RU2257915C2 - Method for treating exacerbations in case of multiple sclerosis - Google Patents

Abstract

FIELD: medicine, neurology.

SUBSTANCE: the method deals with detecting an interferon status followed by medicinal therapy. Moreover, additionally one should determine patient's body area, and at observed degree I of interferon system suppression it is necessary to prescribe "Antilympholin Kz" preparation as medicinal therapy intravenously by drops at course dosage being (0.5-0.6)g x S, where S - patient's body area, every other day, and thioctacide preparation at the dosage of 300-600 mg intravenously by drops daily at a 6-8-d-long course. In case of degrees II and III of interferon system suppression one should prescribe "Antilympholin Kz" at course dosage being 0.4-0.5 g/sq. m and 0.3 -.4 g/sq. m, as for thioctacide - it should be applied at the dosage of 600-900 mg and 900-1200 mg, correspondingly. The method enables to selectively affect the immune system efficiently due to combined prescription of an immunimodulator and a preparation that accelerates its introduction at suppressing the activity of proinflammatory cytokines that prolongs disease remission due to preventing the development of immunological disorders.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, namely to neurology, and is intended for the treatment of exacerbations of multiple sclerosis. Using the proposed method, it is possible to increase the effectiveness of the treatment of exacerbations of multiple sclerosis and reduce the risk of persistent disability.

Multiple sclerosis (PC) is a chronic progressive disease of the nervous system characterized by the occurrence of multiple lesions in the central nervous system. Studies conducted in our country and abroad have revealed a high proportion of PC. In the pathogenesis of multiple sclerosis, congenital immunity disorders, increased permeability of the blood-brain barrier, contact of immunocompetent cells with the main myelin protein, production of antibodies to the main myelin protein, destruction of the myelin sheaths of nerve fibers in the central and peripheral nervous system are essential.

A known method of treating exacerbations of multiple sclerosis with cyclophosphamide. The drug was administered intravenously at a dose of 3 to 5 mg / kg (200 to 400 mg) per day for 10-14 days under the control of blood tests (Neretin V.Ya. et al. "Immunosuppressive therapy of multiple sclerosis", Methodological recommendations, M., MONIKI, 1992, p. 14-15).

The disadvantages of this method are the poor tolerance of the drug to patients, a high risk of complications (hematological, infectious, as well as changes in the gastrointestinal tract and liver). Cyclophosphamide - a derivative of mustard gas, refers to alkylating compounds, the mechanism of action of which is to attach their groups to DNA, which leads to the destruction of the molecule and the cytostatic effect. The drug acts on living lymphocytes and inhibits the humoral effect and non-specific inflammatory reactions, thus not exerting a selective effect on the immunocompetent cell system and contributing to the progression of unwanted immunological disorders.

As a prototype, a method for treating multiple sclerosis with immunomodulatory drugs based on an analysis of the patient’s interferon status was selected: interferon status was preliminarily determined with the subsequent administration of drug therapy. The activity of interferons in the patient’s blood serum and in whole blood samples incubated in RPMI-1640 medium in the presence of standard interferon synthesis inducers is determined by titration of the studied samples on cell culture and subsequent incubation with vesicular stomatitis virus (Application for the invention of the Russian Federation No. 98105888, IPC G 01 N 33/68, publ. 2000).

The disadvantage of this method is the low treatment efficiency due to the lack of consideration of the activity of the autoimmune process, the vagueness of determining the boundaries of interferon status indicators for the appointment of different types of pathogenetic therapy of multiple sclerosis and, as a consequence, the deepening of the autoimmune process in multiple sclerosis.

The task set by the authors is to eliminate these shortcomings by eliminating unwanted immunological disorders by selective action on the immunocompetent cell system, based on taking into account the activity of the autoimmune process, clearly defining the boundaries of interferon status indicators, which allows prescribing adequate pathogenetic therapy depending on the activity of the disease.

To this end, in a method of treating exacerbation of multiple sclerosis, including determining interferon status with subsequent drug therapy, it is proposed to further determine the patient’s body area, as a drug therapy, prescribe the drug "Antilimpholine Kz" intravenously in a dose of (0.5-0.6) g × S, where S is the patient’s body area, every other day, and thioctacid at a dose of 300-600 mg iv daily for a course of 6-8 days with a registered I degree of inhibition of the interferon system, with II and III degree of inhibition of the interferon system analogously to assign "Antilimfolin Ks' in the course dose of 0.4-0.5 g / m ^2, and 0.3-0.4 g / m ^2, and Thioctacid at a dose of 600-900 mg, and 900-1200 mg respectively.

The simultaneous use of "Antilimpholine Kz" and thioctacide allows you to accelerate the administration of the drug "Antilimfolin Kz" and increase its effect by suppressing the activity of anti-inflammatory cytokines.

In patients with an active course of multiple sclerosis that continues after a course of immunosuppressive therapy with glucocorticoids, the interferon status is preliminarily examined and drug therapy is subsequently prescribed (the drug Antilimpholine Cz, which helps to increase the level of anti-inflammatory cytokine α-interferon), taking into account the determination of the patient’s additional body area. In addition, to accelerate the administration of the drug "Antilimfolin Kz" and increase its effect by suppressing the processes of apoptosis and the activity of pro-inflammatory cytokines, the drug thioctacid is simultaneously prescribed. When I degree of inhibition of the system of interferons (α-interferon 160-640 units / ml and γ-interferon 32-128 units / ml) is prescribed treatment with the drug "Antilimfolin Kz" iv drip every other day in the amount of 3-4 injections at a course dose of 0 , 5-0.6 g / m ² and at the same time, thioctacid is administered iv drip at a dose of 300-600 mg daily, at II degree (α-interferon 80-160 units / ml and γ-interferon 16-32 units / ml) - the drug "Antilimfolin Kz" in a course dose of 0.4-0.5 g / m ² and thioctacid in a dose of 600-900 mg, at the III degree (α-interferon <80 units / ml and γ-interferon <16 units / ml ) - preparation "Antilimfolin Ks' in the course dose of 0.3-0.4 g / m ² and tioktats d at a dose of 900-1200 mg.

A significant difference of the proposed method from the prototype is the determination of the boundaries of the interferon status indicators taking into account the activity of the pathological process, which allows you to choose the optimal treatment method for both the initially reduced, sharply suppressed and satisfactory condition of the interferon system, to exclude a significant decrease in these indicators in patients with PC, thereby preventing the further progression of immunological disorders.

Example 1

Patient M., born in 1975, and. 15295. Height 172 cm, weight 75 kg, body area 1.9 m ² .

The diagnosis is multiple sclerosis, cerebrospinal form, remitting course, exacerbation.

In the history of the disease - 3 exacerbations, real deterioration within one month.

Neurological deficit at admission is on a scale of FS = 8 points, EDSS = 3 points.

Immunological examination: the average level before treatment with α-IFN is 240 units / ml, the average level of γ-IFN is 48 units / ml (I degree of inhibition of interferon status), after treatment with α-IFN - 480 units / ml, γ-IFN - 64 u / ml

Treatment: in order to calculate the dose of the drug “Antilimfolin KZ”, we first specify the area of the patient’s skin by nomograms: for a person with a height of 172 cm and a weight of 75 kg, it is S = 1.9 m ² , then taking into account the severity of the inhibition of the interferon system (in a patient, it I degree) calculate the course dose of the drug at the rate of 0.6 g / m ² (0.6 × 1.9 = 1.14 g). At the same time, thioctacid is administered iv intravenously in drops at a degree of inhibition of the interferon system at a dose of 300-600 mg.

Thus, the drug "Antilimfolin KZ" is introduced in a course dose of 1.14 g iv in a drop of 3 injections every other day and iv drip of thioctacid in a dose of 300 mg daily.

After treatment, a neurological deficit on the FS = 6 point scale, EDSS = 2 point. During dynamic observation of the patient for 6 months, a relapse of the exacerbation of the disease was not observed.

Example 2

Patient S., born in 1963, and. 6654. Height 168 cm, weight 70 kg, body area 1.8 m ² . The diagnosis is multiple sclerosis, cerebrospinal form, remitting course, exacerbation.

In the history of the disease - 4 exacerbations of multiple sclerosis, with the latter, the patient received hormone therapy with a positive effect, nevertheless, after the drug was discontinued, the appearance of new symptoms.

Neurological deficit at admission is on a scale of FS = 7 points, on a scale of EDSS = 2 points.

Immunological examination: the average level of α-IFN in the IRL before treatment is 120 units / ml, after treatment - 320 units / ml, the average level of γ-IFN in the IRL before treatment is 24 units / ml, after treatment - 32 units / ml.

The treatment was carried out: to calculate the dose of the drug “Antilimfolin Kz”, we first specify the area of the skin of the patient according to the normograms: for a person with a height of 168 cm and a weight of 70 kg, it is 1.8 m ² , then taking into account the severity of the inhibition of the interferon system (registered in the patient II degree) calculate the course dose of the drug at the rate of 0.5 g / m ² (0.5 × 1.8 = 0.9 g). At the same time, thioctacid is administered daily in / in a drip with a II degree of inhibition of the interferon system at a dose of 600-900 mg.

Thus, the drug "Antilimfolin Kz" is introduced 0.9 g per course, iv drip N.3 and iv drip thioctacid in a dose of 900 mg daily.

After treatment, the neurological deficit on the FS = 5 point scale, on the EDSS scale = 1 point, i.e. Positive neurological dynamics persisted for 1 year.

Example 3

Patient J., born in 1972, and. 21914. Height 170 cm, weight 73 kg, body area 1.85 m ² . The diagnosis is multiple sclerosis, cerebrospinal form, secondary progressive course.

Anamnesis of the disease: 2 exacerbations of the pathological process were noted, after which the disease began to progress steadily. The patient received prednisone, against which there was a positive dynamics. However, with the abolition of hormone replacement therapy, neurological symptoms reappeared.

Neurological deficit at admission is on a scale of FS = 15 points, EDSS = 6 points. Immunological examination: the average level of α-IFN in the IRL before treatment is 80 units / ml, after treatment - 320 units / ml, the average level of γ-IFN in the IRL before treatment is 16 units / ml, after treatment - 24 units / ml.

Treatment: in order to calculate the dose of the drug “Antilimfolin Kz”, we preliminary specify according to the normograms the area of the patient’s skin: for a person with a height of 170 cm and a weight of 73 kg, it is 1.85 m ² , then taking into account the severity of the inhibition of the interferon system (in the patient, it is grade III ) calculate the course dose of the drug at the rate of 0.3 g / m ² (0.3 × 1.85 = 0.555 g). At the same time, thioctacid is administered daily in / in a drip at the III degree of inhibition of the interferon system at a dose of 900-1200 mg.

Thus, the drug “Antilimfolin Kz” was administered 0.56 g per course, i.v. drip N.3 and iv drip thioctacid at a dose of 1200 mg daily.

After treatment, neurological deficit on a scale of FS = 11 points, EDSS = 5 points. A second course of the above treatment was carried out to the patient after 6 months in connection with the onset of symptoms of exacerbation of multiple sclerosis.

The present invention allows to effectively increase the social rehabilitation of the patient, improve the quality of life while reducing economic costs associated with the disability of the patient and the cost of drug provision, increase the duration of remission.

Claims (1)

A method of treating exacerbations of multiple sclerosis, including determining interferon status followed by drug therapy, characterized in that the patient’s body area is additionally determined, as the drug therapy, the drug "Antilimfolin Kz" is administered intravenously in a course dose (0.5-0.6) g × S, where S is the patient’s body area, every other day and thioctacid at a dose of 300-600 mg intravenously daily for a course of 6-8 days with a registered I degree of inhibition of the interferon system, with II and III degree of inhibition of the erferonov similarly assigned "Antilimfolin Ks' in the course dose 0.4-0.5 and 0.3-0.4 g / m ^2, and Thioctacid at a dose of 600-900 mg, and 900-1200, respectively.