Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France.

The benefits provided by disease-modifying treatments in multiple sclerosis have been demonstrated in clinical trials, but the extent to which they can be extrapolated to everyday care is less clear, as are the long-term benefits of treatment. The objective of this prospective observational cohort study performed in France was to evaluate the effectiveness and safety of glatiramer acetate in patients with relapsing-remitting multiple sclerosis over a 5-year period. All neurologists in France were invited to participate and enroll adult patients starting a first treatment with brand glatiramer acetate 20 mg. Given the observational nature of the study, no fixed study visits were imposed; consultations took place according to the investigator's normal practice. Occurrence of disease exacerbations and adverse events was documented and neurological disability evaluated with the EDSS at each consultation. Overall, 852 patients were analysable and 269 took glatiramer acetate continuously for 5 years. Median treatment duration was 3.4 years. Principal reasons for discontinuation were inadequate efficacy (38.9%), local tolerability (22.6%) and personal convenience (21.3%). Age, employment status, baseline EDSS score and number of previous exacerbations were variables associated with treatment persistence. The annualised exacerbation rate (5 years) was 0.41 [95% CI 0.39-0.44]; 316 patients (37.2%) remained exacerbation-free throughout. The risk of confirmed disability worsening (5 years) was 43.8% [95% CI 39.9-47.9%]. The most frequent adverse drug reactions were local injection site reactions (584 patients; 68.5%) and systemic immediate post-injection reactions (168 patients; 19.7%). Overall, these findings are consistent with those of previous clinical trials.

Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

PURPOSE: Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. METHODS: Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. RESULTS: A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). CONCLUSIONS: MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study.

BACKGROUND: Treatment options for patients suffering from progressive forms of multiple sclerosis (MS) remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS). METHODS: Multicenter, randomized, placebo-controlled, proof-of-concept trial. Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC). Clinical response was defined as an increase in MSFC score relative to baseline of > 100%. RESULTS: Thirty-five patients were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being asthenia, rash, nausea, edema, and diarrhea. The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% ± 189 versus -60% ± 190 at month-12, respectively. This positive, albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/22 (32%) assessable masitinib patients reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group. The Expanded Disability Status Scale remained stable for both treatment groups. CONCLUSION: These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS patients and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation.

Short-term tolerance of pulse methylprednisolone therapy in patients with diabetes mellitus.

PURPOSE: To assess the short-term tolerance of pulse methylprednisolone in patients with diabetes. DESIGN: Retrospective study in a national eye center. PARTICIPANTS: Eighty patients with type 2 diabetes, half of them also treated for hypertension, who received 3-day pulse methylprednisolone between January 1999 and December 2002 for eye disorders and were monitored according to a written protocol. MAIN OUTCOME MEASURE: Potentially serious side effects, serial blood glucose measurements, and hypoglycemic interventions during pulse therapy. RESULTS: Each pulse induced about 10 hours later a mean 2-fold peak increase of blood glucose. According to a 14-mmol/l (250 mg/dl) threshold glucose level for intervention, rapid insulin was required in 27 of 27 (100%) and 24 of 53 (45%) patients with glycosylated hemoglobin levels higher than 8% and up to 8%, respectively. In the latter group, patients older than 70 years had a 3-fold increased risk of requiring insulin. Significant side effects were systolic and/or diastolic blood pressure elevation > or = 180/110 mmHg (n = 6), ketosis without acidosis (n = 5), silent myocardial ischemia (n = 1), and disorientation (n = 1). All side effects were transient or controlled successfully by medical intervention. No infectious complication occurred during the treatment period. CONCLUSIONS: Pulse methylprednisolone is globally well tolerated in diabetic patients, but requires strict blood glucose and clinical monitoring.

Intravenous pulse methylprednisolone therapy in eye disease: effect on glucose tolerance.

PURPOSE: To determine which subjects need close glycemic monitoring during intravenous pulse methylprednisolone therapy for eye disease. DESIGN: Retrospective study in a national eye center. PARTICIPANTS: Two hundred twenty-four subjects who received over a one-year period 250 to 1000 mg daily intravenous methylprednisolone over 3 consecutive days for ophthalmologic conditions. METHODS: Blood glucose monitoring during pulse methylprednisolone therapy followed a protocol written in 1995. We analyzed the effects of 3 days of pulse methylprednisolone therapy on glucose tolerance and their clinical implications in diabetic and nondiabetic subjects treated during 2000. MAIN OUTCOME MEASURE: Serial morning fasting blood glucose; that is, before the first pulse and the day after each pulse, blood glucose self-monitoring for diabetic subjects and specific hypoglycemic drug interventions were recorded. RESULTS: All subjects showed a median 50% increase in fasting glucose after the first steroid infusion, without a significant difference between diabetic and nondiabetic subjects. Thereafter, the 196 nondiabetic subjects showed spontaneous decreases of their fasting glucose toward baseline values despite the following infusions, whereas the 28 diabetic subjects (all type 2) demonstrated further increases of blood glucose, and 7 received rapid-release insulin to maintain blood glucose lower than 14 mmol/l. All 5 diabetic subjects with baseline glycosylated hemoglobin >/==" BORDER="0"> 8.3% required insulin therapy. CONCLUSIONS: Close glycemic monitoring seems necessary only for subjects with diabetes during intravenous pulse methylprednisolone therapy for ophthalmologic conditions. The probability of subjects with type 2 diabetes requiring insulin during this therapy does seem to be positively related to the level of pretreatment glycosylated hemoglobin.