The method of treatment of rheumatoid arthritis

 

(57) Abstract:

The invention relates to medicine, namely to rheumatology, and can be used to treat patients with rheumatoid arthritis. For this purpose, is injected methotrexate at a dose of 10 mg per week and prospidin 200-300 mg per week, enter the last drip. The method provides an early and pronounced effect of treatment in reducing complications of immunosuppressive therapy. 6 table.

The invention relates to medicine, namely to rheumatology, and can be used as a method of treatment of rheumatoid arthritis (RA).

There are ways for the treatment of RA. One of them use prospidina [1]. Prospidin - anticancer drug with significant therapeutic breadth, good tolerability, no inhibitory effects on the blood system. The drug acts primarily on cell receptors and membrane and has not only immunocorrective, but also anti-inflammatory activity [2]. In open controlled studies have demonstrated its effectiveness in RA and developed a method of maintenance therapy [4]. Compared to other basic drugs clinical efficacy of prospice by the end of 1 - the beginning of 2 weeks of therapy [4].

The main disadvantage of therapy prospidine: the drug loses its effectiveness with long-term use in connection with the development of resistance.

The prototype is therapy with methotrexate (MT). MT refers to the group of antimetabolites, anti-inflammatory and immunomodulatory effects and is considered the "gold standard" for the treatment of RA, as the most effective and least toxic drug [5]. The effectiveness of MT in a dose of 7.5 to 25 mg per week for RA compared with placebo and other anti-rheumatic drugs confirmed in many controlled studies [3]. MT occupies a Central place in the combined therapy of RA [3, 5].

However, despite the known advantages, MT treatment has its drawbacks: complete remission rarely develops, with the abolition of the drug usually occurs exacerbation during therapy often have to increase the dose of the drug, since the absorption MT decreases with time, some patients resistant to therapy MT, especially in low doses, the drug begins to show a 2-3 month [3, 5].

The essence of the proposed method of treatment is that for efficiency Teisnach actions antirheumatoid base means, their combined purpose seems reasonable enough [5]. This creates the possibility of simultaneous exposure to different pathogenetic links of diseases that can improve clinical effectiveness, and the use of lower doses of each drug reduces the risk of development of drug resistance [3].

The method of combined modality therapy MT and prospidina when RA: inpatient MT is administered in a dose of 10 mg per week/m, prospidin - 300 mg per week/drip in 200 ml of 5% glucose 3-4, in the future, patients receive MT oral dose of 7.5 to 10 mg per week, prospidin 100-200 mg per week/m as maintenance therapy. Dose MT 10 mg per week is selected as the minimum effective and least toxic [3, 5]. Prospidin is administered in a dose of 300 mg per week, which amounts to 50-60% of the dose used in monotherapy [4].

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

Combination therapy MT and prospidina was appointed 29 patients reliable active RA, most of them had systemic manifestations and steroidogenesis (PL. 3). The severity of clinical effectiveness is olesnevich and swollen joints and improvement in at least 3 out of 5 indicators: total activity assessment of the patient and physician on the visual analogue scale (VAS), pain assessment patient (VAS), ESR, CRP (C - reactive protein) and the assessment of functional status according to HAQ (Stanford scale assessment of quality of life). When assessing the effectiveness of therapy also took into account the influence of therapy on the daily requirement for steroids if steroidogenesis. To assess remission applied universally accepted criteria of the American rheumatology Association (ARA).

The results of testing. Combination therapy MT and prospidina led to clinical improvement in most patients (93.1%) are already on the stationary phase, and in 17 patients (58.6 per cent) clinical effect was more than 50% according to the ACR criteria (table. 4) and were combined with a reduction in the need for intra-articular glucocorticoids and the punctures (table. 5, 6). Action therapy began to emerge very quickly for 1-2 week and reached a maximum after 4 week of treatment. By 6 months of therapy, clinical improvement was maintained in all patients, including 4 patients (25%) were recorded remission criteria ARA, in 12 patients (75%) clinical effect was assessed at the level of 50% or more according to the ACR criteria (table. 4). In the whole group, there were significant (p<0,05) lower daily requirement of steroids (table. 5). Drew my attention to the 7 patients (24.1 per cent), that required discontinuation of treatment in 2 of them (6.8 per cent). Cancellations due to the lack of effect of combination therapy was not.

Clinical examples

Example 1: the Patient P. 48 years, history 1344. Admitted to the hospital 12.02.2001 with a diagnosis of Rheumatoid arthritis, arthritis with systemic symptoms (weight loss, rheumatoid nodules, Sjogren syndrome, episcleritis), seropositive, rapidly progressive course, activity II stage, II phase, FNS II. Steroidogenesis.

Upon receipt of a complaint of pain in the small joints of the hands, feet, wrist, shoulder and elbow joints, morning stiffness before lunch, nodules in the elbow joints, feeling of sand in eyes, dry mouth, General weakness, weight loss over the past year to 6 kg Suffers RA 1.5 years, in the last 6 months taking methotrexate at a dose of 10 mg per week and prednisolone 10 mg/day without any noticeable improvements: saved pain, swelling and stiffness in the joints, appeared systemic manifestations of the disease. Attempts to increase the dose of methotrexate resulted in increased liver enzymes and bilirubin. The patient was assigned to combination therapy with methotrexate at a dose of 10 mg in a week/and prospidina 300 mg per week is it (PL.1). No pain and stiffness in the joints, phenomena episcleritis and Sjogren syndrome, the dose of prednisolone is reduced by 50%. Clinical efficacy of treatment 70 according to ACR criteria.

Presents clinical example shows that in a patient with treatment-resistant methotrexate RA was marked by a distinct positive effect in the combination therapy is already on the stationary phase. Side effects were observed. In addition, the patient in the treatment process failed 2 times to reduce the daily dose of prednisolone.

Example 2: the Patient, 44 years of age, medical history 5998. Admitted to the hospital 20.12.2000, with a diagnosis of Rheumatoid arthritis, arthritis with systemic manifestations such as anemia, seropositive, slowly progressive course, activity grade II-III stage, FNS II. Steroidogenesis.

Was admitted with complaints of pain and swelling in the small joints of the hands and feet, wrist, ankle, morning stiffness about 5 hours, and General weakness.

The experience of the disease 20 years. In the last 3 years takes methotrexate 7.5 to 10 mg per week with insufficient effect, and therefore a year ago to therapy was added prednisolone 10 mg/day.

In the hospital the patient would be the end of inpatient treatment joint pain decreased significantly, the number of painful and swollen joints decreased by more than 50%, vanished morning stiffness (table.2). The dose of prednisolone was reduced by half.

At discharge from hospital the patient was assigned to methotrexate 10 mg per week inside and prospidin 200 mg / week in/m When observed by 6 months of treatment of pain and stiffness in the joints no, ESR=10 mm/hour, CRP 2 mg/ml, RF is not detected. NSAIDs and prednisone does not accept. The effectiveness of the treatment is estimated more than 70% ACR criteria. The condition of the patient within the last 3 months is regarded as the remission according to the criteria ARA

This clinical case shows that a patient with a long experience of RA refractory to therapy MT with steroidogenesis was obtained a good response to combination therapy MT and prospidina on the stationary phase, which persisted during maintenance therapy. Side effects are not registered. In addition, the patient was able to cancel NSAIDs and prednisone is already over 2 months of therapy.

In General, the results of testing and clinical examples demonstrate the high efficacy, good tolerability and low toxicity of combination therapy MT and prospidinom. The wedge is a good General results of treatment by 6 months of therapy (25% of patients - remission in 75% of patients improved more than 50% in ACR), a noticeable reduction of the daily requirement of corticosteroids in the case of steroidogenesis.

The authors carried out a comparative analysis of combination therapy MT and prospidine and monotherapy MT in equal treatment time in comparable groups of patients (table. 3). Compared with monotherapy MT clinical efficacy of combination therapy was expressed at earlier stages of observation (1 month), had a more pronounced anti-inflammatory effect during maintenance therapy (table. 4) and reduced the daily requirement of glucocorticoids in the case of steroidogenesis (PL.5). Monotherapy MT revealed the instability of clinical effect in relation to articular syndrome, which required increasing the daily dose of prednisolone (table.5).

Compared with monotherapy MT combination therapy MT and prospidina did not lead to the increase in the frequency of side effects and the withdrawal of treatment due to drug toxicity was not observed discontinuation of therapy because of a lack of effect (table.6).

Thus, in comparison with existing treatments proposed method differs earlier and more pronounced to the wives to the end of inpatient treatment, was preserved during maintenance therapy. The proposed method can significantly reduce the daily requirement for steroids if steroidogenesis and to achieve remission in a larger number of patients (table.4, 5). There is no increase in the frequency and severity of side effects and related cancellations (PL.6).

During the information and patent search by the authors in the available literature is not found similar developments.

Scope: the rheumatology Department of the regional, city and district levels.

Literature

1. Benenson E. Century, the Germans of the Baltic Fleet "Antirheumatoid tool prospidin". A. C. the USSR 1235502, 1986.

2. Mashkovsky M. D. Medicines. - 12th ed. - 1993. T. II. - C. 502-504.

3. E. L. Nasonov, S. K. Solovyov. The use of methotrexate in rheumatology, Moscow, 2000, 128 S.

4. B. F. Nemtsov, E. C., Benenson, O. C. Thymine. "Comparative efficacy of pulse therapy prospidine and methotrexate in rheumatoid arthritis (12-month controlled study)". // Clinical medicine, 8, 1998, S. 25-28.

5. J. A. Sigidin, G. C. Lukin. "Basic (pathogenetic therapy of rheumatoid arthritis", Moscow, 2000, S. 100 - prototype.


 

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