It is clear that many MSers on continuous anti-CD20 therapy are concerned about the risk of developing hypogammaglobulinaemia and subsequent infections. Yesterday, I spoke to several neurologists at the O’HAND investigators meeting in Barcelona who informed me that they are considering giving their ocrelizumab-treated patients hyperimmune globulin replacement therapy (HYPE-Ig-RT) when they develop hypogammaglobulinaemia to prevent serious and potentially fatal infections.
The problem I have with this is that HYPER-Ig-RT is expensive and for it to be covered by the NHS we will need to show that it is cost-effective. In response to these discussions Owen Pearson, an MSologist from Swansea, and I came up with the design of the HYPE study below.
The HYPE study
This is a randomised placebo-controlled trial to assess whether or not HYPE-Ig-RT will work, i.e. reduce the risk of serious infection, infections and mortality in MSers on continuous anti-CD20 therapy. Please note we don’t think this study should be limited to ocrelizumab-treated MSers but should be open to any patient on anti-CD20 therapy, including those on rituximab and ofatumumab.
What do you think of the HYPE study? Do we have clinical equipoise?
Please remember for the payers, i.e. NHS England and insurance companies, to pay for HYPER-Ig-RT we need class 1 evidence to make the financial case to them. This study will test the hypothesis that HYPE-Ig-RT will derisk continuous anti-CD20 therapies and prevent some of the infectious complications related to hypogammaglobulinaemia.
What is the risk of serious infections on anti-CD20 therapies?
The following figures put the serious infection risk, i.e. infections requiring hospitalisation, on ocrelizumab in context. The overall figure is 2.24 serious infections per 100 patient-years. In other words for every 45 patients on ocrelizumab for 12 months one patient will be admitted to hospital with a serious infection. However, if you develop low IgG levels (hypogammaglobulinaemia) the risk rises to 5.48 serious infections per 100 patient-years or for every 18 patients on ocrelizumab for 12 months one patient will be admitted with a serious infection. This is why we are now monitoring peripheral blood immunoglobulin levels on an annual basis in all our patients on anti-CD20 therapy.