Barriers to accessing multiple sclerosis disease-modifying therapies in the Middle East and North Africa region: A regional survey-based study.

BACKGROUND: Multiple sclerosis (MS) management varies markedly between different countries of the Middle East and North Africa (MENA) region based on the availability and accessibility of disease-modifying therapies (DMTs). OBJECTIVE: To evaluate the accessibility to DMTs in each MENA country, identify barriers to treatment and make recommendations for improved access to DMTs across the region. METHODS: This is a descriptive, survey-based study whereby we extracted data collected, between October 2019 and April 2020, for countries in the MENA region by the Multiple Sclerosis International Federation (MSIF) through their Atlas of MS survey. RESULTS: 16 out of 19 countries in the MENA region were included in this study. Sudan and Syria did not have any originator DMTs approved. Interferons were the most widely low-efficacy originator approved DMTs. Three countries did not have any high efficacy DMTs approved. Moreover, follow-on DMTs were approved in half (50%) of the countries. Cost of treatment was the most important barrier, reported in nearly half (47%) of the MENA countries. CONCLUSION: Although most MENA countries have access to DMTs, more than half of countries report problems with treatment continuation, highlighting the need for a targeted regional strategy to address the variations in access to MS treatments.

Cerebrovascular disease in patients with COVID-19 infection: a case series from Lebanon.

COVID-19 has been associated with a variety of multi-organs complications, with an increasing proportion of patients presenting with neurologic manifestations. There is still an uncertainty in the relationship between stroke and COVID-19. Therefore, in this study, the authors report 18 cases of acute stroke occurring in the setting of COVID-19 infection, including 11 ischaemic strokes and 7 haemorrhagic strokes and identified in a Lebanese tertiary hospital. In this case series, patients with ischaemic and haemorrhagic stroke had elevated markers of inflammation and coagulation. Ischaemic stroke patients were treated with different regimens of anti-platelets, anticoagulants, and thrombolytic therapies. Death was the most common outcome observed and was associated with the severity of COVID-19 infection.

Neurological Manifestations of Coronavirus Disease 2019 in Hospitalized Patients: A Lebanese Cohort Study.

BACKGROUND: Concerns regarding potential neurologic complications of COVID-19 are being increasingly reported worldwide. Our objective was to investigate the neurologic complications of COVID-19 among a cohort of Lebanese patients with SARS-CoV-2 infection admitted to Rafik Hariri University Hospital (RHUH), the leading COVID-19 testing and treatment center in Lebanon. METHODS: This is a retrospective, single-center, observational study conducted from March to July 2020 at RHUH, Lebanon. RESULTS: Of 169 hospitalized patients with confirmed SARS-CoV-2 infection (mean {SD} age was 45.75 {19} years and 62.7% were men), 91 patients (53.8%) had severe infection and 78 patients (46.2%) had non-severe infection according to the American Thoracic Society guidelines for community-acquired pneumonia. Overall, 112 patients (66.3%) developed neurologic symptoms: CNS (46.1%), PNS (43.7%), and skeletal muscle injury (2.4%). Compared with patients with non-severe infection, patients with severe infection were significantly older, were male and more likely to have underlying disorders, especially diabetes and cardiac or cerebrovascular disease. Moreover, those patients experienced more typical COVID-19 symptoms at onset of illness such as fever, cough and fatigue. However, there was no significant difference in the frequency of all nervous system manifestations between the severe and the non-severe infection groups (57 {62.6%} vs 55 {70.5%}; p =0.316), except for impaired consciousness, where seven patients had impaired consciousness in the severe group compared to none in the non-severe group (p=0.012). CONCLUSION: A wide variety of neurologic symptoms were detected in our Lebanese cohort of hospitalized COVID-19 patients. A comprehensive knowledge of the neurologic manifestations will help healthcare providers to be more attentive to these complications.

MENACTRIMS practice guideline for COVID-19 vaccination in patients with multiple sclerosis.

Patients with multiple sclerosis (MS) should be vaccinated against COVID-19. All COVID-19 vaccines are effective and do not appear to carry any additional risk for patients with MS. Patients with MS should get a COVID-19 vaccine as soon as it becomes available. The risks of COVID-19 disease outweigh any potential risks from the vaccine. Even if vaccinated, patients with MS should continue to practice standard and recommended precautions against COVID-19, such as wearing a face mask, social distancing and washing hands. There is no evidence that patients with MS are at higher risk of complications from the mRNA, non-replicating viral vector, inactivated virus or protein COVID-19 vaccines, compared to the general population. COVID-19 Vaccines are safe to use in patients with MS treated with disease-modifying therapies (DMTs). The effectiveness of vaccination may be affected by few of the DMTs but yet some protection is still provided. For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy.

Epidemiology of multiple sclerosis in Lebanon: A rising prevalence in the middle east.

BACKGROUND: The epidemiology of multiple sclerosis (MS) has been studied in many countries of the Middle East but the prevalence and incidence of MS in Lebanon is still unknown. OBJECTIVES: To determine the incidence and prevalence of MS in Lebanon. METHODS: Lebanese patients diagnosed with MS between January 2018 and December 2018 were identified using the database of governmental third-party payers. The crude, age- and sex-specific 2018 prevalence and incidence among Lebanese patients were calculated. RESULTS: 2248 MS patients were identified of whom 67.1% were women (female: male ratio 2:1) with a mean age of 41.8 ± 12.96 years. The 2018 prevalence of MS was 62.91 cases per 100,000 persons (95% CI: 60.41 - 65.41). The overall incidence of MS in Lebanon was 8.36 cases per 100,000 (95% CI: 7.45 - 9.27) with a mean age at onset of 34.5 ± 12.5 years. CONCLUSION: This is the first study to assess prevalence and incidence of MS in Lebanon, confirming that Lebanon is a moderate to high-risk area for MS. Those high rates are commensurate with recently published studies from the Middle East, pointing to a significant rise in incidence and prevalence of this disease in our region.

Treatment of multiple sclerosis in special populations: The case of refugees.

Multiple sclerosis was long considered a relatively rare entity in the Middle East, but research over the past 10 years and the publication of the Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis guidelines for multiple sclerosis have allowed diagnosis and treatment to occur more efficiently. Most of the first and second-line disease-modifying therapies approved by the Food and Drug Administration and the European Medicine Agency are available in the Middle East. However, the availability of disease-modifying therapies is quite variable, with some countries having access to all multiple sclerosis disease-modifying therapies, while in others there is only one therapeutic option. Economic limitations remain a challenge for the management of multiple sclerosis, especially in countries of war. Moreover, the burden of multiple sclerosis treatment in Syrian and Palestinian refugees is likely high due to the non-availability of funds to cover the high cost of disease-modifying therapies.

Skin warts during fingolimod treatment in patients with multiple sclerosis.

BACKGROUND: Fingolimod is associated with different infections including lower respiratory tract, herpes virus, cryptococcal meningitis, histoplasmosis, progressive multifocal leukoencephalopathy, atypical mycobacterial infections, kaposi sarcoma and reactivation of hepatitis c. OBJECTIVES: To describe five cases of skin warts in MS patients treated with fingolimod at the American University of Beirut Medical Center (AUBMC) MS center (MSC). METHODS: We reviewed all MS patients treated with fingolimod at our MSC and identified patients who developed skin warts during treatment. We also reviewed a control group of patients treated with different interferons matched for age and sex. RESULTS: Of 220 patients treated with fingolimod at our MSC, 5 (2.2%) developed skin warts. In 220 patients treated with different interferons and matched for age and sex, no cases of skin warts could be detected. CONCLUSIONS: In conclusion, we report five patients who developed skin warts during fingolimod therapy, especially HPV-related, for an overall incidence of 2.2%. Larger cohorts are needed to confirm this proposed higher susceptibility of fingolimod-treated patients to HPV infections.

Risk of relapses during pregnancy among multiple sclerosis patients.

BACKGROUND: Relapse rate in women with Multiple Sclerosis (MS) is reduced during pregnancy especially in the third trimester according to the previous studies. OBJECTIVES: To measure the annual relapse rate (ARR) in women with MS during pregnancy. METHODS: A retrospective study was conducted using prospectively collected data from two MS registries in Kuwait and Lebanon. Demographics, clinical characteristics including relapses, disease modifying therapies (DMTs) and their washout periods were extracted. The annual relapse rates pre and post pregnancies were compared and the relationship between relapses and prior use of different DMTs was assessed. RESULTS: Data of 164 pregnancies (132 MS patients) was reviewed. Mean age and disease duration at the time of pregnancy confirmation were 32.4 ±â€¯5.3 and 7.8 ±â€¯4.7 years respectively. Most patients (91.7%; n = 121) were on DMTs in the year prior to pregnancy. The pre-pregnancy ARR was 0.10 (95% CI: 0.04 - 0.13), which increased to 0.20 (95% CI: 0.13- 0.29) during pregnancy. Most relapses occurred either during the 1st (ARR = 0.24; 95% CI: 0.12 - 0.44) or 3rd (ARR = 0.32; 95%CI: 0.17 - 0.53) trimesters. Fingolimod (31.8%) and natalizumab (22.7%) were the most commonly prescribed DMTs in patients who sustained relapses during pregnancy. The mean washout period was significantly longer among subjects with relapses (9.3 ±â€¯6.6 vs. 2.5 ±â€¯3.9; p < 0.001) than those of without relapses. CONCLUSIONS: Relapse rate during pregnancy was higher than previous studies conducted in patients on platform therapies or untreated. Longer washout period prior to conception was associated with increased relapses especially in fingolimod and natalizumab treated patients.

Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study.

OBJECTIVE: To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. METHODS: Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. RESULTS: A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6-12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p < 0.0001) and from 0.25 to 0.16 in PMS patients (p = 0.593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusion-related reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. CONCLUSION: In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.

Efficacy and safety of natalizumab extended interval dosing.

OBJECTIVE: It is postulated that extending the dosing interval of natalizumab (NTZ) from 4 to 5-8 weeks might decrease the risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess the effect of extended interval dosing (EID) on the therapeutic efficacy of natalizumab. METHODS: We reviewed 85 patients treated at two MS centers in the Middle East with natalizumab for at least 6 months using EID. Patients were shifted after an initial treatment period at standard interval dosing (SID) to an EID ranging from 5-8 weeks. RESULTS: The mean treatment duration on SID and EID was 15.4 ±â€¯11.9 and 11.8 ±â€¯7.0 months, respectively. By the end of SID and EID treatment 95.3% and 93.9% of patients were free of relapses (P = 0.41) with an annualized relapse rate (ARR) of 0.0006 and 0.001 respectively (P = 0.42). The mean EDSS at the end of SID and EID periods was 2.56 ±â€¯1.62 and 2.59 ±â€¯1.61 respectively (P = 0.84). A total of 97.6% and 94.7% of patients had no enhancing lesions on MRI during the SID and EID periods respectively (P = 0.18). There were no cases of PML and the rate of infections was lower during the EID period. CONCLUSION: In patients treated with natalizumab, shifting from SID to EID has no negative effect on efficacy as evidenced by relapse rate, disability progression and MRI activity.

Effectiveness of alternative dose fingolimod for multiple sclerosis.

BACKGROUND: Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. METHODS: We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. RESULTS: Profound lymphopenia (77%), liver function abnormalities (9%), and infections (7%) were the most common reasons for patients to switch to alternate fingolimod dosing. The median follow-up was 12 months on daily dose and 14 months on alternate dose. Most patients (64%) took fingolimod every other day during alternate dosing. Disease activity was similar on alternate dose compared to daily dose: annualized relapse rate was 0.1 on daily dose vs 0.2 on alternate dose (p = 0.25); proportion of patients with contrast-enhancing MRI lesions was 7.6% on daily vs 9.4% on alternate (p = 0.55); proportion of patients with cumulative MS activity (clinical and radiologic disease) was 13.5% on daily vs 18.2% on alternate (p = 0.337). Patients who developed contrast-enhancing lesions while on daily dose were at higher risk for breakthrough disease while on alternate dose fingolimod (odds ratio 11.4, p < 0.001). CONCLUSIONS: These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.

Rebound syndrome after teriflunomide cessation in a patient with multiple sclerosis.

We report a case of relapsing remitting multiple sclerosis (RRMS) with severe rebound syndrome 12weeks following discontinuation of teriflunomide therapy. The patient developed severe clinical relapses with significant increase in the number of brain and spine magnetic resonance imaging (MRI) lesions. She responded well to intravenous and oral steroids and was later maintained on rituximab.

Catastrophic relapses following initiation of dimethyl fumarate in two patients with neuromyelitis optica spectrum disorder.

We report two cases of neuromyelitis optica spectrum disorder (NMOSD) who were misdiagnosed as multiple sclerosis (MS) and developed catastrophic relapses following initiation of dimethyl fumarate. Both patients developed a severe myelitis extending from the cervical cord to the medulla with significant cord swelling, resulting in complete quadriplegia and respiratory difficulties, in addition to severe bilateral visual loss in one patient. It is of note that both catastrophic relapses occurred 2 and 3 months following initiation of dimethyl fumarate.

Three cases of herpes zoster radiculitis in MS patients treated with natalizumab.

Natalizumab was the first FDA-approved monoclonal antibody for the treatment of multiple sclerosis (MS). We report on 3 natalizumab-treated patients who developed herpes zoster infections. In addition to progressive multifocal leukoencephelopathy, other opportunistic infections have been rarely reported during Natalizumab treatment. We believe that clinicians need heightened awareness of these infections in view of the risks of serious complications.

JC virus seroprevalence and seroconversion in multiple sclerosis cohort: A Middle-Eastern study.

OBJECTIVES: To estimate JCV seroprevalence and risk of seroconversion against JCV among MS patients in the Middle East. METHODS: This multicenter study was conducted by implementing a cross-sectional design to assess JCV seroprevalence, and a longitudinal design to assess the risk of JCV seroconversion. Multivariable logistic and Poisson regression analyses were used to assess the relationship between clinical variables and JCV seropositivity and risk of seroconversion. RESULTS: Of 581 MS patients, 64.9% patients were females. Mean age and mean disease duration were 33.9 and 8.4years respectively. JCV seroprevalence was 48.7%. Male gender (p=0.002), age at onset (p=0.001) and disease duration of 20 or more years (p=0.007) were significantly associated with JCV seropositivity. Among patients (n=125), followed longitudinally, the risk of JCV seroconversion was 17.6% (95% CI: 11.4%-25.4%) during a median follow-up of 18months. The proportion of seroreverted and pseudoconverted patients was 4% and 3.2% respectively. CONCLUSIONS: JCV seroprevalence among MS patients in the Middle East was lower than international figures. Male gender, age at onset and disease duration were significantly associated with JCV seropositivity. Risk of JCV seroconversion was higher than previously reported figures. Observed JCV sero-reversion or pseudo-conversion entail watchful period before embarking on a clinical decision.

Safety and efficacy of fingolimod in clinical practice: The experience of an academic center in the Middle East.

BACKGROUND: Few published studies addressed real-world clinical experience with fingolimod especially in the Middle East region. OBJECTIVE: To review our clinical experience with fingolimod at a specialized academic MS center in Lebanon. METHODS: All patients treated with fingolimod at the MS Center between October 2011 and January 2015 were retrospectively identified. RESULTS: A total of 122 patients were included. The first dose observation was uneventful in 98.8% of patients. Annualized relapse rate decreased from 1.16 pre-treatment to 0.29 post-treatment representing a relative risk reduction of 75% (p<0.0001). The proportion of patients with no new T2 or enhancing lesions was 66.3%. Seventy-six (62.3%) patients experienced adverse events with lymphopenia, increase liver enzymes, urinary tract infections and fatigue being the most common. CONCLUSION: Our cohort confirms the effectiveness and safety of fingolimod in a real world setting.

Safety and efficacy of reduced fingolimod dosage treatment.

BACKGROUND: Oral fingolimod is a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapse rate and delays disability progression in patients with relapsing forms of multiple sclerosis (MS). Elevation of liver function tests (LFTs) and reduction in peripheral-blood lymphocyte counts were among the most common adverse events reported in phase II, phase III, and extension studies. OBJECTIVE: To describe eight patients in whom fingolimod dose was reduced to every other day (n=6) or every third day (n=2) due to increased LFTs more than 3 times the upper limit of normal (ULN) (n=2) or decreased lymphocyte count by ≤0.2×10(9)/L (n=6). RESULTS: Fingolimod dose reduction resulted in reversal of laboratory abnormalities. Clinically, none of the 8 patients developed clinical relapses, but five patients had new lesions on magnetic resonance imaging (MRI), one of whom with disability progression, and one patient converted to secondary progressive MS (SPMS). CONCLUSION: Reducing the frequency of fingolimod administration can reverse laboratory abnormalities but may have a negative impact on drug efficacy.

Effect of pharmacy practice program on pharmacy student learning, satisfaction, and efficiency: assessment of introductory pharmacy practice course.

INTRODUCTION: The Lebanese American University (LAU) offers first-year pharmacy students with Introductory Pharmacy Practice Experience (IPPE) courses comprising various activities that provide students with direct patient contact so that they can be geared up for "real-world" pharmacy practice. Routine assessment and improvement in these courses are imperative to ensure efficiency of these courses. This study was conducted to evaluate the quality of our IPPEs courses, determine its impact on student learning and satisfaction, and identify shortcomings in the program for quality improvement purposes. METHODS: A literature review-based questionnaire, consisting of 76 questions with a response options following a 4-point scale (strongly agree = 4 to strongly disagree = 1), was completed by 92 first professional year pharmacy students who finished their hospital and community IPPE at LAU. RESULTS: The students reported a high degree of satisfaction in community and hospital sites in terms of site selection, program schedule, site and school preceptors, and overall satisfaction with the experience. Compared to the hospital setting, students practicing in the community reported significantly higher scores in overall satisfaction. Besides the high satisfaction rate, our results identified improvement measures in some aspects of the program. CONCLUSION: Our IPPE program serves as a successful experiential learning for pharmacy students.

Stress ulcer prophylaxis guidelines: Are they being implemented in Lebanese health care centers?

AIM: To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers. METHODS: A multi-center prospective chart review study was conducted over 8 mo. A questionnaire was distributed to pharmacy students who collected data on demographics, SUP medications, dose, route, duration and associated risk factors. The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines. Institutional review board approval was obtained from each hospital center. RESULTS: A total of 1004 patients were included. 67% of the patients who received prophylaxis did not have an indication for SUP. The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications. Overall, the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample. This misuse was mainly observed in non-teaching hospitals. CONCLUSION: This study highlighted the need, in Lebanese hospitals, to establish clinical practice guidelines for the use of SUP; mainly in non-critical care settings.