The safety of pulse corticosteroid therapy- Systematic review and meta-analysis

Objective: To amass all available evidence from randomized controlled trials regarding the safety of pulse corticosteroids therapy, in order to establish its safety. Patients and Methods: All electronic databases from 1/1966 up to 02/2019 were reviewed to find all randomized controlled trials comparing pulse corticosteroids to oral corticosteroids or to placebo/no treatment. Two reviewers independently extracted and recorded data regarding type of corticosteroid treatment, dosages, length of treatment and follow-up. Risk ratios (RR) with 95% (CI) for differences between pulse corticosteroids and comparator were pooled using a fixed effect meta-analysis. The primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included any adverse events (AEs), AEs requiring discontinuation, AEs per system involved and all-cause mortality. Results: A total of 64 trials were included: 18 trials which compared pulse corticosteroids to oral corticosteroids and 46 trials which compared pulse corticosteroids to placebo/no intervention. Pulse corticosteroids was not associated with increased risk for SAEs for both comparators: RR 0.77 (95% CI 0.52-1.14), and RR 0.99 (95% CI 0.93-1.06), respectively. Sensitivity analysis based on adequate allocation concealment and use of a valid AE grading did not alter the results. Subgroup analysis revealed no increased risk of specific SAEs or AEs with pulse corticosteroids compared to oral corticosteroids. Conclusion: Pulse corticosteroids was not associated with an increase risk of SAEs and should be regarded as safe.