RU2709141C1 - Method of treating rheumatoid arthritis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to rheumatology, physiotherapy and medical rehabilitation, and can be used for treating rheumatoid arthritis. That is ensured by therapeutic electrophoresis on a region of affected joints by transverse technique. Electrophoresis is carried out with solution containing 0.5 ml diprospan, 0.5 ml of dimethylsulphoxide and 5 ml of distilled water. First procedure is carried out with duration of 20 minutes, and following for 30 minutes, alternating every other day. Therapeutic course includes 4–6 procedures.

EFFECT: method provides higher clinical effectiveness, reduced length of treatment, reduced intensity of inflammatory process, improved functional activity of joints, reduction of side effects due to significant prolonged local anti-inflammatory and analgesic effects without intensifying systemic negative action of glucocorticoids as a result of synergetic effect of components of conducted exposure with minimum number of procedures.

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Description

The invention relates to medicine, namely to rheumatology, physiotherapy and medical rehabilitation, and can be used for the complex treatment of rheumatic diseases with joint damage, in particular rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting the synovial membrane of joints and visceral systems (Rheumatology: Clinical recommendations / Edited by Acad. RAMS E.L. Nasonova. - 2nd ed., Rev. And add. - M. : GEOTAR-Media, 2011 .-- S. 90-230). The course of RA is progressive in nature and quickly leads to disability, and the prevalence of RA, the defeat of people of working age, and expensive treatment methods determine the social significance of RA for patients. Currently used drugs significantly improve the quality of life of patients with RA, but do not provide sufficient inhibition of the inflammatory process, destruction in the tissues of the joints, blood vessels and internal organs. Combination therapy with basic anti-inflammatory drugs may not be used in all patients, as it has many contraindications and limitations. The development of new regimens and methods of treating RA, including non-medication, remains today one of the urgent problems of rheumatology and medicine in general.

There is a method of treating rheumatoid arthritis by using intra-articular injections of glucocorticoids (Badokin V.V. Therapy with prolonged crystalline glucocorticoids for diseases of the musculoskeletal system. Neurology, neuropsychiatry, psychosomatics. 2013; (2): 88-92), which consists in the use of the drug Diprospan, which injected into large joints in 1 dose - 1 ampoule containing 1 ml of solution, in medium - 1/2 dose and in small - 1 / 4-1 / 5 doses, and injections are carried out 1 time in 1-2 months, but not more 4 injections a year in one joint.

However, this method of treatment has such disadvantages as invasiveness, postinjection complications, the negative effect of glucocorticoids on the metabolism of articular cartilage, the possibility of infection of the joints, aseptic necrosis of bone tissue, especially the femoral head or epiphyses of the bones of the knee joint, which is observed with repeated use of drugs of this group .

In the literature there is information about the use of physiotherapeutic techniques in the treatment of rheumatoid arthritis, allowing to achieve many positive results, in particular such as anti-inflammatory effect, antioxidant effects, stimulation of specific and nonspecific immunity factors.

A known method of treating rheumatoid arthritis by performing electrophoresis of an aqueous mud extract in the form of a suspension of finely ground shungite rock in water with a mineral: water volume ratio of 3: 1 (Patent for the invention No. 2114649, publ. July 10, 1998).

The disadvantages of the method include the variability of the chemical composition of the drug used, the impossibility of standardization and dosing, as well as the relatively low efficiency due to the lack of prolonged action of the drug, after the procedure, the drug is washed off the skin; in addition, the application of the method is limited due to the impossibility of using natural raw materials outside the resort conditions.

A known method of treating rheumatoid arthritis by electrophoresis of an immunosuppressive drug - 5-fluorouracil to the affected joints by a transverse method with a current strength of 12-15 mA, electrode area 220-300 cm ² for 20-30 minutes daily (Author's certificate No. 1178455, Publ. 09/15/1985).

The disadvantages of this method are low efficiency, due to the fact that 5-fluorouracil acts mainly on proliferating tissues of the hematopoietic organs and the mucous membrane of the gastrointestinal tract (Belousov Yu.B., Moiseev BC, Lepakhin VK "Clinical Pharmacology and Pharmacotherapy. Guidelines for doctors ", M .: Universum, 1993, p. 301), and when administered locally in the joints, only a small part of the drug reaches the hematopoietic organs, and the mucosa of the gastrointestinal tract is not a target organ. The half-life of 5-fluorouracil is 10-20 minutes, so its effect is short-lived, and dermatitis is a typical side effect, which also limits its local use.

As a prototype, a method for the treatment of rheumatoid arthritis was selected, which includes exposure to affected joints by electrophoresis of a 2% pentoxifylline solution, the pentoxifylline solution being injected from the anode at a current of 15 mA, the introduction is carried out for 15 minutes, at a current density of 0.05-0 , 1 mA / cm ² , a course of 10 procedures (Patent for invention No. 2539007. RF. Publ. 10.01.2015. Bull. No. 1).

The disadvantages of this method are as follows: possible side effects in the form of allergic reactions, low efficiency, short remission (Kolosova I.R., Lukina G.V., Sigidin Ya.A., Speransky A.I. Use of pentoxifylline in the treatment of RA. Scientific Practical Rheumatology. 2001; (5): 24-28).

Given the above, in the treatment of rheumatoid arthritis, the problem is to reduce the negative reactions of the body, reduce the intensity of pain and the degree of the inflammatory process, activate the motor regime, reduce the duration of treatment.

The technical result achieved by the invention is to increase the effectiveness of the treatment of rheumatoid arthritis, reduce side effects and reduce the duration of temporary disability due to a significant prolonged local anti-inflammatory and analgesic effect without enhancing the systemic negative effect of glucocorticoids, improving the functional activity of the joints.

It is proposed, as in the prototype, the conduct of drug electrophoresis on the affected joints by a transverse method with a current strength of 15 mA.

The essence of the claimed invention lies in the fact that in a method for the treatment of rheumatoid arthritis, including the conduct of drug electrophoresis on the affected joints using the transverse method, according to the invention, electrophoresis is carried out with a solution containing 0.5 ml of diprospan, 0.5 ml of dimethyl sulfoxide and 5 ml of distilled water moreover, the first procedure is carried out with a duration of 20 minutes, and the next for 30 minutes, alternating every other day, the course of treatment includes 4-6 procedures.

The active component of diprospan is betamethasone, which is contained in the drug in two forms: betamethasone disodium phosphate, which ensures the rapidity of the effect and betamethasone dipropionate, prolonging the therapeutic effect. Betamethasone exhibits high glucocorticoid and negligible corticoid activity. The effect of diprospan is due to its effect on different types of metabolism and a pronounced anti-inflammatory effect: its active components inhibit the production of substances that lead to the development of the inflammatory process. The tool also has an immunosuppressive and anti-allergic effect (MD Mashkovsky "Medicines", M .: New wave, 2005, 15th edition, revised, revised, supplemented with. 576). Betamethasone sodium phosphate is almost completely eliminated from the body within 24 hours after use. Betamethasone dipropionate has slightly different qualities: the process of its absorption from the depot is slow, the substance is metabolized gradually, as a result, the duration of the action is provided.

Dimethyl sulfoxide is a drug widely used in physiotherapeutic practice for the treatment of diseases of the musculoskeletal system of inflammatory origin. Experimental and clinical studies show that dimethyl sulfoxide inhibits inflammatory reactions, the effect is comparable with non-steroidal anti-inflammatory drugs. When applied topically, dimethyl sulfoxide penetrates the articular cavity and is a universal conductor for other drugs. Due to the improvement of the permeability of drugs through the skin, their concentration can be reduced several times without violating the pharmacological activity of the transported substances, which contributes to a deeper penetration into the tissues and in a larger amount than with conventional electrophoresis.

A causal relationship between the set of essential features and the technical result provided by the invention is as follows: electrophoresis with a solution containing diprospan, dimethyl sulfoxide and distilled water can increase the effectiveness of treatment by summing up the therapeutic effect of the pharmaceutical composition and the action of the physical factor, as well as due to the double exposure - a quick effect due to the action of a short fraction of betamethasone disodium phosphate, which provides fast a company achieve the effect and prolonged effect - due to betamethasone dipropionate, prolonging therapeutic effects of glucocorticoids, which increases the anti-inflammatory action; the possibility of a direct effect on the pathological lesion prolongs the physiological effect of the composition used, helps to reduce swelling of the joints, increase their functionality.

The developed pharmaceutical composition in the form of a solution containing 0.5 ml of diprospan, 0.5 ml of dimethyl sulfoxide and 5 ml of distilled water, potentiates the anti-inflammatory effect in comparison with monotherapy with individual drugs. During electrophoresis with a solution of diprospan and dimethyl sulfoxide, drugs accumulate in the upper layers of the skin over the affected joints, which ensures a fast onset of effect due to betamethasone disodium phosphate and the prolonged effect of betamethasone dipropionate at the site of exposure. The presence of dimethyl sulfoxide in the solution increases the speed and depth of penetration of drugs, potentiates the anti-inflammatory effect of the composition, which together reduces the period of relief of local inflammation and has a longer aftereffect compared to known treatment methods.

The ratio of the components of the solution for electrophoresis is selected empirically and is optimal for achieving a technical result. The use of diprospan in a concentration of 0.5 ml is sufficient to provide the necessary therapeutic effect. When the concentration of dimethyl sulfoxide is less than 0.5 ml, a decrease in the effectiveness of the effect is observed, and with an increase in the concentration of dimethyl sulfoxide more than 0.5 ml, the incidence of adverse reactions in the form of skin itching and local redness increases.

The method is as follows.

Immediately before the electrophoresis procedure, a pharmaceutical composition is prepared in the form of a solution of 0.5 ml of diprospan, 0.5 ml of dimethyl sulfoxide and 5 ml of distilled water.

Electrophoresis is carried out on the area of the affected joints according to a transverse procedure, for example, with the Potok-1 apparatus, EMA plant, Ekaterinburg, Russia, at a current density of 0.05-0.1 mA / cm ² .

Hydrophilic cloth pads are moistened with warm water and placed on the patient’s skin on opposite surfaces of the affected joint area - one opposite the other, while the electrodes from conductive graphitized tissue with a current-carrying wire are in the pockets of the hydrophilic pads. The size of the pads is selected individually depending on the size of the affected joint. Under the pad with a “+” charge (anode), a gauze napkin soaked in a warm prepared solution of medicinal substances is placed. Fix the gaskets using a special rubber band.

The first procedure is carried out with a duration of 20 minutes with an initial current of 15 mA. For one procedure, 6 milliliters of a freshly prepared solution of diprospan, dimethyl sulfoxide, and distilled water are used. Before performing the procedures, make sure that there are no scratches, abrasions, maceration, skin rash.

Subsequent procedures are carried out for 30 minutes, alternating every other day. The current strength is increased during the electrophoresis procedures taking into account individual sensations, but not more than 50 mA.

The course of treatment is 4-6 procedures.

The number of procedures less than 4 does not provide a significant decrease in the intensity of the inflammatory process during the exacerbation period, i.e. is insufficient to achieve the expected result. In the case of moderate or high intensity of the inflammatory process, the number of procedures is increased to 6.

The application of the proposed method contributes to a long anti-inflammatory effect by creating a subcutaneous depot of short and prolonged glucocorticoid fractions, and the transdermal route of drug administration allows you to avoid the passage through the gastrointestinal tract and the destruction of drugs.

The method was tested in 10 patients with a verified diagnosis of RA 1-2 degrees of activity, receiving the same basic therapy. The control group consisted of patients with RA, comparable by sex, age, and activity of RA, in the complex of treatment of which physical factors were not included.

Using the proposed method led to a statistically significant decrease in arthralgic syndrome and disease activity, confirmed by a decrease in pain intensity indicators on a visual-analogue scale (VAS) from 63.6 ± 2.22 mm before treatment to 26.7 ± 1.20 mm in its completion and the disease activity index, consisting of several discrete values of the activity of rheumatoid arthritis (DAS28) - 5.68 ± 0.36 units. and 3.37 ± 0.17 units respectively. The dynamics showed a decrease in acute phase indicators - ESR and CRP. Clinical improvement was achieved in the entire group of patients, including patients with a long course of the disease, receiving basic therapy drugs, in the form of a significant reduction in pain, stiffness in the joints, reduction of swelling in the joints, and positive dynamics of laboratory parameters of inflammation.

The presence of a prolonged fraction of betamethasone and the creation of a local subcutaneous “depot” of the drug allowed the use of diprospan electrophoresis according to a shortened scheme while maintaining the aftereffect effect. Carrying out the proposed method against the background of basic therapy allows to reduce the severity of the inflammatory process and to shorten the treatment of RA.

Analysis of adverse events testified to the high efficiency and relative safety of this treatment method.

The method can be recommended as one of the components of the complex treatment of rheumatoid arthritis at various stages of the therapy and can be considered as a replacement for intra-articular injections of glucocorticoids as an affordable non-invasive treatment method.

Examples of the proposed method.

Example 1

Patient D., 53 years old. Diagnosis: rheumatoid arthritis, seropositive, late stage, activity of inflammation III (DAS28 - 6.6), radiologically III art., Functional failure of joints II art. with a violation of the gripping function of the hands, a decrease in carpal force. Hormone dependence syndrome.

The diagnosis of rheumatoid arthritis was established in 2009, taking methotrexate 10 mg per week in combination with folic acid 5 mg per week and methylprednisolone 8 mg per day as the basic therapy. Annually conducted inpatient treatment courses. Attempts to increase the dose of methotrexate made 3 months ago were discontinued due to the appearance of nausea and diarrhea. The patient noted a daily intake of NSAIDs in full therapeutic doses - nimesulide 200 mg per day. Complaints of morning stiffness for 6 hours, pain, swelling, flushing of the small joints of the hands and both knee joints.

On examination, moderate synovitis of the proximal interphalangeal III-IV, metacarpophalangeal joints of both hands, the right knee joint, slight ulnar deviation of the fingers.

In a blood test: HB - 117 g / l, white blood cells 9.3 × 109 / l, ESR - 34 mm / h, rheumatoid factor 64 IU / ml, CRP 20.4 mg / l.

The patient underwent a course of treatment according to the claimed method on the hands and knee joints, and the procedures on the hands and knee joints were alternated every other day. The first procedure was carried out with a duration of 20 minutes, the subsequent 30 minutes. The total number of procedures was 6.

After the course of treatment, morning stiffness decreased to 40 minutes, the synovitis of the small joints of the hands practically disappeared, the synovitis of the right knee joint decreased, joint pain decreased significantly (from 67 mm to 26 mm on a visual analogue scale). The dose of nimesulide taken is reduced to 100 mg per day. Positive dynamics of laboratory indicators was noted - ESR - 21 mm / h, CRP - 6.2 mg / l (DAS28 - 3.24).

Example 2

Patient B., 51 years old. Diagnosis: rheumatoid arthritis, seropositive, ACCP (-), late stage, activity of inflammation III (DAS28 - 6.58), X-ray of III stage, recurrent periarthritis of both knee joints, bilateral Baker's kitties. Functional insufficiency of joints of the II Art. with impaired support and walking function, decreased carpal force. Hormone dependence syndrome.

Secondary osteoarthritis, bilateral gonarthrosis of the III degree, chronic recurrent bursitis (arthroscopy and debriding of the right knee joint 10/27/2015).

Joint syndrome since 2012. I did not seek medical help, I was treated on my own. The diagnosis of rheumatoid arthritis was established in 2013, when, against the background of increased pain, severe morning stiffness, the patient was hospitalized in the therapeutic department at the place of residence. In 2013, the diagnosis of RA was confirmed, basic therapy was prescribed - methotrexate 10 mg per week in combination with folic acid 5 mg per week. After 6 months, methotrexate was canceled and, due to the high activity of the inflammatory process, 16 mg per day was prescribed by methylprednisolone. Repeatedly examined by orthopedic traumatologists. Since 2015, basic therapy with leflunamide has been carried out 20 mg per day, the dose of methylprednisolone taken has been reduced to 4 mg per day. Annually conducted inpatient treatment courses. This hospitalization is associated with exacerbation of RA.

At the time of examination, there are complaints of severe pain in all groups of joints with a maximum in the knee joints, swelling of both knee joints, instability when walking, "crunching" during movements. The duration of morning stiffness is more than 4 hours, periodic subfebrile condition in the evening.

On examination: pain and swelling of the wrist, metacarpophalangeal, proximal interphalangeal joints of the hands, knee, ankle, small joints of the feet; pain and restriction of active movements in the shoulder, elbow, hip joints, right temporomandibular joint.

In the blood test: HB - 109 g / l, white blood cells 4.8 × 109 / l, ESR - 33 mm / h, rheumatoid factor 12.5 IU / ml, ATsPP - 7 IU / ml, CRP 59 mg / l.

The patient underwent a course of treatment according to the claimed method on the hands and knee joints, and the procedures on the hands and knee joints were alternated every other day. The total number of procedures is 6.

After the course of treatment, the morning stiffness decreased to 45 minutes, the synovitis of the small joints of the hands practically disappeared, the synovitis of the knee joints decreased, the pain in the joints decreased significantly (from 78 mm to 27 mm on a visual analogue scale). The pain in the elbow, right temporomandibular joint disappeared. Normalized body temperature. Positive dynamics of laboratory indicators was noted - ESR - 10 mm / h, CRP - 7.4 mg / l (DAS28 - 3.28).

The inventive method is non-invasive, can significantly improve the well-being of patients, avoid increasing the dose of systemic glucocorticoids and reduce the dose of symptom-modifying drugs, minimize the number of side effects.

This method can be included both in the inpatient course and in the course of outpatient treatment of patients with rheumatoid arthritis.

Claims (1)

A method for the treatment of rheumatoid arthritis, including conducting electrophoresis on the affected joints by a transverse method, characterized in that the electrophoresis is carried out with a solution containing 0.5 ml of diprospan, 0.5 ml of dimethyl sulfoxide and 5 ml of distilled water, the first procedure being carried out with a duration of 20 minutes, and the next for 30 minutes, alternating every other day, the course of treatment includes 4-6 procedures.