Efficacy and safety profiles of cladribine in highly active multiple sclerosis: a tertiary MS center experience in Turkey

Introduction: The patients who manifest rapid accumulation of physical and cognitive decline despite treatment with one or more disease-modifying drugs (DMTs) are accepted as highly active multiple sclerosis (HA-MS). Cladribine is an effective treatment option for HA-MS. We aimed to evaluate the efficacy and safety profiles of cladribine HA-MS patients. Method(s): HA-MS patients under cladribine from July 2020-May 2022 were included in the study. Demographic data, disease duration and progression parameters, and Covid-19 infection data were evaluated. Result(s): The study included 82 patients (64 female,18 male). The mean ages were 38.17+/-8.7 years. According to the Lublin classification, 18 (22%) patients had non-active/non-progressive, 35 (42.7%) had active/nonprogressive, 21 (25.6%) had non-active/progressive and 8 (%9.7) patients had active/progressive MS. The mean disease durations were 9.75+/-6.42 years. The mean follow-up duration under cladribine was 8.32+/-5.4 months. The median EDSS score both before and after treatment was 2.5 (0-7) (p=0.086). Fifty (61%) of the patients were switched from first-line DMT, 27 (32.9%) from second-line DMT, and cladribine was the first drug in 4 patients. Most of the patients were switched from interferon/glatiramer acetate (24.4%), teriflunomide (20.7%), and fingolimod (19.5%). 12 (14.6%) of the patients had grade 1, 14 (17.1%) had grade 2, 2 (2.4%) had grade 3 lymphopenia. None of the patients observed had grade 4 lymphopenia. Overall, 24 (29.2%) patients had mild complaints under cladribine. Most common side effects were hair loss (n=8;9,75%), mild ALT/ AST elevation (n=5;6.1%);headaches (n=3;3.7%), mild skin reactions (n=5;6.1%). One patient had a zona zoster infection, while 2 complained of frequent urinary infections. No serious infection, allergic reactions, and malignancy were observed. 8 (9.75%) patients developed attacks under cladribine while under cladribine for at least one month, and the symptoms resolved after intravenous methylprednisolone. 18 (21.95%) patients had Covid-19 infection, and all but 1 had mild symptoms. One patient had a mild MS attack one month after the Covid-19 infection. None of the patients experienced any attacks or severe side effects after the Covid-19 vaccination. Conclusion(s): Cladribine therapy is a well-tolerated and so far effective treatment option for HA-MS patients. Long-term efficacy and safety studies are still needed.

Cladribine treatment in turkish MS patients

Introduction: As a high-efficacy multiple sclerosis (MS) treatment, cladribine necessitates empirical data from diverse populations. Objective(s): To study the efficacy and safety data of cladribine treatment in a real-world setting. Method(s): Patients from eight MS clinics in Turkey were involved in the study. We retrieved the demographic, clinical, MRI, safety, laboratory, COVID-19, and pregnancy records of patients with at least six months of follow-up on cladribine treatment. Result(s): Our study included 210 MS patients (52 males, 158 females;193 relapsing and 17 relapsing-progressive MS). The mean age at MS disease onset was 27.6 years (+/-8.5). Before cladribine treatment, 56.7% of patients used first-line, and 41.9% used both first and second-line therapies. During a mean follow-up period of 13.0 months (+/-4.7) following cladribine treatment, 5.7% of patients experienced a relapse. The shortest duration of relapse following cladribine administration was one week, and the longest duration was 15.3 months. Interestingly, 50% of the relapses occurred within the first three months. Among relapsing patients, five switched from fingolimod, two from dimethylfumarate, and one from ocrelizumab and interferon-beta. The mean annualized relapse rate was 0.41 (+/-0.41) in the two years preceding cladribine and 0.11 (+/-0.55) one year following treatment. At baseline, the mean EDSS score was 2.47 (+/-1.63), and 51.9% of patients ranked below EDSS 3. EDSS progression was observed in 7.6% of patients following cladribine treatment. On cladribine, eight patients (9.4%) exhibited radiological progression. There was no difference in NEDA status between patients switching from first or second-line therapy (p=0.43). COVID was observed in 73 patients, 54 of them had a mild disease course, six had a moderate disease course, and one had a severe disease course. There have been no COVID-related fatalities. There were five pregnancies documented, three of which are currently ongoing. One of the pregnancies ended with healthy childbirth, while the other was terminated in the first trimester with a miscarriage. Conclusion(s): Despite the relatively short duration of follow-up, our study demonstrates that cladribine is effective in providing NEDA. Moreover, switching from fingolimod to cladribine may increase the likelihood of early relapse.

Detection of Face Mask Wearing Condition for COVID-19 Using Mask R-CNN

Due to the COVID-19 pandemic, which has affected the whole world, countries have made it mandatory for people to wear face masks. Because wearing a mask is considered one of the most effective methods to reduce the risk of transmission of the virus. However, it is difficult to manually check whether people are wearing masks. It is aimed to develop a model that detects all kinds of face masks in crowded environments using a deep neural network in this study. Mask R-CNN, which is one of the deep learning algorithms and used for object detection was used to detect and classify people’s mask states. The proposed deep learning model was trained and tested with k-fold cross-validation using a dataset of 853 images containing three classes (with mask, without a mask, incorrect use of mask). ResNet101 backbone was chosen as the backbone architecture and transfer learning was performed using the MS COCO model. The proposed Mask R-CNN model achieves a mAP of 83%, a mAR of 90%, and an F1 score of 86%. These results reveal that the proposed model is successful in mask detection. © 2022, TUBITAK. All rights reserved.

Evaluation of immunoglobulin levels and COVID-19 disease course in patients with multiple sclerosis under ocrelizumab therapy: A tertiary center experience

Introduction: Ocrelizumab, which is approved for the treatment of progressive and relapsing forms of MS, is a CD-20 monoclonal antibody. Susceptibility to hypogammaglobulinemia has recently gained importance in patients under B-cell depleting therapies. Objectives and Aims: We aimed to evaluate the changes in immunoglobulin levels and their effect on the COVID-19 infection in a group of MS patients under ocrelizumab therapy. Methods: Patients under ocrelizumab therapy from December 2017 - May 2021 were included in the study. Immunoglobulin M (IgM), immunoglobulin G (IgG), CD19, CD20 levels were obtained cross-sectionally before the last infusion of ocrelizumab. We also evaluated COVID-19 infection ratio and severity. Results: Among 320 ocrelizumab-treated patients, we included 131 patients who had been tested for IgG, IgM, CD19 and CD20 levels. The female to male ratio was 1.4: 1 and mean age was 44.3 years. While the mean disease duration was 11 years, the mean follow-up period of patients under ocrelizumab treatment was 21 months. 13 (10%) patients had lower serum IgG levels (serum IgG<750mg/dl). Serum IgM levels were found to be low in 33 (25%) of the patients with the mean of 31.85 mg/dl (±12.1). 15 had COVID-19 infection (COVID+ group). The mean serum IgM level of the COVID+ group was 78.03mg/dl (±84.70), 101 mg/dl (±73.03) in the COVID- group (p=0.262). IgG levels of the COVID+ and COVD- groups were 948.3 (±243.4) and 1073 (±256.7) mg/dl respectively (p=0.078). Only 3 patients needed hospitalization because of COVID-19. Two of them had low IgM levels. None of the patients had been needed intensive care or mechanical ventilation. Conclusions: Almost a quarter of our patients had a low level of Ig's as expected. Ig levels should be routinely evaluated to avoid infectious complications.

The outcome of a national MS-Covid-19 study: What the Turkish MS cohort reveals?

BACKGROUND: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. METHODS: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. RESULTS: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. CONCLUSION: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older.