A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis

Abstract

Summary What is known and objective The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head‐to‐head comparisons between these treatments do not exist. Thus, a network of multiple‐treatments meta‐analysis was performed using four clinical outcomes: ‘patients free of relapse’, ‘patients without disease progression’, ‘patients without MRI progression’ and ‘patients with adverse events’. Methods Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m2) using direct and indirect analyses. Results and discussion The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex (‘patients free of relapse’ and ‘patients without MRI progression’) and for Betaferon compared with Avonex (‘patients without disease progression’ and ‘patients without MRI progression’). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: ‘patients free of relapse’ and ‘patients without MRI progression’. Regarding ‘patients with adverse events’, no data were available for all comparisons to make fair inferences. What is new and conclusion This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head‐to‐head comparisons between treatments.

Anti-hsp60 antibody responses based on Helicobacter pylori in patients with multiple sclerosis: (ir)Relevance to disease pathogenesis

“…Over time, most of patients with relapsing-remitting MS (RRMS) acquire a secondary progressive MS (SPMS) clinical phenotype (Katz Sand, 2015). Many immunomodulatory or immunosuppressive treatments are currently available only for (RRMS) (Hadjigeorgiou et al, 2013, while these are uneffective for primary progressive MS or SPMS .…”

Improved clinical behavior of established relapsing-remitting experimental autoimmune encephalomyelitis following treatment with endogenous opioids: Implications for the treatment of multiple sclerosis

“…As the disease progresses, neurodegeneration in the spinal cord and brain is prominent leading to a significant reduction in the quality of life. Current therapies are not completely effective and are designed to target one or more of the symptoms of the disease, rather than targeting diseasebased mechanisms (Fox and Rhoades, 2012;Stoll et al, 2012;Hadjigeorgiou et al, 2013). The mouse model of relapse-remitting experimental autoimmune encephalomyelitis (RR-EAE) induced by proteolipid protein immunizations represents an animal model to study the clinical course of behavior and neuropathology in RR-EAE (Pollinger et al, 2009;Summers De Luca et al, 2010).…”

Endogenous Opioids in the Etiology and Treatment of Multiple Sclerosis

“…At least 12 disease-modifying therapies (DMTs) have received FDA approval, and a few have been developed as oral medications (37)(38)(39). However, the financial burden of individual therapy can range upward to $60K annually (37), and side effects still reduce compliance and thereby overall efficacy (38).…”

“…At least 12 disease-modifying therapies (DMTs) have received FDA approval, and a few have been developed as oral medications (37)(38)(39). However, the financial burden of individual therapy can range upward to $60K annually (37), and side effects still reduce compliance and thereby overall efficacy (38). Randomized clinical trials of enkephalins or LDN are limited (40)(41)(42)(43), possibly because use of LDN has been reported to have a few side effects, and large pharmaceutical companies are not interested in sponsoring studies on a repurposed drug (i.e., LDN) that is already FDA approved at substantially higher dosages.…”