[New opportunities in the treatment of patients with multiple sclerosis (Resolution of the Council of Experts on April 23, 2022, Moscow, JSC «BIOCAD¼)]. / Novye vozmozhnosti v terapii patsientov s rasseyannym sklerozom¼ (Rezolyutsiya soveta ekspertov 23 aprelya 2022 goda, Moskva, AO «BIOKAD¼).

One of the target areas for the development of the Russian pharmaceutical industry at present is the development of next-in-class drugs medicines. These are original, patent-protected drugs that act on known biological targets, improved or modified in structure and mechanism of action compared to existing, successfully proven medicine. The article presents the results of an expert council on the management of patients with multiple sclerosis and the place of new original medicines of the JSC BIOCAD company (SamPEG-IFN-ß1a and divozilimab) in multiple sclerosis therapy algorithm.

[Long-term treatment for multiple sclerosis with interferon beta-1b. Outcomes of an open, retrospective, observational study]. / Dolgosrochnaya terapiya rasseyannogo skleroza interferonom beta-1b. Rezul'taty retrospektivnogo otkrytogo nablyudatel'nogo issledovaniya.

OBJECTIVE: To assess the outcomes of long-term treatment in multiple sclerosis (MS) patients with Infibeta (interferon beta-1b). MATERIAL AND METHODS: The article presents the results a real-world, multicenter, retrospective, observational study of treatment with interferon beta-1b. We enrolled 332 patients with MS who had been receiving Infibeta for at least 8 years. 60.2% of them had a relapsing-remitting MS (RRMS). 73.2% patients received only interferon beta-1b that was initial DMT. RESULTS: During the first year of the treatment, 66% of the patients reported no relapses regardless of the MS type. No relapses in the 8th year of treatment were observed in 86.9% of patients with RRMS and 77.7% with secondary progressive MS (SPMS). The median number of relapses during the whole follow-up period in RRMS patients was 1. The time to first relapse in the subgroup of patients who received interferon beta as the first treatment was longer compared to other treatment (median 4 and 2, respectively, p=0.0017). 42% of patients with RRMS remained progression-free during 8 years of follow-up. The flu-like syndrome was observed in 61.7% for the first year of treatment; in 36.3% it was periodically and was mild in 71.3%. CONCLUSION: The study outcomes confirm a high clinical response to the long-term treatment with Infibeta in patients with RRMS and SPMS and demonstrate that interferon beta-1b is one an optimal option for the initial treatment of patients with moderate disease activity.

[Updated recommendations of the Council of Experts on the use and safety of alemtuzumab (Lemtrada)]. / Obnovlennye rekomendatsii soveta ekspertov po primeneniyu i obespecheniyu bezopasnosti terapii preparatom alemtuzumab (Lemtrada).

Alemtuzumab (Lemtrada) is a recombinant humanized IgG1 kappa monoclonal antibody to the surface cell glycoprotein, a CD52 differentiation cluster. The drug is approved for use in more than 65 countries, including the Russian Federation. The drug is one of the most effective methods of treating patients with aggressive multiple sclerosis, but the risk management plan should be followed. The safety profile of the drug includes infusion-associated reactions, thyroid dysfunction, immune cytopenia, acute cardiovascular events, infections, and other autoimmune diseases. This publication provides updated practical recommendations for the use of the drug and ensuring the safety of patients treated with alemtuzumab.

[New directions of immunocorrection in multiple sclerosis]. / Novye napravleniia immunokorrektsii pri rasseiannom skleroze.

Multiple sclerosis is a central nervous system disease with autoimmune and neurodegenerative mechanisms of development. This disease can lead to severe disability and neurological defects. Although its etiology and pathogenesis remain unclear, research data show that multiple sclerosis is a multifactorial disease, the development of which depends on environmental factors, as well as a genetic predisposition. The impact of these factors lead to the death of neural cells, accompanied by demyelination of nerves and neuronal dysfunction. Therapy of multiple sclerosis is based on the use of anti-inflammatory and immunomodulating substances, however, there are certain disadvantages associated with the constant use of these drugs and a possible change in dosage over time. This review discusses the pathogenesis of multiple sclerosis and the role of various subpopulations of immune cells in the development of diseases, as well as existing approaches to therapy. It is noted that immunoreconstitution therapy has advantages over immunomodulation and immunosuppression maintenance therapy for some patients. Thus, short courses of therapy provide more adequate treatment for patients and lower risks of adverse events associated with chronic immunosuppression. The review also discusses the data of clinical studies on the immunoreconstitution therapy drugs, such as alemtuzumab, ocrelizumab and cladribine. It is noted that nowadays the exact mechanisms underlying this type of therapy remain unclear. In this regard, further studies are needed to explain the therapeutic effects. It is assumed that patients with a high risk of multiple sclerosis progression are the optimal group of patients for the early use of selective immunoreconstitution therapy. Thus, immunoreconstitution therapy may be the treatment of choice for many patients with highle active multiple sclerosis.

[Highly active multiple sclerosis: options for monoclonal antibody therapy]. / Vysokoaktivnyi rasseiannyi skleroz - vozmozhnosti vybora terapii monoklonal'nymi antitelami.

The clinical course of multiple sclerosis (MS) is characterized by great variability. 'Aggressive' MS, a concept used in the last 10 years, is associated with atypical course of the disease, which is manifested by more frequent exacerbations, the rapid increase in disability and pronounced signs of radiological activity according to MRI. The review presents data on the effectiveness of three monoclonal antibody drugs - natalizumab, alemtuzumab and ocrelizumab. In addition, updated data on the safety of monoclonal antibodies are presented to help the physician make a balanced choice of a drug and therapy strategy.

[The efficacy and safety of siponimod in the Russian population of patients with secondary progressive multiple sclerosis]. / Éffektivnost' i bezopasnost' siponimoda u patsientov s vtorichno-progressiruiushchim rasseiannym sklerozom v rossiiskoi populiatsii.

AIM: To study the efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis (SPMS) in the Russian population of the EXPAND study. MATERIAL AND METHODS: Ninety-four patients with SPMS from Russia were included in the analysis. Sixty-three patients received siponimod and 31 patients received placebo. The primary endpoint of the study was time to 3-month confirmed disability progression (3m-CDP) events, other clinical and radiological endpoints were also evaluated. RESULTS: The siponimod group showed a 54% reduction in the risk of 3m-CDP compared with the placebo group (p=0.0334). Secondary endpoints also showed the advantage of the drug over placebo. In the siponimod group, mild adverse events associated with impaired liver function, as well as arterial hypertension, were more common. No patient left the study due to an adverse event. CONCLUSION: The use of siponimod in patients with SPMS in the Russian population reduced the risk of disability progression. Siponimod showed a favorable safety profile.

[Provision of alemtuzumab safety is one of the main components of pharmacovigilance]. / Obespechenie bezopasnosti terapii alemtuzumabom - odna iz glavnykh sostavliaiushchikh farmakonadzora.

Modern multiple sclerosis therapy with disease-modifying drugs is characterized by the risks of dangerous infectious complications. In the last 5 years, there have been several reports of severe, sometimes lethal, listeriosis infection in patients treated with alemtuzumab. This article presents a clinical case of lethal listeriosis meningoencephalitis, which developed within 7 days after the completion of the first cycle of alemtuzumab therapy. In January 2018, a meeting of the expert Council was held, at which the clinical recommendations published in 2017 were revised and updated.

[What do we know about the pathology of gray matter in multiple sclerosis]. / Chto my znaem o patologii serogo veshchestva pri rasseiannom skleroze.

The emergence of modern methods of immunohistochemistry and further development of MRI has led to a deeper understanding of gray matter (GM) pathology in multiple sclerosis (MS). GM involvement can be extensive including both demyelination (cortical lesions) and neuroaxonal damage. The mechanisms of GM damage in MS remain insufficiently studied. There are two concepts: the lesion of GM is primary and is paralleled by changes in white matter (WM), or secondary, i.e. it is a consequence of the pathological process in WM. More research into GM pathology using the latest MRI techniques will contribute to the understanding of pathological changes in both cortical and subcortical GM.

[Issues of the current terminology in multiple sclerosis]. / Voprosy sovremennoi terminologii pri rasseiannom skleroze.

New terminology used by neurologists with multiple sclerosis (MS). The current use of terms 'definite' MS, 'MS signs', 'retrobulbar neuritis' and 'optic neuritis', 'relapse and exacerbation, types of MS course, criteria of effectiveness of MS therapy, NEDA, NEP, NEPAD; the classification therapy methods - 'escalation', 'induction' and therapy of immune reconstitution (TIR), therapy of maintenance/escalation (TME) and discussed.

[Clinical guidelines for the use of dimethyl fumarate in relapsing-remitting multiple sclerosis]. / Klinicheskie rekomendatsii po primeneniiu preparata dimetilfumarat pri remittiruiushche-retsidiviruiushchem rasseiannom skleroze.

Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease. The new oral agent for the treatment of relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate (DMF), helps change the pathogenetic mechanisms of the disease, thus decreasing the rate of exacerbations, slowing down disease progression, and reducing the risk of radiological progression of the disease.

[The search for optimal decision in the treatment of multiple sclerosis: to improve adherence not reducing the efficacy]. / Poisk optimal'noi patogeneticheskoi terapii rasseiannogo skleroza: vozmozhnost' povysit' priverzhennost' bol'nykh terapii, ne snizhaia ee éffektivnosti.

Long-term disease modifying therapy (DMD) therapy is the basis of modern MS treatment, effiecacy of which is modulated by the patient's adherence to therapy. One of the possible solutions of low adherence improvement is the use of innovative drugs and the development of more convenient regimens of injectable medications. This article gives a brief review of peg-interferon ß-1a clinical trials.

[Experience of using interferon Β-1a biosimilans (cinnovex and genfaxon-44) in the Moscow Multiple Sclerosis Center]. / Opyt primeneniia bioanalogov Β-interferona-1a - sinnoveksa i genfaksona-44 v Moskovskom gorodskom tsentre rasseiannogo skleroza.

OBJECTIVE: To study the efficacy and tolerability of generics (interferon beta-1a biosimilans) cinnovex for intramascular introduction and genfaxon-44 for subcutaneous injections in multiple sclerosis (MS). MATERIAL AND METHODS: One hundred patients were treated with cinnovex and 104 patients were treated with genfaxon-44 during one year. Patient's status was assessed using clinical approach, psychometric scales and MRI. RESULTS AND CONCLUSION: The high percentage of withdrawal of treatment due to the lack of clinical effect and intolerance to the drugs was identified during the treatment. Positive effect with respect to stabilization of MS course was found only in patients who earlier did not receive disease-modifying drugs. Double-blind studies are needed to resolve the question of the adequacy of brand-name drugs and generics.

[Widening of possibilities of treatment of multiple sclerosis with the novel oral drug teriflunomide (aubagio)]. / Rasshirenie vozmozhnostei terapii rasseiannogo skleroza novym preparatom dlia priema vnutr' - teriflunomidom (abadzhio).

Teriflunomide is a novel oral medication for relapsing remitting multiple sclerosis (RRMS), which has demonstrated it's efficacy in relapse rate reduction. It's efficacy has been confirmed by MRI results as well. It is safe and well-tolerated, with mild and transitory side effects. Nevertheless, risk management plan should be applied to minimize and monitor possible adverse events.

[Criteria of ineffectiveness of treatment with first-line therapy: how to use MRI results in decision making?]. / Kriterii neéffektivnosti terapii preparatami pervogo vybora: kak sleduet otnosit'sia k dannym MRT v priniatii resheniia? (Po povodu stat'i A.N. Boiko i soavt. "Vybor optimal'nogo preparata patogeneticheskogo lecheniia rasseiannogo skleroza: sovremennoe sostoianie problemy" #10(2), 2014).

The importance of MRI stuides in the control over treatment efficacy in multiple sclerosis and appropriate recommendations on drug substitution during treatment are discussed. We suggest low, middle or high risk in respect to the efficacy of current treatment. Accordingly, drug substitution can be related with the low level of fears for all three criteria or the moderate level for any two criteria or the high level for any one criterion. Since MRI criteria are important, this model appears to be the most rational because the physician can make a decision about treatment escalation if the patient has ≥3 new T2-lesions or ≥3 contrast-enhanced T1-lesions.

[A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma].

UNLABELLED: The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). MATERIAL AND METHODS: The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (p<0.05). We also established a relationship between the tensor and kurtosis parameters of CNAWM and the glioma proliferative activity index (p<0.05). RESULTS: The correlation between all the absolute and normalized diffusion parameters and the glioma proliferative activity index, except absolute and normalized FA and RA values, was found to be statistically significant (p<0.05). Kurtosis (MK, AK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. CONCLUSION: DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.

[Epstein-Barr virus in the pathogenesis of multiple sclerosis (a review)]. / Virus Épshteina-Barr v patogeneze rasseiannogo skleroza (obzor).

Multiple sclerosis is now regarded as a disease, which is based on genetic predisposition. Trigger mechanism are various exogenous factors. The Epstein-Barr virus is thought to be a trigger. This report provides information about possible mechanisms of the influence of the Epstein-Barr virus on the development of multiple sclerosis.

[Side-effects of glucocorticosteroids in multiple sclerosis: a case report of a patient with global amnesia]. / Pobochnye éffekty terapii gliukokortikosteroidami pri rasseiannom skleroze: opisanie klinicheskogo sluchaia s global'noi amneziei

Pulse-doses of corticosteroids are actively used in the treatment of multiple sclerosis relapses. Short pulse-treatment is usually well-tolerated by patients though side-effects may be observed. We described a rare case of transient global amnesia after the pulse-treatment with corticosteroids. A complex examination excluded other causes of amnesia.