Article type
Abstract
"Background: Antigen-specific therapies could be an optimal solution for patients with multiple sclerosis (MS), as they avoid many serious adverse effects (SAE), as they silence only those pathways that contribute to the disease pathogenesis.
Objectives: The objective of this systematic review is to evaluate the efficacy and safety of antigen-specific tolerance-inducing therapeutic approaches (products based on peptides, DNA and T cells) versus placebo or other comparators, where possible, in adult MS patients.
Methods: Phase I, II and III clinical trials (randomized/non-randomized; double blind/single blind/unblinded; single-center/multicenter; single-arm/two-arm) were included. PubMed, CINAHL, Web of Science, Cochrane and International Clinical Trials Registry Platform, ClinicalTrials.gov were searched for published and unpublished studies. Screening, critical appraisal, and data extraction for included studies were carried out by two independent reviewers. All included studies were critically appraised using standardized JBI tools, with no exclusions based on methodological quality. Where possible, studies were pooled in statistical meta-analysis, presented in tabular format, and accompanied by narrative synthesis. The certainty of evidence was assessed using the GRADE approach.
Results: Search yielded 2644 results and in total 26 studies were included in the final analysis. Twelve studies were RCTs and 14 were quasi-experimental. In total, there were 1427 subjects from the RCTs, and 314 from non-RCTs. Sample size of studies ranged from 10 to 612 patients. All studies included adult patients, principally aged 18 to 55/65 years. Critical appraisal scores for the RCTs were in the range 31% to 92%. For quasi-experimental studies, critical appraisal scores were in the range 45% to 78%. Due to high heterogeneity of the studies, efficacy of all antigen-specific treatment remains ambiguous. There were no significant differences in occurrence of AEs and SAEs in intervention compared to the placebo groups. There was a low frequency of SAEs in MS patients during the treatment. The most frequent AEs were local reactions to injection, such as redness, erythema, pain.
Conclusions: Antigen-specific tolerance-inducing therapeutic approaches appear to be safe (low certainty of evidence), but their efficacy remains clinically ambiguous (very low certainty of evidence). Well-designed studies with optimal information size are needed to raise the certainty of conclusions.
"
Objectives: The objective of this systematic review is to evaluate the efficacy and safety of antigen-specific tolerance-inducing therapeutic approaches (products based on peptides, DNA and T cells) versus placebo or other comparators, where possible, in adult MS patients.
Methods: Phase I, II and III clinical trials (randomized/non-randomized; double blind/single blind/unblinded; single-center/multicenter; single-arm/two-arm) were included. PubMed, CINAHL, Web of Science, Cochrane and International Clinical Trials Registry Platform, ClinicalTrials.gov were searched for published and unpublished studies. Screening, critical appraisal, and data extraction for included studies were carried out by two independent reviewers. All included studies were critically appraised using standardized JBI tools, with no exclusions based on methodological quality. Where possible, studies were pooled in statistical meta-analysis, presented in tabular format, and accompanied by narrative synthesis. The certainty of evidence was assessed using the GRADE approach.
Results: Search yielded 2644 results and in total 26 studies were included in the final analysis. Twelve studies were RCTs and 14 were quasi-experimental. In total, there were 1427 subjects from the RCTs, and 314 from non-RCTs. Sample size of studies ranged from 10 to 612 patients. All studies included adult patients, principally aged 18 to 55/65 years. Critical appraisal scores for the RCTs were in the range 31% to 92%. For quasi-experimental studies, critical appraisal scores were in the range 45% to 78%. Due to high heterogeneity of the studies, efficacy of all antigen-specific treatment remains ambiguous. There were no significant differences in occurrence of AEs and SAEs in intervention compared to the placebo groups. There was a low frequency of SAEs in MS patients during the treatment. The most frequent AEs were local reactions to injection, such as redness, erythema, pain.
Conclusions: Antigen-specific tolerance-inducing therapeutic approaches appear to be safe (low certainty of evidence), but their efficacy remains clinically ambiguous (very low certainty of evidence). Well-designed studies with optimal information size are needed to raise the certainty of conclusions.
"