Comparative efficacy of interferon ß versus glatiramer acetate for relapsing-remitting multiple sclerosis.

Interferon ß (INFß) and glatiramer acetate (GA) are widely used in patients with relapsing-remitting multiple sclerosis (RRMS). However, it is still unclear whether they have different efficacy. We performed a systematic search of head-to-head trials for gaining objective reliable data to compare the two drugs, using the Cochrane Collaboration methodology. We identified five randomised-controlled trials (RCTs) (2858 participants) comparing directly INFß versus GA in RRMS. All studies were at high risk for attrition bias. Both therapies showed similar efficacy at 24 months, considering clinical (patients with relapse or progression) and one MRI activity (enhancing lesions) measure. At 3 years, evidence from a single study showed that the relapse rate was higher in the INFß group than in the GA group (risk ratio 1.40, 95% CI 1.13 to 1.74, p 0.002). However, the average reduction in T2-weighted and T1-weighted lesion volume was significantly greater in the INFß group than in the GA group (mean difference (MD) -0.58, 95% CI -0.99 to -0.18, p 0.004, and MD -0.20, 95% CI -0.33 to -0.07, p 0.003, respectively). The number of participants who dropped out of the studies because of adverse events was similar in the two groups. These data support clinicians in the use of these therapies, based on their similar safety and efficacy in the prevention of disease activity, although the different effect on MRI measures and the different tolerability might have a role in the therapeutic choice at the individual level.

Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis.

BACKGROUND: Interferons (IFNs)-beta and glatiramer acetate (GA) were the first two disease-modifying therapies (DMTs) approved 15 years ago for the treatment of multiple sclerosis (MS). DMTs prescription rates as first or switching therapies and their costs have increased substantially over the past decade. As more DMTs become available, the choice of a specific DMT should reflect the risk/benefit profile, as well as the impact on quality profile. As MS cohorts enrolled in different studies can vary significantly, head-to-head trials are considered the best approach for gaining objective reliable data when two different drugs are compared. The purpose of this study is to summarise available evidence on the comparative effectiveness of IFNs-beta and GA on disease course through a systematic review of head-to-head trials. OBJECTIVES: To assess whether IFNs-beta and GA differ in terms of safety and efficacy in the treatment of patients with relapsing-remitting MS (RRMS). SEARCH METHODS: We searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (29 October 2013) and the reference lists of retrieved articles. We contacted trialists and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing directly IFNs-beta versus GA in study participants affected by RRMS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: Five trials contributed to this review. A total of 2858 participants were randomly assigned to IFNs (1679) and GA (1179). The treatment duration was three years for one study and two years for the other four RCTs. The IFNs analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933 participants), IFN-beta 1a 44 mcg (two trials, 441 participants) and IFN-beta 1a 30 mcg (two trials, 305 participants). Enrolled participants were affected by active RRMS. All studies were at high risk for attrition bias.Both therapies showed similar clinical efficacy at 24 months, given the primary outcome variables (number of participants with relapse (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to 1.35)). However at 36 months, evidence from a single study suggests that relapse rates were higher in the group given IFNs than in the GA group (RR 1.40, 95% CI 1.13 to 1.7, P value 0.002).Secondary magnetic resonance imaging (MRI) outcomes analysis showed that effects on new or enlarging T2- or gadolinium (Gd)-enhancing lesions at 24 months were similar (mean difference (MD) -0.01, 95% CI -0.28 to 0.26, and MD -0.14, 95% CI -0.30 to 0.02, respectively). However, the reduction in T2- and T1-weighted lesion volume was significantly greater in the groups given IFNs than in the GA groups (MD -0.58, 95% CI -0.99 to -0.18, P value 0.004, and MD -0.20, 95% CI -0.33 to -0.07, P value 0.003, respectively).The number of participants who dropped out of the study because of adverse events was similar in the two groups (RR 0.95, 95% CI 0.64 to 1.40).The quality of evidence for primary outcomes was judged as moderate for clinical end points, but for safety and some MRI outcomes (number of active T2 lesions), quality was judged as low. AUTHORS' CONCLUSIONS: The effects of IFNs-beta and GA in the treatment of patients with RRMS, including clinical (e.g. patients with relapse, risk to progression) and MRI (Gd-enhancing lesions) activity measures, seem to be similar or to show only small differences. When MRI lesion load accrual is considered, the effect of the two treatments differs, in that IFNs-beta were found to limit the increase in lesion burden as compared with GA. Evidence was insufficient for a comparison of the effects of the two treatments on patient-reported outcomes, such as quality of life measures.

Reduced respiratory muscle strength and endurance in type 2 diabetes mellitus.

BACKGROUND: A restrictive lung function pattern is frequently observed in patients with diabetes mellitus (DM) and has been related to respiratory muscle dysfunction in type 1 DM or in mixed population. We aimed to verify whether such a relationship applies also to type 2 DM patients. METHODS: The respiratory muscle function was explored in 75 non-smoking patients with type 2 DM without pulmonary or cardiac diseases and compared with that of 40 healthy non-smoking control subjects matched by age and sex. Maximal inspiratory and expiratory pressures (MIP, MEP) and maximum voluntary ventilation (MVV), which reflect respiratory muscle strength and endurance, respectively, were measured, and a complete respiratory function assessment was recorded. RESULTS: Patients were in stable metabolic conditions and had, on average, normal total lung capacity and diffusing lung capacity for carbon monoxide. However, MIP and MVV were significantly reduced in comparison with those of control subjects. Both MIP/MEP and MVV significantly correlated with lung volumes and diffusing lung capacity for carbon monoxide. The multiple regression analysis identified age (beta coefficient = -0.238, p = 0.046), glycated haemoglobin (beta coefficient = -0.245, p = 0.047) and total lung capacity (beta coefficient = 0.430, p = 0.016) as independent correlates of MIP, whereas male sex (beta coefficient = 0.423, p = 0.004) and diabetic complications (beta coefficient = -0.248, p = 0.044) were independent correlates of MVV. CONCLUSIONS: In type 2 DM, respiratory muscle strength was reduced and significantly related to lung volumes and quality of metabolic control, whereas impaired endurance of respiratory muscles prevailed in patients with microvascular complications.