The Global Adherence Project (GAP): a multicenter observational study on adherence to disease‐modifying therapies in patients with relapsing‐remitting multiple sclerosis

Background: Most disease‐modifying therapies (DMTs) for multiple sclerosis (MS) are self‐injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing‐remitting MS. Methods: This was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta‐1a (IFNβ‐1a), subcutaneous IFNβ‐1a, IFNβ‐1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long‐term DMTs. Results: Two thousand six hundred and forty‐eight patients were studied, revealing an average treatment duration of 31 months. Seventy‐five percent of patients (n = 1923) were adherent to therapy. The most common reasons for non‐adherence were forgetting to administer the injection (50.2%) and other injection‐related reasons (32.0%). Adherent patients reported better quality of life (P < 0.05) and fewer neuropsychological issues (P < 0.001) than non‐adherent patients. Adherent patients had significantly shorter duration of disease (P < 0.001) and shorter duration of therapy (P = 0.005) than non‐adherent patients. Women were more likely than men to adhere to treatment. Conclusion: Identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long‐term DMTs.     

Safety concerns and risk management of multiple sclerosis therapies

Currently, more than ten drugs have been approved for treatment of relapsing‐remitting multiple sclerosis (MS). Newer treatments may be more effective, but have less favorable safety record. Interferon‐β preparations and glatiramer acetate treatment require frequent subcutaneous or intramuscular injections and are only moderately effective, but have very rarely life‐threatening adverse effects, whereas teriflunomide and dimethyl fumarate are administered orally and have equal or better efficacy, but have more potentially severe adverse effects. The highly effective therapies fingolimod, natalizumab, daclizumab, and alemtuzumab have more serious adverse effects, some of which may be life‐threatening. The choice between drugs should be based on a benefit‐risk evaluation and tailored to the individual patient's requirements in a dialogue between the patient and treating neurologist. Patients with average disease activity can choose between dimethyl fumarate and teriflunomide or the “old injectable.” Patients with very active MS may choose a more effective drug as the initial treatment. In case of side effects on one drug, switch to another drug can be tried. Suboptimal effect of the first drug indicates escalation to a highly efficacious drug. A favorable benefit‐risk balance can be maintained by appropriate patient selection and appropriate risk management on therapy. New treatments will within the coming 1‐2 years change our current treatment algorithm for relapsing‐remitting MS.     

Efficacy of natalizumab in second line therapy of relapsing–remitting multiple sclerosis: results from a multi-center study in German speaking countries

Background:  Natalizumab has been recommended for the treatment of relapsing–remitting multiple sclerosis (RRMS) in patients with insufficient response to interferon-beta/glatiramer acetate (DMT) or aggressive MS. The pivotal trials were not conducted to investigate natalizumab monotherapy in this patient population.
Method:  Retrospective, multicenter study in Germany and Switzerland. Five major MS centers reported all RRMS patients who initiated natalizumab ≥12 months prior to study conduction.
Results:  Ninety-seven RRMS patients were included [69% female, mean age 36.5 years, mean Expanded Disability Status Scale (EDSS) 3.4; 93.8% were pre-treated with DMT], mean treatment duration with natalizumab was 19.3 ± 6.1 months. We found a reduction of the annualized relapse rate from 2.3 to 0.2, 80.4% were relapse free with natalizumab. EDSS improved in 12.4% and 89.7% were progression free (change of >/= 1 EDSS point). Eighty-six per cent of patients with highly active disease (>/= 2 relapses in the year and >/= 1 Gadolinium (Gd)+ lesion at study entry, n  = 20) remained relapse free. The mean number of Gd enhancing lesions was reduced to 0.1 (0.8 at baseline). Discontinuation rate was 8.2% (4.1% for antibody-positivity).
Conclusion:  Natalizumab is effective after insufficient response to other DMT and also in patients with high disease activity.     

Diagnosis and treatment of multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that usually has onset between 20 and 40 years of age. The causes of MS are unknown, but it probably evolves among genetically susceptible individuals as an infrequent response to environmental factors. The diagnosis is based on careful evaluation of the disease history, clinical examination as well as paraclinical examination, aiming to document disseminated disease in both time and space. No cure is available, but corticosteroids can be used for relapses, various symptomatic treatments exist, and several long-term, disease-modifying therapies are available. This article reviews the diagnosis and treatment of MS, focusing on treatment of relapses and disease-modifying therapies.     

Methisoprinol in the treatment of multiple sclerosis.

Twenty-five patients affected by remittent form of multiple sclerosis (MS) were treated with methisoprinol for a period of 2 years. The clinical parameters, recorded during a 2-year observation period preceding onset of therapy, were compared with the analogous measures recorded during treatment. Treatment was associated with significant favourable changes. In fact, there were observed: a reduction in mean annual relapse rate for 22 of 25 patients; an improvement in the clinical status as demonstrated by the reduction of the Kurtzke Disability Status Scale values obtained in 14 of 25 patients; a reduction in the mean period of standard corticosteroid therapy.     

First-ever treatment in multiple sclerosis

BackgroundThe current treated MS population is very different from that of patients in randomized clinical trials.ObjectivesTo study the long-term efficacy and tolerance of fingolimod (FTY) and dimethyl fumarate (DMF), both available as first-line treatment in early-treated treatment-naïve MS patients.MethodsRetrospective analysis of 75 patients from our prospective MS registry fulfilling the inclusion criteria: FTY or DMF as first-line treatment, treatment initiation within 36 months of disease onset and treatment duration > 12 months.ResultsDemographics and MRI characteristics at baseline were similar in both groups (FTY 55 patients, DMF 20), but patients on FTY had higher pretreatment clinical activity (P = 0.008). Twenty-two percent of patients in the FTY group and 15% in the DMF group had highly active disease. At last follow-up (mean: 44.2, SD: 17.3 months), the majority of the patients were still on treatment while 54.5% of FTY and 65% of DMF patients reached NEDA 3 status (P = 0.444). Both treatments significantly decreased relapses and occurrence of new T1 Gd-enhancing lesions (P < 0.001). The main reason for discontinuation was disease activity without severe side effects on either treatment.ConclusionsOur findings support efficacy and tolerance of both drugs in early-treated treatment-naive MS patients, arguing in favour of efficient early immunomodulation in MS patients. Both drugs significantly reduced the incidence of new relapses and Gd-enhancing lesions on treatment with FTY being more frequently prescribed than DMF, especially in patients with evidence of higher clinical disease activity.     

Pathophysiology of multiple sclerosis and the place of teriflunomide

Significant progress in multiple sclerosis (MS) treatment has been made over the last two decades, including the emergence of disease-modifying therapy (DMT). However, substantial unmet medical need persists and has stimulated the search for new therapeutics. Teriflunomide, one of the several oral DMTs under investigation, is a selective inhibitor of de novo pyrimidine synthesis which exerts a cytostatic effect on proliferating T- and B lymphocytes in the periphery and thus has both antiproliferative and anti-inflammatory properties. Anti-inflammatory effects have been demonstrated in rodent MS models, with reductions in macrophage and B- and T-cell infiltration in the central nervous system and preservation of myelin and oligodendrocytes. Delays in disease onset, reductions in disease relapses and improvements in clinical symptoms were also observed. A proof-of-concept clinical trial in patients with relapsing MS demonstrated that teriflunomide significantly reduced magnetic resonance imaging (MRI) activity and improved clinical endpoints, with both effects maintained with longer-term treatment. Additional studies have shown that teriflunomide can be safely added to beta interferon or glatiramer acetate therapy, with some evidence of additional improvements in MRI disease burden and clinical signs. Teriflunomide has an acceptable and manageable safety and tolerability profile. A large clinical programme is underway to further elucidate the role of teriflunomide in the treatment of MS.