الفهرس 
- Multiple Sclerosis Epidemiology, Pathogenesis and DiagnosisOnly 14 pages are availabe for public view
 |  | from | 168 |  |  |
| | | from | 168 | | |
Abstract
Multiple sclerosis is a chronic demyelinating disease of the central nervous system of presumed autoimmune etiology, characterized by localized areas of inflammation, demyelination, axonal loss and gliosis in the brain and spinal cord. Although the clinical presentation and course of the disease are highly variable, several disease types can be recognized, including relapsing remitting (RR), primary progressive (PP), secondary progressive (SP) and clinically isolated syndrome (CIS) (Milo and Miller, 2014).
Current management strategies are focused on treating acute attacks, ameliorating symptoms, and reducing biologic activity through disease-modifying therapies. DMTs modify the course of MS through suppression or modulation of immune function. They exert anti-inflammatory activity primarily in the relapsing phase of MS; they reduce the rate of relapses, reduce accumulation of MRI lesions, and stabilize, delay, and in some cases modestly improve, disability (Hauser and Cree, 2020).
Several oral and infusible DMTs have been approved for the treatment of RRMS. The approval was based on efficacy in phase III clinical trials, with beneficial effects on clinical measures (relapse rate and to a variable extent disability progression) and on magnetic resonance imaging metrics of inflammatory activity and lesion load (new or enlarging T2-lesions, gadolinium-enhancing lesions, and to a variable extent also brain atrophy). Recently, with the approval of ocrelizumab for early PPMS and siponimod (registered in the USA, positive Committee for Human Medicinal Products (CHMP) opinion in the EU) for active SPMS, the first treatment options for progressive forms of MS became available (Saleem et al., 2019).
The common treatment-related adverse events of multiple sclerosis DMTs tended to be mild to moderate, with a few notable exceptions: bradycardia and atrioventricular block with Fingolimod (Calabresi et al., 2014), gastroenteritis with Dimethyl fumarate (Gold et al., 2012) and lymphopenia with Cladribine (Leist et al., 2014). Infusion reactions in monoclonal antibodies and autoimmunity is reported to be a delayed adverse event in almost half of those who receive Alemtuzumab for multiple sclerosis (Tuohy et al., 2015). Opportunistic and often life-threatening infections in DMTs with lymphocyte-depleting effects (Oshima et al., 2019).
Blood monitoring programs are now recommended, including by clinical guidelines for the safe prescription of almost all DMTs, and a risk-stratification program has been introduced to reduce the incidence of progressive multifocal leukoencephalopathy associated with Natalizumab (Montalban et al., 2018).
The current study aimed to assess the effect of different disease modifying drugs on complete blood count, liver enzymes and thyroid profile in a sample of Egyptian Multiple Sclerosis patients attending Ain Shams University hospitals- MS unit.
Methodology:
This is an observational cross-sectional study, conducted in Ain Shams University hospitals - MS Unit, from November 2020 till May 2021, in which 105 Multiple Sclerosis patients were recruited, diagnosis of Multiple sclerosis was according to the revised McDonald criteria (Thompson et al., 2017).
All patients were subjected to extensive history including, Demographic data: Age, Gender, Residence, occupation, marital status, and offspring. Clinical data: Family history of demyelinating disorders, past medical history, age of onset of disease, time from first attack till diagnosis, number of attacks, medical treatment during the attack and current EDSS. Medication data: Type of DMD, time from diagnosis to start of medication. Lab data: CBC, liver enzymes (AST, ALT) and TSH at baseline, 3 and 6 months after starting DMD.
Main results of the current study:
Demographics and clinical characteristics:
The mean age of MS patients was 32.15 ± 8.53 years, ranging from 18 to 58 years. Ninety-eight (73.7%) were females while 35 (26.3%) were males. Eighty-seven (82.86%) had no past medical history and 18 (17.14%) had past medical history of DM, hypertension, or other medical conditions. Eighty-seven (82.9%) patients had no family history of consanguinity or similar conditions, 12 (11.4%) had family history of consanguinity and 6 (5.7%) patients had family history of similar conditions.
Clinical data:
Mean age of illness onset was 27.61 ± 7.57 years, ranging from 14 to 52 years. Median time till diagnosis was 9 months, ranging from 0.5 to 132 months. Median time till start of medications was 2 months, ranging from 0 to 132 months. Median EDSS was 2, ranging from 0 to 7. Type of MS was RRMS in 88 (83.8%) patients, SPMS in 11 (10.4%) patients and PPMS in 6 (5.7%) patients. Median number of attacks was 2, ranging from 1-12. Median duration of medication was 7 months, ranging from 4 to 96 months.
Types of medications:
Thirty (28.6%) patients received interferon beta A1, 28 (26.7%) patients received Fingolimod, 15 (14.3%) patients received Dimethyl fumarate, 11 (10.5%) patients received Rituximab, 10 (9.5%) patients received Ocrelizumab, 10 (9.5%) patients received Teriflunomide, and 1 (1.0%) received Cladribine.
Laboratory data among different study groups:
Interferon: There was a highly significant elevation in AST and ALT in patients receiving interferons compared to other MS medications. Also, there was significant neutropenia after 3m and 6m than before starting medications. Moreover, TSH level was significantly elevated in patients receiving interferons compared to other MS medications.
Fingolimod: There was a highly significant decrease in lymphocytes in patients receiving Fingolimod compared to other MS with mainly grade 2-3 lymphopenia. Also, there was a highly significant decrease in WBCs count and a highly significant neutropenia. Moreover, liver enzymes (ALT and AST) were significantly higher after 3 and 6 m than before starting it.
Dimethyl fumarate: There was a significant elevation in ALT after 3 and 6 months than before starting it.
Teriflunomide (Aubagio) & Rituximab: There was a non-significant difference as regard all laboratory findings.
Ocrelizumab: There was only a significant neutrophilia after 3 and 6ms than before starting it, with no other significant laboratory findings.
Conclusions:
Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Monitoring of lymphocyte counts should be performed as recommended, and individualized action may be required if lymphocyte counts DROP below treatment specific thresholds. Also, frequent liver function tests and thyroid profile monitoring, based on the potential hepatotoxicity and thyroid dysfunction caused by some DMDs.