This is a follow-up to our 9-30-24 post introducing our October Quick Question, “At what FVIII activity level do you order a Nijmegen-Bethesda inhibitor assay (NBA)?” It occurred to me (Geo) that the demand for NBAs may have diminished with the advent of the FVIII bypassing therapies, HemLibra® (emicizumab), soon to be followed by MIM8 and the RNAi “rebalancing” therapeutics concizumab and fitusiran, all currently in trials. As these therapies bypass FVIII, the need to measure FVIII inhibitors may have become academic, except perhaps in specific clinical applications.
I asked Dr. Chad Siniard, director of the UAB Coagulation Laboratory if he’s seen a decline in NBA orders. It turns out that UAB’s lab scientist Laura Taylor has been tracking their volume for several years and has provided the attached graph. (The 2024 data are YTD.) Please comment below about your lab’s NBA volume. Are we all seeing a decrease?
Below, Dr. Emanual Favaloro responds with a report of his lab’s NBA volumes. Click here to see the graph he references in his comment.
Hi George,
We have not seen a clear reduction in FVIII inhibitor orders in our laboratory, despite the introduction of emicizumab. I have sent you a figure by email. There has been a drop in 2024, but as this is data to date, this could just reflect an incomplete dataset or a random variation rather than an indication of a developing trend. A couple of considerations: in our organisation, FVIII inhibitor assays can be ordered by any clinician, either as an electronic order (eOrder) or by paper form. Thus, there is a varied input in clinical expertise for requests. For example, it is not unusual to get an eOrder for FVIII inhibitor on patients being investigated for thrombophilia; here, the clinician presumably wants a FVIII level as a risk factor for thrombosis (i.e., high FVIII level expected). These inappropriate FVIII inhibitor requests are cancelled and replaced with a FVIII level. Second, emicizumab was approved later in Australia (2018) than in the US (2017). Third, most FVIII processed inhibitor requests are negative for inhibitors. Fourth, emicizumab is an expensive product, and although there are obvious other associated cost savings and patient benefits, it is a product that will only be applied to specific (not all) patients. The upshot for all this is that: a) a theoretical reduction in FVIII inhibitor orders will only apply to patients placed on emicizumab, which comprises (even in 2024) a small proportion of our patients; b) FVIII inhibitor orders for initial patient investigations will not fall, and these reflect the majority of orders (i.e., FVIII inhibitor monitoring for patients under treatment with emicizumab with inhibitors reflects a much lower volume of orders).