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 Bethesda inhibitor assay (Nijmegen-Bethesda Assay, NBA)?” It occurred to me (Geo) that the demand for NBAs may have diminished with the 2017 release of HemLibra® (emicizumab), the FVIII bypassing therapy, to be followed by the anticipated 2025 or 2026 approval of MIM8 and the RNAi “rebalancing” therapeutic fitusiran. As these therapies bypass FVIII, the need to measure FVIII inhibitors may have become academic, except perhaps in specific clinical applications.
Our 32 respondents’ answers illustrate there is no agreed-upon decision point:
- 50 U/dL: 5 (16%)
- 30 U/dL: 9 (28%)
- 20 U/dL: 4 (12%)
- 10 U/dL: 6 (19%)
- Any level; comment: 8 (25%)
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.)
On 10-6-24, Dr. Ali Sadeghi-Khomami responded with current data on HemLibra volumes in the USA, Japan, France, Canada, Australia, Germany, and the Netherlands. These are absolute volumes, not per-capita expressions, however, they illustrate the level of adoption varies considerably by country. We await 2024 levels to find if orders have risen.
On 10-4-24, Dr. Emmanuel Favaloro responded: 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).
We look forward to additional comments on this issue.
No comments here.