Instructions for use Arava tablets 10 mg 30 pcs

Arava should only be prescribed to patients after a thorough medical examination. Before starting treatment with Arava, you must be aware of the possible increase in the number of side effects in patients who have previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects. The active metabolite of leflunomide, A771726, has a long half-life, usually ranging from 1 to 4 weeks. Due to the long half-life of leflunomide's active metabolite, A771726, serious adverse effects (e.g., hepatotoxicity, hematoxicity, or allergic reactions, see below) may occur or persist even if leflunomide treatment is discontinued. In this case, a “washing” procedure should be carried out. The procedure can be repeated according to clinical indications. If severe immunological/allergic reactions such as Stevens-Johnson syndrome or Lyell's syndrome are suspected, a complete “washing” procedure is mandatory. Therefore, if such cases of toxicity occur or when switching to another basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out a washout procedure (see below).

Liver reactions Because the active metabolite of leflunomide, A771726, is protein bound and eliminated through hepatic metabolism and bile secretion, it is expected that plasma levels of A771726 may be increased in patients with hypoproteinemia. Arava is contraindicated in patients with severe hypoproteinemia or impaired liver function. (see section "Contraindications".). Rare cases of severe liver damage, in some cases fatal, have been reported during treatment with leflunomide. Most of these cases were observed during the first six months of treatment. Although the causal relationship of these adverse events to leflunomide has not been established, and in most cases there were several additional suspicious factors, strict adherence to treatment monitoring recommendations is considered mandatory. ALT levels should be checked before starting leflunomide therapy and then every 2 weeks for the first 6 months of treatment, followed by once every 6 to 8 weeks. There are the following recommendations for adjusting the dosage regimen or discontinuing the drug, depending on the severity and persistence of the increase in ALT levels. If ALT is confirmed to be 2-3 times the upper limit of normal, reducing the dose from 20 mg to 10 mg per day may allow leflunomide to be continued, provided that this indicator is carefully monitored. If 2-3 times the upper limit of normal ALT persists, or if there is a confirmed rise in ALT levels greater than 3 times the upper limit of normal, leflunomide should be discontinued and a washout procedure should be initiated. Due to possible additive hepatotoxic effects, it is recommended to avoid alcohol intake during treatment with leflunomide.

Hematological reactions A complete clinical blood count, including determination of the leukocyte formula and platelet count, should be performed before starting treatment with leflunomide, as well as every 2 weeks during the first 6 months of treatment and then every 6-8 weeks. In patients with pre-existing anemia, leukopenia and/or thrombocytopenia, as well as in patients with impaired bone marrow function or at risk of developing such disorders, the risk of hematological disorders increases. If this type of phenomenon occurs, a “washing” procedure should be used to reduce the level of A771726 in the blood plasma. If serious hematological reactions, including pancytopenia, occur, discontinue Arava and any other concomitant drug that suppresses bone marrow hematopoiesis and initiate a washout procedure.

Concomitant use with other treatments There is currently no information available regarding the concomitant use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), intramuscular or oral gold preparations, D-penicillamine, azathioprine and other immunosuppressive drugs (except methotrexate). The risk associated with the prescription of complex therapy, especially with long-term treatment, is unknown. Since this type of therapy can lead to the development of additive or even synergistic toxicity (for example, hepato- or hematotoxicity), combinations of this drug with other basic drugs (for example, methotrexate) are not advisable.

Switching to other treatments Because leflunomide remains in the body for a long time, switching to another disease-modifying drug (eg, methotrexate) without an appropriate washout may increase the possibility of additional risks even long after switching (eg, kinetic interactions, organ toxicity). Likewise, recent treatment with hepatotoxic or haematoxic drugs (eg methotrexate) may result in an increased incidence of adverse events, so when starting treatment with leflunomide, it is necessary to carefully consider all the positive and negative aspects associated with taking this drug.

Skin reactions If ulcerative stomatitis develops, leflunomide should be discontinued. Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported in patients receiving leflunomide. If skin and/or mucosal reactions occur, you should stop taking Arava and any other related drug and immediately begin a washout procedure. It is necessary to achieve complete elimination of the drug from the body. In such cases, re-prescribing the drug is contraindicated.

Infections It is known that drugs like leflunomide, which have immunosuppressive properties, make patients more susceptible to various types of infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of decreased immunity). Infectious diseases that arise are usually severe and require early and intensive treatment. If a severe infection occurs, it may be necessary to interrupt leflunomide treatment and initiate a washout procedure. Tuberculin-positive patients should be closely monitored due to the risk of reactivation of tuberculosis.

Respiratory tract reactions Rare cases of interstitial pulmonary disease have been reported during leflunomide therapy. Symptoms such as cough and dyspnea may be a reason to stop taking leflunomide.

Blood pressure Blood pressure levels should be monitored before starting treatment with leflunomide and periodically after starting it.

Interactions Caution should be exercised when prescribing drugs metabolized by CYP2C9 (phenytoin, warfarin, tolbutamide), with the exception of NSAIDs (non-steroidal anti-inflammatory drugs).

Recommendations for men There is no data on the risk of fetotoxicity (associated with the toxic effect of the drug on the father's sperm) when using leflunomide in men. Experimental data in this direction have not been carried out. To minimize the possible risk, men planning to have a child should stop taking leflunomide and use cholestyramine 8 g 3 times a day for 11 days or 50 g of powdered activated carbon 4 times a day for 11 days.

Leflunomide (Arava, Elafra, Leflide)

Doctors recognized the need to quickly suppress inflammatory activity early in treatment. The possibility of inhibiting the progression of the disease has been proven.

Doses and treatment regimens for leflunomide were developed taking into account the characteristics of the drug itself based on the results of preliminary testing of three maintenance doses - 5, 10 and 25 mg/day.

The maximum therapeutic effect was obtained when the drug was prescribed at a dose of 25 mg/day. However, when using this dose, there was a tendency to increase the number of adverse reactions.

To maintain optimal effect and the absence of side effects, the daily dose should be 20 mg.

A dose of 10 mg/day is much less effective, but in some patients it still produces a clear clinical effect, so its use is advisable if the drug is poorly tolerated at the usual dose.

The drug is able to remain in the body for a long time, which allows it to achieve the required concentration in a very short time when using high doses at the beginning of treatment. This possibility was implemented in the standard regimen of leflunomide, according to which patients take the drug 100 mg/day in the first 3 days, and then continuously 20 mg/day. It allows you to create a therapeutic concentration of the active substance in the blood during the 1st week of treatment. The use of high saturating doses in the first 3 days of treatment really allows you to get the effect in a relatively short period of time.

Leflunomide is comparable in effectiveness and tolerability to methotrexate and sulfasalazine. Leflunomide is more effective than sulfasalazine.

The rapid action of leflunomide is also confirmed by the results of magnetic resonance imaging.

Leflunomide provides a significantly more significant reduction in the severity of inflammatory changes in the synovium than methotrexate.

As a rule, patients tolerate treatment well. The most common adverse reactions are diarrhea, hair loss and nausea. There are also skin rashes, headache, abdominal pain, increased levels of liver enzymes in the blood, respiratory infections, oral ulcers, and arterial hypertension.

If adverse reactions occur, a temporary or permanent reduction in the dose of leflunomide to 10 mg/day, as well as complete discontinuation of the drug, is possible. The need to discontinue the drug due to adverse reactions occurs on average in 15% of patients.

During treatment, ALT is monitored monthly. If the ALT level increases 2–3 times compared to the upper limit of normal, the study should be repeated and, if the result is confirmed, the dose of leflunomide should be reduced to 10 mg/day. If, despite a dose reduction, a 2-3-fold increase in ALT concentration persists or an increase in this indicator is observed by more than 3 times compared to the norm, treatment should be stopped and a laundering procedure should be carried out, which is performed using activated charcoal or cholestyramine (in the tape there is a post).

In long-term ill patients, a rapid increase in drug concentration may be associated with a high risk of side effects, so it is advisable to start treatment with a maintenance dose (20 mg/day). When using such a gentle treatment regimen, it will take about 7 weeks to obtain a therapeutic concentration of the drug in the blood and clinical improvement will be achieved later.

At the early stage of the disease, it is very important to achieve improvement as quickly as possible. Therefore, they are offered a standard regimen of leflunomide using high doses of the drug in the first 3 days of treatment.

After 16 weeks of treatment, significant positive dynamics are observed on average in 70% of patients. Already in the first 4 months of treatment, leflunomide not only suppresses the activity of arthritis, but also significantly improves the quality of life of patients.

Currently, there are no restrictions on the duration of its use in RA. The improvement achieved in the early stages of treatment often lasts for several years. At the same time, new types of adverse reactions are not detected, and liver function indicators in most patients remain within normal limits.

Choosing a basic drug in the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a severe disabling disease, for the treatment of which it is necessary to prescribe basic drugs as early as possible. Of the drugs used as baseline drugs, the most widely used today are methotrexate (the gold standard for the treatment of RA) and sulfasalazine. Unfortunately, the number and severity of side effects caused by the use of these drugs sometimes exceed the severity of the therapeutic effect. In this regard, the release of new, safer drugs for the treatment of rheumatoid arthritis (RA) is of particular importance at the moment.

The only new first-line drug for the treatment of this pathology, introduced into clinical practice over the past 10 years, is Arava (leflunomide) produced by pharmaceuticals (France). Possessing an original mechanism of action, Arava significantly improves the clinical course of the disease, the functional state of patients and sharply slows down the radiological progression of RA. The results of clinical studies that examined the relationship between the effectiveness and safety of the drug were discussed at a conference dedicated to the prospects for the treatment of rheumatoid arthritis.

Doctor of Medical Sciences, Professor of the Department of Hospital Therapy No. 1 of NMU Oleg Borisovich Yaremenko gave a review of new data on the study of the effectiveness of Arava in the treatment of RA and the safety of its use.

— During the use of Arava in the world (more than five years), hundreds of thousands of RA patients have accumulated vast experience, allowing us to draw informed conclusions about the role of this drug in the treatment of rheumatoid arthritis. The key point in assessing the need for the use of Arava in basic therapy is the benefit-risk ratio of the therapy.

Numerous long-term studies were conducted in this direction, based on the results of which at the end of 2002 the FDA (USA) commission conducted a general analysis. The following sources of information for assessing the effectiveness and safety of Arava were considered:

clinical trials database;
post-marketing studies of combination therapy;
the Aetna database (the largest adverse event database to date);
analysis of Protocare/Pharmetrics studies;
national data bank on RA therapy;
data from the Acute Liver Failure Case Study Group (USA);
analytical database of side effects.

The results of not only clinical, but also post-marketing studies have clearly shown that Arava is a highly effective drug in the treatment of RA. One of the most significant advantages of the drug is the early onset of clinical action, on average 4 weeks after the start of use. In addition, Arava, to a greater extent than other basic drugs, improves the functional state of patients, and this is reflected in the recommendations of the FDA commission, which recorded new indications for prescribing leflunomide for RA, namely, improving the physical condition of patients (increasing functional activity).

Side effects were also considered by this commission, focusing on the issue of hepatotoxicity, which can significantly limit the use of one or another basic drug.

First of all, the frequency of side effects of Arava and traditional drugs for the basic therapy of RA - methotrexate and sulfasalazine - was compared. When compared with methotrexate, it turned out that the incidence of side effects, both general and those involving increased levels of liver enzymes (ALT and AST), was higher with methotrexate. When compared with sulfasalazine, the incidence of adverse liver reactions was approximately the same.

According to the Aetna database, which contains information on more than 40 thousand medical records, the frequency of hepatic side effects among Arava, methotrexate and other disease-modifying drugs, as well as combination disease-modifying therapy (Arava + methotrexate, Arava + DMARD, methotrexate + DMARD) did not differ significantly or was less when using Arava. Complications such as liver necrosis, hepatic coma, non-infectious hepatitis, parenchymal jaundice, liver cirrhosis, increased liver enzymes and other pathological changes were taken into account.

It should be noted that the incidence of severe conditions (acute liver necrosis, non-infectious hepatitis, parenchymal jaundice and cirrhosis) was lower when taking Arava than when using methotrexate and other basic drugs.

Due to the fact that liver transplantation is quite widely practiced in the United States, it is important to study the effect of the use of Arava on the frequency of such operations. It was found that the incidence of liver transplantation among RA patients taking Arava was 2 times lower than when using other basic drugs.

Thus, after analyzing the frequency of side effects, in particular liver complications, the FDA commission came to the following conclusions:

increased levels of liver enzymes are a common side effect of basic RA therapy and amount to 2-4%;
serious side effects of therapy requiring hospitalization are rare, their frequency is about 0.01-0.02%;
the frequency of side effects with Arava therapy is at least no higher than that with other basic drugs for the treatment of RA;
the ratio of the benefits of Arava therapy to the risks of the therapy is favorable.

Thus, Arava is a highly effective basic drug for the treatment of RA; in comparison with methotrexate and sulfasalazine, it is less likely to cause side effects, which indicates a positive benefit-risk ratio and allows Arava to be widely used as a basic drug for RA.

Just six months after the above meta-analysis, many new publications, reviews and meta-analyses, as well as the results of randomized trials, have appeared that confirm or complement the existing information.

In particular, a fairly large study was completed in China (C. Bao, S. Chen, Y. Gu et al.), in which about 500 patients took part. It compared the effectiveness of Arava and methotrexate. It turned out that according to the criteria of the American College of Rheumatology (ACR 20), the number of positive clinical responses to treatment with Arava was slightly higher than to therapy with methotrexate (62.5% compared with 60.1% after three months; 67.2% compared with 61.3% six months after the start of treatment). In this study, the incidence of serious adverse events requiring drug discontinuation was significantly lower with Arava (16.8% compared with 28.2% with methotrexate).

A rather original approach to assessing the effectiveness and tolerability of basic therapy for RA was used by English scientists (F. Wolfe, B. Stephenson, J.-J. Doyle), who chose the following main criteria: the number of cases of changes in the basic therapy regimen (or drug) and the duration of treatment drug. The study lasted 3 years; Arava and methotrexate were used as basic therapy in RA patients.

The therapy changes were as follows:

prescribing another drug as an additional one;
discontinuation of the drug, prescription of another.

The number of cases of changes in basic therapy was 55.5% for Arava and 57.3% for methotrexate, the duration of effective treatment before changing therapy was 15 months for Arava and 14 months for methotrexate.

The press published data from a meta-analysis of controlled clinical trials of the effectiveness and safety of Arava in the treatment of RA (M. Osiri, V. Robinson et al.), which covered 6 clinical studies that included 2044 RA patients. The data obtained confirmed the existing information about the effectiveness and safety of Arava therapy.

In particular, the meta-analysis emphasized:

2 times more patients responded to treatment with Arava after 6 and 12 months according to the ACR 20 criterion compared to the placebo group;
the effect of treatment with Arava develops quickly - within 4 weeks;
Arava improves all clinical parameters and slows the radiographic progression of RA at 6 and 12 months of treatment;
the number of patients dropping out during treatment with Arava is lower compared to the placebo group. In terms of side effects during two years of treatment, Arava is comparable to sulfasalazine and methotrexate.

In 2001, for the first time at the American Congress of Rheumatology, a group of Canadian researchers reported that, according to their data, the effectiveness of Arava in doses of 10 mg and 20 mg was not significantly different, and the number of side effects when using a dosage of 20 mg was slightly higher than when using a 10 mg dosage. To confirm these data, a double-blind randomized study was conducted. It involved 400 patients (83.3% of them women, average age 55.5 years) from 70 centers. The average duration of the disease was 9.6 years, in 92.5% of cases - functional class according to ACR II / III. The double-blind phase lasted 24 weeks.

This study found that the number of patients who responded to treatment according to ACR criteria was approximately the same when using Arava at doses of 10 and 20 mg, both according to ACR 20 criteria (50 and 57%, respectively) and ACR 50 criteria ( 20 and 26%, respectively), as well as ACR 70 (7 and 10%, respectively).

When studying various dosages of Arava, another very important criterion from a clinical point of view was taken into account - the effect of the dosage of Arava on the dose of glucocorticoids. For this purpose, the study included only those patients who started taking glucocorticoids before Arava was prescribed. The following results were obtained: glucocorticoids were canceled in 2% of patients when using 10 mg of Arava and in 7% when using 20 mg; the dose was reduced in 17 and 19% of patients, respectively; an increase in the dose of glucocorticoids was observed in 22 and 7%, respectively.

As for the side effects of Arava at different dosages, no statistically significant differences could be identified, except for an increased incidence of diarrhea and nausea when using Arava at a dose of 20 mg.

This meta-analysis allows us to draw conclusions.

The effectiveness of Arava doses of 10 and 20 mg is almost equal.
The use of Arava at a dose of 20 mg allows, in contrast to a dose of 10 mg, to reduce the dose of glucocorticoids.
Arava at a dose of 20 mg is more appropriate to use in patients with higher activity of the process, that is, with the simultaneous use of glucocorticoids.
Data on the efficacy and safety profile of Arava confirm information obtained in previous international clinical studies.

Judging by the accumulated data, the greatest experience in using Arava in Ukraine is in the clinic of the Department of Therapy, Faculty of Medicine No. 2, Vinnitsa National Medical University. N. I. Pirogov (N. A. Stanislavchuk and S. V. Shevchuk). This clinic conducted an interesting study in which the effectiveness of treatment with methotrexate (9.2 mg/week), Arava (20 mg/day) and Arava (10 mg/day) in combination with methotrexate (7.5 mg) was assessed in three groups of patients. /week). It should be emphasized that this is the fourth study in the world to study the combined effects of Arava and methotrexate and the only study in which such small doses of Arava and methotrexate were used. All previous studies examined the effect of Arava at a dose of 20 mg, methotrexate at a dose of 15 mg.

According to the authors, one month after the start of therapy, the response to treatment according to the ACR 20 criterion was on average 2 times higher in the groups of patients receiving Arava than when using methotrexate alone. There were no significant differences in response to Arava monotherapy and its combination with methotrexate. 2 months after the start of the study, the best response to treatment was obtained when using Arava in combination with methotrexate, the least pronounced effect was observed with methotrexate monotherapy. After 6 months, the effectiveness rates for combined treatment (Arava + methotrexate) increased sharply and were one and a half times higher than those for monotherapy with Arava or methotrexate, the therapeutic response to which remained virtually unchanged.

Approximately the same pattern was observed when using the DAS criterion recommended by the European League Against Rheumatism.

Side effects were most pronounced in the group of patients receiving combination treatment (Arava + methotrexate); the rate of treatment discontinuation in this group due to side effects was 19.5%, which was 2 times higher than the same indicators for methotrexate monotherapy (8.2% ) and Arava (10%). Side effects were mainly diarrhea and elevated liver enzymes.

In addition, the drug was found to have a number of additional clinical and laboratory effects, which allows us to consider expanding the indications for the use of Arava.

Even at the preclinical stage of the study, a significant decrease in the level of uric acid and phosphates in the blood was revealed when using leflunomide. Reducing phosphate levels remains without practical application, since its clinical significance is unclear. Reducing uric acid levels is of great interest. It was to test this phenomenon in a clinical setting that this year Spanish authors (F. Perez-Ruiz, JM-J. Nolla) conducted a study, the results of which indeed confirmed a significant decrease in uric acid levels when using Arava and some time after its discontinuation.

These properties allow the use of Arava in patients with rheumatoid arthritis with concomitant hyperuricemia or gout.

Attempts have been made to use this drug to treat inflammatory joint diseases, as well as systemic connective tissue diseases. It should be considered advisable to prescribe Arava as an adjuvant for spondyloarthropathies (psoriatic arthritis, ankylosing spondylitis), SLE and vasculitis.

The most convincing evidence comes from psoriatic arthritis, which rheumatologists often call the “little brother” of rheumatoid arthritis. Unfortunately, the problem of basic therapy for psoriatic arthritis is even more complex than for rheumatoid arthritis. The effect of the main drugs (sulfasalazine, methotrexate, cyclosporine, azathioprine, gold preparations) is extremely low in the presence of articular syndrome in the psoriasis clinic.

To date, only two open studies have been conducted to study the effectiveness of Arava in the treatment of psoriatic arthritis (Liang and Scarpa). Their results are as follows:

Liang: improvement in all criteria after using Arava at a dose of 10-30 mg per day for 23 months.
Scarpa: improvement in arthritis but no effect on skin after 3 months.

A randomized, blind study (Treatment with Leflunomide in Psoriatic Arthritis, TOPAS) was also completed - a multicenter, double-blind, placebo-controlled study in which Arava was used to treat patients with psoriatic arthritis for 6 months according to the following regimen: 100 mg per day for 1- 3 days, then 20 mg per day. The results of this study showed that in 188 patients who received Arava, improvement in PsARC response criteria was observed in almost 60% of cases, which is 2 times higher than in the placebo group. According to the modified ACR criteria, the same pattern was revealed: Arava was effective in 36.3% compared to 20% when taking placebo.

Positive changes in articular syndrome with the use of Arava were reflected in the physical condition of patients, which improved 4 times compared to placebo.

Almost half of the patients experienced improvement in a number of other (non-articular) manifestations of psoriasis, which was 2 times greater than the placebo effect. In particular, there was a positive effect on the condition of the skin and mucous membranes, which none of the basic drugs has provided so far.

Side effects were consistent with those previously reported, with a slightly higher incidence of diarrhea. This may be explained by the more stringent diagnostic criteria in the study, since a higher rate was also observed in the placebo group.

The TOPAS study led to the following conclusions:

Arava demonstrated superior efficacy compared to placebo in the treatment of patients with psoriatic arthritis;
when treated with Arava, both joint and skin manifestations of the disease improve;
Arava has an acceptable safety profile and is generally well tolerated by patients.

Numerous studies on the experience of using Arava in clinical practice have shown its high effectiveness, comparable to the effectiveness of traditional basic drugs, as well as acceptable safety indicators for its use, which allows us to recommend the drug for the basic treatment of rheumatoid arthritis, as well as other diseases, in particular psoriatic arthritis. The drug enjoys well-deserved attention from practitioners all over the world, which was once again proven by an interactive survey of rheumatologists organized at the EULAR Congress in 2003 (in Lisbon). According to this survey, 74% of rheumatologists use Arava (leflunomide) for combination therapy for rheumatoid arthritis and 57% for the treatment of psoriatic arthritis.

The data presented in the review report by Oleg Borisovich Yaremenko was confirmed and supplemented by the experience of using leflunomide by Ukrainian clinicians at the Institute of Cardiology named after. N.D. Strazhesko, who was presented by an employee of the institute, Elena Alekseevna Garmish.

— The purpose of the study conducted at the Institute was to evaluate the effectiveness and safety of the use of leflunomide for 12 months in patients with rheumatoid arthritis.

To assess the effectiveness of treatment, we used: ACR remission criteria; articular (SI), pain (BI) and inflammatory (VI) Ritchie indices; the duration of morning stiffness was determined; the patient's functional ability according to the Lee, HAQ indices; number of erosions according to radiography and MRI; changes in the synovium according to MRI.

The study included 19 patients, average age 45.4 years, with the following characteristics of the course of RA:

The duration of the disease was more than 2 years in 14 patients (group II) (on average 5.5 years); in only 5 patients (group I) - less than 2 years (average 6.8 months);
X-ray stage I of the disease - in 5 patients; II - in 8 and III - in 7 patients;
I degree of disease activity was present in 3 patients; II - in 9 and III - in 7 patients;
All patients took NSAIDs according to the standard regimen; 90% of patients needed corticosteroids.

Leflunomide (Arava) was used at a dose of 100 mg per day for the first 3 days, then 20 mg per day for a year.

According to ACR criteria, convincing data on the effectiveness of Arava were obtained: according to ACR 20 criteria, the proportion of responders to therapy increased from 57% after the first month of using the drug to 72% at the end of the year; according to ACR 50 criteria - from 31 to 55%, respectively; response to therapy according to ACR 70 criteria appeared in the 3rd month and increased from 5 to 27% by the end of the year.

When assessing the dynamics of the number of swollen and painful joints, the following data were obtained: the number of painful joints decreased by an average of 69%, swollen joints by 76%, while the response in group I patients (that is, with a shorter duration of the disease) was much more pronounced.

Due to the decrease in pain and swelling of the joints, their functional activity increased, it improved by an average of 45%, which was more pronounced in group I patients.

The positive effect of Arava was also noted in relation to the dynamics of pain and RA activity according to VAS, as well as when analyzing other indicators. In particular, the Ritchie indices, which reflect the increase in the rate of effect of the drug, show that by the end of the first month of taking Arava, its effectiveness is about 40%, which gradually increases and is maintained until the 12th month. In accordance with this, the Lee index, which reflects the patient's disability, decreases.

The effectiveness of Arava was assessed by the number of bone erosions. Before Arava’s appointment, according to X-ray data in group I, only one case of erosion was noted (in the wrist area), according to MRI - 20 erosions, most of them in the bones of the wrist. In group II, 24 erosions were identified using radiography, and 113 erosions using MRI in all anatomical areas (the predominant number were in the bones of the wrist). Joint effusion was also detected in 8 patients and tenosynovitis in 3 patients.

The results of instrumental research methods after 12 months of using Arava showed:

according to X-ray examination, no increase in the number of erosions was registered;
according to MRI data, in 6 out of 10 patients the dynamics of erosion stopped, in 4 the contour of erosion changed (became clearer, which was regarded as stabilization of the process);
the thickness of the synovial membrane decreased from 5±1.9 to 2.47±0.7 mm;
Joint effusion and tenosynovitis were absent in all patients.

The effect of Arava on the need for NSAIDs and corticosteroids deserves special attention. After treatment, 55% did not need to take NSAIDs, 44% of patients did not need corticosteroids; By the 12th month of using Arava, 5 patients in group I and 3 patients in group II were completely stopped taking NSAIDs and corticosteroids; in the remaining patients, the dose of corticosteroids was reduced.

We continue to monitor 7 patients who have been continuously taking Arava for 2 years. They do not need to use corticosteroids; they occasionally take NSAIDs. The effectiveness of Arava in all patients also does not decrease in comparison with what was achieved by the 12th month of the study.

The drug was discontinued in only one patient due to exacerbation of bronchial asthma (but we do not associate this directly with the effect of this drug). Among the side effects, gastrointestinal disorders were observed in the form of increased motility, some loosening of stools and nausea (2 patients), hair loss (2 patients), leukopenia (1 patient). Therefore, in 2 patients (with leukopenia and gastrointestinal pathology), the dose of Arava was reduced to 10 mg per day.

An interesting case of a decrease in proteinuria in one of the patients who was prescribed Arava with proteinuria of 9.9 g/l, which developed as a result of taking another drug. By the end of the year, the patient's proteinuria level decreased to 0.66 g/l, and a pronounced anti-inflammatory effect was observed.

Based on these data, we can conclude that Arava (leflunomide) is a highly effective drug in the treatment of rheumatoid arthritis at all stages of the disease, the therapeutic effect of which is stable throughout the entire treatment period. Considering the relationship between the effectiveness and safety of leflunomide, Arava can be recommended for the basic treatment of rheumatoid arthritis, both in monotherapy and in combination with methotrexate or sulfasalazine.

Source of information: https://www.esus.ru

The article was published on the website https://www.rusmg.ru