A recent systematic review and network meta-analysis examined treatment efficacy and safety of immunosuppressives (i.e., azathioprine, danazol, cyclosporine, cyclophosphamide, vincristine, vinblastine, mycophenolate mofetil, and dapsone), monoclonal antibodies (i.e., rituximab), thrombopoietin receptor agonists (i.e., eltrombopag and romiplostim), or a combination of these agents or splenectomy for the management of primary immune thrombocytopenia. Treatment outcomes included platelet response, platelet count, bleeding, and serious adverse events (SAEs). Randomized, controlled trials published and listed in Medline or Scopus before September 21, 2018, were eligible for inclusion. The study was conducted following Preferred Reports of Systematic Review and Meta-Analysis guidelines.
The primary outcome was achievement of a platelet count of >30 X 109/l or > 50 X 109/l, depending on the original study criteria. Secondary outcomes included quantitative platelet counts at 6 weeks post-treatment, bleeding, or composite SAEs, including death, thrombosis, or serious infection.
A total of 14 randomized, controlled trials were included in the systematic review. All studies examined platelet response and 12 of the studies also evaluated platelet counts. Eleven of these studies analyzed the composite of SAEs.
The median study and follow-up periods were 6 weeks and 24 weeks, respectively. The median age range in the studies were 34 to 59 years.
When platelet response was studied, eltrombopag produced a fourfold higher response, and romiplostim had a 4.82 higher response compared with placebo, which were both statistically significant. Eltrombopag, romiplostim, and rituximab were also associated with higher platelet counts. Eltrombopag was also associated with a significantly lower risk of bleeding, and a positive trend was observed for the other agents. Romiplostim, but not eltrombopag, was associated with a significantly lower risk of SAEs compared with placebo.
Twelve of the 14 studies were included in the network meta-analysis. It found that eltrombopag ranked as the best treatment for platelet response followed by romiplostim, rhTPO (recombinant human thrombopoietin) + rituximab, placebo, and rituximab, with eltrombopag and romiplostim being significantly more effective than rhTPO + rituximab and rituximab monotherapy. None of the drugs studied significantly affected the platelet count outcome, but romiplostim ranked the best followed by eltrombapag, rhTPO + rituximab and rituximab monotherapy.
Rituximab had the lowest risk of bleeding followed by eltrombopag and romiplostim, but compared with placebo, this was not statistically significant, except for eltrombopag. Conversely, the greatest risk of bleeding was associated with placebo followed by romiplostim, eltrombopag, and rituximab.
The highest risk of SAEs were associated with rhTPO + rituximab followed by rituximab, eltrombopag, placebo, and romiplostim; romiplostim’s risk was lower than placebo’s risk for SAEs.
Other findings of the network meta-analysis included that romiplostim had the greatest effect on platelet count and the least risk of SAEs, with the second most beneficial platelet response. Eltrombopag was the most efficacious but was associated with increased SAEs compared with romiplostim and placebo. rhTOP + rituximab and rituximab monotherapy were associated with the greatest risk of SAEs, but rituximab monotherapy had the smallest bleeding risk.
This systematic review and network meta-analysis provides guidance to pharmacists and other healthcare professionals on how best to manage patients with persistent immune thrombocytopenia.
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