RU2231356C1 - Method for treatment of ankylosing spondylarthritis - Google Patents

Abstract

FIELD: medicine, rheumatology.

SUBSTANCE: invention can be used for treatment of patients with ankylosing spondylarthritis. Method involves using prospidin in the dose 300 mg per a week by intravenous route administration as the basic therapy on stationary stage and then in the dose 100-200 mg by intramuscular administration on ambulatory stage. Method provides the early and prolonged clinical effect in treatment.

EFFECT: enhanced effectiveness of treatment.

6 tbl, 2 ex

Description

The invention relates to medicine, namely to rheumatology, and can be used as a method of treating ankylosing spondylitis (AS).

There are treatments for AS. One of them is the use of physiotherapy, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics (1). The main disadvantages of this therapy are the lack of effectiveness of these drugs, their inability to suppress the activity of the disease and inhibit further progression. Attempts have been made to treat AS with aminoquinoline drugs, bisphosphonates, D-penicillamine, levamisole, gold preparations, cyclophosphamide, azathioprine, high doses of methylprednisolone, antibodies to tumor necrosis factor alpha, to interleukin-6. However, these treatment methods are also not widespread, either due to lack of effectiveness, or because of the high cost of drugs.

Currently, sulfasalazine (SF) and methotrexate (MT) are considered the most promising drugs in the treatment of AS (1, 2, 6, 7, 8). A meta-analysis of the materials of five controlled studies indicates the following favorable clinical effects of SF: a decrease in the duration of morning stiffness by 28.8%, a decrease in the severity of morning stiffness by 30.6%, a decrease in pain intensity by 26.7%, a decrease in ESR by 9.2 %, overall improvement in the condition of patients by 7.1% (6). The disadvantages of SF therapy: the lack of effectiveness of SF, the clinical effect is more obvious only with the peripheral form of the recently developed AS with high laboratory activity of the disease, some patients are resistant to therapy.

The prototype is MT therapy. There are 16 clinical observations in the literature indicating a certain effectiveness in treating patients with severe AS with low doses of MT (2). An open test was conducted of the effectiveness of MT patients with severe AS, responding poorly to NSAIDs and SF. MT at a dose of 7.5-15 mg per week reduced the need for NSAIDs in almost 30% of patients. Currently, a six-month comparative study of SF and MT in AS has been performed, which has demonstrated the comparable clinical efficacy of both drugs in this disease (2, 7).

Disadvantages of MT therapy: lack of effectiveness of therapy, some patients are resistant to therapy, complete remission develops quite rarely, the effect of drugs begins to appear at 2-3 months of treatment (2, 7, 8). The essence of the proposed method of treatment is that to increase the effectiveness of AS treatment, prospidine is used (3). Prospidine is an antitumor drug with significant therapeutic breadth, good tolerance, and the absence of an inhibitory effect on the hematopoiesis system. The drug acts mainly on cell receptors and membranes and has not only immunocorrective, but also anti-inflammatory effect (4). Open controlled trials have proven its effectiveness in RA and developed a supportive therapy technique (5). Compared with other basic drugs, the clinical efficacy of prospidine is expressed at the earlier stages of treatment (1-2 months), the anti-inflammatory effect of the drug appears already at the end of the 1st to the beginning of the 2nd week of therapy (5).

Prospidine therapy method for AS: at a stationary stage, prospidine is prescribed at a dose of 300 mg per week intravenously in 200 ml of 5% glucose No. 3-4, in the future, patients receive prospidine at a dose of 100-200 mg per week intramuscularly as maintenance therapy. A dose of prospidine 300 mg per week was selected as the least effective and least toxic.

To assess the effectiveness and tolerability of the proposed method of treatment, the authors conducted a number of studies.

Prospidine therapy was prescribed to 18 patients with a reliable diagnosis of AS (according to the modified New York AS criteria). The inclusion criteria were: the presence of signs of disease activity, peripheral arthritis, rheumatoid factor seronegativity, stability, the effectiveness of anti-inflammatory NSAID therapy for at least one month before the study, the absence of signs of the following diseases in the anamnesis: psoriasis, Reiter's syndrome, inflammatory bowel diseases (ulcerative colitis, Crohn's disease), the absence of severe pathology of the internal organs. The initial patient data are presented in table. 1. To evaluate the therapeutic effect, 27 clinical and laboratory indicators were used: pain in the spine according to the visual analogue scale (VAS), stiffness in the spine in minutes, severity of stiffness according to YOUR, symptom of Forestier, Ott, Schober, Thomayer, chin-sternum distance , chest excursion, vertebral index, joint pain according to YOUR, the number of swollen and painful joints, joint index, general well-being, fatigue, local pain according to YOUR, BASDAI, Stanford functional status assessment QOL scale (HAQ) and HAQ-AS, quality of life evaluation by SF-36, ESR, C - reactive protein (CRP), fibrinogen, protein fraction, immunoglobulins A, M, J, circulating immune complexes (CIC). When evaluating the effectiveness of therapy, the effect of therapy on the daily requirement for NSAIDs was also taken into account. An individual assessment of the effectiveness of therapy took into account the dynamics of the analyzed parameters by 25% or more compared with the initial value. It included the following five categories: a very good effect (positive dynamics of more than 75% of the changed indicators); good effect (from 51 to 75% of indicators); insignificant effect (from 26 to 50% of indicators); lack of effect (from 0 to 25% of indicators); deterioration (negative dynamics of at least one indicator in the absence of positive dynamics of other parameters). A total and individual assessment of the effectiveness of therapy was carried out after 1, 3 and 6 months of treatment.

Testing Results

Prospidine therapy led to clinical improvement in most patients (94.4%) already at the stationary stage, and in 10 patients (55.5%) there was a positive dynamics of more than 50% of the indicators (Table 2), which was combined with a decrease in the need for NSAIDs (tab. 3). The effect of therapy began to manifest itself very quickly - at 1-2 weeks and reached a maximum by 4 weeks of treatment. By the 6th month of therapy, clinical improvement continued in all patients, including in 9 patients (50%) the clinical effect was estimated at more than 50% (Table 2). In the whole group, a significant (p <0.001) decrease in the daily requirement for NSAIDs was observed (Table 3). Noteworthy was the good tolerability of prospidine therapy. A side effect (Table 4), which required the abolition of treatment, was detected in 1 patient (5.6%). Cancellation due to lack of effect was not.

Clinical examples

Example 1. Patient Z., 27 years old, medical history No. 1443, was admitted to the hospital on 4.10.2000 with a diagnosis of Ankylosing spondylitis, peripheral form with systemic manifestations (fever, carditis, degree 1 AV block), activity of the III degree, 2-sided sacroileitis of the III degree, HLA B-27 +, FN II. Upon receipt of a complaint of pain in the cervical, thoracic and lumbar spine, sacroiliac, knee and ankle joints, morning stiffness in the spine and joints before lunch, fever up to 38 ° C, general weakness, cardialgia, shortness of breath when walking fast. Ill 3 months ago. For 3 months, he took NSAIDs without noticeable improvement: pain, swelling and stiffness in the joints persisted, and systemic manifestations of the disease appeared. The patient was prescribed therapy with 300 mg of prosidin per week intravenously in 5% glucose No. 4. During treatment, the patient showed a positive dynamics of clinical indicators (table. 5). The pain and stiffness in the joints, fever, cardialgia, shortness of breath, weakness disappeared. NSAIDs do not accept. The clinical effectiveness of therapy of more than 75% is a very good effect. The presented clinical example shows that in a patient with severe AS resistant to NSAID therapy, a distinct positive effect was noted during the treatment with prospidine already at the stationary stage. The resulting clinical effect was maintained during the maintenance therapy with prospidinum at a dose of 200 mg per week intramuscularly. Side effects were not identified. In addition, the patient during the treatment managed to cancel the NSAIDs.

Example 2. Patient B., 34 years old, medical history No. 2394. Was admitted to the hospital 05/20/1998 with a diagnosis of Ankylosing spondylitis, peripheral form with systemic manifestations (subfebrile condition, weight loss), activity of the III degree, 2-sided sacroileitis of the III stage, HLA B-27 +, FN II. Received complaints of pain in the cervical, thoracic, lumbar spine, hip, ankle, shoulder, elbow joints, morning stiffness in the spine and joints during the day, low-grade fever, general weakness. Experience of the disease is 12 months. For 9 months, she took MT 7.5-10 mg per week with insufficient effect, in connection with which 4 months ago, prednisolone 20 mg per day was added to therapy. In the hospital, the patient was prescribed therapy with prosidin 300 mg per week by intravenous drip No. 4. By the end of the inpatient treatment phase, pain and stiffness in the joints decreased significantly, the number of painful and swollen joints decreased by more than 50% (Table 6). The dose of prednisolone was halved. Upon discharge from the hospital, the patient was prescribed prospidine 200 mg per week intramuscularly. When observed by the 6th month of therapy: joint pains are insignificant, there is no stiffness. Prednisone does not take. The effectiveness of the therapy was rated as good. Over the next 42 months, against the background of maintenance therapy at the outpatient stage (prospidine 100 mg per week), the patient retained the obtained clinical effect. This clinical example shows that in a patient with AS resistant to therapy with low doses of MT and prednisolone, a good response was obtained to therapy with prospidine at the stationary stage, which continued during maintenance therapy. Side effects are not registered. In addition, the patient was able to cancel prednisone in the second month of therapy.

In general, the results of testing and the given clinical examples demonstrate high efficacy, satisfactory tolerance and low toxicity of prospidin therapy. Clinical effectiveness can be traced by the rapid onset of anti-inflammatory effect (1-2 weeks), by good overall treatment results by the 6th month of therapy (in 50% of patients - an improvement of more than 50%), by a noticeable decrease in the daily requirement for NSAIDs.

The authors conducted a comparative analysis of MT and prospidine therapy in equal treatment periods, in comparable groups of patients (Table 1). Compared with MT monotherapy, the clinical efficacy of prospidin therapy was expressed at the earlier stages of observation (1 month), had a more noticeable anti-inflammatory effect during maintenance therapy (Table 2) and led to a decrease in the daily requirement for NSAIDs (Table 3). MT monotherapy revealed instability of the clinical effect in relation to the articular syndrome, which required an increase in the daily dose of NSAIDs (Table 3).

Compared to MT therapy, prospidin therapy did not lead to an increase in the frequency of side effects and withdrawal of treatment due to drug toxicity; there was no withdrawal of therapy due to lack of effect (Table 4).

Thus, in comparison with existing methods of treatment, the proposed method has an earlier and pronounced clinical effect. Significant clinical effect appeared already at the end of the 1st, beginning of the 2nd week of therapy, was expressed at the end of the inpatient phase of treatment, and remained in the process of maintenance therapy. The proposed method can significantly reduce the daily need for NSAIDs (table. 3). In this case, there is no increase in the frequency and severity of side effects and related cancellations (Table 4).

LITERATURE

1. Nasonova V.A., Bunchuk N.V. Rheumatic diseases. - M., 1997, p. 313 - 314.

2. Nasonov EL, Soloviev S. K. The use of methotrexate in rheumatology. - M., 2000, 128 p. - prototype.

3. Benenson E.V., Nemtsov B.F. Antirheumatoid drug prospidine. - A.S. 1235502, USSR, 1986.

4. Mashkovsky M.D. Medicines 12th ed. T II. - M., 1993, p. 502 - 504.

5. Nemtsov B.F., Benenson E.V., Timina O.V. The comparative effectiveness of pulse therapy with prosidinum and methotrexate in rheumatoid arthritis (12-month controlled study) // Clinical Medicine. - 8. - 1998. - P.25-28.

6. Gran. J., Hasby. G .: Ankylosing spondilitis. Current drug treatment. Drugs 1992; 44: 586-603.

7. Creemers M.S. W., Franssen M. J. A., Levinus B. A., et al. Methotrexate in severe ankylosing spondilitis: an open study. J. Rheumatol. 1995; 22: 1104-1107.

8. Sampaio-Barros P.D., Costallat L.T., Bertolo M.B. Methotrexate in the treatment of AS. Scand. J. Rheumatol., 2000, 29, 3, 160-162.

Claims (1)

A method for the treatment of ankylosing spondylitis, including non-steroidal anti-inflammatory drugs, characterized in that when they are ineffective, they carry out "basic" therapy with prospidine at a dose of 300 mg per week at the stationary stage, by intravenous drip and at a dose of 200-100 mg intramuscularly at the outpatient stage.

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