Gianmarco Imperiali

Background: Despite the fact that thiocolchicoside has been widely used in the treatment of musculoskeletal pain, its efficacy has never been systematically evaluated. We carried out a systematic review and meta-analysis of randomized clinical trials (RCTs) to appraise the existing evidence on the efficacy of thiocolchicoside for musculoskeletal pain management. Methods: The literature search was performed on multiple databases, extracting reports of RCTs evaluating the efficacy of thiocolchicoside compared to placebo or no exposure. The reduction in pain intensity was evaluated through between-groups mean differences (MDs) in Visual Analogue Scale (VAS) scores after the intervention. The pooled effect estimates were compared to a minimally important difference (MID) of 1 point on a scale from 0 to 10. Results: We retrieved eight RCTs, including a total of 1397 patients. All the included studies were determined as being at high risk of bias. Seven trials evaluated patients with acute low back pain. After 2–3 days of treatment, the pooled MD in VAS score was −0.49 (95%CI = −0.90; −0.09) compared to controls. After 5–7 days of treatment, the summary MD was −0.82 (95%CI = −1.46; −0.18). Conclusions: Although thiocolchicoside was found to significantly reduce patient-reported low back pain, the clinical impact was very small, as the pooled effect estimates were below the MID, and the overall certainty of evidence was very low. In light of the safety concerns raised by the European Medicine Agency, an in-depth analysis on the risk–benefit balance of thiocolchicoside is required.

Several vaccines against chikungunya fever have been developed and tested, and one has been recently licensed. We performed a meta-analysis to estimate the immunogenicity and safety of all chikungunya vaccines that have been progressed to clinical trial evaluation (VLA1553; mRNA-1388/VAL-181388; PXVX0317/VRC-CHKVLP059-00-VP; ChAdOx1 Chik; MV-CHIK). We included trials retrieved from MedLine, Scopus, and ClinicalTrials.gov. The outcomes were the rates of seroconversion/seroresponse and serious adverse events (SAEs) after the primary immunization course. We retrieved a total of 14 datasets, including >4000 participants. All candidate chikungunya vaccines were able to elicit an immunogenic response in ≥96% of vaccinated subjects, regardless of the vaccination schedule and platform used, and the seroconversion/seroresponse rates remained high 6 to 12 months after vaccination for most vaccines. Four of the five candidate vaccines showed a good overall safety profile (no data were available for ChAdOx1 Chik), with no significant increase in the risk of SAEs among the vaccinated, and a low absolute risk of product-related SAEs. Overall, the present findings support the potential use of the candidate vaccines for the prevention of chikungunya and the current indication for use in adult travelers to endemic regions of the licensed VLA 1553 vaccine. In order to extend chikungunya vaccination to a wider audience, further studies are needed on individuals from endemic countries and frail populations.

The TAK-003 dengue vaccine was licensed in Europe in December 2022, and the official recommendations from most EU countries are still under formulation. To support policymakers, we performed a meta-analysis to quantify TAK-003’s immunogenicity, efficacy and safety among seronegative and seropositive populations after the administration of one or two vaccine doses. We included trials retrieved from MEDLINE, Scopus and ClinicalTrials.gov. The outcomes were the rates of seroconversion, virologically confirmed dengue fever and serious adverse events after each vaccine dose. Data were combined using random-effect proportion or head-to-head meta-analyses. We retrieved a total of 19 datasets, including >20,000 participants. TAK-003 showed an excellent safety profile, and the immunogenicity after two doses against the four DENV serotypes was ≥90% among both adults and children/adolescents who were either seronegative or seropositive at baseline. A single dose was able to elicit a high immunogenic response among adults (≥70%) and children/adolescents (≥90%). The primary two-dose immunization course halved the risk of all types of virologically confirmed dengue fever among seropositive children/adolescents, but seronegative minors were only protected against the diseases caused by DENV-1 and DENV-2. Overall, the results support the use of TAK-003 for the prevention of dengue fever in the pediatric population of endemic countries. Uncertainties remain on the use of a single vaccine dose in non-endemic countries.