Search

Background: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far., Objective: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS)., Methods: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function., Results: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT)., Conclusion: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups., Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation., Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants., Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5)., Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS)., Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting MS., Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity., Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p  = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p  = 0.029)., Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing-remitting MS. Our results suggest a superiority of NTZ over FTY.

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy., Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo., Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo., Results: Recruitment was stopped prematurely due to slow inclusions ( n  = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) ( p  = 0.79))., Conclusion: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.

The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.

Objective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT)., Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts., Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5-6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4-18.4) months after rituximab ( p < 0.0001)., Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses., Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy., Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis., Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78)., Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

Background: Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study., Objective: To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study., Methods: Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits., Results: A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo., Conclusion: MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Prof. Ayman Tourbah has received consulting fees, travel grants and reports institutional financial compensation for patient visits during the trial from MedDay Pharmaceuticals and consulting and lecturing fees, travel grants and research support from Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono, Teva Pharmaceuticals and Roche. Prof. Gilles Edan reports personal fees from Biogen Idec and Novartis and grants and personal fees from Merck Serono, Teva, Sanofi and Bayer, outside the submitted work. Prof. Sandra Vukusic reports clinical trial support from MedDay Pharmaceuticals, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals and Genzyme; advisory or consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis and Teva Pharmaceuticals; and invited congress support from Biogen Idec, Merck Serono, Novartis and Genzyme. Prof. Jérôme De Sèze reports clinical trial support from MedDay Pharmaceuticals, Biogen Idec, Merck Serono, Bayer, LFB, UCB, AB Sciences, Sanofi-Aventis, Teva Pharmaceuticals and Genzyme; advisory or consultancy fees from Biogen Idec, Merck Serono, Bayer, LFB, Sanofi-Aventis, Teva Pharmaceuticals, Almirall and Allergan; and invited congress support from Biogen Idec, Merck Serono, Bayer, LFB, Sanofi-Aventis, Teva Pharmaceuticals, Genzyme and Allergan. Dr Olivier Gout reports personal fees and non-financial support from Biogen Idec, Teva Pharmaceuticals, Genzyme and Novartis and personal fees from Merck, outside the submitted work. Prof. Gilles Defer reports personal fees from Biogen Idec, Novartis, Sanofi-Aventis, Genzyme and Teva Pharmaceuticals; grants from Novartis, Merck Serono and Teva Pharmaceuticals; and funding for travel from Merck Serono, Biogen Idec, Guerbet, Sanofi-Aventis, Novartis, Genzyme and Teva Pharmaceuticals, outside the submitted work. Prof. David-Axel Laplaud reports personal fees from Biogen and Teva Pharmaceuticals and grants and personal fees from Novartis and Genzyme, outside the submitted work. Prof. Thibault Moreau reports personal fees and non-financial support from Biogen, Novartis, Sanofi-Genzyme, Bayer, Merck, Teva Pharmaceuticals and Almirall, outside the submitted work. Prof. Bruno Brochet received grants from MedDay Pharmaceuticals during the conduct of the study; personal fees and non-financial support from Biogen Idec, Novartis and Genzyme; grants from Merck Serono; grants, personal fees and non-financial support from Teva Pharmaceuticals; and grants and non-financial support from Bayer, outside the submitted work. Dr Frédéric Sedel is CEO and a shareholder at MedDay Pharmaceuticals (the study sponsor). Prof. Jean Pelletier has received consulting and lecturing fees, travel grants and unconditional research support from Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono and Teva Pharmaceuticals. Dr Christine Lebrun-Frenay, Prof. Michel Clanet, Dr Caroline Papeix, Prof. Marc Debouverie, Prof. Pierre Clavelou and Prof. Pierre Labauge have nothing to disclose., (© The Author(s), 2016.)

Background: Mitoxantrone has been approved for patients with worsening relapsing-remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone., Objectives: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd(+)) lesions, and its safety., Methods: Eighteen patients with active RRMS and SPMS (⩾ 1 cerebral Gd(+) lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12., Results: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 (p = 0.01). The annual relapse rate was reduced by 87% (p < 10(-4)). Two patients experienced a transient reduction in left ventricular fraction., Conclusion: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS., (© The Author(s), 2016.)

An association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) has been suggested. The purpose of this study was to compare the disease course of patients with both MS and IBD with that of patients with isolated MS or isolated IBD. Sixty-six MS-IBD patients were identified and were matched with 251 isolated MS and 257 isolated IBD controls. Main outcomes were scores using the Expanded Disability Status Scale (EDSS) in MS and extent of disease extension in IBD at last clinical evaluation. After a median 12 years of disease duration, the median EDSS and the percentages of patients reaching an EDSS of 3.0 and 4.0 were significantly lower in MS-IBD patients than in controls. MS had no impact on IBD. MS course appears to be milder in patients with concomitant IBD., (© The Author(s) 2013.)

Objective: The objective of this study was to assess the prevalence and incidence of multiple sclerosis (MS) in the Lorraine region, in France., Methods: Data from three sources - Regional Health Insurance System, medical records departments and the Lorraine registry of MS - and a capture-recapture method with log-linear models were used to estimate the prevalence and incidence of MS., Results: We identified 7193 records of reported MS corresponding to 4299 unique suspected cases of MS existing on 31 December 2008, in Lorraine. On the basis of the 4001 validated cases, the observed crude prevalence of MS was 170.9 cases per 100,000 inhabitants (95% confidence interval [CI]: 165.7; 176.3), and the observed annual crude incidence of MS was 4.4 cases per 100,000 inhabitants (95% CI: 3.6; 5.4). With the capture-recapture method, the estimated prevalence of MS was 4405.7 (95% CI: 4261.5; 4629.7), so an estimated 405 cases were not identified by the three sources. The estimated prevalence was 188.2 cases per 100,000 inhabitants (95% CI: 182.7; 193.8), and the estimated annual incidence was 8.5 cases per 100,000 inhabitants (95% CI: 7.3; 9.7)., Conclusions: The capture-recapture method allowed us to estimate an additional 10.1% of unobserved prevalent cases and to anticipate 47.5% of unobserved incident cases.

Background: Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies., Objective: To describe HRS patients and compare them with NMO patients., Methods: We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database., Results: Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup., Conclusion: The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.

Background: One single center study has provided support for a home-based approach to the therapeutic management of multiple sclerosis (MS) relapse., Objective: To report a multicenter series of patients with MS who were treated at home for a relapse with a 3-day course of intravenous methylprednisolone., Methods: The home administration of intravenous methylprednisolone was coordinated by four MS networks in France; patients with MS with a relapse were referred by their neurologists, and treatment was administered by a local nurse. We analyzed the safety and efficiency of this approach and estimated the related cost savings. Patients completed a patient satisfaction questionnaire., Results: Eight hundred and seven patients received intravenous methylprednisolone at home. The mean disease duration was 10.3 +/- 7.9 years. Treatment was often prescribed by community-based neurologists. The delay between prescription and treatment was 2.8 +/- 0.5 days if treatment was initiated at home and 1.9 +/- 3.0 days if treatment was initiated in hospital (the subsequent two injections were always administered at home). Home treatment was well tolerated; three serious side effects requiring hospital transfer were observed (anxiety, thoracic oppression, and arrhythmia), which were fully reversible. Overall, 93.8% of patients were satisfied with the treatment approach, and 98% wished to receive future treatment courses at home. The overall cost savings of home-based treatment versus hospital-based treatment were evaluated at EUR1,091,482., Conclusion: Safety data, patient satisfaction, and economic considerations support home-based treatment of MS relapses with intravenous methylprednisolone, provided strict patient selection criteria are observed and the process is coordinated and closely monitored by an MS network.

Objective: The currently published works regarding the multiple sclerosis (MS) natural history report data were collected most often on population of patients recruited in MS centers. The aim was to compare the natural history of a population of patients followed in a MS centre (MSC) with patients followed outside a MS centre (NMSC)., Methods: Cases were identified through the LORSEP cohort, a network of neurologists (private ambulatory practice, hospitals, and MS centers) in France., Results: A total of 3602 patients had been analyzed: 1036 MSC patients and 2566 NMSC patients. No difference was observed regarding gender and initial symptoms. Conversely, MSC patients were younger at MS onset and were more likely to have a primary progressive initial form. Median times (years) to the EDSS scores of 3, 4, and 6 were 5.8 (5.0-6.8), 8.4 (7.9-9.0), 16.0 (14.8-18.1) in the MSC group, respectively, whereas corresponding times were 8.4 (7.9-9.0), 12.3 (11.4-13.4), 19.1 (18.0-20.2) in the NMSC group. These differences according to the type of MS supervision were statistically significant for EDSS3 (P < 0.0001), EDSS4 (P < 0.0001), and EDSS6 (P = 0.01), respectively. These findings were confirmed in Cox multivariate models., Conclusions: The patients followed in a MS centre had earlier disability than patients managed otherwise. Analyses exclusively conducted in patients with MS supervised in specialized centers may falsely misestimate the times needed to reach major disability landmarks. Before using registries to study the natural history of MS, efforts should be performed to verify in how far data are exhaustive and to understand the local health care system.

Background: Multiple Sclerosis in North African migrants (MS-NA) is more aggressive with mostly primary progressive forms and cerebellar symptoms. Despite an earlier onset in NA patients, the disease progresses more rapidly, with a higher proportion showing incomplete recovery from the first relapse, a shorter time between the first two relapses, a higher number of relapses in the first 5 years, and a shorter time to reach an EDSS of 4.0 and 6.0. We collected data and studied the impact of disease-modifying therapies (DMT) in NA patients with MS, among the 4144 MS patients treated in our MS clinics., Methods: We performed a descriptive population-based study of MS-NA patients. Data were crossed with expected age- and gender-matched characteristics available in our EDMUS databases for the period 1995-2007., Results: A total of 133 patients, representing 66% of the MS-NA patients included in the database were identified: mean age at the first documented symptom: 29.7 years; mean time from diagnosis to the beginning of DMT: 1.2 years. 40% of MS-NA patients had an EDSS >3 at the beginning of treatment (vs. 25%; P=0.002). A majority of patients were treated initially with immunomodulatory drugs (MS-NA: 48% vs. CT: 51%, P=0.8). NA patients were treated earlier after diagnosis (1.3 years vs. 4.5 years, P=0.003), with the frequent use of immunosuppressive drugs: for remitting forms, mitoxantrone (18.5% vs. 7.8%, P=0.0001) and for progressive forms, cyclophosphamide (38% vs. 28%, P=0.003)., Conclusions: Considering EDSS follow-up during DMT, MS-NA patients appear as responsive as other MS patients to treatment, despite the earlier treatment prescription and the more frequent use of immunosuppressors.

Background: Prior to the era of immunomodulating or immunosuppressive (IS) treatments Multiple Sclerosis (MS) was linked to reduced rates of cancer. Method A descriptive study of MS patients with a documented oncological event was performed. From 1 January 1995 to 30 June 2006, we collected and studied the profile of 7,418 MS patients gathered from nine French MS centers. We evaluated the incidence of cancer in a Cancer Risk In MS Cohort., Results: Thirty one patients (1.75%) with confirmed MS had a history of cancer: mean age at MS diagnosis of 37.9 years and a mean age at cancer diagnosis of 46.4 years. The most frequent cancers were breast (34.5%), gynecological (12.5%), skin (10.2%), acute leukemia and lymphoma (5.9%), digestive (8.8%), kidney and bladder (5.1%), lung (3.4%) and central nervous system (3%). Calculated standardized incidence rates were 0.29 (0.17-0.45) for men and 0.53 (0.42-0.66) for women. The incidence of cancer in this MS population was lower than that expected for the general population. Matched to age, gender and histology, cancers in MS were associated with a young age and exposure to IS treatments. When considering all patients, treated patients had a 3-fold higher risk of developing cancer, if they had a history of IS (P = 0.0035). For treated patients, the cancer sites were more likely the breast, the urinary tract, the digestive system and the skin., Conclusion: Our data suggest that MS patients do not have an increased risk of cancer. Rather for several types of cancer a significantly reduced risk was observed, except for breast cancer in women treated with IS. The relative increased risk of breast cancer in MS women under IS treatment warrants further attention.

Purpose: Fatigue is a frequent and common symptom of multiple sclerosis (MS) that can interfere with patients' everyday activities. There is no objective scale for assessing fatigue in French MS patients. The objective of this study was to adapt an English language scale for use with French patients., Methods: The Fatigue Impact Scale was translated and culturally adapted into French by a committee of medical and linguistic specialists. The psychometric properties of this new instrument, called EMIF-SEP were assessed., Results: EMIF-SEP is composed of 40 items. Four dimensions of this scale (cognitive, physical, social role and psychological) were identified by factor analysis. Each dimension had a high internal consistency (Cronbach's alpha >0.80). The test-retest reproducibility was very satisfactory; intra-class correlation coefficients were all above 0.70., Conclusion: EMIF-SEP is the first scale for assessing MS-related fatigue which has been adapted to French-speaking patients. It is useful for clinical practice and MS-related research.

This study aims to describe the prevalence and incidence rates of multiple sclerosis (MS) in Lorraine, France, and its secular trend from 1990 to 2002. Cases were sourced from the regional network of MS healthcare workers in the Lorraine region and include all cases with definite or probable MS according to Poser's criteria. We identified 2718 patients with MS on 31 December 2004. The prevalence rate was 120/100,000 (95% confidence interval [CI]: 119-121). Between 1990 and 2002, the average age- and sex-adjusted annual incidence rate was 5.5/100,000 (95% CI: 4.4-6.6). During this same period, there was a significant increase in overall incidence in women but not in men. The mean age at MS onset, disability score five years after onset, number of relapses during the first five years, and proportion of first attack with sequelae or polysymptomatic symptoms were not significantly different between each annual cohort during the study period. The prevalence and incidence rates of MS we found in our study were higher than in previous studies in France. The increase in incidence of MS between 1990 and 2002, mostly in women, was not related to better ascertainment of patients with mild disability.

We assessed the different sets of diagnostic criteria for primary progressive multiple sclerosis (PPMS), in order to determine their sensitivity when applied to a cohort of 261 PPMS patients. According to the Thompson criteria, 168 patients (64.4%) had definite PPMS, 84 patients (32.2%) had probable PPMS, and nine patients (3.4%) had possible PPMS; according to the McDonald criteria, 180 patients (69%) had PPMS; according to the revised McDonald criteria, 194 patients (74.3%) had PPMS. Our findings indicate that the revised McDonald criteria are more sensitive than the original McDonald criteria, but less sensitive than the Thompson criteria.

The objectives of this study were to assess the benefits of 1) mitoxantrone after three years of follow-up and 2) disease-modifying treatment (DMT) after stopping mitoxantrone. A retrospective analysis was performed on 304 patients with active relapsing-remitting (RR) or progressive multiple sclerosis (PMS) who were treated with mitoxantrone. After mitoxantrone therapy, some patients received DMT (interferon-beta or glatiramer acetate) while others did not. The disease course of the two groups was evaluated by the Expanded Disability Status Scale (EDSS) before and after mitoxantrone and then every year for three years. The mean EDSS score at starting mitoxantrone and three years after stopping mitoxantrone respectively, were: 3.3 (1.3) and 3.2 (1.7) for the RRMS patients and 5.9 (1.2) and 6.4 (1.4) for the PMS patients. Before starting mitoxantrone, demographic and clinical parameters of predictive disability were not significantly different between patients who received DMT or not. The variation of EDSS between time of stopping mitoxantrone and three years later was significantly different (+0.9 versus +0.3; P=0.03) for patients with RRMS. We found that mitoxantrone treatment induces stable disease up to two years after discontinuation of mitoxantrone therapy. In the third year, patients without DMT deteriorated.

Introduction: In a number of controlled trials it was established that mitoxantrone has a beneficial effect on disease progression in multiple sclerosis (MS) patients with a worsening disease course. The aim of this study was to investigate the use of mitoxantrone in clinical practice, and especially to describe predictive parameters of its effectiveness under these conditions., Objectives and Methods: In a retrospective, open-label mitoxantrone study we analysed 94 MS patients (49% relapsing remitting MS (RRMS), 41% secondary progressive MS and 10% primary progressive MS) who received monthly 20 mg i.v. mitoxantrone and 1 g i.v. methylprednisolone for six months, and selected as a criterion of effectiveness the percentage of patients with an Expanded Disability Status Scale (EDSS) improvement of at least one point (confirmed after one year) after stopping the treatment. A multivariate analysis was undertaken to assess the predictive value of five parameters on mitoxantrone effectiveness: (1) total number of relapses since disease onset and before treatment, (2) number of relapses within the past 24 months before treatment, (3) number of relapses in separate areas within the past 24 months before treatment, (4) active MRI scans (including Gd-enhanced lesions), and (5) clinical course of MS., Results: During the observation period from 1 January 1997 to 30 May 2000 more than 44% of the patients improved by one point or more on the EDSS (confirmed after one year), 39% remained stable and 17% deteriorated. In patients with a RRMS course three or more relapses within the past 24 months preceding treatment, and at least one Gd-enhancing lesion resulted in a strong relative benefit (i.e., relative risk) of mitoxantrone effectiveness. In contrast, total number of relapses since disease onset had no impact on disease evolution and disability progression. Multivariate analysis revealed the number of relapses in separate areas within the past 24 months before treatment as the strongest predictive parameter (P < 0.001)., Conclusion: Mitoxantrone is effective in improving and stabilizing patients with a worsening MS course in routine clinical practice. Several strong predictive parameters of mitoxantrone effectiveness were investigated among which the number of relapses in separate areas within the past 24 months before treatment was found to be the strongest parameter to predict clinical improvement.