RU2476213C1 - Method for integrated treatment of secondary osteoarthrosis accompanying rheumatoid arthritis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to a therapy of the patients suffering rheumatoid arthritis accompanied by secondary osteoarthrosis. The presented method for integrated treatment involves: Methotrexate 7-15 mg per os 1 time a week, non-steroid anti-inflammatory preparations, diacerein 50 mg - 2 times a day in a combination with the exposure to low-intensity laser light, including the exposure of knee joints to skin infrared pulse laser light along a projection of a joint space, and the exposure of blood to supravenous red laser light.

EFFECT: implementing the method ensures an evident analgesic, anti-inflammatory effect, a reduced length of morning stiffness, improved functional capacity and expanded range of motion in the injured joints, as well as lower consumption of non-steroid anti-inflammatory preparations thereby reducing a rate of related side effects.

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Description

The invention relates to medicine, namely to internal medicine.

Rheumatoid arthritis is a chronic systemic inflammatory disease of the connective tissue with damage to mainly peripheral joints as a progressive symmetrical erosive-destructive polyarthritis. Rheumatoid arthritis affects about 0.4-1% of the population, of which 13 to 47%, according to various authors, become ill after 50 years, having by this time in 82% of cases, in addition to the underlying disease, several concomitant diseases: osteoarthritis, osteoporosis, arterial hypertension , coronary heart disease, atherosclerosis, etc.

Along with the steadily progressive destructive damage to the joints, comorbid conditions associated with rheumatoid arthritis are one of the leading causes of a decrease in the quality of life and an increased risk of disability in patients with rheumatoid arthritis (Michaud K., Wolfe F., 2007). Secondary osteoarthrosis acts as the most common concomitant disease in rheumatoid arthritis.

In a randomized study by Jean - Pierre Valat "The study of the effectiveness of diacerein in the symptomatic treatment of osteoarthrosis of the knee joints", the dynamics of clinical indicators was evaluated: WOMAC index, pain according to YOUR movement, need for paracetamol, global patient assessment, tolerance and patient response according to OMERACT-OARSI criteria. In this study, the assessment of clinical efficacy was not confirmed by modern laboratory parameters, which reflect the main pathogenetic processes occurring in these comorbid conditions. The criterion for excluding patients from the study was the presence of diseases of the musculoskeletal system. Thus, patients with rheumatoid arthritis in combination with secondary osteoarthritis, which is most common in the practice of a rheumatologist, were not included in the study (ClinicalTrials. Gov Identifier: NCT00445276).

In a clinical study by Pelletier JP et al. “The efficacy and safety of diacerein in the treatment of osteoarthritis of the knee: a double-blind, placebo-controlled study,” included in the diacerein research group, the dynamics of the indicators of the clinical effectiveness of the drug, as well as the selection of the most effective dose of the drug, are evaluated. However, the genesis of osteoarthritis, idiopathic or secondary, was not specified. Thus, the effect of the drug was not considered from the point of view of a single effective means not only for the treatment of osteoarthritis, but also for the comorbid state that is the cause of this disease. The search for optimal complex therapy has not been carried out, which enhances the clinical effect of drug therapy and reduces the need for non-steroidal anti-inflammatory drugs (Arthritis Rheum. 2000 Oct; 43 (10): 2339-48. PMID: 11037895 [PubMed - indexed for MEDLINE] Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Pelletier JP, Yaron M, Haraoui B, Cohen P, Nahir MA, Choquette D, Wigler I, Rosner IA, Beaulieu AD. Source Center hospitalier de 1'Universite de Montréal, Hôpital Notre-Dame, Quebec, Canada.).

A large number of studies have been carried out, where a positive clinical and pathogenetic effect of low-intensity laser radiation in patients with rheumatoid arthritis and osteoarthritis is proved. But the studies did not analyze the effectiveness of laser therapy in the presence of a comorbid disease - secondary osteoarthritis in patients with rheumatoid arthritis; systemic approaches to treatment were not used, given the common pathogenetic mechanisms of disease development.

In the dissertation, A. Revazova “The effectiveness of laser therapy in the complex treatment of patients with rheumatoid arthritis” did not take into account the presence of concomitant diseases and did not use modern anticytokine drugs (abstract of thesis ... Candidate of Medical Sciences: 14.00.05 / A.A. Revazova; Sever.-Ossetin. Honey. Acad. - Vladikavkaz, 2002. - 22 pp. Bibliography: p.22. - B.ts.).

Closest to the claimed is the "Method for the treatment of moderate and severe manifestations of the articular syndrome in rheumatoid arthritis" (No. 2198004). In the presented study, along with the study of a non-pharmacological method of treatment - phonophoresis, insufficient attention is paid to the correction and optimization of the pharmacological treatment of rheumatoid arthritis. Temporary improvement in the clinical picture of the disease masks the patient’s current condition and contributes to the uncontrolled progression of the disease. Currently, long-acting drugs are widely used in the treatment of patients with rheumatoid arthritis, which can not only improve the clinical symptoms of patients, but also slow down the progression of the disease, i.e. possessing a disease-modifying effect. Thus, in this method, the issues of pharmacological correction using modern disease-controlling drugs are not considered. In addition, given the high prevalence of secondary osteoarthritis in patients with rheumatoid arthritis, the possible additional contribution to the clinical picture of the joint syndrome of the presence of this comorbid state is not considered, which must be taken into account in the treatment of the underlying disease.

Achievable technical result is the optimization of treatment of secondary osteoarthrosis (OA) in rheumatoid arthritis (RA). The specified result arises due to:

- simultaneous effects on inflamed knee joints and periarticular structures currently involved in the pathological process and, at the same time, affect the systemic mechanisms of the pathogenesis of rheumatoid arthritis and osteoarthritis;

- a comprehensive treatment regimen achieves all the main goals of the treatment of patients with RA with secondary osteoarthritis: pronounced analgesic, anti-inflammatory effects, reducing the duration of morning stiffness, improving functional abilities and increasing range of motion in the affected joints and practically does not have side effects;

- reducing the need for non-steroidal anti-inflammatory drugs, thereby reducing the frequency of side effects.

The destruction of cartilage with rheumatoid arthritis leads to the symptoms characteristic of osteoarthritis - degenerative changes in the bones, overgrowth of osteophytes, etc. Thus, with rheumatoid arthritis secondary osteoarthrosis develops. Secondary osteoarthritis contributes to the deterioration of the underlying disease, accelerates the progression of rheumatoid arthritis, which leads to premature disability of patients.

Traditionally, in the treatment of rheumatoid arthritis, basic drugs (methotrexate - the "gold standard") have been used, which have an immunosuppressive effect and symptomatic rapid-acting drugs (NSAIDs).

Thus, the treatment of patients with rheumatoid arthritis does not take into account the most common comorbid disease secondary osteoarthritis. It is necessary to search for new methods of treating patients with rheumatoid arthritis with secondary arthrosis, slowing down the progression of the cartilage destruction characteristic of osteoarthritis, with a simultaneous effect on the pathogenetic mechanisms of both the underlying and the concomitant diseases, enhancing the positive effect of the basic treatment.

The proposed method used the combined use of traditional therapy for rheumatoid arthritis and the combined use of an interleukin-1 inhibitor and LILR, which has an anti-inflammatory, regenerative, slowing down cartilage destruction and analgesic effect, thereby enhancing the effect of the drugs taken and reducing the need for non-steroidal anti-inflammatory drugs. It is this combination that allows optimally affecting the main pathogenetic processes, which is manifested by positive clinical and laboratory dynamics in patients with rheumatoid arthritis with secondary osteoarthrosis.

The method is as follows.

Patients undergo therapy, which consists of:

1) traditional drug therapy:

- the basic drug is methotrexate from 7 to 15 mg per os 1 time per week for a long time. The dose was selected taking into account the activity of the underlying disease.

- non-steroidal anti-inflammatory drugs (NSAIDs),

2) an inhibitor of interleukin-1 (diacerein 50 mg -2 times a day),

3) laser therapy using low-intensity laser radiation.

Thus, all patients received basic treatment - methotrexate and NSAIDs, as well as diacerein and LLLT. Diacerein is registered for the treatment of primary and secondary osteoarthrosis. Thus, acting on secondary osteoarthritis, we achieve a positive effect on the course of the underlying disease - rheumatoid arthritis.

Diacerein belongs to the group of inhibitors of interleukin-1. It has an inhibitory effect on the production and activity of interleukin-1. The main pathogenetic effect of diacerein and its active metabolite rhein in osteoarthritis is the inhibition of IL-1 synthesis, suppression of expression of IL-1 receptors on the surface of chondrocytes, which helps to reduce the sensitivity of cells to the action of this cytokine.

The intracellular metabolite blocks the activation and translocation of NFkB into the nucleus, thereby reducing the expression of NFkB-dependent genes, including those responsible for the production of anti-inflammatory cytokines: TNF-α, IL-1, IL-6, nitric oxide and MP, which contribute to the enhanced destruction of the components of the cartilage matrix.

The technique of laser therapy includes cutaneous laser irradiation of the knee joints along the projection of the joint gap and intravenous laser irradiation of blood with exposure through the skin and venous wall of the vascular bundle in the ulnar fossa. For cutaneous irradiation using infrared pulsed laser radiation with a wavelength of 0.89 microns. The pulse frequency is 80-1500 Hz, the pulse power is 5 W, the exposure time in the field is 1-2 minutes, in one session the total radiation time does not exceed 10-15 minutes.

For supravenous laser irradiation of blood, red laser radiation with a power of 2.5 mW, a wavelength of 0.63 μm, a frequency of 80 Hz was used. The duration of the procedure is 1 min left and right.

Laser therapy was carried out with a Mustang 2000 semiconductor laser optical device with MLOK1, KLO3 radiating heads.

Before the first procedure and at the end of the course of inpatient treatment, the levels of necrosis factor in the patients were determined to be swollen alpha, interleukins - 1.6, highly sensitive C-reactive protein. The effectiveness of complex therapy was assessed before and 10-14 days after the start of treatment, based on the dynamics of clinical and laboratory parameters.

We treated 33 patients with secondary osteoarthritis against the background of rheumatoid arthritis.

The chosen method of complex treatment using an interleukin-1 inhibitor and low-intensity laser radiation contributed to increasing the efficiency of treatment of patients with secondary osteoarthritis in rheumatoid arthritis, having a positive effect on the course of the underlying disease against the background of basic treatment. The selected treatment regimen reduces the frequency of side effects by reducing the need for non-steroidal anti-inflammatory drugs. All patients were divided into 2 groups.

The first group included 17 people who, in addition to traditional therapy, including methotrexate and NSAIDs, received an interleukin-1 inhibitor in combination with low-intensity laser radiation, in the 2nd group, patients (n = 16) received only traditional drug therapy.

The dynamics of clinical and laboratory parameters in patients with secondary osteoarthritis with rheumatoid arthritis under the influence of treatment using an interleukin-1 inhibitor and a combination of the drug with laser therapy (M ± m) is shown in the table below.

Indicators Patients with RA in combination with secondary OA n = 33 treated with 1 group 2 group (n = 17) (n = 16) YOUR at rest (mm) 1-3 day 40.6 ± 1.82 39.8 ± 1.86 10-14 day 24.3 ± 1.33 * 28.2 ± 1.72 YOUR on the move (mm) 1-3 day 58.7 ± 1.82 60.2 ± 1.67 10-14 day 37.9 ± 1.76 * 45.8 ± 1.82 * YOUR on palpation (mm) 1-3 day 59.7 ± 2.1 60.2 ± 1.4 10-14 day 32.8 ± 1.5 * 47.4 ± 1.3 * The overall assessment of the health status of the patient YOUR (mm) 1-3 day 80.2 ± 1.67 78.1 ± 1.53 10-14 day 50.4 ± 1.77 60.2 ± 1.33 WOMAC 1-3 day 125.2 ± 2.66 126.2 ± 2.42 10-14 day 75.2 ± 1.44 * 109.4 ± 2.32 * Lequesne 1-3 day 12.7 ± 0.32 13.1 ± 0.41 10-14 day 9.1 ± 0.42 * 10.2 ± 0.24 * The number of swollen joints 1-3 day 5.2 ± 0.32 6.1 ± 0.42 10-14 day 1.1 ± 0.42 * 3.1 ± 0.24 * Number of painful joints 1-3 day 10.2 ± 0.32 11.2 ± 0.33 10-14 day 3.2 ± 0.45 * 6.5 ± 0.31 * CRP 1-3 day 18.36 ± 2.16 19.5 ± 2.19 10-14 day 12.24 ± 1.95 * 13.22 ± 1.32 * DAS28 1-3 day 4.7 ± 045 5.4 ± 0.35 10-14 day 2.6 ± 0.54 * 2.9 ± 0.32 * ESR 1-3 day 45.22 ± 1.86 40.7 ± 1.95 * 10-14 day 32.62 ± 1.75 36.5 ± 1.97 * IL -1 (pg / ml) 1-3 day 24.6 ± 1.6 23.2 ± 1.4 10-14 day 19.1 ± 1.8 ** 18.6 ± 1.2 ** IL-6 (pg / ml) 1-3 day 28.6 ± 1.5 26.6 ± 1.6 10-14 day 15.7 ± 0.8 ** 19.2 ± 1.2 ** TNF-α (pg / ml) 1-3 day 26.8 ± 1.8 25.2 ± 1.3 10-14 day 17.8 ± 1.2 ** 19.22 ± 1.4 ** R * <0.001 ** <0.05

1) WOMAC Index (Western Ontario and McMAster Universities Osteoarthritis Index), developed by N. Bellamy et al. - they are used to assess the effectiveness of the treatment of osteoarthritis of the knee joints, it is a questionnaire for self-completion by patients and contains 24 questions characterizing pain, stiffness and functional activity 48 hours before the assessment using YOUR (visual analogue scale).

2) The Lequesne index (questionnaire) is an algo-functional index, with gonarthrosis, it characterizes not only pain, but also the severity of the patient's condition.

3) DAS28 - an indicator of a quantitative assessment of the activity of the disease rheumatoid arthritis, calculated by the formula.

Example No. 1.

Patient L., 60 years old, suffers from seropositive RA for 12 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) and traditional physiotherapeutic procedures.

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

On examination, there was a swelling, sharp pain on palpation (pain on YOUR alone - 7 cm, when moving - 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. Limited function and significantly painful on palpation and during movement of the knee joints.

According to the results of clinical and laboratory data, the diagnosis was established: Rheumatoid arthritis, seropositive polyarthritis, activity 3, stage 3 (erosive), secondary gonarthrosis (R Art. 2), synovitis of the right knee joint, FNII.

In addition to the traditional therapy with methotrexate at a dose of 10 mg / week for a long time and NSAIDs (diclofenac 50 mg / d), the patient underwent a course of laser therapy in combination with an interleukin-1 diacerein inhibitor (arthroker 50 mg × 2 times / day) according to the above procedure. The course of treatment using LLLT was 14 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 cancel taking NSAIDs.

The data of biochemical and laboratory treatment methods were characterized by significant positive dynamics (shown in the table below).

Indicator 1-3 day 10-14 day YOUR at rest (mm) 70 twenty YOUR on the move (mm) 60 thirty YOUR on palpation (mm) 70 40 The overall assessment of the health status of the patient YOUR (mm) 60 thirty Morning stiffness (min) 120 40 WOMAC 124 70 Lequesne 12.8 7 DAS 28 5.2 2,3 CRP (mg / L) twenty 8 ESR mm / h 45 24 TNF-α (pg / ml) 25,2 17.1 IL-1 (pg / ml) 23.8 17.1 IL-6 (pg / ml) 27,2 18.6 Need for NSAIDs (diclofenac) 50 mg / day no

Example No. 2.

Patient A., 52 years old, suffered from rheumatoid arthritis for 10 years. For the past 4 years, she has been taking methotrexate at a dose of 16 mg continuously every week.

Clinical diagnosis: rheumatoid arthritis, seropositive, act II, Art. VI, secondary polyosteoarthrosis, 2-sided gonarthrosis (R - Art. III) FN II art.

Against the background of basic pathogenetic therapy, methotrexate 15 mg × 1 r / week for a long time with NSAIDs (nize 100 mg × 1 r / day) underwent a course of laser therapy according to the proposed method in combination with diacerein 50 mg / 2 times a day for 14 days . The treatment results are presented in the table below.

The dynamics of the clinical course of the disease

Indicator 1-3 day 10-14 day YOUR at rest (mm) 60 thirty YOUR on the move (mm) 70 40 YOUR on palpation (mm) 70 fifty The overall assessment of the health status of the patient YOUR (mm) 70 40 Morning stiffness (min) 180 80 WOMAC 135 86 Lequesne 18.7 10,2 DAS 28 6.2 3,1 CRP (mg / L) 23 fourteen ESR mm / h 54 28 TNF-α (pg / ml) 28.6 20,4 IL-1 (pg / ml) 26.9 18.6 IL-6 (pg / ml) 26.5 20.8 Need for NSAIDs nimesulide 100 mg / day no

Based on the results presented in the table, the positive dynamics of the disease was confirmed not only by clinical parameters, but also by laboratory markers of the disease.

Claims (3)

1. A method for the complex treatment of secondary osteoarthritis in rheumatoid arthritis, including taking a drug and exposure to a physical factor, characterized in that methotrexate 7-15 mg per os once a week, non-steroidal anti-inflammatory drugs, diacerein 50 mg - 2 are taken as drugs once a day, and as a physical factor use the effect of low-intensity laser radiation, including cutaneous infrared pulsed laser irradiation of the knee joints on the projection of the articular th slit and adrenal irradiation of blood using red laser radiation. 2. The method of complex treatment of secondary osteoarthritis with rheumatoid arthritis according to claim 1, characterized in that the skin irradiation is carried out with a pulse frequency of 80-1500 Hz, a pulse power of 5 W, exposure duration on the field of 1-2 minutes, the total radiation time in one session no more than 10-15 minutes 3. A method for the complex treatment of secondary osteoarthritis with rheumatoid arthritis according to claim 1, characterized in that the supravenous irradiation of blood is carried out with an exposure of 1 minute, with a power of 2.5 mW, a frequency of 80 Hz.