Documented Adherence to 3-monthly Blood Monitoring of Dimethyl Fumarate (DMF) in Multiple Sclerosis (MS) during the COVID-19 pandemic at Two Hospital Sites
Disease-modifying therapies (DMTs) used in the treatment of multiple sclerosis (MS) are associated with potentially serious adverse effects, some of which are preventable through regular blood monitoring. During the COVID-19 pandemic, adherence to the recommended blood monitoring of DMTs has been challenging, partly due to reduced face-to-face patient contact with health services. In response to this, the Association of British Neurologists (ABN) published advice on minimum safety monitoring for DMTs (1), as shown in Table 1 below.
Table 1: Minimum safety monitoring for DMTs during the COVID-19 pandemic
|DMT||Normal monitoring recommendation||Recommendation until risk of COVID-19 clarified or passed|
|Dimethyl fumarate||3 monthly||6 monthly if stable and lymphocytes above 0.5|
|Fingolimod||1,3,6,12 months, then every 6-12 months||6 monthly in first year, then 12 monthly if stable|
|Alemtuzumab||Monthly||3 monthly FBC, U&E, LFTs, TFTs|
|Ocrelizumab||Every 6 months||Prior to dosing|
|Interferon beta-1a||3 months, 6 months, then 6 monthly||3 months after starting, then none required|
|Glatiramer acetate||None required||None|
|Cladribine||2 months and 6 months after each course, 2 monthly if lymphocytes <0.5||No change to 2 month test; Delay 6 month test if 2 month bloods are stable and lymphocytes >0.5|
|Teriflunomide||2 weekly for 6 months, then 2 monthly if stable||Monthly for first 6 months, then 4 monthly if stable|
|Natalizumab||Every 3 months||6 monthly JCV|
Abbreviations: FBC = full blood count, U&E = urea and electrolytes, LFTs = liver function tests, TFTs = thyroid function tests
In January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) published updated advice on the risk of progressive multifocal leukoencephalopathy (PML) with dimethyl fumarate (DMF) associated with mild lymphopenia (2). This document strengthened the requirement for 3-monthly monitoring of full blood counts, including lymphocytes. In addition, where previous guidance was to consider interruption of DMF therapy if lymphocyte counts fall below 0.5x109/L for more than 6 months, the updated guidance advised revaluation of treatment in patients with lymphocyte counts between 0.5x109/L and 0.8x109/L sustained for more than 6 months.
To audit documentation of adherence to blood monitoring for dimethyl fumarate at two hospital sites using the Electronic Patient Record (EPR) system.
A list of people with MS on DMF treatment at two hospital sites using the EPR system was obtained from the Trust Homecare Services database on 1st Oct 2021. The pharmacy dispensing database was used to confirm that the patients identified were on treatment with DMF. For patients on current treatment with DMF, the two most recent blood results were obtained from the Trust EPR system where available, noting the date of blood results and lymphocyte counts if these were <0.8x109/L. Any documentation in the notes of blood results performed by other healthcare providers was also noted.
A total of 85 patients on DMF from the two hospital sites were identified, of whom one patient (subject 10) had not yet commenced therapy and was therefore excluded. 54% of patients had documentation of blood monitoring within 3 months of October 2021 (range 21st June 2021 – 18th October 2021), 21% within 3-6 months, 5% within 6-9 months, 8% within 9-12 months and 12% more than 12 months prior (Table 2). Of the 84 patients on DMF, 79 had documentation of a previous FBC, of which 48% had an interval of ≤ 3 months from latest blood results, 13% were between 3-6 months, 22% were between 6-9 months, 11% were between 9-12 months and 6% were >12 months from latest blood results (Table 2).
Table 2: Time interval (in months) between blood monitoring
|Between latest results and time of audit (n=84)||Between last two results where applicable (n=79)|
|No. of patients with documented blood results within 3 months (%)||54%||48%|
|No. of patients with documented blood results between 3-6 months (%)||21%||13%|
|No. of patients with documented blood results between 6-9 months (%)||5%||22%|
|No. of patients with documented blood results between 9-12 months (%)||8%||11%|
|No. of patients with documented blood results between >12 months (%)||12%||6%|
Details of the time intervals for FBC and corresponding lymphocyte counts are shown in Table 3 below. 11 out of 84 patients (13%) had mild lymphopenia (lymphocyte counts between 0.5x109/L and 0.8x109/L), of whom 5 (subjects 29, 57, 58, 62, 83) did not have documented FBCs within 3 months of the audit period, although it was noted that subject 22 was also receiving care from a different country. Seven out of 79 patients (9%) with documentation of a previous FBC had mild lymphopenia, four (60%) of whom had a time interval of ≤3 months between the latest two documented FBCs.
Table 3: Lymphocyte counts and time interval of last documented blood monitoring
Documentation of adherence to 3-monthly blood monitoring of DMF was suboptimal, where only 54% of patients had documentation of FBC within 3 months of the audit period, and 75% within 6 months. For patients with previous blood results, the interval between the last two blood results were within 3 months for 48% of patients and within 6 months for 61% of patients. The lower adherence to blood monitoring for the previous blood results were possibly due to the COVID-19 pandemic, with adherence improving as services gradually returned to normal.
The suboptimal adherence to 3-monthly blood monitoring may have been due to the following:
- Lack of documentation where blood monitoring may have been done by another healthcare provider;
- Inadequate staffing levels, including administrative staff, to enable maintenance of an up-to-date database and to enable adequate patient follow-up.
Proposals to enable better adherence to and documentation of 3-monthly blood monitoring for DMF, which is crucial to providing a safer service and better patient care, are as follows:
- Closer working between members of the MS multidisciplinary team (MDT) and service managers;
- Utilisation of the existing pharmacy database to enable maintenance of an up-to-date database to allow better tracking of blood results;
- Increase current staffing levels within the MS MDT, including administrative, nursing and pharmacy staff through a business case.
- Coles A, Lim M, Giovannoni G, Anderson P, Dorsey-Campbell R, Qualie M. ABN guidance on the use of disease-modifying therapies in multiple sclerosis in response to the threat of a coronavirus epidemic [Internet]. 2020 [cited 2021 Aug 26]. p. 1–9. Available from: https://cdn.ymaws.com/www.thea...
- Medicines and Healthcare products Regulatory Agency. Dimethyl fumarate (Tecfidera): updated advice on the risk of progressive multifocal leukoencephalopathy (PML) associated with mild lymphopenia [Internet]. Drug Safety Update. 2021 [cited 2021 Oct 17]. Available from: https://www.gov.uk/drug-safety...
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