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6ER-009 Can tolerability and safety of daa-2 for hepatitis c be estimated only by randomised clinical trials? a systematic review with meta-analysis
  1. C Della Costanza1,
  2. A Bignamini2,
  3. P Minghetti1
  1. 1University of Milan, Hospital Pharmacy, Milan, Italy
  2. 2University of Milan, Department of Statistics, Milan, Italy


Background Every year an increase in new cases of patients with chronic hepatitis C (CHC) from HCV has been registered. The availability of second-generation DAA (DAA-2) has permitted a rise of SVR rates compatible with a good safety profile.

Purpose To research literature evidence regarding existence of tolerability and safety data obtained from a comparison between DAA-2 and standard of care.

Material and methods The review included RCT and other CT concluded and published until 20 June 2017, related to patients with CHC treated with DAA-2 (sofosbuvir; simeprevir; ledipasvir; daclatasvir; ombitasvir; paritaprevir; dasabuvir) in monotherapy or combined therapy, compared with gold standard (PegIFN ±Ribavirin (RBV) ±first generation DAA (DAA-1). Adverse reactions (ADR) data were searched during the treatment period and not beyond 30 days from the end of it. Databases Cochrane Central Register of Controlled Trials/Central, Embase and Pubmed were consulted: the research methodology adopted was the one with MeSH Terms when available. For included studies the meta-analysis with R was made.

Results The articles identified were 174. Some (nine) were recognised by more databases and the articles (168) that did not find correspondence with the primary endpoint and did not belong to inclusion criteria were discarded. The studies included were six: five RCT and one observational study. The serious adverse events (SAE) and interruptions of therapy data between exposed (treated) and not-exposed (controls) patients were used for meta-analysis. One study that did not report the SAE numbers for controls was excluded from the meta-analysis. No differences in the effect between treated and controls were observed, neither for SAE incidence nor for interruptions treatment incidence. The 95% CI of the OR around the evaluation of the overall effect included the value 1: OR: 0.702 (95% CI: 0.381 to 1.295) and OR: 0.769 (95% CI: 0.277 to 2.138), respectively. The overall effect for SAE and interruptions resulted with P0.257 and P0.615, respectively.

Conclusion No substantial differences remained in SAE and the interruptions rate between the two treatments, DAA-2 and gold standard. Furthermore, a significant heterogeneity between studies was observed. The introduction of large registries would be useful in valuing the risk of ADRs, their nature and the real frequency of SAE in the population, that can be barely estimated only by RCT.

References and/or Acknowledgements R Core Team.

No conflict of interest

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