Imperial College NHS Trust
Pharmacy

Author Of 3 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

LB1167 - Reported Covid19 symptoms in patients on oral Disease Modifying Treatmentss (DMTs) at a single centre (ID 1493)

Presentation Number
LB1167
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There is concern amongst the MS community regarding increased risk of COVID-19 infection in patients on Disease Modifying Therapies (DMTs). Guidance from the Association of British Neurologists (ABN) recommends to continue most oral DMTs during the pandemic.

Objectives

To identify number of patients on oral DMTs in a single centre who reported COVID-19 symptoms. To identify how this compares to national infection rate, whether there was a link to lymphocyte counts prior to infection and how many patients stopped or interrupted treatment.

Methods

Patients on oral DMTs (dimethyl fumarate (DMF), teriflunomide (TF) & fingolimod (FING)) were identified through a local database. The pharmacy team called these patients to advise on DMT monitoringduring the pandemic. Patients were also asked if they had experienced any symptoms of COVID-19 infection, had been tested, or had stopped treatment . Recent lymphocyte counts were obtained.

Results

501 patients on oral DMTs were identified (14 on TF, 169 on FING, 318 on DMF). 50% of these were contacted. (DMF=174, FING=71, TF=10). The average age of those on treatment was 45, average EDSS 2.2, and average time on DMT 3.7 years. Of those asked 90% (229) reported that they had not exprienced COVID-19 symptoms. 10% (26) reported that they had experienced COVID-19 symptoms (3 on TF, 8 on FING, 15 on DMF). According to a recent study by the UK Office of National statistics, of those individuals providing blood samples in the UK, 7% tested positive for antibodies to COVID-19. Of those who reported symptoms the last recorded lymphocyte counts were all within accepted ranges, with a mean of 1.2 (TF 2.0, DMF 1.5, FING 0.4). One patient taking DMF died due to COVID-19. Further data will be presented on the average lymphocyte counts in those who did not report symptoms, number of patients who went on to be tested for COVID-19 and the number who stopped or interrupted treatment.

Conclusions

Results present real world data on COVID-19 infection in patients on oral DMTs for MS and how these relate to lymphocyte count and infections rates in general population.

Collapse
Disease Modifying Therapies – Risk Management Poster Presentation

P0318 - Early monitoring of B cells on ocrelizumab may help to identify those at risk of adverse effects (ID 923)

Presentation Number
P0318
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody used in the treatment of MS. The drug targets CD20 and acts to reduce circulating B cells. Infection is a known adverse effect of treatment. It is not a requirement of the licence to monitor the effect of OCR on B cells counts and the relationship between B cell count and adverse effects is unknown.

Objectives

We aimed to assess the impact of OCR infusions on B cell counts in our patient group and whether there is a relationship between B cell count & adverse events such as infusion reactions or infections

Methods

Lymphocyte subsets were measured for each patient at baseline and before each subsequent infusion. Patients who had received OCR were identified from hospital records & lymphocyte subset results obtained from pathology reports. Date of infusions were noted and B cell data was correlated to determine average counts before or after each dose. Patient records were examined retrospectively to identify reports of adverse events including infection. These were then related to the degree of B cell suppression.

Results

170 people with MS (pwMS) received infusions of ocrelizumab from Sept 2018 to March 2020. Baseline B cell subsets were collected on 145 of these. The mean count ±SD was 279mm3 ±175 (range 44-1290) . Sampling was performed on average 92±62 days prior to dosing. 136 individual pwMS had sampling performed after the first infusion (194 samples in total). In 101 pwMS, between the first and second infusion, the mean B cell counts were 15mm3 ±32.6 . Samples were performed 171±40 days after the first infusion. In 32 pwMS sampled between second and third infusions, mean cell B counts were 13.9mm3 ±29.6 . Samples were performed 353±63 days after the 2nd infusion. In the naïve subgroup (n=10 vs n=71 not naive) there was a more significant drop in B cells 7.7 vs 18.6 (p=0.038) with treatment. However they did not experience more adverse effects. Adverse effects were seen in 54/83 subjects. 21/54 had infusion related reactions. 43 reported infections including herpes (1), cellulitis (1), gastroenteritis (6), upper (18) or lower respiratory tract (7), urinary tract infections (22) or other infection (8). In those who had adverse effects there was no difference in the B cell counts at baseline. However, those who developed infections had a significant reduction in B cells (infection 6mm3 vs no adverse effects 28mm3, p=0.045). This difference persisted after the second dose (infection 5mm3 vs no adverse effects 27mm3, p=0.19). There was however no difference in the absolute lymphocyte counts (p=0.8) , CD8 or NK cells.

Conclusions

This data suggests that regular monitoring of B cell counts, rather than absolute lymphocyte counts, may be a method of identifying those patients at risk of adverse effects, such as infection, following ocrelizumab.

Collapse
Observational Studies Poster Presentation

P0902 - Real world evidence of progression independent of relapsing activity among MS patients treated with Alemtuzumab. (ID 1165)

Speakers
Presentation Number
P0902
Presentation Topic
Observational Studies

Abstract

Background

Background:Disability accumulation can result from progression independent of relapsing activity (PIRA) even during the RR phase.

Objectives

Aims: We assessed the contribution of PIRA to the development of permanent disability, among RRMS treated with Alemtuzumab(ATZ).

Methods

Methods: retrospective data from 147 RRMS patients, who received ATZ at Imperial College Healthcare Trust, followed up for 3 mean years. PIRA was defined as 1.5point increase of EDSS if baseline EDSS was 0, 1point increase if baseline EDSS was <5.5, or 0.5point increase if baseline EDSS was >= 5.5,90days from the previous relapse. The logistic regression analysis was used to assess factors affecting the risk of PIRA.

Results

Results In the whole group female predominated (60%), 19% were treatment naïve and 81% were escalated to ATZ from previous DMTs; 15% (n = 23) received one course of ATZ only. At first ATZ infusion, the mean age was 42 years, the mean disease duration was 8 years and the mean EDSS score was 4. During the observation period, the EDSS remained stable in 58% (n=84) or improved in 11% (n = 17), while it worsened by 1.5 mean point (min 0.5 max 4.5) in 31% (n = 46). Among patients who experienced EDSS worsening, disability accumulation was related to PIRA in 76% (n = 35), while in only a minority (n = 11) it resulted from relapse-associated worsening. Compared to the whole group, patients with PIRA had at first ATZ infusion same mean EDSS score (4, p =0.8), but they had longer disease duration (11 versus 7 mean years, p=0.007), were significantly older both at disease onset (36 vs 32 mean years, p=0.046) and at commencement of the therapy (47 vs 40 mean years, p=0.001). In addition, in the PIRA group vast majority (94%) of patients were escalated to ATZ after lack of response to previous DMTs. The logistic regression analysis confirmed that older age at first ATZ course (OR 6.7, p=0.037) and being escalated to ATZ from previous DMTs (OR 1.1, p= 0.002) are factors significantly associated with higher risk of PIRA.

Conclusions

Conclusions We confirmed in the real-world setting that in a large proportion of patients the disability accumulation can occur despite effective therapeutic relapse suppression. Older patients receiving ATZ as escalation therapy are more likely to experience PIRA.

Collapse

Presenter Of 2 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

LB1167 - Reported Covid19 symptoms in patients on oral Disease Modifying Treatmentss (DMTs) at a single centre (ID 1493)

Presentation Number
LB1167
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There is concern amongst the MS community regarding increased risk of COVID-19 infection in patients on Disease Modifying Therapies (DMTs). Guidance from the Association of British Neurologists (ABN) recommends to continue most oral DMTs during the pandemic.

Objectives

To identify number of patients on oral DMTs in a single centre who reported COVID-19 symptoms. To identify how this compares to national infection rate, whether there was a link to lymphocyte counts prior to infection and how many patients stopped or interrupted treatment.

Methods

Patients on oral DMTs (dimethyl fumarate (DMF), teriflunomide (TF) & fingolimod (FING)) were identified through a local database. The pharmacy team called these patients to advise on DMT monitoringduring the pandemic. Patients were also asked if they had experienced any symptoms of COVID-19 infection, had been tested, or had stopped treatment . Recent lymphocyte counts were obtained.

Results

501 patients on oral DMTs were identified (14 on TF, 169 on FING, 318 on DMF). 50% of these were contacted. (DMF=174, FING=71, TF=10). The average age of those on treatment was 45, average EDSS 2.2, and average time on DMT 3.7 years. Of those asked 90% (229) reported that they had not exprienced COVID-19 symptoms. 10% (26) reported that they had experienced COVID-19 symptoms (3 on TF, 8 on FING, 15 on DMF). According to a recent study by the UK Office of National statistics, of those individuals providing blood samples in the UK, 7% tested positive for antibodies to COVID-19. Of those who reported symptoms the last recorded lymphocyte counts were all within accepted ranges, with a mean of 1.2 (TF 2.0, DMF 1.5, FING 0.4). One patient taking DMF died due to COVID-19. Further data will be presented on the average lymphocyte counts in those who did not report symptoms, number of patients who went on to be tested for COVID-19 and the number who stopped or interrupted treatment.

Conclusions

Results present real world data on COVID-19 infection in patients on oral DMTs for MS and how these relate to lymphocyte count and infections rates in general population.

Collapse
Disease Modifying Therapies – Risk Management Poster Presentation

P0318 - Early monitoring of B cells on ocrelizumab may help to identify those at risk of adverse effects (ID 923)

Presentation Number
P0318
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody used in the treatment of MS. The drug targets CD20 and acts to reduce circulating B cells. Infection is a known adverse effect of treatment. It is not a requirement of the licence to monitor the effect of OCR on B cells counts and the relationship between B cell count and adverse effects is unknown.

Objectives

We aimed to assess the impact of OCR infusions on B cell counts in our patient group and whether there is a relationship between B cell count & adverse events such as infusion reactions or infections

Methods

Lymphocyte subsets were measured for each patient at baseline and before each subsequent infusion. Patients who had received OCR were identified from hospital records & lymphocyte subset results obtained from pathology reports. Date of infusions were noted and B cell data was correlated to determine average counts before or after each dose. Patient records were examined retrospectively to identify reports of adverse events including infection. These were then related to the degree of B cell suppression.

Results

170 people with MS (pwMS) received infusions of ocrelizumab from Sept 2018 to March 2020. Baseline B cell subsets were collected on 145 of these. The mean count ±SD was 279mm3 ±175 (range 44-1290) . Sampling was performed on average 92±62 days prior to dosing. 136 individual pwMS had sampling performed after the first infusion (194 samples in total). In 101 pwMS, between the first and second infusion, the mean B cell counts were 15mm3 ±32.6 . Samples were performed 171±40 days after the first infusion. In 32 pwMS sampled between second and third infusions, mean cell B counts were 13.9mm3 ±29.6 . Samples were performed 353±63 days after the 2nd infusion. In the naïve subgroup (n=10 vs n=71 not naive) there was a more significant drop in B cells 7.7 vs 18.6 (p=0.038) with treatment. However they did not experience more adverse effects. Adverse effects were seen in 54/83 subjects. 21/54 had infusion related reactions. 43 reported infections including herpes (1), cellulitis (1), gastroenteritis (6), upper (18) or lower respiratory tract (7), urinary tract infections (22) or other infection (8). In those who had adverse effects there was no difference in the B cell counts at baseline. However, those who developed infections had a significant reduction in B cells (infection 6mm3 vs no adverse effects 28mm3, p=0.045). This difference persisted after the second dose (infection 5mm3 vs no adverse effects 27mm3, p=0.19). There was however no difference in the absolute lymphocyte counts (p=0.8) , CD8 or NK cells.

Conclusions

This data suggests that regular monitoring of B cell counts, rather than absolute lymphocyte counts, may be a method of identifying those patients at risk of adverse effects, such as infection, following ocrelizumab.

Collapse