Emerging Therapies for Relapsing Multiple Sclerosis

Cohen, Jeffrey A.

doi:10.1001/archneurol.2009.104

Cited by 31 publications

(25 citation statements)

References 49 publications

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“…natalizumab, rituximab, azathioprine, MMF, cladribine, and fingolimod) [Berger and Houff, 2009;Cohen, 2009;Hemmer et al 2006]. All of the newer agents have limited short-term safety data when compared with the interferons and glatiramer acetate.…”

Section: Discussionmentioning

confidence: 99%

“…There are now five agents in phase III clinical trials that appear promising in providing superior efficacy, greater convenience of oral administration, and improved adherence for our MS patients. These include cladribine, FTY-720, dimethylfumarate , laquinimod and teriflunomide [Cohen, 2009;Menge et al 2008]. The latter agent is related to the approved drug leflunomide, which has long been utilized for the treatment of rheumatoid arthritis.…”

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confidence: 99%

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A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis

Frohman

Cutter²,

Remington

et al. 2010

Ther Adv Neurol Disord

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Abstract:Background: Mycophenolate mofetil (MMF, CellCept Õ ) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). Objective: To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex Õ at 30 mcg) in relapsingremitting MS (RRMS). Methods: We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. Results: Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. Conclusions:The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis

Frohman

Cutter²,

Remington

et al. 2010

Ther Adv Neurol Disord

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“…Current lead candidates as "oral MS therapies" include cladribine and fingolimod (FTY720), which have reported Phase 3 data (CLARITY, FREEDOMS and TRANSFORMS trials), followed by drugs such as teriflunomide, laquinimod and dimethyl-fumarate (BG-12) which are still in the early stages of Phase 3. 11,12 Briefly, data from the cladribine and fingolimod programs is clearly encouraging from the perspective of increased efficacy, but also raised significant safety concerns such as carcinogenicity (cladribine) or fatal herpes virus infections (fingolimod). This is perhaps not unexpected from drugs that have widespread effects on human biology and whose target lacks specificity for a particular disease process.…”

Section: Development Of Mab Therapy For Multiple Sclerosis: Failures mentioning

confidence: 99%

Monoclonal antibody therapy in multiple sclerosis

Fontoura

2010

mAbs

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Faculty of Medical Sciences; New University of Lisbon; Lisbon, Portugal in natalizumab-treated MS patients, as well as in patients with lymphoma, lupus and rheumatoid arthritis, treated with rituximab and autoimmune-type complications in alemtuzumab-treated MS patients underlines the fact that extended efficacy comes with significant clinical risks. The challenge is then how best to utilize therapies that have evidently superior efficacy in a chronic disease of young adults to obtain the best benefit-risk ratio and how to monitor and prevent emergent safety concerns.

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“…[17][18][19][20] In these severe or rapidly-evolving cases, more potent treatments such as natalizumab or mitoxantrone may provide better efficacy and are often used as second-line therapy. 21 While current treatment options have managed to reduce relapse rates to a more acceptable level, they are still by no means satisfactory.…”

Section: The Impact Of Current Disease-modifying Therapies On Prognosismentioning

confidence: 99%

Emerging Therapies in Multiple Sclerosis—New Decisions in the Formulation of Treatment Strategies

Buckle¹

2010

US Neurology

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Disease-modifying therapies (DMTs) for treating multiple sclerosis (MS) are entering a period of rapid and profound change that will greatly expand treatment options and improve quality of life for the approximately 2.5 million people worldwide who suffer from this chronic, disabling disease.1 Five of the currently-approved DMTs are given by injection at frequent intervals and have a range of adverse effects, notably 'flu-like symptoms and injection site reactions. These effects can be a problem not only for patients who are newly prescribed the treatments, but also for some patients who experience 'injection fatigue' after years of continuous administration. 2 The probable approval within the next few years of a more effective monoclonal antibody treatment (alemtuzumab) 3 and several of the new oral DMTs (laquinimod, cladribine fingolimod, teriflumomide, and BG00012) 2,4-7 will represent a landmark change that could substantially alter approaches to MS treatment. DMTs are widely used in the treatment of patients with MS in North America and have changed the prognosis in many patients for the better. 8-10However, in other territories they are often either not used commonly enough or not initiated early enough in the disease course to be effective. Factors including conservatism among physicians, delays in diagnosis and treatment initiation, fear of adverse events, and high cost or limited healthcare coverage can limit DMT use in these regions.The aim of this article is to consider the way in which existing treatments have changed the outlook for MS patients and to assess the intravenous and oral treatments currently in late-stage development.Once given regulatory approval, these therapies are likely to have a dramatic effect on the choice and convenience of MS treatments.Therefore, it is timely to discuss the decision-making process neurologists go through prior to initiating treatment and during ongoing treatment and to reflect on the impact these novel therapies will have on this process. The Impact of Current Disease-modifying Therapies on PrognosisIn 1993, the first pivotal trial of interferon beta-1β (IFNβ-1β) was published, illustrating its efficacy in relapsing-remitting MS (RRMS). AbstractThe therapeutic options available to neurologists treating multiple sclerosis (MS) are profoundly changing. Hitherto, disease modifying therapies (DMTs) were entirely administered by injection and were only able to retard disease progression. The frequency of site reactions and flu-like symptoms has made adherence to treatment problematic and resulted in resistance from some patients. The recent approval of the first oral DMT in MS (fingolimod) and the development of other oral agents will provide much more attractive options to both physicians and patients and may promote earlier commencement of treatment. The development of the monoclonal antibody alemtuzumab may for the first time provide a MS treatment that will, in certain patients with relapsing disease, restore some degree of lost neurologic function. Therefore...

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Emerging Therapies for Relapsing Multiple Sclerosis

Cited by 31 publications

References 49 publications

A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis

A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis

Monoclonal antibody therapy in multiple sclerosis

Emerging Therapies in Multiple Sclerosis—New Decisions in the Formulation of Treatment Strategies

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