RU2018320C1 - Method for treatment of juvenile rheumatic arthritis - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: rheapherone is applied to patients rectally together with commonly used non-steroid and hormonal preparations. Dose of rheapherone is 70-100000 units per 1 kg of body mass (daily dose being not more 2 million units). Said preparation is used at 12 hourly intervals within 10-12 days. Further preparation is used 3 times a week within 5-6 months. Simultaneously α-tocopherol and ascorbic acid are applied at age dose, the former preparation being injected rectally, the latter one intramuscularly. EFFECT: decreases activity of the disease, prevents complications of medicinal therapy. 1 tbl

Description

 The invention relates to medicine, namely to pediatric rheumatology, and can be used to treat juvenile rheumatoid arthritis (JuRA).

 Juvenile rheumatoid arthritis is a disease that is based on immunopathological processes and is characterized by a chronic course with a systemic lesion of the connective tissue, mainly the musculoskeletal system.

 Known methods of treating juvenile hypertrophy with anti-inflammatory and basic therapy, including the use of non-steroidal anti-inflammatory drugs and hormones. However, as a result of treatment, various complications of drug therapy develop, including hormone dependence, osteoporosis, Cushing's syndrome, as well as secondary amyloidosis, etc.

The closest in technical essence to the proposed method is a method for the treatment of juvenile arthritis, including, in addition to anti-inflammatory and basic therapy, the use of vitamin, namely "oxydevitis" (24,25-dihydroxyvitamin D ₃ ). This method allows you to extend the periods of remission in this disease.

 However, since the basic therapy in this case is the same as in the analogues, it is not possible to avoid the indicated complications of drug therapy. In addition, in the acute progressive course of juvenile arthritis, generally accepted methods of treatment do not reduce the degree of disease activity and, in essence, in these cases are of little effect.

 The aim of the invention is to reduce the degree of activity of the disease in its progressive course and the prevention of complications of drug therapy.

 This goal is achieved by the fact that along with NSAIDs and hormonal drugs, reaferon is administered rectally to patients at 70-100 thousand units / kg / day (no more than 2 million units / day) every 12 hours for 10-12 days daily, then 3 times per week, 1 time per day for 5-6 months against the background of rectal administration of α-tocopherol and intramuscular administration of ascorbic acid in age dosages.

A comparative analysis of the proposed solution with the prototype shows that the claimed method differs from the prototype in that it involves the administration of Reaferon, a drug that is a recombinant genetically engineered α ₂ -interferon, and vitamins E and C to patients with URA. The specified composition of drugs in the method of treatment of URA never been used before. This allows us to conclude that the claimed method of treatment meets the criteria of the invention of "novelty."

A comparison of the proposed method of treatment with others shows that it is known to use α ₂ interferon in the treatment of a number of diseases, for example, some viral infections. However, Jura does not belong to typical viral infections and the use of interferon preparations for its treatment is not at all obvious. This allows us to conclude that the claimed method of treatment meets the criteria of the invention "significant differences".

 The method is as follows: concentrated reaferon is dissolved in physiological saline at a rate of 250 thousand / ml. The introduction is carried out after an act of defecation or a cleansing enema through an atraumatic catheter into the rectal ampoule to a depth of not more than 4 cm. The drug is administered every 12 hours, due to the pharmacokinetics of interferon. The introduction of interferon into this section of the intestine is due to the fact that its capillary system does not enter the portal vein of the liver. This protects the administered drugs from rapid inactivation in the reticuloendothelial system of the liver.

EXAMPLE EXAMPLE 1. Patient Sh 6 months 3 years, entered the office in September 1988, complaining of an increase in body temperature to 39-40 ^{° C,} joint pain. From the anamnesis it is known that a girl from a II normally proceeding pregnancy of II urgent delivery. Earlier development without features. Heredity is not burdened. An allergic history - intolerance to penicillin and aspirin.

Currently the disease from March 1987 at the age of 1 year 11 months when 4 weeks after suffering bronchitis, about which received inpatient treatment, developed fever up to 40 ^{° C,} tenderness and swelling of l / s, z / v joints polilimfoadenopatiya , hepatosplenomegaly. Diagnosed with Jura, a systemic form, the beginning of the type of Still disease. At the place of residence, she received treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in combination with 7.5 mg / s prednisone with a weak positive effect (completely prednisone was canceled in VII-87). In August 1987 (2 years 4 months), an exacerbation of the disease was noted involving the knee joints in the pathological process. Due to the inability to reduce clinical activity and laboratory activity (ESR-48 mm / h), she was hospitalized in the children's department of the Institute of Rheumatology of the Academy of Medical Sciences of the USSR, where non-steroidal anti-inflammatory therapy was strengthened, hydrocortisone was injected into the knee and g / st joints as the base drug is prescribed auranofin. Against the background of this therapy, there was a tendency to an improvement in the general condition, some subsidence of clinical activity, but high laboratory activity remained. In the future, a worsening of the condition is observed - the progression of the articular syndrome, morning stiffness has grown, a fever of up to 40 ^° C has appeared, mainly at night and in the morning, and therefore, for the correction of therapy, she was re-hospitalized in our clinic in February 1988. Upon receipt, the condition is serious. Long morning stiffness. Systemic increase in all groups l / y. Amyotrophy of the muscles of the upper and lower extremities. The pathological process involves small joints of the hands, both l / s, both ulnar, both humeral, small joints of the feet, both g / st, both knee, both t / b joints, the cervical spine, changes in the affected joints are exudatively proliferative with a predominance of exudative component in l / z, g / st and knee joints. An increase in the size of the liver was +3.0 cm, and the spleen was +1.0 cm. Pronounced laboratory activity (ESR-64 mm / h) was noted. In urine tests, inconsistent proteinuria. Due to the severity and uncontrollability of the pathological process, prednisolone 10 mg / s (0.9 mg / kg / s) was added to the therapeutic complex. Against the background of this therapy, a slight improvement was noted - morning stiffness, fever disappeared, exudative manifestations in the joints became less, ESR decreased to 34 mm / h. However, after 1 week of deterioration again - exacerbation articular syndrome, raising the temperature to 38 ^C. The addition of a second anti-inflammatory drug therapy (rengazila) in / with the entered hydrocortisone possible to stabilize the state, however noted kushingoida development characteristics. In the future, an attempt was made to reduce the dose of prednisone from 10 to 7.5 mg / s, which led to an exacerbation of the pathological process, and therefore in September 1988 he was again hospitalized for treatment correction.

Upon admission, the girl’s condition is serious. Fever up to 39-40 ^about C. The skin is pale. Signs of a cushingoid. Polylymphoadenopathy. Atrophy of the muscles of the hands, forearms, legs. Almost all joints are involved in the pathological process, exudative changes are expressed only in l / s and g / st joints. Tachycardia up to 120 beats. in minutes An increase in liver size + 5.0 cm, spleen + 2.0 cm. In blood tests, a decrease in HB level to 87 g / l, an increase in ESR to 58 mm / h, an increase in transaminase levels were noted. In urinalysis, proteinuria is up to 0.4 g / l. With a gum biopsy, secondary amyloidosis was diagnosed. In the department, the girl’s condition progressively worsened - intoxication symptoms increased, hepatolienal syndrome, lymphadenopathy increased, hectic fever appeared. In blood tests, a further decrease in HB level to 39 g / l, an increase in ESR to 70 mm / h was noted. Due to the extreme severity of the condition after the consultation, it was decided to increase the dose of prednisone to 15 mg / s orally and 60 mg i / m. A catheter is inserted into the subclavian vein. Detoxification therapy has begun. Erythromass and washed red blood cells were infused 4 times. The condition stabilized somewhat, but the temperature continued to rise to febrile numbers. Pronounced hepatolienal cider. In this connection, a course of pulse therapy with metipred 250 mg iv was carried out for 3 days, against which a decrease in temperature was noted. However, after its cessation, the fever again assumed a hectic character. Overgrown symptoms of intoxication, a sharp depletion of the body. The condition was regarded as extremely serious. Due to the uncontrollability of the pathological process, reaferon 750 thousand units was added to the therapy. (70 thousand units / kg / s) for 10 days 2 times a day after 12 hours in combination with antioxidants vit. E and C. Against the background of this treatment, a clear positive effect was noted, the condition improved significantly, the fever disappeared, the symptoms of intoxication, lymphadenopathy, joint syndrome, the size of the liver and spleen decreased. In blood tests, the level of HB increased to 62 g / l, ESR decreased to 21 mm / h. A feature of this observation is the short-term redness of the skin after each administration of reaferon.

 In satisfactory condition, the girl was discharged home with recommendations to continue treatment with reaferon 1 million units. 2 times a week in combination with vit. E and C, prednisone 15 mg / s with a gradual dose reduction. To date, the observation of the girl continues. The condition is stable. The dose of prednisolone was reduced to 5 mg / s.

Example Example 2 Patient B., 14 years old, was admitted to the children's department of the Institute of Rheumatology, Medical Sciences of the USSR in June 1989, with complaints of fever up to 40 ^{° C} during the day, the presence of the trunk maculopapular rash and limbs at the height of fever, pain in the elbow, t / b, knee and g / st joints.

 From the anamnesis it is known that a girl from IV normal pregnancy, IV urgent birth. Earlier development without features. Heredity is not burdened. Allergic reactions are not noted.

Sick of Jura since the fall of 1983 (6 years). The debut of the disease according to the Wissler-Fanconi type of subsepsis involving the elbow, knee, g / st and small joints of the hands and feet in the pathological process. Since 1985, observed in the department. She received various treatment complexes, including NSAIDs and auranofin with a good effect. Remission continued until March 1988, when after sanatorium treatment was exacerbation of underlying disease - fever up to 39 ^{° C,} arthralgia. Hormone therapy was prescribed to the girl at the place of residence - prednisone 60 mg / s. The development of pronounced signs of cushingoid caused the need to reduce the dose of prednisolone. With a decrease in the dose of prednisone to 10 mg / s, an exacerbation of the underlying disease was noted, manifested by fever, severe arthritis with an exudative component and limited movement in the joints, laboratory activity (ESR-58 mm / h), which required an increase in the daily dose of prednisolone to 12.5 mg and connection with / from the introduction of steroids. In September 1988 marked adrenal crisis - fever up to 40 ^{° C,} drop in blood pressure to 80/40 mmHg , severe weakness, pallor, hyperhidrosis, and therefore the dose of prednisone is again increased to 15 mg / s. In January 1989, methotrexate 10 mg / kg / week was added to the therapeutic complex. In March 1989, during a course of intravenous administration of hydrocortisone in the knee, g / st and l / s joints, it was possible to reduce the dose of prednisolone to 7.5 mg. In June 1989, an exacerbation of the disease was noted for no apparent reason, and therefore was hospitalized for treatment correction.

Upon receipt, the condition is serious. Temperature up to 40 ^о С, stiffness throughout the day, spotty-papular rash on the body, signs of cushingoid. Systemic increase in all groups l / y. Almost all joints are involved in the pathological process, changes in them are mainly proliferative in nature, the pain component is most pronounced in the l / s and knee joints. Movement in all affected joints is limited. An increase in liver size is +2.0 cm. In blood tests, an increase in ESR is determined to 58 mm / h. During a biochemical blood test, an increase in the level of transaminases was found, which is most likely associated with the use of methotrexate, and therefore the latter was canceled. Attempts to stabilize the girl’s condition by redistributing the daily rhythm of prednisolone intake (7.5 mg), by taking a course of T-activin were unsuccessful - severe arthralgia, febrile fever, rash persisted.

Due to the severity of the condition, long-term rise in temperature to 40 ° ^C, severe pain in the joints of the girl decided to hold the 3rd year plasmapheresis combined with pulse therapy.

On 16 / VI-89 and 19 / VI-89, 2 courses of plasmapheresis were performed, 20 / VI-89, 1 session of pulse therapy with metipred 0.75 and 0.4 cyclophosphamide, after which the girl did not have a fever during the day but then again it marked rise in temperature to 39 ^° C 22 / VI-'89 placed third plasmapheresis course. 23 / IV-89 g. - 2nd session of pulse therapy with metipred and cyclophosphamide. The measures taken allowed to lower the temperature, to reduce the pain component in the joints, but from 26 / VI-89, fever was again noted to febrile numbers. Given the risk of developing septic complications, kefzol 1.5 g / s i / m was added to the therapy. 28 C / VI-'89 prednisolone dose increased to 40 mg / s, against which there was a slight improvement - the temperature decreased to 37,4-37,7 ^{° C,} less steel disturb arthralgia. But with the 20 / VII-'89 reappeared fever up to 39 ^{° C,} narosla morning stiffness, joint pain intensified. Since 21 / VII-89, 1 million units of reaferon were added to the therapeutic complex. 2 times a day with an interval of 12 hours in combination with vit. E and C for 10 days. Since 22 / VII-89, there has been a normalization of temperature, an improvement in general condition, and a decrease in morning stiffness. With 25 / VII, a decrease in the dose of prednisone was started. Despite this condition continued to improve, not fever, joint pain was not bothered, the size of the liver and spleen decreased, l / y. ESR decreased to 30 mm / h. The dose of prednisone was reduced to 32.5 mg / s. On 24 / VIII-89, in a satisfactory condition, the girl was discharged home with recommendations to continue treatment with reaferon and to carry out a gradual reduction in the dose of prednisone. At home, the condition remained stable, the dose of prednisolone was reduced to 10 mg / s. Observation of the girl continues.

 PRI me R 3. Patient J., 4.5 years old, was admitted to the department in November 1989 with complaints of febrile temperature, morning stiffness, pain in l / s and knee joints.

 From the anamnesis it is known that the girl is from I pregnancy, proceeding with toxicosis II, I urgent birth. Earlier development without features. Often sick with respiratory infections. No allergic reaction noted. Heredity is not burdened.

 This disease in III-88 (3 years 11 months) 3 weeks after the flu with the onset of pain and swelling of both l / s, knee, g / st and small joints of the hands and feet. NSAIDs were initially treated at the place of residence irregularly without a clear positive effect. Since X-88, it has been observed in the children's department of the Institute of Rheumatology of the Academy of Medical Sciences of the USSR. Therapy was prescribed with prednisone 10 mg / s, indomethacin and methotrexate 5 mg / week. Initially, stabilization of the condition was noted - morning stiffness disappeared, exudative manifestations in the joints decreased, and a dose reduction of prednisolone was started. However, in VII-89, after acute respiratory infections, an exacerbation of the disease was noted - the appearance of severe arthritis in the knee joints. Due to the identification of elevated levels of transaminases, methotrexate was canceled. Attempts to stabilize the state by administering a / c administration of hydrocortisone and connecting a second NSAID were unsuccessful and the girl was hospitalized for treatment correction.

Upon receipt, a moderate condition. Periodically fever up to 38 ^° C Morning stiffness for 3 hours. Polilimfodenopatiya. Almost all joints are involved in the pathological process, changes in them are exudative-proliferative in nature with a predominance of the exudative component in the l / s, knee and g / st joints. Movement in all affected joints is limited. The size of the liver is increased +2.0 cm, the edge of the spleen is palpated. When examined in blood tests, an increase in ESR up to 50 mm / h is determined.

 Due to the ineffectiveness of the previous therapy, the girl was prescribed reaferon of 70 thousand units / kg / s - 750 thousand units. in combination with vit. E and C.

 Under the influence of the therapy, stabilization of the condition was noted, morning stiffness disappeared, the temperature returned to normal, the size of the lungs decreased, exudative manifestations in the joints became smaller, ESR decreased to 28 mm / h. Discharged home in satisfactory condition with recommendations to continue treatment with reaferon.

 Received reaferon in combination with antioxidants vit. E and C for 6 months. - against the background of the treatment, there was no exacerbation of the underlying disease, no laboratory activity was noted. The incidence of acute respiratory infections has decreased. The dose of prednisolone is reduced to 2.5 mg / s. Observation of the girl continues.

 The advantages of the proposed method are illustrated in the table.

Thus, the proposed method for the treatment of juvenile rheumatoid arthritis has the following advantages compared to the prototype method:
- the absence of drug complications when using α ₂ interferon (reaferon) in the treatment of juvenile complex;
- the use of α ₂ interferon can reduce the clinical and laboratory activity of the disease. A positive effect is manifested during the 1st month of treatment;
- the use of α ₂ -interferon helps to reduce the incidence of various viral and infectious diseases, previously leading to an exacerbation of the pathological process;
- the absence of the need for constant laboratory monitoring of the function of the liver, kidneys, blood-forming organs allows for treatment on an outpatient basis.

Claims (1)

 METHOD FOR TREATING JUVENILE RHEUMATOID ARTHRITIS, including background therapy and administration of reaferon, characterized in that, in order to increase the effectiveness of treatment and reduce complications due to differentiated effects on the immune system, reaferon is administered reactively and additionally carry out antioxidant therapy with vitamins C and E.

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