RU2360717C1 - Therapy of patients suffering from rheumatoid arthritis with applying combination of tumour necrosis alpha factor antibodies - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: complex therapy involves basic and nonsteroid antiinflammatory drugs combined with exposure to low intensity laser light. Additionally, said complex therapy includes sublingual introduction of Arthrofoon dosed 8 tablets a day completely absorbed with 2 tablets taken 4 times a day at regular intervals within protracted therapeutic courses 3-6 months.

EFFECT: evident anaesthetising, antiinflammatory and immunomodulatory effect, decreased duration of morning stiffness, improved functional capacities and higher affected joint range of motions, prolonged remission.

2 cl, 2 tbl, 2 ex

Description

The invention relates to medicine, namely to internal medicine, and can be used in rheumatology for the treatment of patients with rheumatoid arthritis.

The most common method for treating patients with rheumatoid arthritis is the combined use of two classes of drugs: anti-inflammatory and basic anti-rheumatoid drugs. One of the main basic drugs is methotrexate (MTX), in which the anti-inflammatory and immunosuppressive effects develop after a few months. The therapeutic effect of glucocorticoids (GA) is manifested in a quick anti-inflammatory effect. Long-term use of low doses of HA is also immunosuppressive, i.e. pathogenetic action, which suggests that this group of drugs has a basic effect (Rational pharmacotherapy of rheumatic diseases: a guide for practitioners / V.A. Nasonova [et al.] / edited by V.A. Nasonova, E.L. Nasonova. - M.: Litter, 2003. - 507 p .; Evsikova MD. Safety of basic anti-inflammatory therapy. - Abstract for the degree of candidate of medical sciences, 2006, 22 pp.).

The disadvantages of the method: the use of long-term even small doses of HA is fraught with the development of such negative phenomena as impaired fat metabolism and weight gain in treated patients. Often, the use of HA is accompanied by an increase in blood glucose as a result of a violation of carbohydrate metabolism. One of the main side elements of the effect of HA on the bone structure of patients with PA is the development of steroid osteoporosis. The use of methotrexate and other drugs (leflunamide, sandimmun, and others) in patients with RA is accompanied by no less complications. They have a high risk of side effects: myelosuppression, pathological changes in the gastrointestinal tract, kidneys and peripheral blood, as well as the risk of developing hematologic diseases, severe allergic reactions, opportunistic infections, lymphoproliferative processes, lupus-like syndrome, and the production of antimeric antibodies.

A popular way to suppress inflammation in patients with RA is the method of local exposure to inflamed joints with large doses of HA.

Intra-articular administration of HA along with widespread use is a “relief manipulation”, which has many side effects and complications associated with both the HA itself and the administration technique. The most serious side effects and complications include: septic complications, increased destruction of cartilage and subchondral bone, exacerbation of synovitis, increased blood pressure, up to a hypertensive crisis, exacerbation of pancreatitis, especially in patients with diseases of the gastrointestinal tract, changes in blood rheology and adhesive properties of the venous wall, up to the occurrence of thrombophlebitis of various localization.

One of the common methods for treating patients with RA is the combined use of basic anti-inflammatory drugs and low-intensity laser radiation.

Inclusion in the treatment of patients with rheumatoid arthritis of ultra-low doses of antibodies to tumor necrosis factor-α (TNF-α) (arthrofoone). The drug was prescribed 2 tablets 4 times a day sublingually for 6 months. (Ultra-low doses of antibodies to tumor necrosis factor-α (Artofon drug): efficacy in treating patients with rheumatoid arthritis / V.I. Petrov [et al.] // Bulletin of Experimental Biology and Medicine. - 2003. - Appendix No. 1 . - S.72 - 76.)

Disadvantages of the method: insufficient anti-inflammatory and analgesic effects, inability to directly affect the focus of rheumatoid inflammation - affected joints.

Close to the claimed method is a method of laser therapy for patients with rheumatoid arthritis. (Ilych-Stoyanovich O. Infrared pulsed laser therapy for rheumatoid arthritis: a methodical guide for doctors / O. Ilych-Stoyanovich. Tver: Provincial Medicine LLC, 2001. - 24 pp .; Illarionov V.E. Technique and methodology of laser therapy procedures (reference). - M.: 1994. - 178 p.) The technique of laser exposure is carried out cutaneously in the infrared spectrum with a wavelength of 0.89-1.3 μm with a total session time of 10 minutes, for a course of 10-12 daily procedures, a repeated course is carried out after three weeks.

Disadvantages of the method: it does not take into account the activity of the disease, the dynamics and nature of local inflammatory changes in the joint structures during treatment and, as a result, due to deep penetration into the tissues, should not exceed the dose of the total session for more than 10 minutes. The frequency of courses is every three weeks. The lack of anti-inflammatory effect does not directly affect the pro-inflammatory cytokines.

The purpose of the invention: to increase the economic and pathogenetic effectiveness of the treatment of patients with rheumatoid arthritis, to achieve pronounced analgesic and anti-inflammatory effects, prolonged remission of the disease and, as a result, improve the ability of patients to work fully.

This goal is achieved using a combination of low-intensity laser radiation (LLLT) and antibodies to TNF-α (the drug "Artrofon"). One of the approaches in the treatment of RA in recent years is the effect on pro-inflammatory cytokines, in particular, inhibition of TNF-α - a cytokine of macrophage origin, which normally regulates the interaction of cells of the immune system. There are enough experimental and clinical data indicating the important role of TNF-α in the pathogenesis of inflammatory and degenerative changes in the joints.

For example, an arthrofoon contains ultra-low doses of antibodies to TNF-α. The drug modulates the production and functional activity of TNF-α by reducing the local and systemic production of a number of pro-inflammatory cytokines, inflammatory mediators, as well as immunomodulatory effects.

LILR also has an inhibitory effect on the level of markers of activation of the immune system in patients with RA, such as soluble receptors of tumor necrosis factor α (rFNO-αP), the level of which is closely correlated with the activity of the immuno-inflammatory process in RA.

The method is as follows.

The indications for the inclusion of LLLT and ultra-low doses of antibodies to TNF-α in the complex therapy of patients with RA are the clinical signs of the joint syndrome - synovitis, arthralgia, swelling and configuration of the joints, limitation of their functional mobility, morning stiffness.

The technique of laser therapy consists in cutaneous laser irradiation of the affected joints along the projection of the joint space with a scanning method or sequentially in the fields. Irradiation can be carried out in a lying or sitting position. We irradiated the following joints: temporomandibular joint, sternoclavicular joint, acromioclavicular joint, shoulder joint, elbow joint, metacarpophalangeal joints of the hand, proximal interphalangeal joints of the hand, hip joint, knee joint, ankle joint, and calcaneal joint , metatarsophalangeal joints of the foot, interphalangeal joints of the hands, cervical spine.

Laser therapy was performed with a semiconductor laser apparatus, for example, Mustang 2000, using a radiating head, for example LO3-2000. For cutaneous irradiation, infrared pulsed laser radiation with a wavelength of 0.89 μm was used, infrared wavelengths range from 0.7 to 1.2 μm, and the pulse frequency was from 80 to 1500 Hz.

We have identified the following provisions that allow the most effective and safe inclusion of LLLT and antibodies to TNF-α in the complex treatment of patients with RA:

Before each laser therapy procedure in a patient with RA, joint pain during palpation was determined by the Ritchi index (Ritchi D). The LLLT pulse repetition rate was 1500 Hz with high local pain sensitivity (3 points according to the Richie index). At a lower pain sensitivity (1-2 points on the Richie index), the pulse repetition rate was 80 Hz. The Richie index was traced in dynamics, in order to reduce the frequency of impulses from 1500 to 80 Hz as the initially expressed pain sensations decreased. The duration of exposure on the field ranged from 1 to 4 minutes and was selected depending on the number of fields and pain sensitivity according to the Richie index. In one session, the total radiation time did not exceed 15-20 minutes. Laser therapy was carried out in courses, each course included 10-15 procedures, daily 1 time per day, for example, a weekend break per week. Within one year, a patient of RA underwent 3 courses of laser therapy, the interval between courses was an average of 3-4 months. In addition to LLLT, the drug “Arthrofoon” was included in the complex therapy of patients with RA at a dose of 8 tablets per day, 2 tablets 4 times a day sublingually until completely absorbed at regular intervals outside the meal as part of complex therapy together with anti-inflammatory drugs. Arthrofoon was prescribed to patients with RA for a long time, courses of 3-6 months.

Clinical use cases

1. Patient L., 42 years old, suffers from seropositive RA for 8 years. During the course of the disease, treatment was repeatedly carried out in a specialized hospital where modern pathogenetic methods of treatment were used, including the administration of glucocorticosteroids parenterally, intraarticularly in combination with NSAIDs, the disease of control drugs (methotrexate, delagil) and traditional physiotherapeutic procedures.

On an outpatient basis, she constantly took maintenance doses of NSAIDs and the disease control drug, methotrexate, was used. Despite the ongoing therapy, no apparent improvement was noted.

On examination, swelling, sharp pain on palpation (pain on YOUR - 6 cm) and a significant restriction of movements in the proximal interphalangeal joints of 2-4 fingers of both hands, as well as the wrist, elbow, knee and ankle joints were noted. Limited function and significantly painful on palpation and during movement of the shoulder joints, cervical spine.

Based on the results of clinical and laboratory data, the diagnosis was established:

Rheumatoid arthritis, seropositive polyarthritis, activity III, stage III, FN 2.

The patient underwent a course of laser therapy in combination with the administration of small doses of antibodies to tumor necrosis factor alpha (arthrofoone) according to the above method. The course of treatment LINI amounted to 15 sessions.

After the end of therapy, the patient's condition improved markedly:

the number of painful and the number of swollen joints decreased, the pain in the joints almost completely disappeared, which allowed to stop taking NSAIDs. The data of biochemical and laboratory treatment methods were characterized by significant positive dynamics: ESR - decreased to 20 m / g compared with the initial before treatment - 52 mm / hour. RF - 5 mm (before treatment - 20 mm). CRP - 10 mg / l (before treatment - 25 mg / l).

Table 1 Dynamics of indicators of the course of the disease in patient L. during treatment with an arthrophone and LILR INDICATOR BEFORE TREATMENT AFTER TREATMENT RICHI Joint Index 48 twenty The number of swollen joints (NPV) twenty 8 The number of painful joints (CHBS) twenty 8 NEO YOUR mm 60 twenty The duration of morning stiffness, min 160 thirty DAS Index 6.4 3.9 ESR, mm 52 twenty

2. Patient A., 32 years old, suffered from rheumatoid arthritis for 10 years. Over the past 4 years, she has been continuously taking 8 mg of prednisone per day and once a week 10 mg of methotrexate.

Clinical diagnosis: rheumatoid arthritis, seropositive polyarthritis of the II stage of activity, stage III, F11 stage Against the background of pathogenetic therapy, a course of laser therapy was carried out according to the proposed method in combination with the administration of 8 tablets per day of arthropoon. The treatment results are presented in table 2.

table 2 The dynamics of the course of the disease in patient A. in the course of treatment with an arthrophone and LLLT INDICATOR BEFORE TREATMENT AFTER TREATMENT RICHI Joint Index 25 7 The number of swollen joints (NPV) 12 6 The number of painful joints (CHBS) 12 6 NEO YOUR mm fifty fifteen The duration of morning stiffness, min 120 40 DAS Index 4.9 2.7 ESR, mm 36 16

Long-term results showed the achievement of stable remission for 2 years in treated patients.

Thus, our treatment technique allows us to simultaneously affect all inflamed joints and periarticular structures that are currently involved in the pathological process, and at the same time affect the systemic mechanisms of the pathogenesis of RA.

To correct the dose of laser radiation during treatment for each individual patient, the Ritchie index for each joint was used. A mandatory assessment of pain sensitivity by the Ritchie index in patients with RA before each laser therapy procedure made it possible to adjust the frequency of the LLLT pulses, the exposure on the field, and the number of fields as needed.

The developed method achieves all the main goals of treating RA: pronounced analgesic, anti-inflammatory effects, reducing the duration of morning stiffness, improving functional abilities and increasing range of motion in affected joints, and practically does not have side effects.

In addition, significant positive dynamics of the vast majority of clinical and laboratory parameters reflecting the functional status of patients and the activity of the systemic inflammatory process was noted, in particular, the periods of temporary disability of patients were significantly reduced, the periods of remission of patients were extended, and as a result, the quality of life of patients improved, provided that the volume was significantly reduced drug therapy, which determines its economic benefit.

The main advantages of the technique

The basis of the impact in our treatment method is the principle of using small doses of infrared pulsed laser radiation and ultra-low doses of antibodies to TNF-α. This treatment technique allows you to simultaneously affect all inflamed joints and periarticular structures currently involved in the pathological process, and at the same time affect the systemic mechanisms of RA pathogenesis. To correct the dose of laser radiation during treatment for each individual patient, the Ritchie index for each joint was used. A mandatory assessment of pain sensitivity according to the Ritchie index in patients with RA before each laser therapy procedure made it possible to adjust the frequency of LLLT pulses, exposure to the field and the number of fields as necessary. Correctly selected pulse frequency, low power flux density and radiation energy created the possibility of applying laser radiation to many fields, which, in turn, allows you to affect all joints and periarticular structures involved in the pathological process.

The developed method achieves all the main goals of treating RA: pronounced analgesic, anti-inflammatory effects, reducing the duration of morning stiffness, improving functional abilities and increasing range of motion in affected joints, and practically does not have side effects.

The proposed treatment of RA allows to achieve significant positive dynamics of the vast majority of clinical and laboratory parameters that reflect the functional status of patients and the activity of the systemic inflammatory process. Allows you to reduce the average time of temporary disability of patients by 10-12 days. Extends the period of disease remission from 6 months to 1.5 years. It allows you to significantly reduce the amount of drug therapy, which determines its economic benefit.

Bibliography

Rational pharmacotherapy of rheumatic diseases: a guide for practitioners / V.A. Nasonova [et al.] / Ed. V.A. Nasonova, E.L. Nasonova. - M .: Litter, 2003 .-- 507 p.

Evsikova M.D. The safety of basic anti-inflammatory therapy. - Abstract for the degree of candidate of medical sciences, 2006, 22 p.

Ultra-low doses of antibodies to tumor necrosis factor-α (the drug "Artofon"): effectiveness in the treatment of patients with rheumatoid arthritis / V.I. Petrov [et al.] // Bulletin of experimental biology and medicine. - 2003. - App. No. 1. - S. 72-76.

Ilych-Stoyanovich O. Infrared pulsed laser therapy for rheumatoid arthritis: a manual for doctors / O. Ilych-Stoyanovich. - Tver: LLC Provincial medicine, 2001. - 24 p.

The clinical effectiveness of infrared pulsed laser therapy in patients with rheumatoid arthritis / O. Ilych-Stoyanovich [et al.] // Clinical medicine. - 1999. - No. 6. - S.20-23.

Annex 1

Assessment of the severity of the articular syndrome by the method of Ritchi D. Joint pain during palpation is determined by the Ritchie index (D. Ritchi): 0 - no pain, 1 - the patient says that the palpation is painful, 2 - the patient wrinkles, 3 - the patient pulls back his hand or moves away from researcher. The Richie Index includes an assessment of 53 joints; its maximum possible value is 78 points, because some joints are combined into groups. Each of the 3 multiple groups of joints (metacarpophalangeal, proximal, interphalangeal and metatarsal) is considered for a given limb as a single joint, and its pain is characterized by only one assessment. When characterizing such paired joints as temporomandibular, sternoclavicular, only one assessment is taken for each pair (corresponding to the most painful of the two joints of the same name).

Claims (2)

1. A method of treating patients with rheumatoid arthritis, including complex therapy with basic and non-steroidal anti-inflammatory drugs and exposure to low-intensity laser radiation, characterized in that the complex therapy additionally includes the preparation of arthrofoon in a dose of 8 tablets per day, 2 tablets 4 times a day, sublingually until complete resorption at regular intervals with long courses of 3-6 months. 2. The method according to claim 1, characterized in that the pulse repetition rate of low-intensity laser irradiation (LLLT) is changed depending on the pain sensitivity according to the Richie index: with high joint pain, the Ritchie index is 3 points, the pulse repetition rate of the LLLT is 1500 Hz, with a decrease in pain sensitivity during therapy to 1-2 points, the pulse repetition rate is reduced to 80 Hz; Laser therapy sessions are carried out with a duration of exposure on the field of 1-4 minutes once a day, in a course of 10-15 procedures, the total radiation time does not exceed 15-20 minutes when irradiating no more than 2 joints.