Seropositive rheumatoid arthritis - symptoms and choice of therapy

Etiology

The reasons for the development (etiology) of RA have not been definitively established. It is believed that the disease is based on two factors:

genetic
– hereditary predisposition to autoimmune processes, which is confirmed by frequent family diseases;
infectious
– past viral infections; for example, Epstein-Barr virus, which causes infectious mononucleosis.

The risk of developing RA increases under the influence of the following triggers: hypothermia, stress, hormonal imbalances, injuries, living in a cold, humid climate, etc.

Causes and risk factors

To date, it has not been possible to establish the exact causes of the development of rheumatoid arthritis. There are theories whose supporters claim that the disease occurs under the influence of the following factors:

Genetic mutations;
Hormonal dysfunction;
Impact of adverse environmental factors.

Scientists identify the main factors that provoke the development of rheumatoid arthritis: smoking, dysbacteriosis.

Most patients with rheumatoid arthritis secrete a specific antigen LA-DR4. But the fact of its detection does not indicate that a person will necessarily develop an autoimmune disease. However, the presence of the antigen increases the risk of rheumatoid arthritis.

Residents of environmentally polluted cities are more likely to suffer from rheumatoid arthritis. There is a connection between hormonal levels and periods of exacerbation of rheumatoid arthritis. This confirms the fact that women suffer from this disease more often than men. The following external factors play a role in the occurrence of the disease:

Epstein–Barr virus;
Retroviruses;
Parvovirus B19;
Antigens and stress proteins of bacteria;
Smoking;
Chemical compounds;
Coal dust;
Medicinal substances.

The development of the disease can be provoked by endogenous factors - citrullinated proteins and peptides. They take an indirect part in the development of rheumatoid arthritis against the background of genetic predisposition. The risk of developing the disease is associated with the carriage of antigens.

Researchers are working on a version that the human microbiome can provoke the onset of rheumatoid arthritis. Microbiome is the totality of all opportunistic microbes that inhabit the human body. It is believed that their activities can negatively affect many processes, including the immune system. Despite this assumption, definitive evidence indicating a link between infections and rheumatoid arthritis has not yet been identified.

Expert opinion
Author: Elena Yurievna Panasyuk
Rheumatologist, doctor of the highest category, member of the Association of Rheumatologists of Russia
According to global statistics, rheumatoid arthritis is diagnosed in 40 people per 100 thousand population. The majority of cases are women. In 50-70% of cases, disability is observed several years after diagnosis. These data suggest that rheumatoid arthritis is a common degenerative autoimmune lesion of the musculoskeletal system.
The uncontrolled course of rheumatoid arthritis is dangerous due to possible complications. The spread of the pathological process often affects the cardiovascular and respiratory systems. Mortality due to rheumatoid arthritis increases depending on the stage of the disease. At later stages of development, the ability to self-care is lost, and associated complications appear. The share of deaths from infections associated with rheumatoid arthritis accounts for ¼ of cases.
At the Yusupov Hospital, neurologists use CT, MRI and X-ray to diagnose rheumatoid arthritis. Research is carried out using modern and precise equipment. In this way, it is possible to diagnose the disease in the initial stages. In accordance with the data obtained, individual therapy is prescribed.

Pathogenesis of seropositive arthritis

The mechanism of development of seropositive arthritis (pathogenesis) is associated with a breakdown of the immune system. It develops this way:

Normally, the body produces antibodies in response to infection; these are protein compounds - immunoglobulins (Ig), the purpose of which is to connect with an infectious pathogen (antigen) and neutralize it;
in RA, altered Igs are produced, the immune system does not recognize them, mistakes them for foreign particles (antigen) and produces antibodies to them, which are called rheumatoid factor (RF); the resulting antigen-antibody complexes are deposited in tissues, maintaining inflammation and destroying articular surfaces;
inflammation and tissue damage are also maintained and progressed due to the production of excess amounts of pro-inflammatory (inflammation-supporting) cytokines - molecules that normally transmit information and regulate inflammatory reactions along with anti-inflammatory cytokines.

In the seropositive form of arthritis, rheumatoid factor is detected in the blood, and in the seronegative form it is either absent or present in insignificant quantities. Why this happens has not been established.

The inflammatory process first causes swelling of the periarticular tissues, including the inner surface of the joint capsule, the synovial membrane, becoming inflamed and swollen. The next stage is the growth of connective tissue cells in it - pannus. The pannus covers the articular surfaces of the bones, destroys cartilage and bone tissue, then grows into the joint space and closes with the opposite side, making the joint immobile (ankylosis).

Symptoms of seropositive arthritis

Seropositive rheumatoid arthritis usually has a gradual onset. Less commonly, the onset may be subacute, with more severe symptoms. But in any case, the disease is steadily progressing, so it is very important to identify it as early as possible and begin treatment.

First signs

The very first symptoms of seropositive rheumatoid arthritis that you should pay attention to are:

malaise, weakness, increased fatigue;
slight increase in temperature (may not be);
morning stiffness that lasts about half an hour is one of the most important signs of seropositive arthritis
symmetrical damage to 3 or more slightly painful small joints with slight swelling of the hands or feet; a positive transverse compression test of the hand or foot—pain appears; this is the main clinical difference between seropositive arthritis and seronegative arthritis, in which 1–2 large joints are initially asymmetrically affected;
vague muscle pain.

Clear signs

Symptoms of seropositive arthritis

Signs of seropositive rheumatoid arthritis with further development of the disease are divided into articular and extra-articular.

Any form of arthritis has serious complications, so you should not delay treatment.
See how easily the disease can be cured in 10-12 sessions.

Articular signs of seropositive RA are symmetrical damage to the small joints of the fingers and hands and similar changes on the feet:

stiffness of movement in the morning for at least an hour;
symmetrical damage to 3 or more small joints of the hands and feet; the affected joints are painful, swollen, deformed, while various pathological processes may predominate in nearby areas: inflammation or deformation;
fingers are deformed in the interphalangeal areas and may acquire a spindle-shaped shape;
subluxations develop, the hands turn outward and look like “walrus flippers”;
with arthritis, hammer-shaped toes appear, flat feet, the feet are turned outward - foot valgus;
Less commonly, large joints (knees, elbows, wrists) may be involved in the process.

Chondroprotectors: what are they, how to choose, how effective are they?

Joint pain at rest

Extra-articular signs of seropositive RA:

skin - the appearance of small painless subcutaneous formations - rheumatoid nodules;
enlarged, painless lymph nodes;
low hemoglobin (anemia) with dizziness and headaches;
decrease in volume (atrophy) and muscle soreness;
ulcerative-necrotic lesions of the skin and nails due to inflammation of the walls of blood vessels - systemic vasculitis;
pain along the nerves;
damage to internal organs: heart (pericarditis), lungs (pleurisy), kidneys (glomerulonephritis);
enlarged liver and spleen;
the patient is exhausted, depression increases.

One of the forms of long-term seropositive arthritis is Felty's syndrome. The clinical picture is characterized by a decrease in the number of leukocytes in the blood, which significantly increases the risk of infection, enlargement of the liver and spleen, and damage to internal organs. It is rare and has a severe course.

Without timely treatment, seropositive rheumatoid arthritis leads to severe complications:

osteoporosis due to bone loss of calcium;
aseptic (without infection) necrosis (death) of the articular surfaces of the arms and legs;
subluxations, dislocations and fractures;
pinched nerve trunks and severe pain;
skeletal muscle atrophy;
complete exhaustion;
amyloidosis - deposition in the internal organs of amyloid - a substance that disrupts their function; occurs rarely in seropositive arthritis.

Seropositive arthritis of the knee

basic information

Rheumatoid arthritis results from changes in the body's immune system that (for unknown reasons) attack the soft tissue of the joints, causing inflammation, swelling and pain. If the process continues, damage to the cartilage and other soft tissues can lead to joint deformities.

In a healthy joint, cartilage evenly covers the bone, acting as a cushion and allowing the bones in the joint to slide smoothly over each other. The joint is contained in a joint capsule, which is lined with synovium (synovium). The synovium produces synovial fluid, a clear fluid that lubricates and nourishes the joint. The surrounding muscles, tendons and ligaments support the joint, allowing it to move smoothly and without pain.

Rheumatoid arthritis causes inflammation and thickening of the usually thin synovium, which leads to the accumulation of synovial fluid and causes pain and swelling. In addition, the cartilage and bones inside the joint can be damaged and destroyed, leading to loss of function and joint deformity.

Rheumatoid arthritis can affect any joint in the body, but usually affects the small joints in the hands and feet. As the disease progresses, other, larger joints may be affected. Joints are usually affected symmetrically (both the left and right sides of the body).

The condition can develop at any age, although it is most likely to develop between the ages of 25 and 50.

Stages of the disease

Seropositive rheumatoid arthritis has 4 stages of development:

The initial stage
is the development of the disease lasting up to 6 months; The main symptom is morning stiffness.
Early stage
– from six months to a year; the symptoms of polyarthritis are more pronounced, significant swelling of the joint tissues appears.
Advanced stage
– from one to two years with all clinical manifestations.
The late stage
– more than two years, is accompanied by joint deformities, contractures, disability and complications from internal organs.

Radiological stages of seropositive arthritis:

Development of osteoporosis of the articular surfaces of bones.
Narrowing of the joint space, the beginning of the destruction of cartilage tissue.
Significant destruction of cartilage and bone tissue of articular surfaces, deep erosion; subluxations;
Closing of the joint space and the formation of ankylosis - immobility of the limb.

Crunching in joints - when to worry

Intra-articular injections of hyaluronic acid

Diagnostics

The diagnosis of seropositive rheumatoid arthritis is made on the basis of characteristic clinical signs and is confirmed by:

Laboratory research:
biochemical blood test - increasing the level of C-reactive protein (CRP) - a blood plasma protein that signals the presence of inflammation;
immunological tests:
determining the presence of rheumatoid factor;
detection of anti-citrullinated antibodies (ACCP) - may appear earlier than RF, at the initial stage of development, therefore they are an early diagnostic sign;
detection of increased blood levels of pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha).
Instrumental research:
MRI
– early (pre-radiological) disorders are detected;
Ultrasound
reveals changes in periarticular tissues and a decrease in the volume of synovial fluid.

Treatment of seropositive arthritis

Currently, all specialists adhere to the tactics of early detection and active treatment of seropositive RA. This tactic allows in most cases to avoid disability and maintain a decent quality of life.

The main method of treating seropositive arthritis is drug therapy, other methods are of auxiliary value. This includes diet, physiotherapeutic procedures, therapeutic exercises, massage, folk and homeopathic remedies.

Drug treatment

Treatment of seropositive arthritis

Seropositive rheumatoid arthritis begins to be treated as early as possible, using several medications at once - symptomatic and basic.

Symptomatic drugs include medications that eliminate joint inflammation and pain, but do not act on the mechanism of disease development (pathogenesis). They are prescribed in short courses to eliminate acute symptoms of seropositive RA. This:

Nonsteroidal anti-inflammatory drugs (NSAIDs):
Nimesulide
is a more modern effective drug that has a minimum of side effects; prescribed orally in tablet form.
Glucocorticosteroid hormones (GCS - Prednisolone, Dexamethasone, Betamethasone) eliminate symptoms even faster, but have many side effects and require constant increase in dosage. Prescribed strictly according to indications in short courses, including injection into the joint cavity.

Basic drugs include medications that have a strong effect on the pathogenesis of the disease. They are prescribed in long courses, periodically checking the effectiveness of therapy with diagnostic tests. Such drugs include:

Basic anti-inflammatory drugs (DMARDs)
– Methotrexate, Sulfasalazine, Leflunomide. Suppress autoimmune processes, prescribed in long courses in the form of injections or oral administration; 2nd line drugs of this group, the use of which is not always practiced, include Tauredon (a gold drug), which suppresses immune processes and inflammation.
Genetically engineered biological drugs (GEBD, biological agents)
- this includes the most modern group of drugs (Infliximab, Tocilizumab, Abatacept, Rituximab) they contain antibodies to pro-inflammatory cytokines or suppress the functioning of certain parts of the immune system. Prescribed as part of complex drug therapy, sometimes causing allergic reactions.

Additional treatment methods

The attending physician may also include in the complex therapy of seropositive arthritis to alleviate the patient’s condition:

homeopathic and folk remedies;
physiotherapeutic procedures;
procedures for blood purification - plasmapheresis, hemosorption;
courses of physical therapy (physical therapy) and massage - physical activity is necessary, as it is the prevention of deformities and contractures;
in case of irreversible changes in the joints and their destruction in the later stages, when therapeutic measures have proven ineffective, refer the patient for surgery.

Treatment

Rheumatologists at the Yusupov Hospital provide combination therapy for rheumatoid arthritis. Doctors at the therapy clinic use medications, diet, exercise and surgery. When treating rheumatoid arthritis, doctors at the Yusupov Hospital undertake the following goals:

Reducing or eliminating symptoms of the disease;
Slowing down or preventing destruction, deformation and dysfunction of joints;
Improving the quality of life of patients;
Achieving sustainable remission of the disease;
Reducing the risk of developing diseases that have a similar development mechanism;
Increasing the life expectancy of patients.

After a diagnosis of rheumatoid arthritis is made, the patient is explained that this is a serious chronic disease that he will have to live with. For this reason, the patient needs to participate in the treatment process. This largely determines the success of treatment.

Doctors at Yusupov Hospital use a multidisciplinary approach. It is based on the use of non-pharmacological and pharmacological treatment methods, the involvement of specialists from other specialties (physiotherapists, orthopedists, cardiologists, neurologists, nephrologists, psychologists). If the patient does not have serious joint deformities, his ability to work remains, but significant physical activity is contraindicated for him.

Patients are advised to avoid factors that can provoke an exacerbation of the disease, stop smoking and limit alcohol consumption. In order to maintain optimal body weight, nutritionists at the Yusupov Hospital are developing a balanced diet. The diet includes foods high in polyunsaturated fatty acids (olive oil, fish oil), vegetables, and fruits.

Rehabilitation clinic specialists develop an individual complex of physical therapy, which is aimed at strengthening the muscular system. It includes swimming, walking, cycling. Physiotherapy for rheumatoid arthritis is applied after an in-depth assessment of the patient's condition. Orthopedic methods are used aimed at the prevention and correction of joint deformities and instability of the cervical spine. It should be emphasized that non-drug treatments for rheumatoid arthritis have a moderate and short-term beneficial effect. They do not affect the progression of the disease.

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Drug treatment

Rheumatoid arthritis is one of the most difficult diseases to treat. The chronic course of the pathology is characterized by periodic relapses and remissions. The main goals of drug therapy are to relieve exacerbations and reduce the rate of disease progression. If medications are ineffective, surgery is performed.

Doctors use the following medications to treat rheumatoid arthritis:

Disease-modifying antirheumatic drugs (DMARDs);
Nonsteroidal anti-inflammatory drugs (NSAIDs);
Glucocorticoids.

For rheumatoid arthritis, basic therapy is carried out with methotrexate, leflunomide, hydroxychloroquine and sulfasalazine. Less commonly prescribed are azathioprine, D-penicillamine, gold salts, cyclosporine and minocycline. BMAPs can reduce or prevent joint damage and preserve joint function and structure. Basic therapy for rheumatoid arthritis allows one to obtain good control over the clinical manifestations of the disease, improve joint function, the patient’s quality of life, and slow down or stop the formation of erosions. Before starting therapy, doctors at the Yusupov Hospital inform patients about the possible side effects of drugs used in the treatment of rheumatoid arthritis.

Painkillers for rheumatoid arthritis quite quickly and effectively eliminate joint pain and swelling, improve joint function, and reduce morning stiffness. Nonsteroidal anti-inflammatory drugs provide these beneficial clinical effects. Having high analgesic and anti-inflammatory activity, NSAIDs are not able to modify the course of the disease and prevent joint destruction. In this regard, rheumatologists do not use them as independent therapy in patients with rheumatoid arthritis.

In the treatment of rheumatoid arthritis today, exclusively synthetic glucocorticoids are used. They have pronounced immunosuppressive and anti-inflammatory activity with minimal or even zero mineralocorticoid effects. Patients tolerate methylprednisolone better. It is the drug of choice for patients with arterial hypertension, unstable mental health, excess body weight and a predisposition to ulcerative lesions of the gastrointestinal tract.

When treating rheumatoid arthritis, doctors at the therapy clinic use the following options for using glucocorticoids:

Local (intra-articular and periarticular);
Local (cutaneous) in the form of an ointment;
Systemic (orally, intramuscularly or intravenously).

In the absence of the effect of basic therapy, rheumatologists prescribe biological drugs to patients suffering from rheumatoid arthritis. These are medicines that are obtained using genetic engineering methods. Their targets are key proinflammatory cytokines, their receptors and immunocompetent cells.

Important advantages of immunobiological agents are their relative safety and high specificity, which ensures selectivity of influence on specific parts of immunopathogenesis with minimal impact on the normal mechanisms of functioning of the immune system.

Doctors at the Yusupov Hospital take an individual approach to the choice of drug therapy for rheumatoid arthritis. This allows you to select treatment in accordance with the stage of development of the disease, the presence or absence of concomitant pathologies. In their work, doctors at the Yusupov Hospital are guided by national and European standards for the treatment of rheumatoid arthritis.

Exercise and Weight Stabilization

Treatment of rheumatoid arthritis is not complete without weight stabilization. To do this, you need to change your lifestyle. For patients diagnosed with rheumatoid arthritis, rehabilitation specialists select a load that will have a positive effect on the joints without overloading them. You should limit the duration of a static position and swim in the pool.

Doctors have developed 5 basic nutritional rules that must be followed when diagnosed with rheumatoid arthritis:

Exclusion from the diet of highly allergenic foods. It has been noted that citrus fruits, chocolate, whole milk, oatmeal, pork, nightshades and rye increase the frequency of exacerbations of rheumatoid arthritis;
Limit or completely exclude meat products. It has been proven that after switching to a dairy-plant diet, more than 40% of patients noted an improvement in their condition;
Eating enough vegetables and fruits. These products contain a sufficient amount of phytochemicals that have anti-inflammatory and analgesic effects;
Eating gentle foods. Treatment of rheumatoid arthritis involves prescribing a sufficient number of medications that affect the gastrointestinal tract. In this regard, it is recommended to limit the intake of fatty, spicy, hot, smoked foods. It is necessary to limit the intake of strong tea or coffee. Products must be prepared by stewing, boiling or baking;
Including calcium-rich foods in your daily menu. Glucocorticosteroids help flush the element out of the body. Therefore, soybeans, sesame seeds, fermented milk products, and leafy greens are added to the diet.

Compliance with the above principles will minimize the risks of exacerbation of rheumatoid arthritis and normalize weight.

Approach to the treatment of seropositive arthritis in our clinic

We combine proven techniques of the East and innovative methods of Western medicine.
Read more about our unique method of treating arthritis

Specialists at the Paramita clinic in Moscow have extensive experience in treating seropositive rheumatoid arthritis. A patient who seeks help for the first time is first given a full examination and only then is prescribed a course of therapy, the peculiarity of which is a combination of the most modern Western and traditional Eastern, time-tested techniques. Treatment measures are selected for each patient strictly individually. Their effectiveness is periodically assessed. Our methods (how we treat):

drug therapy with the inclusion of the latest drugs, herbal medicine, folk and homeopathic remedies; this combination allows you to carry out the course faster, more efficiently and reduce the drug burden on the patient;
physiotherapeutic procedures - prescribed depending on the stage of the disease and the general condition of the patient;
kinesitherapy, taping, complexes of therapeutic exercises and medical massage - the most effective treatment methods are used to maintain limb mobility, all procedures are prescribed by a doctor and carried out under the supervision of a physical therapy instructor;
PRP therapy is the latest method that allows you to quickly restore lost motor functions; is based on stimulating the regenerative properties of the body with the patient’s own blood platelets, processed using special techniques;
reflexology (RT) - the impact of acupuncture, moxibustion, acupressure on acupuncture points (AP) on the body, reflexively associated with internal organs and tissues; the doctors of our clinic are proficient in all RT methods, as they were trained in China and Tibet;
pharmacopuncture – introduction of modern highly effective drugs into AT.

Treatment of seropositive arthritis in the clinic

Doctors at our clinic not only relieve, but also prevent exacerbation of seropositive arthritis by regularly carrying out anti-relapse measures. As a result, patients are free from exacerbations for a long time and have a high level of quality of life.

About arthritis

Arthritis is a disease that is triggered by infection, a malfunction of the immune system or metabolism. The main sign of arthritis is the inflammatory process: swelling, redness of the skin and increased temperature in the area of the affected joint. The negative effects of arthritis can extend beyond the joints: the heart, kidneys and liver are at risk.

200	25-40	18%
There are more than two hundred types of arthritis: with different manifestations and causes	Young and middle-aged people are at risk	Arthritis accounts for the most disabilities according to WHO statistics

Symptoms

The first signs of the disease, as a rule, are:

sharp pain - during movement or rest,
swelling in the area of the affected joint - constant or recurring,
redness and increased temperature of the affected area - can be felt by touch,
stiffness of movement in the morning.

Arthritis can occur in a latent form - in this case, symptoms appear after exposure to provoking factors: stress, overwork, hypothermia or infection.

Symptoms also include manifestations of the inflammatory process in the body:

increase in body temperature to 38-39 degrees;
loss of strength and chills;
conjunctivitis;
changes in blood test values: for example, increased ESR and high leukocyotosis;
pain when urinating.

The severity of arthritis can vary, and progress is not necessarily rapid. However, if you do not pay attention to the problem, arthritis becomes chronic and can lead to disruption of internal organs and disability: incapacity, modification of joints and limbs.

Treatment and prevention

The prescribed treatment will depend on the severity of the diagnosis. If during diagnosis the patient does not have damage to internal organs, treatment is relatively simple. The patient may be prescribed:

anti-inflammatory and painkillers,
physiotherapeutic procedures,
diet and abstinence from alcohol,
reducing physical stress on the affected joint.

In cases where the disease has affected the organs, the patient undergoes an additional treatment program to the main one aimed at supporting them:

additional examinations,
drug therapy,
special diet.

Among the various forms of arthritis, there are some serious diseases that are important to diagnose in time:

Rheumatism is an inflammatory disease of connective tissue that affects large and medium-sized joints, and also has specific manifestations: it can manifest itself sharply and pass on different joints, as if moving from one to another.

Rheumatism does not deform the joints, but lack of treatment is fraught with serious complications: for example, kidney disease and heart disease.

The cause may be previous infectious diseases: sore throat, otitis media and the like. Children aged 7 to 14 years are most often at risk. Heredity also influences the development of the disease.

Rheumatoid arthritis is a chronic disease in which the inflammatory process affects both joints and many organs. For example, eyes, lungs, heart and blood vessels. Belongs to the group of systemic connective tissue diseases. The disease most often affects women over 60 years of age.

It progresses slowly, affects several joints at once and spreads symmetrically. As the disease progresses, the joints lose mobility, become painful and swollen. Characteristic nodules appear on the joints affected by inflammation.

A feature of rheumatoid diagnosis is the use of special laboratory tests that allow an accurate diagnosis to be established. Rheumatoid arthritis is difficult to treat, using potent drugs. Therefore, it is very important to suspect and diagnose this disease in the early stages.

Gouty arthritis or gout is a progressive joint disease that occurs due to disturbances in the metabolism of uric acid in the blood and the deposition of salts in the joint tissues. Most often it begins with damage to the big toes.

Gout usually affects older people, mostly men. But there are also cases of the disease at a younger age.

The treatment of rheumatism, systemic diseases, and gout differs from the treatment of, for example, allergic or reactive arthritis. Only a doctor can make a correct diagnosis and prescribe adequate treatment.

It is easier to prevent a disease than to treat it, so we recommend that you take care of prevention and carefully monitor your health:

give up bad habits - smoking, drinking alcohol, poor nutrition;
develop the habit of rational exercise - exercise, stretching, balanced training;
strengthen the immune system - consult a doctor regarding mineral and vitamin complexes, flu vaccinations.

Prevention of relapses of seropositive arthritis

To live without exacerbations in a state of stable remission, the patient must:

be aware of triggers and avoid them;
lead a healthy lifestyle, engage in exercise therapy;
eat properly regularly, monitor your weight;
Be sure to regularly observe a doctor and, on his recommendation, take courses of anti-relapse therapy.

Well, if an exacerbation does begin, run to the doctor! At the Moscow clinic "Paramita" they know a lot about the treatment of seropositive rheumatoid arthritis!

Literature:

Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In the book. : Rheumatology. National leadership. Ed. E. L. Nasonova, V. A. Nasonova. Moscow: GEOTAR-Media; 2008. pp. 290–331.
Nasonov E.L., Mazurov V.I., Karateev D.E. and others. Draft recommendations for the treatment of rheumatoid arthritis of the All-Russian public organization “Association of Rheumatologists of Russia” - 2014 (part 1). Scientific and Practical Rheumatology 2014;52:477–94.
Molina JT, Garcia FJB, Alen JC, et al. Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes. Rheumatol Clin 2015;11:3-8.
Tornero Molina J, Calvo Alen J, Ballina J, et al Recommendations for the use of parenteral methotrexate in rheumatology. Reumatol Clin 2021. pii: S1699-258X(16)30162-0.
Espinosa F, Fabre S, Pers YM. Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications. Ther Adv Musculoskelet Dis 2016;8:107-18.

Themes

Joints, Pain, Treatment without surgery Date of publication: 04/10/2020 Date of update: 11/12/2020

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Severe variant of rheumatoid arthritis

The course of RA is highly variable. This is due to many reasons. The patient may be resistant to treatment or cannot tolerate it. Delay in prescribing therapy with disease-modifying anti-inflammatory drugs (DMARDs) also worsens the prognosis in RA. In addition, it is known that inflammation in the synovium can begin to develop long before the first clinical symptoms of the disease appear. It is known that serological tests such as rheumatoid factor (RF) and/or antibodies to cyclic citrullinated peptide (ACCP) are detected in the blood of patients with RA several years before the onset of arthritis (up to 10 years) [4] (Fig. 1).

A morphological study of the synovial membrane obtained from patients in the first months of the onset of arthritis showed that not everyone showed signs of acute rheumatoid inflammation; in some patients, clear signs of chronic synovitis were observed already in the first biopsy [5]. It was in these patients that a more torpid variant of RA was observed with a poor response to DMARD therapy. The severity of the condition of a patient with RA at each stage depends on the level of inflammatory activity, which determines the severity of joint pain, stiffness, and functional impairment. With adequate therapy and suppression of activity before the development of irreversible anatomical changes in the joints (destruction, deformation), the function of the joints is restored (Fig. 2). A severe variant of the course of the disease occurs with inadequate or ineffective therapy, and is determined by the degree of persistent loss of the patient’s functional ability not only for professional work, but also for self-care. Therefore, the earliest possible start of anti-inflammatory therapy is of fundamental importance in RA.

In the last decade, diagnostic criteria for the early stages of RA have been introduced into healthcare practice [6] for timely referral of the patient to a rheumatologist and early initiation of therapy. And the emergence of new ACR/EULAR classification criteria in 2010 made it possible to start treatment with DMARDs as early as possible [7]. It is ideal to start DMARD therapy immediately after the first symptoms of inflammation in the synovium appear: morning stiffness, joint pain and swelling, which is reflected in these criteria: the presence of polyarthritis involving small joints has the greatest weight. In practice, a patient with the onset of RA sometimes goes through a long path of consultations and diagnostic measures before meeting with a rheumatologist.

In addition, the onset of the disease may be clinically mild and the symptoms of the disease increase slowly, making it difficult to establish a diagnosis of RA. According to foreign authors [8] and our data [9], with the acute onset of RA, the long-term outcome of the disease is better than with a gradual onset of the disease. Probably, the acute onset of the disease forces the patient to quickly seek medical help, and the doctor in this case quickly determines the diagnosis and begins therapy. Our data indicate a better outcome of RA, assessed after 15 years of disease in terms of the degree of preservation of the function of the musculoskeletal system, the severity of destruction in the joints, the frequency of long-term remissions and patient survival, when DMARDs are prescribed in the first 6 months. from the onset of arthritis symptoms [10].

Delay in initiation of DMARDs results in poorer response to these drugs, as has been shown in controlled trials [11]. Methotrexate is considered the first-line drug; other DMARDs (leflunomide, sulfasalazine) are used at the beginning of treatment if methotrexate cannot be prescribed. DMARD therapy in many patients leads to suppression of the activity and progression of RA, especially when prescribed in the first months of the disease. But starting therapy in a very early period of the disease (1–2 months of illness) does not in all cases allow achieving a pronounced effect (clinical remission or maintaining low RA activity). First, the patient may not respond to DMARDs; secondly, in many patients, the effectiveness of DMARDs decreases after 1–2 years of therapy; in some patients, sequential changes in basic drugs occur due to symptoms of intolerance.

When sequentially prescribed DMARDs are ineffective and/or intolerable, a severe form of RA develops. The most significant parameters for determining the severity of RA are the severity of destructive changes in the joints and the degree of persistent loss of functional ability of the joints, up to the loss of the patient’s ability to self-care.

A large number of randomized clinical trials (RCTs) were devoted to identifying the most effective therapeutic strategies in the treatment of patients with RA: treatment results were compared with sequential monotherapy of DMARDs, with their combination both at the onset of the disease (step-down strategy) and after adding 2- 3rd, 3rd drugs if the first drug is ineffective (step-up strategy). The latest EULAR 2013 recommendations [12] suggest the use of a combination of DMARDs at the onset of treatment, which is based on the results of several randomized open trials [13–15].

A comparative assessment of the effectiveness of monotherapy with methotrexate, sulfasalazine, antimalarial drugs, cyclosporine A, leflunomide and their combinations [16–23] did not show a clear advantage of combination therapy of DMARDs over their use as monotherapy. A number of studies have shown that after 6, 12 and 24 months. the clinical effect was more pronounced when using a combination of DMARDs (either with a “step-up” or “step-down” strategy) [19, 21, 24–28]; according to other authors [29, 30], there were no significant differences in the effect of monotherapy or combination of DMARDs on activity indicators. When the study period was extended (up to 5 years), no advantage was noted in the effect of the combination of DMARDs over monotherapy on the activity of RA [16, 28, 29]. Evaluation of radiological changes in joints after 1–2 years did not show any advantages of combination treatment in the MASCOT study [21], and the combination of cyclosporine A and methotrexate in 2 studies after 6 [31] and 12 [32] months. suppressed the progression of destruction to a greater extent than methotrexate monotherapy. In the FIN-RACo study, the change in Larsen score was significantly less when using a combination of DMARDs after 2 years [19], but after 5 years there were no significant differences between combination therapy and monotherapy [20]. It should be noted that the combination of DMARDs was more effective than monotherapy with different DMARDs only when methotrexate was used in the combination.

In addition, interesting data were obtained when assessing the effectiveness of double combinations of DMARDs with a triple combination: the effectiveness of methotrexate + sulfasalazine, methotrexate + hydroxychloroquine and a combination of all 3 drugs was compared [13]. According to the ACR effectiveness criteria, the triple combination was superior to the double combination, but only in the group of patients who had not previously received methotrexate. In the group of patients previously treated with methotrexate, the effect of the triple combination did not exceed the effect of combined use of methotrexate and hydroxychloroquine.

Very interesting are the data obtained as a result of the TICORA study [17, 33], which compared the results of 18-month treatment of 2 groups of RA patients: in the 1st group, treatment was carried out with strict monthly monitoring of changes in RA activity according to DAS (“tight” control ), and therapy was adjusted in accordance with the dynamics of DAS (“intensive” group). In group 2, treatment was carried out routinely without such strict control. By the end of the study, remission was achieved in 65% of patients in group 1 and only in 16% of patients in group 2. The increase in the number of erosions was less in group 1. Controlled treatment (“intensive” group) was accompanied by more frequent correction of therapeutic tactics (use of a combination of DMARDs, escalation of their dose, use of intra-articular injections of GC). The authors, when analyzing these results, concluded that control of treatment provides the best results, regardless of the choice of DMARDs.

The same conclusion was made by JM Albers et al. [34] when assessing the results of 4 different regimens of using DMARDs: strict control over the success of treatment ensures similar results of therapy with various DMARDs. When evaluating treatment with methotrexate in patients with early RA (disease duration <1 year) in the CAMERA study [22, 23], it was also concluded that strict monthly monitoring of the dynamics of disease activity (“tight” control) and timely correction of therapy can achieve significantly better results over 2-year follow-up period. Thus, in the intensive control group (n=76), the remission rate was 50%, and with the routine treatment (n=55) – 37% (p=0.03) [23]. These data coincide with our opinion, based on the results of a longer open study of the effectiveness of basic therapy in 240 patients: improvement in the outcome of RA (functional state of the joints, X-ray picture) depends not only on the timing of the start of treatment, but also on the degree of continuous monitoring of the progress of treatment [10]. Also, these data created the prerequisites for the development of a modern RA treatment strategy “Treat to target,” when the main goal of treatment is to achieve remission, and the alternative goal is to achieve low RA activity [35].

But even with a competent approach to the treatment of patients with RA in accordance with the treatment strategy “Treat to achieve the goal” introduced in our country with classical DMARDs (early initiation of therapy and constant monitoring of the degree of suppression of activity and progression of the disease), a severe form of RA still develops. According to our data and literature data, in 15–25% of patients, sequentially prescribed DMARDs do not lead to a significant effect (good effect according to EULAR criteria or more than 50% improvement according to ACR criteria) or lead to adverse reactions and the need to discontinue DMARDs. The creation of genetically engineered biological drugs (GEBPs) has made it possible to significantly optimize the treatment of patients with RA.

Currently, 5 tumor necrosis factor-α (TNF-α) blockers are registered in the Russian Federation: infliximab, adalimumab, certolizumab pegol, golimumab, etanercept, the CD20-binding drug rituximab, an inhibitor of soluble membrane receptors for interleukin-6 - tocilizumab and abatacept. All of these drugs have demonstrated high efficacy in patients with insufficient response to DMARDs, including methotrexate. Treatment with rituximab is usually carried out when TNF-α inhibitors are ineffective, although the drug can be used as a first-line biological therapy for special indications (for example, living in a tuberculosis-endemic area), which is also noted in the latest EULAR recommendations (2013) [12]. The remaining GEBDs may be the first representatives of this group, prescribed in the absence of effect from DMARDs.

Taking into account the high cost of treatment with GEBD, the issue of selecting patients for GEBD therapy seems important. As was shown in the BEST study [13], if 2 sequentially prescribed classical DMARDs are ineffective, further use of other DMARDs does not lead to the development of an effect. Therefore, in many European countries and in Russia, one of the criteria for selecting patients for the prescription of a GB is the ineffectiveness of 2 DMARDs, one of which should be methotrexate. As an analysis of RCTs shows, starting therapy immediately with a combination of biologically active drugs and methotrexate has no advantages over sequentially increasing therapy if the effect of methotrexate is insufficient [36]. However, in the presence of unfavorable prognosis factors (high activity involving a large number of joints, high concentrations of RF and ACCP, progression of joint destruction), the issue of using a DMARD is discussed after the ineffectiveness of the first DMARD.

Classic DMARDs are capable of exerting a pronounced effect at the onset of RA and suppressing the radiological progression of destruction in a significant number of patients. In our practice, patients with an established diagnosis of RA are immediately prescribed methotrexate; if there are contraindications, the choice of DMARDs is discussed individually. The patient is then monitored monthly until there is a pronounced effect, with therapy correction carried out on an individual basis. During the first 3 months. treatment, it must be established whether there is an effect and what its severity is. Such control over the degree of suppression of activity allows for timely adjustment of therapy, if required. With 50% (or more) improvement, further during the first year of therapy, it is assessed whether there is suppression of the progression of erosive arthritis. Insufficient anti-inflammatory effect or the appearance of new erosions in the joints of the hands and feet, the development of destruction of large joints, and the persistence of extra-articular manifestations should lead to a change in therapy: increasing the dose of methotrexate or switching to its subcutaneous injections, changing DMARDs, a combination of DMARDs, or their combination with a GEBD. Involvement in symptomatic therapy, the desire to suppress disease activity with frequent intra-articular or IV administration of glucocorticoids in the absence of a sufficient and stable effect of DMARDs do not prevent the development of severe RA. These measures can only be an addition to the treatment of DMARDs, but not a substitute for it.

Thus, to prevent loss of function in patients with RA, that is, to prevent the development of a severe form of the disease, the doctor must ensure the following:

early administration of DMARDs to all patients with RA;
provide patient education explaining the goals of therapy, the need for long-term (many months and many years) treatment, and monitoring drug tolerability;
constant monitoring of the degree of suppression of activity and progression of the disease with an objective assessment of the quantitative severity of the articular syndrome and destructive changes in the joints, and the tolerability of therapy;
if 2 sequentially prescribed DMARDs are ineffective, raise the question of the need to prescribe a GIBD.

To objectively monitor the activity of RA at each stage of treatment, the doctor must record the number of painful and swollen joints, the severity of pain as assessed by the patient, the general condition as assessed by the patient and the doctor using a visual analogue scale, as well as laboratory parameters (ESR and C-reactive protein) . Monitoring the success of therapy using the DAS28 composite index makes it possible to objectify the control of changes in RA activity.

Thus, the introduction of new classification criteria for RA, the presence of active DMARDs and an arsenal of physical therapy certainly creates the prerequisites for a significant improvement in the outcomes of RA and maintaining the quality of life of patients.

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