk of PML associated with this treatment, so it can be used in JCV seropositive individuals. However, bradyarrhythmias can result, so a baseline EKG, along with vital sign monitoring and an EKG at dosing and six hours after administration are recommended. The risk of undetected macular edema can be mitigated by obtaining a baseline ophthalmologic exam with follow-up exams every 3-4 months. Spirometry at similar intervals can monitor lung function. The risk of infection can be reduced by providing varicella zoster immunization before treatment initiation, avoiding concurrent steroid use when possible, and avoiding administration of live attenuated vaccines.
Among the oral agents, teriflunomide is an option for many patients. It carries an overall 32% reduction in RR of relapse and a 30% decrease in HR for disability progression. Hepatic and renal function must be monitored, and patients should be counseled about risk for neuropathy, alopecia, and hypertension. Blood pressure should be monitored regularly. Teriflunomide is pregnancy category X, with teratogenicity shown in animal models (though available human data do not show elevated risk of adverse pregnancy outcomes). Clinicians should provide pretreatment counseling to avoid pregnancy; if pregnancy should occur, the drug should be eliminated immediately with cholestyramine or activated charcoal.
Dimethyl fumarate is taken as a twice-daily capsule, and shows an overall 53% decrease in RR of relapse and a 38% reduction in HR for disability progression. There is a theoretic risk of PML with this medication, so checking JCV serology before starting treatment is recommended. Baseline and follow-up CBC and liver function testing can monitor for the risk of elevated liver enzymes and lymphopenia. GI side effects are common; flushing can be minimized with the co-administration of aspirin.
Returning to treatment strategies, Cree proposed considering a “maximal efficacy” rather than a tiered approach. In this model, the most efficacious treatment should be the first one considered, if patient characteristics allow. Natalizumab might then be the first drug considered for JCV-negative individuals. Fingolimod would also be an initial choice, with efficacy arguably superior to the interferons. Cree also made the point that oral medications are better tolerated and may result in better adherence than self-injectibles, another important consideration. The maximal efficacy approach may allow for early disease modification, reducing inflammation initially, with later transition to a “maintenance” phase with what are now considered first-line treatments. This treatment strategy, with initial use of potentially cytotoxic medications to modify disease course, borrows from oncology. Cree encouraged industry and academia to conduct more long-term observational studies comparing the two approaches; in this way, clinicians can be guided to help patients reach the best outcomes.
Source: HCP Live Copyright HCPLive 2006-2014 (02/05/14)
Beta2-adrenergic agonist use and the risk of multiple sclerosis: a total population-based case-control study.
OBJECTIVE: The aim of this study was to investigate whether the use of fenoterol, a beta2-adrenergic agonist, was associated with multiple sclerosis (MS) risk by conducting a total population-based case-control study in Taiwan.
METHODS: A total of 578 patients with newly diagnosed MS who had a severely disabling disease (SDD) certificate between January 1, 2002 and December 1, 2008 comprised the case group. These cases were compared with 2890 gender-, age-, residence-, and insurance premium-matched controls. Fenoterol use was analyzed using a conditional logistic regression model that controlled for asthma, chronic obstructive pulmonary disease (COPD), salbutamol and steroid use.
RESULTS: Compared with the group of people who did not use fenoterol, the adjusted odds ratios were 0.67 (95% confidence interval (CI) = 0.48-0.93, p = 0.016) for the group prescribed fenoterol below 2.25 cumulative defined daily dose (cDDD) and 0.49 (95% CI = 0.33-0.71, p < 0.001) for the group with a cumulative fenoterol use of more than 2.25 cDDD. The dose-response relationship was similar within the non-asthma patients. The associations were similar between males and females, but differences between age groups were observed.
CONCLUSIONS: The results of this study suggest that fenoterol use may reduce the risk of MS.
Tsai CP, Lin FC, Lee CT.
Sources: Mult Scler. 2014 Apr 14. [Epub ahead of print] & Pubmed PMID: 24732071 (22/04/14)
Therapy optimisation in MS: a prospective observational study of therapy compliance and outcomes(14/03/14)
Data sources for MS research are numerous but rarely provide an objective measure of drug therapy compliance coupled with patient-reported health outcomes. The objective of this paper is to describe the methods and baseline characteristics of the Therapy Optimisation in MS (TOP MS) study designed to investigate the relationship between disease-modifying therapy compliance and health outcomes.
Methods: TOP MS was designed as a prospective, observational, nationwide patient-focused study using an internet portal for data entry.
The protocol was reviewed and approved by Sterling IRB. The study was registered with ClinicalTrials.gov.
It captured structured survey data monthly from MS patients recruited by specialty pharmacies. Data collection included the clinical characteristics of MS such as MS relapses.
Disability, quality of life and work productivity and activity impairment were assessed quarterly with well-validated scales. When events like severe fatigue or new or worsening depression were reported, feedback was provided to treating physicians.
The therapy compliance measure was derived from pharmacy drug shipment records uploaded to the study database. The data presented in this paper use descriptive statistics.
Results: The TOP MS Study enrolled 2966 participants receiving their disease-modifying therapy (DMT) from specialty pharmacies.
The mean age of the sample was 49 years, 80.4% were female, 89.9% were Caucasian and 55.7% were employed full or part time. Mean time since first symptoms was 11.5 years; mean duration since diagnosis was 9.5 years.
Patient-reported EDSS was 3.5; 72.2% had a relapsing-remitting disease course. The most commonly reported symptoms at the time of enrollment were fatigue (74.7%), impaired coordination or balance (61.8%) and numbness and tingling (61.2%).
Half of the sample was using glatiramer acetate and half was using beta-interferons.
Conclusion: Demographic and clinical characteristics of the TOP MS sample at enrollment are consistent with other community-based MS samples, and the sample appears to be representative of DMT users in the US. TOP MS data can be used to explore the associations between disease-modifying therapy compliance and health outcomes.Trial registration: ClinicalTrials.gov (NCT00819000).
Author: Patricia K CoyleBruce A CohenThomas LeistClyde MarkowitzMerriKay Oleen-BurkeyMarc SchwartzMark J TullmanHoward Zwibel
Credits/Source: BMC Neurology 2014, 14:49
Source: 7thSpace Interactive © 2014 7thSpace Interactive (14/03/14)>
UK multiple sclerosis risk-sharing scheme: a new natural history dataset and an improved Markov model(20/01/14)
Objectives: In 2002, the UK's National Institute for Health and Care Excellence concluded that the multiple sclerosis (MS) disease modifying therapies; interferon-β and glatiramer acetate, were not cost effective over the short term but recognised that reducing disability over the longer term might dramatically improve the cost effectiveness. The UK Risk-sharing Scheme (RSS) was established to ensure cost-effective provision by prospectively collecting disability-related data from UK-treated patients with MS and comparing findings to a natural history (untreated) cohort. However, deficiencies were found in the originally selected untreated cohort and the resulting analytical approach. This study aims to identify a more suitable natural history cohort and to develop a robust analytical approach using the new cohort.
Design: The Scientific Advisory Group, recommended the British Columbia Multiple Sclerosis (BCMS) database, Canada, as providing a more suitable natural history comparator cohort. Transition probabilities were derived and different Markov models (discrete and continuous) with and without baseline covariates were applied.
Setting: MS clinics in Canada and the UK.
Participants: From the BCMS database, 898 ‘untreated’ patients with MS considered eligible for drug treatment based on the UK's Association of British Neurologists criteria.
Outcome measure: The predicted Expanded Disability Status Scale (EDSS) score was collected and assessed for goodness of fit when compared with actual outcome.
Results: The BCMS untreated cohort contributed 7335 EDSS scores over a median 6.4?years (6357 EDSS ‘transitions’ recorded at consecutive visits) during the period 1980–1995. A continuous Markov model with ‘onset age’ as a binary covariate was deemed the most suitable model for future RSS analysis.
Conclusions: A new untreated MS cohort from British Columbia has been selected and will be modelled using a continuous Markov model with onset age as a baseline covariate. This approach will now be applied to the treated UK RSS MS cohort for future price adjustment calculations.
Jacqueline Palace, Thomas Bregenzer, Helen Tremlett, Joel Oger, Fheng Zhu, Mike Boggild, Martin Duddy, Charles Dobson
Source: BMJ Open Copyright © 2014 by the BMJ Publishing Group Ltd (20/01/14)
Patients who received early and consistent disease modifying treatment at the first signs of multiple sclerosis – often called clinically isolated syndrome (CIS) – appeared to have a slower progression to disability than patients who were treated mainly for additional MS exacerbations, researchers reported here.
Over a 12-month period, patients treated 50% to 80% of the time following the first CIS event reduced their risk of progression -- as measured by the Expanded Disability Status Scale score -- by 45% compared with patients who received disease-modifying treatments less than 50% of the time or not at all (95% CI 0.39-0.79, P=0.001), and patients treated for more than 80% of the time following diagnosis reduced their risk of disability progression by 68% (95% CI 0.22-0.49, P<0.001), said Vilija Jokubaitis. PhD, post-doctoral fellow in neuroimmunology at the University of Melbourne.
"What was very interesting about this finding was that the patients who appeared to be worse after their CIS and MRI evaluation and who were treated early, did better than patients whose treatment was delayed," she said in her oral Young Investigators report at the annual meeting of the European Association for the Treatment and Research In Multiple Sclerosis.
About three-fourths of these patients were classified on the basis of T2 lesion enhancement as having relapsing-remitting multiple sclerosis at first treatment. Jokubaitis suggested that because their initial examinations looked worse, the patients were treated more aggressively, and that appeared to have long-term benefits in preventing progression.
"Study after study has shown that early treatment with disease-modifying drugs benefits patients with CIS," said Margaret Burnett, MD, assistant clinical professor of neurology and pathology at the University of Southern California in Los Angeles.
"It kills me that some places still are not treating CIS," she told MedPage Today. "These findings presented here are corroborating evidence that we should be treating CIS and we should make every effort to provide continuous treatment."
In the study, Jokubaitis and colleagues reviewed data involving 1,989 patients for whom complete records were available. The patients had a combined 6,724 years of follow-up with a median follow-up of 3 years per patient – ranging from 9 months to 9.9 years.
Of those patients, 1,339 were treated with disease-modifying agents, either interferon-based products or glatiramer acetate (Copaxone). The researchers included 307 patients who had sustained disability progression over 12 months.
The goal of the study was to determine predictors of progression, and the investigators found that advancing age was a weak prognosticator of disability progression – a 17% increased risk per decade (P=0.006). They also found that pyramidal system dysfunction was a strong predictor of disability progression – with higher imaging pathology translating to a 46% increased risk of disease progression (P=0.008).
Jokubaitis acknowledged that teasing out how treatment affected outcomes was confounded by the fact that sicker patients at diagnosis were more likely to be treated early and consistently, which helped them avoid disease progression.
She and her colleagues did scrutinize the different disease-modifying agents used in the study, but found all of them were successful in delaying progression and none appeared significantly better than the other, although treatment with glatiramer acetate approached significance compared with interferon-beta 1a intramuscular injection (P=0.052) in an ad-hoc analysis.
"Cumulative disease-modifying treatment duration significantly delays progression of multiple sclerosis," Jokubaitis said.
Co-Author Marie Trojano, MD, professor of neurology at the University of Bari in Italy, and president of ECTRIMS, told MedPage Today that concerns that clinically isolated syndromes might not be true multiple sclerosis should be discarded. "There really should not be a disease called CIS. Imaging scans can tell us these events are early multiple sclerosis."
Jokubaitis disclosed commercial interests with Novartis. Co-authors disclosed commercial interests with Biogen Idec, Bayer-Schering, sanofi, Merck-Serono, Teva, Genzyme, Roche, EMD-Serono, GSK and Biologix.
Trojano disclosed commercial interests with Biogen-Idec, Bayer-Schering, sanofi, Merck-Serono, Teva and Novartis.
Burnett had no disclosures.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis Source reference: Jokubaitis V et al, "Predictors of 12-month confirmed disability progression after onset of clinically isolated syndrome (CIS) suggestive of multiple sclerosis" ECTRIMS 2013; Abstract 59.
Source: Medpage Today © 2013 MedPage Today, LLC (03/10/13)