Epilepsy in type 1 Chiari malformation

We reported a post-marketing experience of 190 patients affected by relapsing multiple sclerosis on treatment with natalizumab. Clinical findings during pre-treatment period and throughout the study were documented. Magnetic resonance imaging (MRI) scans were performed at baseline and at 6, 12, and 24 months of therapy. Cumulative proportions of patients disease activity free (i.e. absence of relapses, disability progression, MRI activity) were measured as efficacy endpoints. Despite that the baseline characteristics suggested a more severe course of disease in our sample than that of the AFFIRM trial, data on effectiveness of natalizumab were comparable. At 1 year of treatment we found 80 and 70% patients free from relapses and MRI activity, respectively, that is similar to 75 and 62% detected in the AFFIRM trial. Moreover, only 5% of our patients showed a progression of disability after a mean follow-up time of 15 months. Finally, the presence of antibodies anti-Natalizumab was strongly related to the occurrence of relapses (p = 0.002) and MRI activity (p < 0.001) even in the post-marketing experience.     

Clinical effects of natalizumab on multiple sclerosis appear early in treatment course

In clinical practice natalizumab is typically used in patients who have experienced breakthrough disease during treatment with interferon beta (IFNβ) or glatiramer acetate. In these patients it is important to reduce disease activity as quickly as possible. In a phase II study, differences between natalizumab and placebo in MRI outcomes reflecting inflammatory activity were evident after the first infusion and maintained through a 6-month period, suggesting a rapid onset of natalizumab treatment effects. To explore how soon after natalizumab initiation clinical effects become apparent, annualized relapse rates per 3-month period and time to first relapse were analyzed in the phase III AFFIRM study (natalizumab vs. placebo) and in the multinational Tysabri^® Observational Program (TOP). In AFFIRM, natalizumab reduced the annualized relapse rate within 3 months of treatment initiation compared with placebo in the overall population (0.30 vs. 0.71; p < 0.0001) and in patients with highly active disease (0.30 vs. 0.94; p = 0.0039). The low annualized relapse rate was maintained throughout the 2-year study period, and the risk of relapse in AFFIRM patients treated with natalizumab was reduced [hazard ratio against placebo 0.42 (95 % CI 0.34–0.52); p < 0.0001]. Rapid reductions in annualized relapse rate also occurred in TOP (baseline 1.99 vs. 0–3 months 0.26; p < 0.0001). Natalizumab resulted in rapid, sustained reductions in disease activity in both AFFIRM and in clinical practice. This decrease in disease activity occurred within the first 3 months of treatment even in patients with more active disease.     

The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL

The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNβ)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, ≥ 3), Expanded Disability Status Scale score (≤ 3.5, > 3.5), number of T2 lesions (< 9, ≥ 9), presence of gadolinium-enhancing (Gd+) lesions (0, ≥ 1), age (< 40, ≥ 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., ≥ 2 relapses in the year before study entry and ≥ 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: ≥ 9 T2 lesions at baseline, ≥ 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNβ-1a treatment. These results indicate that natalizumab is effective in reducing disability progres- sion and relapses in patients with relapsing MS, particularly in patients with highly active disease. An erratum to this article is available at .     

Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis

"Disease activity free" in relapsing-remitting multiple sclerosis (RRMS) is a new concept introduced by the results of the AFFIRM study. Our objective was to analyze the clinical and radiological efficacy of natalizumab treatment in actual clinical practice and compare it with the post hoc analysis of the AFFIRM study. All patients with RRMS who began treatment with natalizumab at our two French MS centres between April 2007 and May 2008 were included and followed-up for at least 2 years. No measurable disease activity ("disease activity free") was defined as no activity on clinical measures (no relapses and no sustained disability progression) and radiological measures (no gadolinium-enhancing lesions and no new T2-hyperintense lesions on cerebral MRI). A total of 193 patients were included. Natalizumab was discontinued in 25.9% of cases before the completion of 2 years of treatment. In our cohort, we observed patients with more severe disease than in the AFFIRM study. The proportion of patients remaining free of clinical activity during 2 years of treatment was lower than in the AFFIRM study (37.8% vs. 64.3%). The proportion of patients remaining free of radiological activity during 2 years of treatment was higher than in the AFFIRM study (68.9% vs. 57.7%), while the proportion of patients remaining free of disease activity during 2 years of treatment was comparable to the AFFIRM study (33.3% vs. 36.7%). Natalizumab seems to be as effective in a real-life setting as in pivotal and post hoc studies. The confirmation of such benefits is important because of the progressive multifocal leukoencephalopathy risk.     

Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS

Standard clinical endpoints in multiple sclerosis (MS) studies, such as disability progression defined by the expanded disability status scale (EDSS) and annualized relapse rate, may not fully reflect all aspects of therapeutic benefit experienced by patients. Pivotal studies showed that natalizumab is effective both as monotherapy (AFFIRM study) and in combination with interferon beta-1a (IFNβ-1a) (SENTINEL study) in patients with relapsing MS. We present AFFIRM and SENTINEL data demonstrating the efficacy of natalizumab on prespecified tertiary endpoints, including extent of confirmed change in EDSS score from baseline, time to sustained progression to EDSS milestone scores, hospitalizations, corticosteroid use, and time to confirmed progression of cognitive deficits. Natalizumab significantly reduced changes in EDSS scores (P < 0.001) and proportion of patients progressing to an EDSS score ≥4.0 (P < 0.001) and ≥6.0 (P = 0.002) compared with placebo. Natalizumab + IFNβ-1a significantly reduced changes in EDSS scores compared with placebo + IFNβ-1a (P = 0.011). Based on 0.5 standard deviation change in paced auditory serial addition test-3 score, natalizumab treatment reduced the risk of confirmed progression of cognitive deficits by 43% compared with placebo (HR 0.57 [95% CI 0.37, 0.89], P = 0.013); however, no significant difference between groups was seen in SENTINEL. Natalizumab, both as monotherapy and in combination with IFNβ-1a, significantly reduced the annualized rate of MS-related hospitalizations (by 64 and 61%, respectively) and the annualized rate of relapses severe enough to require steroid treatment (by 69 and 61%, respectively) compared with placebo and placebo + IFNβ-1a (P < 0.001). These analyses underline beneficial effects of natalizumab therapy in relapsing MS patients.     

Demographic and clinic characteristics of French patients treated with natalizumab in clinical practice

Natalizumab is the first selective adhesion molecule inhibitor indicated for treatment of active relapsing-remitting multiple sclerosis (RRMS). Natalizumab has been available in France since April 2007. The aims of this study are to analyze demographic, clinical, and tolerance data from French patients with RRMS treated with natalizumab in actual clinical practice and to draw comparisons with patients in the pivotal AFFIRM study. All patients with RRMS in the Nord-Pas de Calais and Alsace regions of France treated with natalizumab at any time since April 2007 were included. Variables analyzed included previous treatments; disability status [Expanded Disability Status Scale (EDSS) score]; annualized relapse rate (ARR) at baseline and after 12 months of treatment; and adverse events. Data from 384 patients (72% female) were evaluated. Mean baseline EDSS score was 3.53 and mean baseline ARR was 2.19, both significantly greater than in AFFIRM. One hundred twenty-seven patients completed 12 months of treatment; mean EDSS score in this group was 3.02 (14% reduction) and mean ARR was 0.59 (73% reduction). Although these patients had significantly different baseline characteristics and greater disability compared with patients receiving natalizumab in AFFIRM, average disability remained stable and ARR declined by 73%. Tolerability was similar to that observed in AFFIRM.     

A longitudinal uncontrolled study of cerebral gray matter volume in patients receiving natalizumab for multiple sclerosis

Objective: Brain atrophy in multiple sclerosis (MS) selectively affects gray matter (GM), which is highly relevant to disability and cognitive impairment. We assessed cerebral GM volume (GMV) during one year of natalizumab therapy. Design/methods: Patients with relapsing–remitting (n = 18) or progressive (n = 2) MS had MRI ～1 year apart during natalizumab treatment. At baseline, patients were on natalizumab for (mean ± SD) 16.6 ± 10.9 months with age 38.5 ± 7.4 and disease duration 9.7 ± 4.3 years. Results: At baseline, GMV was 664.0 ± 56.4 ml, Expanded Disability Status Scale (EDSS) score was 2.3 ± 2.0, timed 25-foot walk (T25FW) was 6.1±3.4 s; two patients (10%) had gadolinium (Gd)-enhancing lesions. At follow-up, GMV was 663.9 ± 60.2 mL; EDSS was 2.6 ± 2.1 and T25FW was 5.9 ± 2.9 s. One patient had a mild clinical relapse during the observation period (0.052 annualized relapse rate for the entire cohort). No patients had Gd-enhancing lesions at follow-up. Linear mixed-effect models showed no significant change in annualized GMV [estimated mean change per year 0.338 mL, 95% confidence interval ?9.66, 10.34, p = 0.94)], GM fraction (p = 0.92), whole brain parenchymal fraction (p = 0.64), T2 lesion load (p = 0.64), EDSS (p = 0.26) or T25FW (p = 0.79). Conclusions: This pilot study shows no GM atrophy during one year of natalizumab MS therapy. We also did not detect any loss of whole brain volume or progression of cerebral T2 hyperintense lesion volume during the observation period. These MRI results paralleled the lack of clinical worsening.     

Treatment effect of natalizumab on relapse outcomes in multiple sclerosis patients despite ongoing MRI activity

Natalizumab treatment significantly reduced the annualised relapse rate and MRI activity over 2 years compared with placebo in phase III trials when administered as monotherapy in AFFIRM or in combination with interferon β-1a (IFNβ) in SENTINEL. The post hoc analyses reported here sought to determine the effect of natalizumab treatment on relapse activity in the minority of patients who continued to show MRI activity (ie, ≥ 1 gadolinium enhancing (Gd+) lesions or new or enlarging T2 hyperintense lesions) over 2 years in these trials. These analyses demonstrated that natalizumab treatment, both alone (AFFIRM) and in combination with IFNβ (SENTINEL), resulted in a reduced annualised relapse rate despite the presence of Gd+ lesions (p=0.004 and p=0.008, respectively) or new or enlarging T2 hyperintense lesions (each p<0.0001). Thus patients treated with natalizumab show clinical benefit even in the presence of continued MRI activity. Long term clinical outcome of these patients has not been studied.     

Observations during an elective interruption of natalizumab treatment: a post-marketing study

In this prospective post-marketing study, 21 patients with multiple sclerosis treated with natalizumab for 24 consecutive months elected a trial of treatment interruption (90-180 days). During a mean duration of treatment interruption of 111.5 days 4 patients (19.0%) experienced a relapse and 9 out of 19 (47.4%) had MRI activity. Number of contrast-enhancing lesions at baseline was lower than during treatment interruption, but the difference was not significant. These findings suggest that disease activity may return after the last infusion of natalizumab. Patients should have regular MRI assessment during treatment interruption to rapidly identify any return of disease activity. The aim of this study was to determine the optimal duration for temporary interruption of natalizumab therapy in patients who have received continuous therapy with natalizumab for 24 months.     

Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients

A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease. All patients had discontinued therapy with natalizumab after at least 24 weeks on therapy, and had been followed 3–12 months (mean 8.9 months) after cessation of natalizumab therapy. The annualised relapse rate before start of natalizumab therapy was 0.94 (95 % confidence interval [CI] 0.88–1.00), 0.47 (95 % CI 0.43–0.52) during natalizumab therapy, 0.63 (95 % CI 0.51–0.76) 1–6 months after natalizumab and 0.55 (95 % CI 0.42–0.70) 7–12 months after natalizumab. However, 83 (22 %) of the patients could be classified as showing rebound of relapses, defined as a higher individual relapse rate after cessation of natalizumab than before natalizumab. These patients had a higher annualised relapse rate during natalizumab therapy. For the whole patient group, the relapse rate after discontinuation did not exceed the pre-natalizumab relapse rate at any time, but 22 % of the patients showed rebound of relapses after discontinuation of natalizumab.     

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing‐remitting multiple sclerosis

Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing‐remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease‐modifying treatments (DMTs). Methods: A retrospective, observational study was carried out. All patients (n = 45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon‐beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium‐enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25‐Foot Walk Test and on the Timed 100‐Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. Results: Sixty‐two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse‐mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. Conclusions: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs.     

Interferon beta in secondary progressive multiple sclerosis

Abstract Background and objective Observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data from a cohort of secondary progressive multiple sclerosis (SPMS) patients treated with interferon beta (IFNβ-1b) at our MS clinic. Methods This was an independent, open-label, non-randomised, observational study. Within the period 1998 to 2005, all patients with SPMS who started therapy with IFNβ-1b at our centre were studied. Each patient was included in a follow-up protocol collecting demographic and baseline clinical data. Results We studied 146 SPMS patients with a median follow-up of 60 months. Over the total study period, 62.2% of patients had confirmed progression. The analysis of the time to con- firmed progression showed that patients with two or more relapses in the 2 years before IFNβ initiation, had a higher risk of disability increase than those patients with less than two relapses (p = 0.002). Multiple regression analysis showed disease activity in terms of relapses as the only factor to predict increase of disability during the follow-up period. A significant proportion of patients (36%) stopped treatment during the follow-up period. IFNβ was safe, although some unexpected adverse events were observed. Conclusions A higher disease activity before the beginning of treatment with IFNβ in SPMS patients with a given EDSS rank could identify those with faster disability progression after treatment initiation.     

Natalizumab is effective in multiple sclerosis patients switching from other disease modifying therapies in clinical practice

Natalizumab is one option for multiple sclerosis patients responding poorly to classical immunomodulators, but pilot studies did not point to its effectiveness as a second-line therapy. Aim of this study was to assess the efficacy of natalizumab as second-line therapy in patients switching from disease modifying therapies (DMTs) in a clinical setting. We retrospectively selected patients who had been treated with natalizumab for at least 12 months after switching from one or more DMTs. We collected clinical and neuroradiological data and we analysed the reduction in annualised relapse rate (ARR), the change of Expanded Disability Status Scale (EDSS) and the reduction of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI) of the brain at 12 months of natalizumab and of previous DMT therapy. Fifty patients were included in the analysis (11 males, 39 females).We observed a reduction of ARR on natalizumab (p = 0.000) and a statistically significant different trend of relapse event between the two treatments (p = 0.0149). EDSS was stable during natalizumab therapy whilst it showed an increase on DMTs (p = 0.0244). The number of CELs decreased significantly (p = 0.006) during the 12 months of treatment with natalizumab, whilst it was stable on DMTs. Natalizumab showed to decrease ARR, stabilize EDSS, increase the percentage of CELs free patients and decrease the number of CELs in a group of 50 poor responders to classical DMT, after the first 12 months of therapy.     

Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis

After discontinuation of natalizumab (NAT), multiple sclerosis (MS) disease activity often recurs. We assessed the recurrence of clinical disease activity during the first year after switching from NAT to fingolimod (FTY) in patients with relapsing-remitting MS. The number of relapses and the annualized relapse rate (ARR) before, during and after NAT discontinuation were determined and compared between 26 MS patients who switched to FTY within 24 weeks, and 10 MS patients who remained without disease modifying therapy (therapy free group = TFG). Median follow-up post-NAT discontinuation was 55.1 weeks. In a subgroup (n = 20), the occurrence of contrast-enhancing-lesions (Gd+) on magnetic resonance imaging (MRI) was determined. Eleven patients (42 %) in the FTY group and seven patients (70 %) in the TFG had one or more relapses after cessation of NAT during follow-up (p < 0.05). One of the 11 (9 %) patients in the FTY group and 6/9 (67 %) patients in the TFG showed Gd+ lesions during follow-up (p < 0.05). Patients who switched to FTY ≤ 12 weeks after NAT discontinuation (n = 9) showed a trend for a lower post-NAT ARR compared to patients who started FTY therapy >12 weeks after NAT was stopped (n = 17). Most relapses in the FTY group occurred just before or within 8 weeks after starting FTY. Our observation suggests that initiation of FTY treatment after NAT discontinuation reduces the recurrence of disease activity compared to withdrawal without further immunomodulatory treatment. In the FTY group the ARR tended to depend on the time interval between discontinuation of NAT and initiation of FTY.     

Natalizumab reduces serum pro-angiogenic activity in MS patients

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0?±?3.9 and 22.5?±?2.6, p?<?0.0001) and higher osteopontin levels (65.7?±?24.3 ng/ml and 65.9?±?16.6 ng/ml, p?=?0.019 and p?=?0.029, respectively) than HCs (9.0?±?2.2; 48.5?±?7.8 ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs?=?0.373, p?=?0.043). After 1 year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9?±?2.1, p?<?0.005; 49.3?±?20.0 ng/ml, p?=?0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.     

Headache and Chiari malformation in young age: clinical aspects and differential diagnosis

To evaluate the efficacy and safety of natalizumab in patients with active relapsing–remitting multiple sclerosis (MS). We included 285 MS patients receiving natalizumab. Clinical, neuroradiological and safety data were registered every 6 months. Neutralizing antibodies (NABs) were tested after 6 months of treatment. After 1 year, the annualized relapse rate decreased to 0.26, with a significant reduction compared to the previous year (2.13). At 24 months the proportion of “relapse free” patients was 78% while that of “MRI free” patients was 69%. Considering clinical and MRI cumulative activity, “disease free” patients were 63% at 24 months. A total of 18 patients showed NABs positivity. We reported 34 cases of treatment interruptions. In conclusion, our data confirm the remarkable efficacy of natalizumab in a group of patients with higher disease activity than that of pivotal studies.     

Swedish natalizumab (Tysabri) multiple sclerosis surveillance study

A post-marketing surveillance program was implemented to monitor the safety and open label efficacy of natalizumab since its launch in Sweden August 2006. Patients are registered in the Swedish multiple sclerosis (MS)-registry that has a nationwide coverage using a standardized follow-up that includes EDSS, MSSS, SDMT, MSIS-29, and recording of adverse events (AEs). As of 31 January, 2010, 1,115 patients had been included, of which 363 were treated ≥24 months. Dropout rate was 10%, mainly due to planned pregnancy. Serious AEs were rare, but included three cases of progressive multifocal leukoencephalopathy (PML), none of which had received previous immunosuppressive therapy. All analyzed clinical outcome parameters showed significant improvements compared to baseline for patients exceeding 24 months of treatment. Our results demonstrate good general tolerability and sustained efficacy of natalizumab for patients with severe MS, though the risk of PML remains a concern.

     

Modeling the cost-effectiveness of a new treatment for MS (natalizumab) compared with current standard practice in Sweden

OBJECTIVE: To estimate the cost-effectiveness of a new treatment (natalizumab) for multiple sclerosis (MS) compared with current standard therapy with disease-modifying drugs (DMDs) in Sweden. METHODS: A Markov model was constructed to illustrate disease progression based on functional disability (the Expanded Disability Status Scale (EDSS)). The effectiveness of natalizumab was based on a 2-year clinical trial in 942 patients (AFFIRM). The effectiveness of current DMDs was estimated from a matched sample of 512 patients in the Stockholm MS registry. Patients withdrawing from treatment were assumed to follow the disease course of 824 patients with relapsing-remitting disease at onset in the Ontario natural history cohort. Costs and utilities are based on a recent observational study in 1339 patients. All data sets were available at the patient level. Main results are presented from the societal perspective, over a 20-year time frame, in 2005 Euros (euro1 = 9.25 SEK). RESULTS: In the base case, treatment with natalizumab was less expensive and more effective than treatment with current DMDs. When only healthcare costs were considered, the cost per quality-adjusted life year gained with natalizumab was euro38 145. Results are sensitive only to the time horizon of the analysis and assumptions about effectiveness of natalizumab beyond the trial. CONCLUSIONS: This cost-effectiveness analysis used registry data, cohort and observational studies to extrapolate the efficacy findings of natalizumab from the AFFIRM clinical trial to measure effectiveness in clinical practice. The analysis results suggest that for the population considered, natalizumab provides an additional health benefit at a similar cost to current DMDs from a societal perspective.     

Natalizumab vs interferon beta 1a in relapsing-remitting multiple sclerosis: a head-to-head retrospective study

Background – No head‐to‐head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS). Aim – To retrospectively compare the efficacy of natalizumab vs IFN beta 1a SC (44 μg; Rebif^®) on clinical and radiological findings in two matched cohorts of patients with MS. Patients and methods – We retrospectively enrolled two cohorts of 42 patients (F/M: 35/7) with relapsing‐remitting multiple sclerosis treated with natalizumab or IFN beta 1a for at least 12 consecutive months. Outcome measures were annualized relapse rate (ARR), changes in expanded disability status scale (EDSS) score, and number of contrast‐enhancing lesions (CELs) at magnetic resonance imaging (MRI). Results – In both groups, the ARR in the 12 months of treatment was lower than in the 12 months before therapy (0.24 vs 1.50 in natalizumab‐treated group, P < 0.0000; 0.55 vs 1.10 in IFN beta 1a‐treated group, P = 0.0006), being the effect of natalizumab significantly stronger (P = 0.0125). EDSS reduction was significantly different between the two groups in favor of natalizumab (P = 0.0018). The frequency and number of CELs per patient were decreased in both groups. In the second year, the treatment affected ARR and EDSS progression in the two groups of patients similarly to the first year, whereas number of CELs decreased more significantly in natalizumab group (P = 0.008). Conclusions – After 12 and 24 months of therapy, natalizumab was more effective than IFN beta 1a SC on both disease activity and disability progression. Prospective head‐to‐head studies would be helpful to further evaluate the differences observed in the MRI outcomes.     

Effect of interferon-β1α therapy on multiple sclerosis based on gadolinium-enhancing or active T2 magnetic resonance imaging outcomes: a meta-analysis

Objectives: Interferon-beta1alpha (IFN-β1α) is widely used to modify the course of relapsing-remitting multiple sclerosis. However, many patients have relapses. The purpose of this study was to evaluate magnetic resonance imaging (MRI) as a predictor of IFN-β1α treatment efficacy in patients with MS.

Methods: PubMed, Embase, and the Cochrane Library were searched to identify eligible studies. Manual searches were also conducted. All eligible trials included MS patients who received IFN-β1α based on gadolinium-enhancing or active T2 MRI lesions for determination of relapse rates.

Results: Of 499 identified studies, we included 10 trials reporting data on 6,037 MS patients. IFN-β1α therapy significantly reduced the risk of relapse (RR: 0.87; 95% confidence intervals (CI): 0.76–0.99; p = 0.032). Furthermore, baseline median T2 lesion volume was found to be related to IFN-β1α therapy and relapse (p = 0.018). Subgroup analysis suggested that IFN-β1α therapy was associated with reduced risk of relapse (RR: 0.82; 95%CI: 0.71–0.94; p = 0.005 versus placebo). However, there was no significant difference in the risk of relapse compared to treatment with low dose IFN-β1α (RR: 0.93; 95%CI: 0.80–1.08; p = 0.337) or glatiramer acetate (RR: 0.93; 95%CI: 0.77–1.14; p = 0.506). Finally, IFN-β1α therapy significantly increased the risk of injection-site disorders, influenza-like syndrome, and alanine transferase elevation.

Discussion: Effects of IFN-β1α therapy are associated with a statistically significant impact on baseline median T2 lesion volume. However, the safety outcomes are significantly worse in patients who receive IFN-β1α therapy.