THERAPY OF OSTEOARTHROSIS WITH DRUGS "ARTRADOL" AND "ARTRAKAM" IN COMORBID PATIENTS

Osteoarthritis problem

The problem of osteoarthritis in the Russian Federation is one of the most pressing, occupying a leading position among all diseases of the musculoskeletal system in terms of prevalence.
Epidemiological studies conducted over the past 3-5 years show that verified osteoarthritis by clinical and radiological manifestations is present in no less than 13% of the population of various ages, and its prevalence increases significantly in the elderly. This disease negatively affects performance, social activity, and self-care at home, significantly worsening the quality of life. Previously, osteoarthritis was called a degenerative disease; now, according to leading experts, it is a chronic inflammatory process that affects not only cartilage tissue, but also the joint capsule, tendons, ligaments, and subchondral bone. Of particular interest is damage to the shoulder joints, and it should be noted that the opinion on the etiopathogenesis and clinical manifestations of this pathology is ambiguous.

Currently, the definition of “humeroscapular periarthritis” is not used; in our study, in accordance with the modern classification, patients with the following nosology related to periarticular lesions of the shoulder joints were included:

• Tendinitis of the rotator cuff muscles and bicipital tendinitis M 75.2 ;
• Calcific tendinitis M 75.3 ;
• Subacromial (impigment) collision syndrome M 75.1 ;
• Retractile capsulitis M 75.0 ;

Purpose of the study: to evaluate the effectiveness, safety and tolerability of the drugs “Artradol” and “Artracam” in patients with periarticular lesions of the shoulder joints (humeral periarthritis).

Materials and methods: the study included 120 patients with periarticular lesions of the shoulder joints, namely:

• Rotator cuff tendinitis and bicipital tendinitis – 34 people
• Calcific tendinitis – 38 people
• Subacromial (impigment) impingement syndrome – 27 people
• Retractile capsulitis – 21 people

We observed over time 47 (39.17%) men and 73 (60.83%) women, whose average age was 54.5 ± 8.37 years in the range from 45 to 75 years. There were 32 (26.66%) working in observation groups. There are 11 (9.17%) unemployed people of working age, 77 (64.17%) pensioners.

In the first (control) observation group, no chondroprotective drugs were prescribed, including Artradol and Artracam.

In the second group, every other day Artradol was administered intramuscularly, the dry substance was dissolved in 1 ml of water for injection. The first three injections contained a dose of 0.1 g, starting with the fourth injection, the dose increased to 0.2 g.

In the third group, Artracam was prescribed as a chondroprotector; the contents of one sachet were dissolved by patients in 200 ml of water and taken orally once a day for 6 weeks.

In the fourth group, a combined prescription of “Artradol” and “Artracam” was carried out according to the scheme of alternating intramuscular administration of “Artradol” 0.2 mg and “Artracam” 1 sachet orally every other day.

In the study, 35 0.1 mg ampoules of Artradol and 20 sachets of Artracam were prescribed per course of treatment per patient.

The study included patients with periarticular lesions of the shoulder joints (diagnosis of glenohumeral periartitis according to the ACR criteria of 1987). They had radiographic stage II or III of osteoarthritis of the acromioclavicular joint according to Kellgren-Lawrence. All patients signed informed consent.

The initial exclusion criteria were patients with secondary gonarthrosis, infectious arthritis, systemic inflammatory diseases, gout, pseudogout, Paget's disease, intra-articular fractures, ochranosis, acromegaly, hemochromatosis, Wilson's disease, primary chondromatosis, chondrocalcinosis, concomitant severe diseases (uncontrolled arterial hypertension, unstable angina pectoris, cardiovascular failure, diabetes mellitus type 1. Severe liver and kidney diseases), with a stomach or duodenal ulcer within the last month, with bleeding or a tendency to bleeding, with a history of thrombophlebitis, pregnancy, lactation, as well as body mass index more than 40 kg/m2. Also, individuals included in the study were not required to undergo intra-articular injections of any drugs within 6 weeks before the start of the study. Patients with known hypersensitivity to chondroitin sulfate or glucosamine sulfate were excluded.

The observed patients had a pronounced need to take non-steroidal anti-inflammatory drugs (NSAIDs) (within 30 days over the last 3 months). At the beginning of the study, NSAIDs were not discontinued; patients continued taking this group of drugs in accordance with the individual presence of contraindications, followed by a dose reduction or discontinuation of NSAIDs based on their well-being. So, they took: Nimesulide in a daily dose of 200 mg in the form of sachets or Nise tablets, Ketoprofen intramuscularly 100 mg or 2 capsules (200 mg) per day, Meloxicam tablets or injections 15 mg per day, Ibuprofen 1200 mg-2400 mg in capsules per day, Airtal 1 tablet 2 times a day or 1 sachet 2 times a day, Naysilat 600 mg 2 times a day in the form of tablets, strictly 1 hour before meals, Ibuklin 1 tablet 3 times a day before meals or 2-3 hours after food without chewing.

Assessing the need for NSAIDs, we emphasize that 97.5% of the patients included in the study took NSAIDs regularly. As mentioned above, the personalized selection of NSAIDs was controlled, taking into account contraindications and predicted unwanted side effects. The optimal dose of NSAIDs was selected, since in more than 13.33% it was unreasonably overestimated or underestimated.

During the therapy period, intra-articular injections of glucocorticoids, hyaluronic acid preparations and any other drugs were not performed. Also excluded from the list of prescriptions were drugs that have chondroprotective properties, such as anticoagulants, antiplatelet agents, fibrinolytics, and physiotherapy procedures were not performed.

Patients included in the study suffered from comorbid diseases. We identified 58 patients with verified nosologies, which accounted for 48.3% of all examined. Note that hypertension was diagnosed in 51 (42.5%), spondyloarthrosis of the thoracic and lumbosacral spine - in 29 (24.2%), atherosclerosis - in 21 (17.5%), discirculatory encephalopathy 2 - in 4 (3.3%), coronary heart disease – in 3 (2.5%), chronic obstructive bronchitis – 2 (1.6%), chronic cholecystitis outside the acute stage – 2 (1.6%), duodenal ulcer (history of exacerbations 1 and 2 years ago, respectively) - 2 (1.6%), chronic pyelonephritis, chronic renal failure stage I - 1 (0.8%), type 2 diabetes mellitus in the compensated stage - 1 (0. 8%). In 62 patients, comorbid conditions were not diagnosed, which amounted to 51.6%.

Patients were prescribed supportive pharmacotherapy for concomitant pathology: diuretics in combination with ACE inhibitors, as well as beta-blockers for the treatment of hypertension, NSAIDs and chondroprotectors for the treatment of spondyloarthrosis, statins for the correction of dyslipidemia, nootropics for patients with dyscirculatory encephalopathy, choleretic drugs and hepatoprotectors - for patients with chronic cholecystitis, proton pump inhibitors - for patients with peptic ulcer disease. Treatment of comorbid conditions was coordinated with specialists in the profile of concomitant pathology.

In the observed patients, initially, using a visual analog scale (VAS, mm), pain at night in bed, pain while sitting or lying down, pain in an upright position, pain when moving the upper limbs (active and passive) and pain on palpation were determined.

Table 1 Initial parameters of pain syndrome in observed patients (n=120)

Table 2 Initial severity of pain syndrome in observation groups

Table 3 Initial parameters of the WOMAC questionnaire in observed patients (n=120)

Table 4 Initial expression of WOMAC questionnaire parameters in observation groups

Initially, statistically significant differences in the parameters presented in table. 2 and table. 4 were not observed in the observation groups.

To quantitatively assess coordination in the observation groups, we conducted the “Get Up and Walk” test, which determined the ability to get up from a chair without support within an estimated time in seconds, as well as on a numerical rating scale (NRS) in points.

Table 5 Initial parameters of the “Get up and go” test in observation groups

Safety assessment was carried out according to the following indicators: frequency and nature of adverse events that developed during the observation period, their relationship with the study drug (no connection, unlikely, possible, probable, definite, unknown).

An adverse event was considered to be any medical event that occurred to the patient during participation in the study, regardless of connection with the therapy. The criterion for early exclusion of a patient from their study was the development of serious adverse events (events leading to death, threatening the patient’s life, and also requiring surgical intervention and additional therapy). All cases of adverse events were recorded in the study chart and primary documentation, and were also sent to the study sponsor.

During the study, blood test parameters were monitored: clinical (hemoglobin, leukocytes, ESR) and biochemical (AST, ALT), urine analysis.

During the open study, patients were excluded according to the following criteria: ineffectiveness of therapy for the underlying disease - persistence or worsening of pain requiring treatment adjustment, serious adverse events, refusal to participate in the study, as well as violation of the protocol.

Material and methods

The study included 358 patients with stage I–II OA of various locations.

Inclusion criteria:

1. Presence of one of the following symptoms:

• pain and crepitus in the knee joints,
• morning stiffness ≤ 30 min.

2. Presence of pain syndrome requiring drug therapy

• (40 mm or more on the visual analogue scale (VAS)).

3. The duration of the articular syndrome is no more than 10 years.

Exclusion criteria:

• High inflammatory activity,
• Reliable signs of another rheumatic disease,
• The presence of an ulcer of the gastric or duodenal mucosa in the acute stage,
• Severe concomitant pathology.

Taking into account the above criteria, 358 patients were included in the study. Of these, OA of the knee joints - 210 (59%) patients, polyosteoarthrosis - 97 (27%) patients, and OA of the hip joints - 51 (14%) patients (Fig. 1).

Rice. 1 Distribution of the sample of study patients by type of disease.

The average age of the patients was 54.5±2.02 years. The duration of the disease was on average 6.7±1.24 years.

The diagnosis of OA was established according to the criteria of Altman (1991). To determine the radiological stage of arthrosis, the classification of Kellgren and Laursen (1957) was used.

All 358 patients received complex therapy, including symptom-modifying fast-acting drugs (paracetamol/NSAIDs). As a structure-modifying slow-acting drug, patients received Flexinovo 1 tablet per day for 3 months. The effectiveness of therapy was assessed by the dynamics of joint pain using the Visual Analogue Scale and the Lequesne functional severity index over 3 months. Additionally, the number of patients who completely stopped taking painkillers was assessed.

Research results

Based on the results of observation of groups of patients, we identified the dynamics of clinical indicators (Tables 6, 7).

Table 6 Dynamics of pain syndrome in observation groups

Note: * p<0.05; ** — p<0.01 – significance of intergroup differences after treatment.

Table 7 Dynamics of the severity of parameters of the WOMAC questionnaire in observation groups

Note: * p<0.05;
** — p<0.01 – significance of intergroup differences after treatment. As a result of the therapy, both in the second and third groups, and during combination therapy, there was a positive dynamics of pain, stiffness and difficulties in daily activities, which proves the high effectiveness of monotherapy with the drugs “Artradol” and “Artracam”, with the synergistic effect of their joint administration .

Table 8 Dynamics of quantitative assessment of the coordination test “Get up and go”

Note: * p<0.05;
** — p<0.01 – significance of intergroup differences after treatment. Significant dynamics of the coordination test “Get up and go” characterizes the expansion of daily activities and improvement of self-care of the observed patients.

The study assessed the effectiveness of therapy by the doctor and the patient, which was calculated against the background of continuous use of NSAIDs.

Table 9 Efficacy of initial therapy in patients included in the study, assessed by physicians and patients

Table 10 Adverse side effects identified during observation in the study groups

According to the data presented in Table 10, the drugs “Artradol” and “Artracam” are well tolerated, both in monotherapy and in combination therapy. The occurrence of undesirable side reactions was observed during monotherapy with Artradol in 10%, and with Artracam in 9.99%. During a course of combination therapy, an increase in undesirable side reactions was revealed to 3.32%. No serious adverse events were identified.

The association of adverse events with drug intake was possible or probable. To correct undesirable side effects, dietary measures were carried out; if gastralgia developed, NSAIDs were discontinued and antispasmodics were prescribed (once in all groups). When nausea occurred, the duration of which did not exceed 10 hours, metoclopramide was prescribed. The appearance of flatulence and facial redness did not require medication. Synovitis was controlled by prescribing NSAIDs in adequate doses. There was no need to discontinue therapy in the observation groups.

The need for NSAIDs in the observation groups decreased: after two weeks in 24 (80%) patients in group 2, in 23 (76.7%) in group 3, in 27 (90%) in group 4. After 1 month, the need for regular NSAID use continued to decrease. 27 (90%) in group 2 refused to take non-steroidal drugs, 28 (93.3%) in group 3, and 29 (96.7%) in group 4.

While monitoring patients with comorbid pathology, we did not identify any negative drug interaction reactions, which did not require changing the recommendations of specialists in the relevant field.

Discussion

News of medicine and pharmacology in the field of treatment of diseases of the joints and spine

conclusions

• The use of Flexinovo, 1 tablet once a day for 3 months, in complex therapy of patients with OA of the knee joints, OA of the hip joints and polyosteoartosis reduces the severity of pain and the need for painkillers. Increases functional activity and quality of life of patients.
• Flexinovo is well tolerated. The use of Flexinovo, 1 tablet once a day for three months, is safe in terms of the development of side effects.

Thus, the data obtained confirm the effectiveness of Flexinovo in the complex therapy of OA of large joints and the feasibility of its use in general medical practice.

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