Clinical guidelines for the treatment of rheumatoid arthritis. Rheumatoid arthritis: clinical situations and treatment algorithms. Year of information update

Title: Rheumatoid arthritis.

Introduction

ICD 10: M05, M06.
Year of approval (frequency of revision): 2018 (review every 5 years).
ID: KP250.
professional associations.
Association of Rheumatologists of Russia.

Year of information update

Professional associations

Association of Rheumatologists of Russia.

List of abbreviations

ABC** - abatacept**.
ADA** – adalimumab**.
ALA - anti-drug antibodies.
ALT, alanine aminotransferase.
AST, aspartate aminotransferase.
ACB - antibodies to cyclic citrullinated proteins.
ACCP - antibodies to cyclic citrullinated peptide.
DMARDs are basic anti-inflammatory drugs.
VAS is a visual analogue scale.
HIV is the human immunodeficiency virus.
GIBP - genetically engineered biological preparations.
GC - glucocorticoids.
GLM** — golimumab**.
GTT, gamma-glutamyl transpeptidase.
GC** – hydroxychloroquine**.
CHF - congestive heart failure.
IHD - ischemic heart disease.
ILD is an interstitial lung disease.
IL - interleukin.
IgG - immunoglobulin G.
INF** – infliximab**.
I-TNF-α - inhibitors of TNFa.
LEF** – leflunomide**.
HDL - high density lipoproteins.
LDL - low density lipoproteins.
VLDL are very low density lipoproteins.
LFK - physiotherapy exercises.
MRI - magnetic resonance imaging.
MT** — methotrexate**.
NDA - undifferentiated arthritis.
NSAIDs are non-steroidal anti-inflammatory drugs.
NR is an undesirable reaction.
PBP is the patient's assessment of pain.
OZP - the overall assessment of the disease by the patient.
PMS - proximal interphalangeal joint.
PJF - metacarpophalangeal joint.
PLF - metatarsophalangeal joint.
RA - rheumatoid arthritis.
RCTs are randomized clinical trials.
RTM** – rituximab**.
RF, rheumatoid factor.
SIR - standard infusion reactions.
SLE is systemic lupus erythematosus.
ESR - erythrocyte sedimentation rate.
CRP - C-reactive protein.
SULF** - sulfasalazine**.
TsDMARDs are targeted synthetic DMARDs.
TCZ** – tocilizumab**.
TNF, tumor necrosis factor.
Ultrasound - Ultrasound.
CZP** – certolizumab pegol**.
NPJ - number of painful joints.
NPV is the number of swollen joints.
EGDS - esophagogastroduodenoscopy.
ET - occupational therapy.
ETC** – etanercept**.
ACR - American College of Rheumatology.
CDAI - Clinical Disease Activity Index.
DAS - Disease Activity Index.
EULAR - European League Against Rheumatism,.
HAQ - Health Assessment Questionnaire.
NICE - National Institute for Health and Care Excellence.
SDAI - Simplified Disease Activity Index.

Terms and Definitions

Undifferentiated arthritis (NDA). Inflammatory lesion of one or more joints, which cannot be attributed to any specific nosological form, since it does not meet the classification criteria for rheumatoid arthritis (RA) or any other disease.
Early rheumatoid arthritis (RA). Duration less than 12 months (from the onset of symptoms of the disease, and not the diagnosis of RA).
Expanded RA. Duration greater than 12 months, meeting the classification criteria for RA (ACR/EULAR, 2010).
Clinical remission of RA. Absence of signs of active inflammation, remission criteria - - FPS, NPV, CRP (mg / %) and VAVR less than or equal to 1 or SDAI less than 3.3 (criteria ACR / EULAR, 2011).
Persistent remission of RA. Clinical remission lasting 6 months or more.
Antirheumatic drugs. Anti-inflammatory drugs with different structures, pharmacological characteristics and mechanisms of action used to treat RA and other rheumatic diseases.
Non-steroidal anti-inflammatory drugs (NSAIDs). A group of synthetic drugs with symptomatic analgesic, antipyretic and anti-inflammatory effects associated primarily with inhibition of the activity of cyclooxygenase, an enzyme that regulates the synthesis of prostaglandins.
Glucocorticoids (GC). Synthetic steroid hormones with natural anti-inflammatory activity.
Low doses of GC. Less than 10 mg/day of prednisone (or an equivalent dose of another GC).
High doses of GC. More than 10 mg/day of prednisolone (or an equivalent dose of another GC).
Standard DMARDs (DMARDs). A group of synthetic anti-inflammatory drugs of chemical origin that suppress inflammation and the progression of joint destruction.
Genetically engineered biological preparations (GEBP). A group of drugs of biological origin, including monoclonal antibodies (chimeric, humanized, fully human) and recombinant proteins (usually include the Fc fragment of human IgG) obtained using genetic engineering methods that specifically suppress the immune-inflammatory process and slow down the progression of joint destruction.
Rheumatoid factors (RF). IgM autoantibodies, less often IgA and IgG isotypes, reacting with the Fc fragment of IgG.
Antibodies to citrullinated proteins (ACP). Autoantibodies that recognize the antigenic determinants of the amino acid citrulline, which is formed during the post-translational modification of proteins, are most commonly detected by antibodies to cyclic citrullinated peptide (ACCP) and antibodies to modified citrullinated vimentin (AMCV).
Adverse drug reaction (AR). Any adverse event that develops at the time of clinical use of a medicinal product and is not related to its obviously expected therapeutic effects.
lipid profile. This is a biochemical analysis that allows you to objectify disorders in the fat metabolism of the body, which include cholesterol, HDL, LDL, VLDL, triglycerides, atherogenic coefficient.

Description

Rheumatoid arthritis (RA) is an immunoinflammatory (autoimmune) rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and systemic damage to internal organs, leading to early disability and reduced life expectancy of patients.

The reasons

RA belongs to the group of chronic non-communicable inflammatory diseases, the etiology of which is unknown. Most researchers are inclined in favor of a multifactorial etiology of the disease, the development of which is due to the interaction of genetic and environmental factors. The contribution of each of the components can be insignificant, and only with their accumulation is it possible to realize the disease. It is most likely that the heterogeneity of RA is due to the variability of genes that play an important role in susceptibility to RA. The most studied and established association for RA is with the HLADRB1 gene, especially with alleles encoding the amino acid sequence in the third hypervariable region of the DRB1 chain, the so-called shared-epitope (SE). There is evidence of susceptibility to the development of RA depending on the number of copies of SE, which indicates a dose-dependent effect to a certain extent. Residents of the European region are characterized by the association of RA with DRB1*0401 alleles. The role of hormonal factors, such as the production of sex hormones, is discussed, since estrogens have an immunostimulatory effect, including in relation to B-cell activity, while androgens have an immunosuppressive effect. Among the environmental factors, the role of bacterial (stomatogenic) and viral infections is discussed, a certain role is assigned to chemicals, stress, and occupational hazards. It is most reliably established that smoking is an important environmental factor in the development of RA.
As a factor initiating autoimmune mechanisms, the role of excessive citrullination (replacement of the normal amino acid arginine with an atypical one - citrulline) of proteins observed in response to smoking, hypoxia, infection of the oral cavity (periodontitis), under the influence of the enzyme peptidyl arginine deaminase, is assumed. Citrullination of proteins can trigger the activation of immunocompetent cells (dendritic cells, macrophages, T- and B-lymphocytes), associated with impaired tolerance to these modified proteins, due to genetic factors (carriage of HLA-DR4), leading to an imbalance between the synthesis of "pro-inflammatory" cytokines - tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1, IL-17 and anti-inflammatory cytokines (IL-10, soluble antagonist of IL1, soluble TNFα receptors, IL4). The development of an immune response to citrullinated proteins is manifested by the synthesis of ACB, sometimes long before the clinical debut of the disease. Activated cells produce pro-inflammatory cytokines such as IL-1, TNF-α, IL-6, IL-8, activating T-lymphocyte helpers (Helper) type 1 (Th1) and Th17 cells. Stimulated Th1 and Th17 cells produce IL-2, TNF-α, IFN-γ, IL-17, IL-21, which cause activation of B-lymphocytes. The latter are transformed into plasma cells producing autoantibodies predominantly of the IgG isotype. At the same time, mast cells that secrete inflammatory mediators (heparin, serotonin, etc.) are activated. As a result, exudative-proliferative inflammation of the synovial membrane of the joints (synovitis) occurs, characterized by the formation of lymphocytic infiltrates, the accumulation of macrophages, the development of neoangiogenesis, the proliferation of synovial membrane cells and fibroblasts with the formation of aggressive tissue - pannus. Pannus cells secrete proteolytic enzymes that destroy cartilage, while under the influence of hyperproduction of pro-inflammatory cytokines (TNF-α, etc.), osteoclasts are activated, which leads to osteoporosis (local and systemic) and further destruction of bone tissue with the formation of erosions (usur). In the development of extra-articular manifestations, the same cellular immune-inflammatory mechanisms play a role, as well as the occurrence of immunocomplex vasculitis associated with the production of autoantibodies (ACB, RF).

Epidemiology

RA is a common and one of the most severe human immunoinflammatory diseases, which determines the great medical and socio-economic significance of this pathology. The prevalence of RA among the adult population in different geographical areas of the world ranges from 0.5 to 2%. According to official statistics, about 300 thousand patients with RA are registered in Russia, while according to the Russian epidemiological study, about 0.61% of the general population suffers from RA. The ratio of women to men is 3:1. The disease occurs in all age groups, but the peak incidence occurs in the most able-bodied age - 40-55 years. RA causes persistent disability in half of patients during the first 3-5 years from the onset of the disease and leads to a significant reduction in their life expectancy, both due to the high incidence of cardiovascular pathology, severe infections, oncological diseases, and the complications associated with RA. with a systemic immune-inflammatory process - rheumatoid vasculitis, AA amyloidosis, interstitial lung disease, etc.;

We rarely think about how much routine work our hands do, especially our fingers. And we don’t really notice when they turn red and hurt. “Think about it? It will pass!” - unfortunately, many of us argue this way, and this is the biggest mistake.

Rheumatoid arthritis, which chooses joints as a target, mostly small ones - hands, feet, comes on slowly, but, as they say, is true. Not having received a worthy rebuff, it can also affect large joints - ankle, elbow, shoulder, knee, hip.

Of the famous people, the French artist Renoir suffered from rheumatoid arthritis. At first, the disease immobilized his fingers, and he painted his paintings, holding the brush in his fist or tying it to his arm. Fifteen years after the onset of the disease, in 1912, the disease took possession of the artist's body so much that he stopped moving at all.

Treatment

Rheumatoid arthritis has, so to speak, its own business card: it affects the joints on both sides, that is, symmetrically. For example, if the knee joint of the left leg is affected, then there is no hope that the knee joint of the right leg will remain unaffected.

At first, the disease will signal with pain. Then puffiness, redness, swelling of the joint will appear, and if it is more neglected, it can increase and deform. The joints are hot to the touch. If you press them, the pain intensifies many times over. In this case, the patient feels tired, overwhelmed, sometimes the body temperature rises.

Worst of all, the affected joints behave in the morning hours - at this time they are stiff, stiff. This is due to the nighttime stagnation of the inflammatory fluid. For example, the patient's hands resemble rubber gloves filled with water, and there is an irresistible desire to stretch them.

However, attention must be paid to the duration of such a state. If it lasts only a few minutes, most likely there is no serious cause for alarm. In rheumatoid arthritis, the stiffness lasts for at least half an hour, and at the maximum - the whole day.

For the treatment of rheumatoid arthritis, doctors use non-steroidal anti-inflammatory drugs (NSAIDs), the purpose of which is to quickly pacify pain and muffle inflammation. Among them are ibuprofen, naproxen, diclofenac, meloxicam in combination, for example, with omeprazole to protect the gastric mucosa.

However, neither NSAIDs nor analgesics are able to stop the complex inflammatory process of joint destruction. For these purposes, there are basic, that is, basic, preparations.

Since rheumatoid arthritis is a highly complex disease, therefore, the drugs will be very serious. I will list the pros and cons of the so-called basic funds. There is a deep misconception that rheumatoid arthritis is treated exclusively with hormonal drugs. Yes, hormones are used, but not always?

Basic, basic, drugs for the treatment of rheumatoid arthritis are divided into synthetic and biological. The first are produced by synthesis in the laboratory (these are methotrexate, hydroxychloroquine, sulfasalazine, leflunomide); the second ones are grown on special cultures of cells or bacteria using genetic engineering technologies.

Biologics include infliximab (Remicade), adalimumab (Humira), rituximab (MabThera), and abatacept (Orencia).

The action of these drugs is aimed at reducing the activity of the immune system and, therefore, stop inflammation and further destruction of the joints. Drugs are prescribed depending on the aggression of the disease.

In mild forms of rheumatoid arthritis, sulfasalazine, plaquenil will come to the rescue; with a moderate course - methotrexate. To reduce the side effects of its action, this drug is taken with folic acid (1 mg per day for 7 days) or other drugs of a similar effect.

Yes, medical practice shows that many patients are afraid to take methotrexate due to the fact that it is considered an anticancer drug. And absolutely in vain. Pay attention to the dosage prescribed by the doctor: from 7.5 mg per week with a gradual increase to 25 mg per week.

Compared to the treatment of oncological diseases, it is much less. This is first. And secondly, methotrexate is considered the "gold standard" in the treatment of rheumatoid arthritis, not only in our country, but throughout the world.

If the above remedies do not help, here glucocorticoid hormones, in particular, prednisone, are already used. This is also a "problem" drug, to which patients are wary.

It is worth clarifying that prednisolone itself does not cure rheumatoid arthritis, but is used only in combination with other drugs, and at a low dosage - 5-10 mg per day (this is 1-2 tablets per day).

The course of treatment will depend on the patient's condition, but should not exceed six months. In higher doses, prednisolone can be prescribed only for a short time with an atypical course of the disease. For example, with Still's disease of adults or rheumatoid vasculitis.

If you take prednisolone for a longer period of time to control arthritis, contact your doctor to reconsider your treatment regimen or at least further reduce the dosage.

With prolonged thoughtless intake of glucocorticoids, a serious blow is dealt to the endocrine system, causing complications such as diabetes mellitus, hypertension, osteoporosis, obesity, and pancreatitis.

And, finally, in the most advanced forms of rheumatoid arthritis, when, as they say, nothing helps, the so-called “heavy artillery” is used in the form of biological preparations, which are mentioned above.

The advantage of these drugs is that they selectively, pointwise, act on the links of the immune system, blocking inflammatory foci and thereby preventing further destruction of the joint.

Often, biological drugs act on the same front as synthetic ones, most often with methotrexate. For example, the following treatment regimens are used: enbrel 50 mg once a week methotrexate 20 mg once a week; humira 40 mg once every 2 weeks methotrexate 25 mg once a week.

After such treatment, a positive result occurs very quickly, literally in a few days, but there are two "buts" that put them in the category of unpopular: high price, tens of thousands of rubles, and the consequences of excessive suppression of the immune system - allergic reactions, infectious complications ...

Yes, there is a program of the Ministry of Health on high-tech medical care for the population. And, fortunately, it works. If you have severe rheumatoid arthritis, see your rheumatologist.

The reasons

The culprit of most rheumatic diseases is the immune system. Rheumatoid arthritis is no exception. For what reason does the immune system perceive its own joints as foreign and tries to destroy them?

Alas, there is no clear answer to this question yet. There are several versions regarding the atypical behavior of the immune system. Most experts are inclined in favor of the genetic nature. Like, if one of the relatives had similar problems with the joints, most likely, you will also have them.

Smokers are definitely at risk. Medical practice shows that people with nicotine addiction suffer from rheumatoid arthritis much more often, and the disease itself is much more aggressive compared to those who have never taken a cigarette in their mouths.

Other scientific versions - various viruses contribute to the occurrence of rheumatoid arthritis, including infections of the oral cavity; physical injuries - fractures, dislocations, torn ligaments and tendons.

By the way, the story of Renoir confirms this. Shortly before the first signs of illness appeared in the artist in 1897, he fell off a cyclist and suffered a broken arm.

RA belongs to the group of chronic non-communicable inflammatory diseases, the etiology of which is unknown. Most researchers are inclined in favor of a multifactorial etiology of the disease, the development of which is due to the interaction of genetic and environmental factors. The contribution of each of the components can be insignificant, and only with their accumulation is it possible to realize the disease.

It is most likely that the heterogeneity of RA is due to the variability of genes that play an important role in susceptibility to RA. The most studied and established association for RA is with the HLADRB1 gene, especially with alleles encoding the amino acid sequence in the third hypervariable region of the DRB1 chain, the so-called shared-epitope (SE).

There is evidence of susceptibility to the development of RA depending on the number of copies of SE, which indicates a dose-dependent effect to a certain extent. Residents of the European region are characterized by the association of RA with DRB1*0401 alleles. The role of hormonal factors, such as the production of sex hormones, is discussed, since estrogens have an immunostimulatory effect, including in relation to B-cell activity, while androgens have an immunosuppressive effect.

Among environmental factors, the role of bacterial (stomatogenic) and viral infections is discussed, a certain role is assigned to chemicals, stress, and occupational hazards. It is most reliably established that smoking is an important environmental factor in the development of RA.

As a factor initiating autoimmune mechanisms, the role of excessive citrullination (replacement of the normal amino acid arginine with an atypical one - citrulline) of proteins observed in response to smoking, hypoxia, infection of the oral cavity (periodontitis), under the influence of the enzyme peptidyl arginine deaminase, is assumed.

Citrullination of proteins can trigger the activation of immunocompetent cells (dendritic cells, macrophages, T- and B-lymphocytes), associated with impaired tolerance to these modified proteins, due to genetic factors (carriage of HLA-DR4), leading to an imbalance between the synthesis of "pro-inflammatory" cytokines - tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1, IL-17 and anti-inflammatory cytokines (IL-10, soluble IL1 antagonist, soluble TNFα receptors, IL4).

The development of an immune response to citrullinated proteins is manifested by the synthesis of ACB, sometimes long before the clinical debut of the disease. Activated cells produce pro-inflammatory cytokines such as IL-1, TNF-α, IL-6, IL-8, activating T-lymphocyte helpers (Helper) type 1 (Th1) and Th17 cells.

Stimulated Th1 and Th17 cells produce IL-2, TNF-α, IFN-γ, IL-17, IL-21, which cause activation of B-lymphocytes. The latter are transformed into plasma cells producing autoantibodies predominantly of the IgG isotype. At the same time, mast cells that secrete inflammatory mediators (heparin, serotonin, etc.) are activated.

As a result, exudative-proliferative inflammation of the synovial membrane of the joints (synovitis) occurs, characterized by the formation of lymphocytic infiltrates, the accumulation of macrophages, the development of neoangiogenesis, the proliferation of synovial membrane cells and fibroblasts with the formation of aggressive tissue - pannus.

Pannus cells secrete proteolytic enzymes that destroy cartilage, while under the influence of hyperproduction of pro-inflammatory cytokines (TNF-α, etc.), osteoclasts are activated, which leads to osteoporosis (local and systemic) and further destruction of bone tissue with the formation of erosions (usur).

Diagnostics

Characterized by a variety of options for the onset of the disease. In most cases, the disease begins with polyarthritis, less commonly, manifestations of arthritis can be moderately expressed, and arthralgia, morning stiffness in the joints, deterioration in general condition, weakness, weight loss, low-grade fever, lymphadenopathy, which may precede clinically pronounced joint damage, predominate. A number of variants of the onset of the disease are described: Symmetrical polyarthritis with a gradual (over several months) increase in pain and stiffness, mainly in the small joints of the hands (in half of the cases). Acute polyarthritis with a predominant lesion of the joints of the hands and feet, severe morning stiffness (usually accompanied by the early appearance of RF in the blood). Mono-oligoarthritis of the knee or shoulder joints, followed by rapid involvement of the small joints of the hands and feet in the process. Acute monoarthritis of large joints resembling septic or microcrystalline arthritis. Acute oligo- or polyarthritis with severe systemic effects (febrile fever, lymphadenopathy, hepatosplenomegaly), more often observed in young patients (reminiscent of Still's disease in adults). "Palindromic rheumatism": multiple recurrent attacks of acute symmetrical polyarthritis of the joints of the hands, less often of the knee and elbow joints; last several hours or days and end with complete recovery. Recurrent bursitis and tenosynovitis, especially in the area of ​​the wrist joints. Acute polyarthritis in the elderly: multiple lesions of small and large joints, severe pain, diffuse edema and limited mobility. Received the name "RS3PE syndrome" (Remitting Seronegative symmetric synovitis with Pitting Edema - remitting seronegative symmetric synovitis with "pincushion" edema). Generalized myalgia: stiffness, depression, bilateral carpal tunnel syndrome, weight loss (usually develops in old age and resembles polymyalgia rheumatica); the characteristic clinical signs of RA develop later. In a significant part of patients, RA debuts with uncharacteristic clinical manifestations, and therefore the diagnosis according to existing criteria cannot be established during the initial examination. This condition is usually classified as undifferentiated arthritis (UA). Among patients with LDA, at least 30% develop typical RA within 1 year of follow-up. In practice, the following clinical variants of NDA are most common: Oligoarthritis of large joints (knee, ankle, shoulder, hip). Asymmetric arthritis of the joints of the hands. RF seronegative oligoarthritis of the joints of the hands. Unstable polyarthritis. Therapeutic approaches for NDA are similar to those for RA. To identify extra-articular manifestations (Sjogren's syndrome, neuropathy, cutaneous vasculitis, interstitial lung disease (ILD)) of RA, it is recommended that all patients with peripheral arthritis and patients with an established diagnosis of RA be interviewed to identify complaints characteristic of Sjogren's syndrome, neuropathy, cutaneous vasculitis and ILD . I I, recommendation level B.   It is recommended that an articular status assessment (determination of the number of inflamed joints, which takes into account both swelling and tenderness of the joints) of a patient with RA by a rheumatologist for diagnosis, assessment of disease activity and monitoring the effectiveness of therapy is recommended. I, the level of persuasiveness of recommendations - A.

The diagnosis of rheumatoid arthritis is based on “three pillars. Not only the clinical picture, which I described, is taken into account, but also the X-ray of the joints, laboratory diagnostics.

An x-ray will show ulceration of the cartilage, but in the early stages of the disease, he does not always see the pathology. In this case, you can use magnetic resonance imaging or ultrasound of the joints.

MRI and ultrasound are able to notice the destruction of cartilage tissue much earlier. In addition, these methods help to see the inflammation of the soft periarticular tissues.

As for laboratory diagnostics, literally all patients with arthritis have changes in blood parameters: increased ESR and C-reactive protein. And in about a third of patients in the blood there are special antibodies called "rheumatoid factor" (RF).

There is also a new immunological method - the determination of antibodies to cyclic citrullinated peptide (ACCP). It helps to identify the disease in 60 percent of patients. At the same time, it is important to know that the level of RF and ACCP reflects the presence of the disease, and not its activity. However, the higher the score, the more severe the disease.

Probably, you will ask: “But what about those patients who do not have specific indicators?” In this case, the doctor has the right to make a diagnosis based on his own observations. Looks at which joints are affected, how the disease proceeds, determines the scale of articular disorders from x-rays.

Bibliography

ABC** - abatacept**. ADA** – adalimumab**. ALA - anti-drug antibodies. ALT, alanine aminotransferase. AST, aspartate aminotransferase. ACB - antibodies to cyclic citrullinated proteins. ACCP - antibodies to cyclic citrullinated peptide. DMARDs are basic anti-inflammatory drugs.

VAS is a visual analogue scale. HIV is the human immunodeficiency virus. GIBP - genetically engineered biological preparations. GC - glucocorticoids. GLM** — golimumab**. GTT, gamma-glutamyl transpeptidase. GC** – hydroxychloroquine**. CHF - congestive heart failure. IHD - ischemic heart disease.

ILD is an interstitial lung disease. IL - interleukin. IgG, immunoglobulin G. IF**, infliximab**. I-TNF-α - inhibitors of TNFa. LEF** – leflunomide**. HDL - high density lipoproteins. LDL - low density lipoproteins. VLDL are very low density lipoproteins.

LFK - physiotherapy exercises. MRI - magnetic resonance imaging. MT** — methotrexate**. NDA - undifferentiated arthritis. NSAIDs are non-steroidal anti-inflammatory drugs. NR is an undesirable reaction. PBP is the patient's assessment of pain. OZP - the overall assessment of the disease by the patient. PMS - proximal interphalangeal joint.

PJF - metacarpophalangeal joint. PLF - metatarsophalangeal joint. RA - rheumatoid arthritis. RCTs are randomized clinical trials. RTM** – rituximab**. RF, rheumatoid factor. SIR - standard infusion reactions. SLE is systemic lupus erythematosus. ESR - erythrocyte sedimentation rate.

CRP - C-reactive protein. SULF** - sulfasalazine**. TsDMARDs are targeted synthetic DMARDs. TCZ** – tocilizumab**. TNF, tumor necrosis factor. Ultrasound - Ultrasound. CZP** – certolizumab pegol**. NPJ - number of painful joints. NPV is the number of swollen joints. EGDS - esophagogastroduodenoscopy.

ET - occupational therapy. ETC** – etanercept**. ACR - American College of Rheumatology. CDAI - Clinical Disease Activity Index. DAS - Disease Activity Index. EULAR - European League Against Rheumatism,. HAQ - Health Assessment Questionnaire. NICE - National Institute for Health and Care Excellence. SDAI - Simplified Disease Activity Index.

Physical activity

One of the frequently asked questions: can patients with rheumatoid arthritis exercise?

Developing stiff and stiff joints is not only possible, but necessary! Otherwise, with their prolonged immobility, a persistent restriction of movement will develop, or, if scientifically, contracture. However, when starting physiotherapy exercises, in order to avoid unnecessary problems, read the useful rules.

First, you can’t train your joints if you have chronic infectious diseases or serious heart problems. Secondly, you should not start physical exercises during a period of severe exacerbation of the disease, when pain is acutely felt.

Thirdly, it is impossible to include strength exercises in the complex, which will cause additional harm to diseased joints. Fourthly, training sessions should be regular and systematic.

As you know, rheumatoid arthritis affects various joints - the shoulders, hips, knees, feet and, most often, as already mentioned, the hands. To develop them, I recommend the following exercises.

• Lay the brushes on the table next to each other. On the count of "one-two" turn them palms up, on the count of "three-four" - palms down.
• The starting position is the same. On the count of “one-two”, raise the hands without lifting your fingers from the table, on the count of “three-four”, as if rolling, on the contrary, raising your fingers and not tearing off the base of the palm.
• Clenching your hands into fists, stretch them out in front of you. First rotate the brushes clockwise, then the same number of times in the opposite direction.
• Touch each of the fingers of the left and right hands in turn to the thumb, pressing on the pads and as if grasping something round.
• Having prepared a soft tennis ball, squeeze it in your hand, roll it on the surface of the table, roll it between your palms.
• Relaxing your palms, rotate the hands at the wrist joint. First one way, then the other
• Putting a stick in front of you, move your fingers as if you were going up and then going down a rope.
• Rub your palms together as if you were making fire.

Perform each exercise depending on your condition, but at least 5-7 times. During the day, it is desirable to repeat the entire complex twice, and preferably three times. This will be called consistency and regularity.

Terms and Definitions

Undifferentiated arthritis (NDA). Inflammatory lesion of one or more joints, which cannot be attributed to any specific nosological form, since it does not meet the classification criteria for rheumatoid arthritis (RA) or any other disease.

Early rheumatoid arthritis (RA). Duration less than 12 months (from the onset of symptoms of the disease, and not the diagnosis of RA). Expanded RA. Duration greater than 12 months, meeting the classification criteria for RA (ACR/EULAR, 2010). Clinical remission of RA. Absence of signs of active inflammation, remission criteria - - FPS, NPV, CRP (mg / %) and VAVR less than or equal to 1 or SDAI less than 3.3 (criteria ACR / EULAR, 2011).

Persistent remission of RA. Clinical remission lasting 6 months or more. Antirheumatic drugs. Anti-inflammatory drugs with different structures, pharmacological characteristics and mechanisms of action used to treat RA and other rheumatic diseases.

Non-steroidal anti-inflammatory drugs (NSAIDs). A group of synthetic drugs with symptomatic analgesic, antipyretic and anti-inflammatory effects associated primarily with inhibition of the activity of cyclooxygenase, an enzyme that regulates the synthesis of prostaglandins.

Glucocorticoids (GC). Synthetic steroid hormones with natural anti-inflammatory activity. Low doses of GC. Less than 10 mg/day of prednisone (or an equivalent dose of another GC). High doses of GC. More than 10 mg/day of prednisolone (or an equivalent dose of another GC).

Standard DMARDs (DMARDs). A group of synthetic anti-inflammatory drugs of chemical origin that suppress inflammation and the progression of joint destruction. Genetically engineered biological preparations (GEBP). A group of drugs of biological origin, including monoclonal antibodies (chimeric, humanized, fully human) and recombinant proteins (usually include the Fc fragment of human IgG) obtained using genetic engineering methods that specifically suppress the immune-inflammatory process and slow down the progression of joint destruction.

Rheumatoid factors (RF). IgM autoantibodies, less often IgA and IgG isotypes, reacting with the Fc fragment of IgG. Antibodies to citrullinated proteins (ACP). Autoantibodies that recognize the antigenic determinants of the amino acid citrulline, which is formed during the post-translational modification of proteins, are most commonly detected by antibodies to cyclic citrullinated peptide (ACCP) and antibodies to modified citrullinated vimentin (AMCV).

Adverse drug reaction (AR). Any adverse event that develops at the time of clinical use of a medicinal product and is not related to its obviously expected therapeutic effects. lipid profile. This is a biochemical analysis that allows you to objectify disorders in the fat metabolism of the body, which include cholesterol, HDL, LDL, VLDL, triglycerides, atherogenic coefficient.

Food

Fortunately, you don’t need to follow any special diet, but I would recommend diversifying the menu. Since there is active inflammation in the body and energy consumption increases, the meals of patients with rheumatoid arthritis should contain sufficient amounts of calcium, protein, vitamin D3, and omega-3 fatty acids.

These helpers invisible to the eye are found in meat, milk, cheeses, fish, fruits, vegetables, greens. Limit yourself in sweet, fatty, starchy foods. Taking many basic drugs provokes the endocrine system, so why overload it?

Unfortunately, rheumatoid arthritis is considered an incurable disease. But to restrain its offensive, transferring it to the stage of stable remission, is quite within our power, if there is a desire and, most importantly, aspiration. Take care of yourself! Video "The Best Treatment for Rheumatoid Arthritis"

Epidemiology

RA is a common and one of the most severe human immunoinflammatory diseases, which determines the great medical and socio-economic significance of this pathology. The prevalence of RA among the adult population in different geographical areas of the world ranges from 0.5 to 2%.

According to official statistics, about 300 thousand patients with RA are registered in Russia, while according to the Russian epidemiological study, about 0.61% of the general population suffers from RA. The ratio of women to men is 3:1. The disease occurs in all age groups, but the peak incidence occurs in the most able-bodied age - 40-55 years.

Other arthritis (M13), Other rheumatoid arthritis (M06), Seropositive rheumatoid arthritis (M05)

Rheumatology

general information

Short description

All-Russian public organization Association of Rheumatologists of Russia

Clinical recommendations "Rheumatoid arthritis" passed the public review, agreed and approved on October 5, 2013, at a meeting of the Plenum of the Board of the RDA, held jointly with the profile commission of the Ministry of Health of the Russian Federation in the specialty "rheumatology". (President of the RDA, Academician of the Russian Academy of Sciences - E.L. Nasonov)

Rheumatoid arthritis (RA)- an autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis (synovitis) and systemic damage to internal organs. The prevalence of RA among the adult population is 0.5-2% (in women 65 years old, about 5%). The ratio of women to men is 2-3:1. All age groups are affected, including children and the elderly. The peak onset of the disease is 40-55 years. Screening is not performed. RA is characterized by a variety of variants of the onset of the disease. In most cases, the disease begins with polyarthritis, less often with mono- and oligoarthritis, sometimes manifestations of arthritis can be moderately expressed, and arthralgia, morning stiffness in the joints, deterioration in general condition, weakness, weight loss, low-grade fever, lymphadenopathy, which may precede clinically pronounced joint damage.

Classification

Clinical classification of RA

Classification of rheumatoid arthritis (adopted at the meeting of the Plenum of the Association of Rheumatologists of Russia on September 30, 2007)

1. Main diagnosis:
1. Seropositive rheumatoid arthritis (M05.8)
2. Seronegative rheumatoid arthritis (M06.0)
3. Special clinical forms of rheumatoid arthritis:
- Felty syndrome (M05.0)
- Adult-onset Still's disease (M06.1)
4. Probable rheumatoid arthritis (M05.9, M06.4, M06.9)

2. Clinical stage:
1. Very early stage: duration of illness< 6 месяцев
2. Early stage: disease duration 6 months. - 1 year
3. Advanced stage: disease duration > 1 year with typical RA symptoms
4. Late stage: the duration of the disease is 2 years or more + severe destruction of small (III-IV X-ray stage) and large joints, the presence of complications

3. Disease activity:
1. 0 = remission (DAS28< 2,6)
2. 1 = low (2.6< DAS28 <3,2)
3. 2 = medium (DAS28 3.2 - 5.1)
4. 3 = high (DAS28 > 5.1)

4. Extra-articular (systemic) manifestations:
1. rheumatoid nodules
2. cutaneous vasculitis (necrotizing ulcerative vasculitis, nail bed infarcts, digital arteritis, livedoangiitis)
3. vasculitis of other organs
4. neuropathy (mononeuritis, polyneuropathy)
5. pleurisy (dry, effusion), pericarditis (dry, effusion)
6. Sjögren's syndrome
7. eye damage (scleritis, episcleritis, retinal vasculitis)

5. Instrumental characteristic:
1. The presence of erosions (using radiography, possibly MRI, ultrasound):
- non-erosive
- Erosive
2. X-ray stage (according to Steinbroker, modification):
I - periarticular osteoporosis
II - osteoporosis + narrowing of the joint space, there may be single erosions
III - signs of the previous stage + multiple erosions + subluxations in the joints
IV - signs of the previous stage + bone ankylosis

6. Additional immunological characteristic - anticitrulline antibodies:
1. ACCP - positive
2. ACCP - negative

7. Functional class:
I - fully preserved: self-service, non-professional and professional activities
II - retained: self-service, professional activities, limited: non-professional activities
III - retained: self-service, limited: non-professional and professional activities
IV - limited: self-service, non-professional and professional activities

8. Complications:
1. secondary systemic amyloidosis
2. secondary arthrosis
3. osteoporosis (systemic)
4. osteonecrosis
5. tunnel syndromes (carpal tunnel syndrome, compression syndromes of the ulnar, tibial nerves)
6. subluxation in the atlanto-axial joint, including with myelopathy, instability of the cervical spine
7. atherosclerosis

Comments on the RA Classification:

1. To the heading "Main diagnosis":
Seropositivity and seronegativity are determined by a test for rheumatoid factor, which must be carried out using a reliable quantitative or semi-quantitative test (latex test, enzyme immunoassay, immunonephelometric method).

Where NPJ is the number of painful joints, NPJ is the number of swollen joints out of the following 28: shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal, knee,
ESR - erythrocyte sedimentation rate according to the Westergren method,
OOSZ - a general assessment of the patient's state of health in mm on a 100 mm visual analogue scale

B) It is acceptable to use other methods for calculating activity, for which good comparability with DAS28 has been proven

2. To rubric 5 "Instrumental characteristics":
A detailed description of the radiological stages:
1 stage. Minor periarticular osteoporosis. Single cystic enlightenment of bone tissue. Slight narrowing of the joint spaces in individual joints.
2 stage. Moderate (pronounced) periarticular osteoporosis. Multiple cystic enlightenments of the bone tissue. Narrowing of joint spaces. Single erosions of articular surfaces (1-4). Minor bone deformities.
3 stage. Moderate (pronounced) periarticular osteoporosis. Multiple cystic enlightenments of the bone tissue. Narrowing of joint spaces. Multiple erosions of the articular surfaces (5 or more). Multiple pronounced bone deformities. Subluxations and dislocations of joints.
4 stage. Moderate (pronounced) periarticular (common) osteoporosis. Multiple cystic enlightenments of the bone tissue. Narrowing of joint spaces. Multiple erosions of bones and articular surfaces. Multiple pronounced bone deformities. Subluxations and dislocations of joints. Single (multiple) bone ankylosis. Subchondral osteosclerosis. Osteophytes on the edges of the articular surfaces.

3. To rubric 7 - Description of characteristics for determining the functional class:
· Self service: dressing, eating, personal care, etc.
· Non-professional activities: elements of recreation, leisure, sports, etc., taking into account gender and age
· Professional activity: work, study, housekeeping (for domestic workers), taking into account gender and age.

Examples of the formulation of clinical diagnoses:

Seropositive rheumatoid arthritis (M05.8), advanced stage, activity II, erosive (X-ray stage II), with systemic manifestations (rheumatoid nodules), ACCP (-), FC II.

Rheumatoid arthritis, seronegative (M06.0), early stage, activity III, non-erosive (X-ray stage I), ACCP (+), FC I.

Seropositive rheumatoid arthritis (M05.8), late stage, erosive (X-ray stage III), activity II, with systemic manifestations (rheumatoid nodules, digital arteritis), ACCP (? - not studied), FC III, complications - carpal tunnel syndrome on the right, secondary amyloidosis with kidney damage.

Probable rheumatoid arthritis (M06.9), seronegative, early stage, activity II, non-erosive (X-ray stage I), ACCP (+), FC I.

Diagnostics

Diagnostic criteria and differential diagnosis of RA

Patients with new-onset inflammatory joint disease include:
Very early RA - a condition with a duration of symptoms of 3-6 months (potentially reversible condition)
Early RA, or "early established RA" - the first 1-2 years of the disease (when the first signs of disease progression can be determined, such as the presence or absence of a typical erosive process in the joints)
Undifferentiated arthritis (currently the term "undifferentiated peripheral arthritis" - NPA is used) - an inflammatory lesion of one or joints that cannot (at the moment) be attributed to any particular nosological form, that is, does not meet the classification criteria for RA or any other disease. About 1/3 of NPA patients develop RA within 1 year of follow-up.

In the presence of a classic clinical picture, especially with a typical lesion of the hand, the diagnosis of RA is not difficult. The problems of early diagnosis of RA are as follows:
- the classic clinical picture is observed, as a rule, in patients with long-term RA, and at the beginning of the disease a number of typical clinical (for example, ulnar deviation of the fingers and rheumatoid nodules), immunological (rheumatoid factor) and radiological (bone erosion) symptoms may be absent ;
- the onset of RA is characterized by pronounced heterogeneity of symptoms;
- there are no truly pathognomonic symptoms in RA;

The most difficult in terms of diagnostics is the group of patients with LPA, since these patients require dynamic monitoring and repeated examinations to verify the diagnosis. Based on clinical practice, all patients with RA and suspected RA are divided into the following diagnostic groups (corresponding ICD10 codes are indicated in brackets):
Seropositive rheumatoid arthritis (M05.8)
Seronegative rheumatoid arthritis (M06.0)
Probable rheumatoid arthritis (M05.9, M06.4, M06.9)
Undifferentiated arthritis (M13.0, M13.1, M13.8, M13.9)

Due to the fact that the diagnosis of RA must be verified by a rheumatologist, a key factor in early diagnosis is the earliest possible referral of the patient to a rheumatologist. For general practitioners, it is recommended to use the EULAR criteria for clinical suspicion of RA in order to select patients for a consultation with a rheumatologist (modified):
Swelling of at least one peripheral joint that can be reliably determined on examination
a positive symptom of "compression" of the hands and / or feet
Morning stiffness lasting 30 minutes or more.

To verify the diagnosis, the use of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (American College of Rheumatology/European League Against Rheumatism Rheumatoid arthritis classification criteria) is recommended.
In order to make a diagnosis of RA according to the new criteria, the doctor must fulfill three conditions.
Determine if the patient has at least one swollen joint according to the physical examination.
Exclude other diseases that may be accompanied by inflammatory changes in the joints.
Score at least 6 points out of 10 possible in 4 positions describing the features of the disease picture in this patient (Table 1).

Table 1. Classification Criteria RA ACR/EULAR 2010

Three categories of patients stand out in particular, who do not meet the criteria at the time of examination, but who, nevertheless, can be reliably diagnosed with RA.

1. Patients who have erosions typical of RA on radiographs. The erosive lesion characteristic of RA is well described in many monographs, atlases and guidelines, however, there is still no unambiguous definition of “erosion typical of RA”. Therefore, significant personal experience of the rheumatologist and radiologist may be required for a reliable diagnosis.

2. Patients with a significant age of RA who previously met the diagnostic criteria for this disease.

3. Patients with early stage RA who do not meet the criteria at baseline but begin to meet criteria as the disease progresses during follow-up. If there are insufficient scores for the diagnosis of RA, the assessment can be repeated and cumulative (that is, taking into account all the changes identified during the observation period).

A separate category is patients with LPA, who for a long time may not meet the criteria for RA (or any other specific nosological form). In this case, it is necessary to evaluate the prognosis in terms of the development of RA or other pathology. The main factor of an unfavorable prognosis for the development of RA is the detection of anticitrulline antibodies in the patient (primarily antibodies to the cyclic citrullinated peptide - ACCP).

Instrumental diagnostics in RA
Instrumental research methods are not included in the criteria for the diagnosis of RA, but are widely used for the following purposes:
Identification of early structural damage, which allows clarifying the diagnosis in cases where the criterion-based assessment does not give unambiguous results
verification of the diagnosis of RA at a late stage of the disease, when the activity of the inflammatory process can spontaneously decrease and the phenomena of bone and cartilage destruction predominate
assessment of the rate of progression of structural damage for prognostic purposes
Monitoring response to therapy
verification of structural disorders before orthopedic and surgical treatment and orthotics

X-ray of the joints

Plain radiographs of the hands and distal feet (DOS) are required to confirm the diagnosis, establish the stage, and assess the progression of joint destruction in RA. Plain radiographs of the hands and DOS are recommended at the initial examination and then annually in all patients with RA.. Patients with advanced stage RA (see Section 2.5) with Steinbroker stages 3 and 4 receive less frequent hand radiography and DOS, the frequency being determined by the specific clinical situation.

For RA, the multiplicity and symmetry of lesions of the small joints of the hands and DOS are characteristic. The initial manifestations of the disease should be looked for in joints typical for RA:

1. Early radiological symptoms of arthritis are found: in the 2nd and 3rd metacarpophalangeal joints; 3 proximal interphalangeal joints; in the joints of the wrists; wrist joints; styloid processes of the ulna; 5 metatarsophalangeal joints.

2. Typical for RA are symmetrical radiographic changes in the metacarpophalangeal joints, proximal interphalangeal joints; in the joints of the wrists; metatarsophalangeal joints and 1 interphalangeal joints of the feet

3. With more pronounced radiological stages of RA (3 and 4 stages according to Steinbroker), changes can be detected in the distal interphalangeal joints of the hands and proximal interphalangeal joints of the feet.

4. RA does not begin with damage to the distal interphalangeal joints of the hands and feet; proximal interphalangeal joints of the feet

5. Bone ankylosis in RA is detected only in the intercarpal joints; 2-5 carpometacarpal joints and, less often, in the joints of the tarsus.

There are no X-ray changes characteristic of RA in the large joints of the upper and lower extremities, in the joints of the axial skeleton. Radiographic symptoms of arthritis in this group of joints are nonspecific and can be found in other rheumatic diseases. Concerning radiography of large joints in RA is not recommended as a routine method and is carried out only in the presence of specific indications (suspicion of avascular necrosis, etc.).

To determine the radiological stage, a modified classification of RA according to Steinbroker is used:

Stage I - periarticular osteoporosis; single cysts

Stage II - periarticular osteoporosis; multiple cysts; narrowing of the joint space, there may be single erosions (1-4);

Stage III - stage II symptoms + multiple erosions (5 or more) + dislocations or subluxations in the joints;

Stage IV - stage III symptoms + bone ankylosis.

Form of the disease: non-erosive; erosive.

The timing of the appearance of the main radiographic symptoms of RA:
1. In acute onset and active course of RA, periarticular osteoporosis and single cysts can be detected within 1 month of the disease; multiple cysts and narrowing of joint spaces from 3 to 6 months; first erosion within 1 year of disease
2. The appearance of the first symptoms after a few months (up to 1 year) from the onset of the disease is considered more typical; erosion for 2-3 years from the onset of the disease
3. Bone ankylosis of the wrist joints can be detected after 10 years or more (depending on the course of erosive arthritis in the wrist joints)

Features of the course of RA in terms of the dynamics of the development of radiological changes:

1. In the classical course of RA, erosions in the joints cannot precede periarticular osteoporosis, cysts and narrowing of the joint spaces in the joints of the hands and DOS

2. Bone ankylosis in RA does not form in the interphalangeal, metacarpophalangeal and metatarsophalangeal joints of the hands and DOS, in the 1st carpometacarpal joints. RA is characterized by ankylosing of the intercarpal, carpometacarpal, and, less commonly, tarsal joints.

Chest X-ray is indicated for all patients to detect rheumatoid lesions of the respiratory system and concomitant lung lesions (for example, tuberculosis, COPD, etc.) at the initial examination and then annually (more frequent should be justified by the clinical situation).

Computed tomography of the lungs appropriate in case of clinical suspicion of:
RA-related diffuse (interstitial) or focal (rheumatoid nodes) lung disease
a disease of the chest organs, which can cause damage to the joints during the differential diagnosis of RA (sarcoidosis, malignant neoplasms, etc.)
Concomitant pathology that may affect the choice of therapy or is an undesirable reaction to treatment (tuberculosis, methotrexate pneumonitis, etc.)

Magnetic resonance imaging (MRI)

MRI is a more sensitive method for detecting synovitis in the onset of RA than standard joint radiography. MRI symptoms of arthritis are nonspecific. Similar MRI changes may be present in other inflammatory joint diseases and in clinically "normal" joints. Changes detected by MRI (synovitis, tenosynovitis, bone marrow edema and bone erosion) allow predicting the progression of joint destruction. MRI of the hands is indicated for patients with early RA and LPA.

Ultrasound examination (ultrasound) of the joints used in 2 main varieties:
Ultrasound of the hand
UI of large joints

With ultrasound of the joints, the following are evaluated:
On the "gray scale" - thickening of the synovial membrane, the presence of effusion in the joint, violation of the contour of the articular surface (corresponding to erosion), changes in the periarticular tissues (tenosynovitis)
· with power Doppler study - localization, prevalence and intensity of the signal, which allows to judge the severity of proliferative inflammation.

Ultrasound of the hand has a diagnostic and prognostic value in early RA, and also allows you to assess the depth of remission against the background of antirheumatic therapy. Currently not enough data to consider ultrasound as a more accurate method than accurate clinical examination of the joints.
The use of MRI and ultrasound of the joints provides valuable additional data, but the evaluation of the results of these studies is not standardized enough, in this regard, at present can not be recommended to justify the diagnosis or make decisions about therapy based on data from these studies alone, without an appropriate clinical and laboratory basis.

Methods for assessing RA activity
In RA, there is no single symptom that can reliably assess disease activity. The main method of objectifying inflammation activity is the use of complex activity indices.

The following indexes are recommended:
DAS28 -Disease Activity Score for 28 joints (modified with ESR and CRP)
SDAI - Simplified Disease Activity Index
CDAI - Clinical Disease Activity Index
All of the above indices are based on the following main clinical and laboratory parameters:
The number of swollen joints (SJJ) and the number of painful joints (TJJ) out of 28 (carpal, metacarpophalangeal, proximal interphalangeal hands, shoulder, elbow, knee joints are taken into account)
General assessment of the severity of symptoms on a 100-mm horizontal visual analogue scale: a doctor's overall disease activity score (OOAV) and a patient's overall health score (PHA)
ESR in mm per hour (mm/h) according to Westergren's method
CRP in blood serum, determined by a quantitative method.

Formula to calculate DAS28:

Assessment of disease activity using DAS28:

0 = remission (DAS28< 2,6)
- 1 = low (2.6< DAS28 <3,2)
- 2 = medium (DAS28 3.2 - 5.1)
- 3 = high (DAS28 > 5.1)

Table 3. Assessment of response to therapy according to the DAS28 index

Formula for calculating SDAI:
SDAI=NPV+NBS+OOAB+HZB+SRP
Notes: 1) OOAB and OOZB are approximated to a scale from 0 to 10; 2) CRP is measured in mg/dL
Assessment of activity and response to therapy according to SDAI:
Activity score:
. Remission ≤3.3
. Low activity 3.3-11
. Moderate activity 11.1-26
. High activity > 26
Assessment of response to therapy:
. Moderate response - 7 points reduction in SDAI
. Significant response - 17 points reduction in SDAI

Formula for calculating CDAI:

CDAI=NPV+NBS+OOAB+OOZB

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Treatment

1. The main goal of RA pharmacotherapy- achieving remission (or low activity) of the disease (A) as well as reducing the risk of comorbid diseases (FROM).
2. Treatment of patients with RA should be carried out by rheumatologists (as an exception, a general practitioner, but with the advisory support of a rheumatologist) with the involvement of specialists from other medical specialties (orthopedists, physiotherapists, cardiologists, neuropathologists, psychologists, etc.) and be based on close interaction between doctor and patient (FROM).
3. Patients should be advised to avoid factors that can provoke an exacerbation of the disease (intercurrent infections, stress, etc.), stop smoking, strive to maintain a normal body weight (FROM).
4. The main place in the treatment of RA is occupied by drug therapy: non-steroidal anti-inflammatory drugs (NSAIDs), simple analgesics, glucocorticoids (GCs), synthetic basic anti-inflammatory drugs (DMARDs) and targeted therapy agents, which are currently represented by genetically engineered biological drugs (GIBDs). ) (BUT). Non-drug therapies are in addition to medication and are used in certain groups of patients for specific indications.
5. To reduce pain in the joints, NSAIDs are used, which have a good symptomatic (analgesic) effect, but do not affect the progression of joint destruction, the prognosis of the disease and can cause severe adverse reactions (AR) from the gastrointestinal tract and cardiovascular system (BUT). To reduce the risk of NR, the use of NSAIDs in RA should be as limited as possible.
6. Treatment of GCs (low / medium doses) is recommended in combination with DMARDs as a component of combination therapy for RA, to relieve exacerbation before the development of the effect of DMARDs (bridge therapy) or as monotherapy in case of ineffectiveness (or impossibility) of prescribing DMARDs and GIBD; taking GC is accompanied by the development of side effects that require careful monitoring (BUT). The use of HA in RA should be limited to strict indications and carried out by rheumatologists.
7. DMARD therapy should be carried out for all patients with RA without exception and should be administered as early as possible (within 3-6 months from the moment the symptoms of the disease develop) (BUT)
8. In the course of treatment, the effectiveness of therapy should be carefully monitored (every 1-3 months), the treatment regimen should be “selected” depending on the activity of the disease (BUT); the effect of DMARDs and GEBAs on the progression of joint destruction should be assessed every 6-12 months in early RA (AT) and every 12 months for advanced RA and be taken into account when choosing therapy, regardless of its clinical effectiveness (FROM).
9. When choosing therapy for DMARDs and GEBD, it is necessary to take into account the duration of the disease (< 6 мес. - ранняя стадия; >6 months - advanced stage) and the presence of unfavorable prognosis factors (rheumatoid nodules, vasculitis, Felty's syndrome, positive results of the determination of RF and ACCP, as well as an increase in ESR and CRP) (FROM).

Treatment with standard DMARDs
10. Methotrexate (MT) is a first-line drug for the treatment of RA with proven efficacy and safety (A). In patients who started treatment with MT for the first time, the ratio of efficacy / safety / cost in favor of monotherapy with MT compared with combination therapy with MT and other standard DMARDs and monotherapy with biologics (BUT).
11. If there are contraindications (or poor tolerance) for the appointment of MT, you should prescribe leflunomide, sulfasalazine (BUT).
12. Before prescribing MT, risk factors for adverse reactions (AR) (alcohol intake) should be assessed, laboratory parameters (AST, ALT, albumin, complete blood count, creatinine, glucose, lipids, pregnancy test), markers of viral infections (HIV, hepatitis B/C) perform a chest x-ray (C); patients should be informed about the merits of therapy and possible adverse reactions (B)
13. Treatment with MT should be initiated at a dose of 10-15 mg/week, increased by 5 mg every 2-4 weeks up to 20-30 mg/week depending on efficacy and tolerability (AT).
14. In case of insufficient efficacy and tolerability (not severe adverse reactions) of oral MT, it is advisable to prescribe a parenteral (subcutaneous) form of the drug (B).
15. During treatment with MT, it is mandatory to take at least 5 mg of folic acid per week. (A)
16. At the beginning of treatment or with an increase in the dose of MT, the determination of ALT / AST, creatinine, a complete blood count should be carried out every 1-1.5 months until a stable dose of MT is reached, then every 3 months; clinical assessment of NR and risk factors should be performed at each patient visit (FROM). Treatment with MT should be interrupted when the concentration of ALT / AST increases > 3 upper limit of normal (ULN); resume treatment at a lower dose after normalization of indicators. With a persistent increase in the level of AST / ALT > 3 ULN, the dose of MT should be adjusted; if an increase in the level of AST / ALT > 3 ULN persists after the withdrawal of MT, appropriate diagnostic procedures should be carried out. (C)
17. In patients with early RA who have risk factors for an unfavorable prognosis, high disease activity, and are resistant to MT monotherapy, it is advisable to prescribe a combination therapy of MT and other standard DMARDs - leflunomide, sulfasalazine and hydroxychloroquine (FROM).
18. Combination therapy of MT and LEF should be carried out with caution due to the high risk of developing adverse events (gastroenterological and hepatic) (B); combination therapy of MT and LEF has no advantages over combination therapy of MT and other standard DMARDs.

Application of GIBP
19. For the treatment of RA, genetically engineered biological preparations are used - GIBP (see Table 4), which include TNF-a inhibitors (infliximab - INF, adalimumab - ADA, etanercept - ETC, certolizumab pegol - CTZ, golimumab - GLM) , anti-B cell drug - rituximab (RTM), T-lymphocyte co-stimulation blocker - abatacept (ABC) and interleukin 6 receptor blocker - tocilizumab (TCZ) (BUT).
20. The use of GEBAs is recommended in case of insufficient efficacy (moderate / high disease activity), monotherapy with MT or combination therapy with MT and other DMARDs, which should be used in adequate doses for ≥ 3 months. The drugs of choice are TNF-a inhibitors, which have similar efficacy and toxicity. (level of evidence A-C).
21. To increase the effectiveness of therapy and reduce the immunogenicity of a number of drugs, it is advisable to combine GEBD with the use of MT. (BUT).
22. In patients with MT intolerance, monotherapy with TNF-a inhibitors (ADA, ETC, CZP), IL-6R blocker (TCZ) or combination therapy with GIBD and other standard DMARDs is possible (AT).
23. In case of insufficient effectiveness of the first TNF-a inhibitor, it is advisable to prescribe a GEBP with other mechanisms of action (ABC, RTM, TCZ) (BUT), another TNF-a inhibitor or MT (in patients not treated with MT) (AT)
24. In case of insufficient effectiveness of 2 TNF-a inhibitors, GEBP with other mechanisms of action (ABC, RTM, TTZS) should be prescribed. (V/S).
25. In patients resistant to standard DMARDs, it is possible to prescribe ABC, TCZ or RTM as the first GIBD, which do not differ in efficacy and safety from TNF-a inhibitors (BUT).
26. It is advisable to prescribe RTM to patients with RA who are seropositive for RF and/or ACCP, who have extra-articular manifestations of RA or are combined with other autoimmune disorders, or who have contraindications for prescribing TNF-a inhibitors. ; to maintain the effect, it is necessary to conduct repeated courses of RTM 6 months after the previous course (AT).
27. In patients resistant to ABC, RTM or TCZ, the following therapeutic options are possible: prescribing any previously unused GEBA or DMARD; use of new antirheumatic drugs. In cases of multidrug resistance, combination therapy with RTM and TNF-a inhibitors may be discussed, since RCT data indicate the efficacy and acceptable toxicity of combination therapy with RTM (at low doses) and TNF-a inhibitors (ETC and ADA) (C).
28. Upon reaching a stable remission lasting at least 6 months, a gradual withdrawal of NSAIDs and then GCs (subject to existing dose titration recommendations) may be recommended. After the abolition of GCs and NSAIDs, a gradual, carefully controlled discontinuation of GIBD treatment is possible. While maintaining a stable remission as a joint decision of the rheumatologist and the patient, it is possible to reduce the dose and gradually cancel DMARDs. In case of insufficient stability, DMARD remissions are prescribed indefinitely, including for life (B/C).

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Rheumatoid arthritis (RA) is one of the most common and severe chronic immune-inflammatory diseases, leading to early disability of patients, there is a high level of premature mortality due to RA. Only timely diagnosis and early active treatment of patients with RA can improve the prognosis and outcomes of the disease.
The article discusses clinical situations and management algorithms for patients with RA at various stages of the disease (early, advanced and late), approaches to the treatment and prevention of osteoporotic fractures, as well as cardiovascular and gastrointestinal complications in elderly patients. The main goal of RA therapy is to achieve remission or at least low disease activity. The choice of treatment tactics is determined by the stage of RA, the activity of the disease, the presence of unfavorable prognostic factors, comorbid conditions, as well as the effectiveness of previous treatment. The early stage of RA is the most favorable for effective basic therapy. In accordance with the “Treat to target” principle, careful monitoring of disease activity is required (monthly with moderate and high activity, and every 3 months with low activity) and timely correction of basic therapy. In case of insufficient effectiveness of standard therapy with basic anti-inflammatory drugs (DMARDs), the appointment of genetically engineered biological drugs (GIBP) is indicated.

Keywords: rheumatoid arthritis, diagnostics, treatment algorithms, osteoporosis, fractures, NSAID gastropathy.

For citation: Muradyants A.A., Shostak N.A. Rheumatoid arthritis: clinical situations and treatment algorithms // RMJ. Rheumatology. 2016. No. 2. P. -95.

For citation: Muradyants A.A., Shostak N.A. Rheumatoid arthritis: clinical situations and treatment algorithms // BC. 2016. №2. pp. 89-95

Rheumatoid arthritis (RA) is one of the most common and severe chronic immune-mediated inflammatory diseases which result in early disability and high early mortality. Early diagnosis and active treatment of RA can improve prognosis and outcomes. The paper reviews clinical situations and management strategies of RA at different stages of the disease (i.e., early, advanced, and late), treatment algorithms, and approaches to prevent osteoporotic fractures, cardiovascular, and gastrointestinal complications in elderly patients. The main goal of RA therapy is to achieve remission or, at least, low disease activity. Treatment approach depends on RA stage, disease activity, factors associated with unfavorable outcome, comorbidities, and the efficacy of prior treatment. Basic therapy is the most effective in early RA. Treat-to-target approach recommends careful monitoring of RA activity (every month in high disease activity and every 3 months in low disease activity) and proper correction of basic therapy. In low efficacy of standard therapy with basic anti-inflammatory drugs, bioengineered drugs are recommended.

keywords: rheumatoid arthritis, diagnostics, treatment approaches, osteoporosis, fractures, NSAID gastropathy.

For citation: Muradyants A.A., Shostak N.A. Rheumatoid arthritis: clinical situations and treatment algorithms // RMJ. Rheumatology. 2016. No. 2. P. -95.

The article is devoted to rheumatoid arthritis - clinical situations and treatment algorithms

Rheumatoid arthritis (RA) - a chronic systemic immunoinflammatory disease of unknown etiology, accompanied by the development of symmetrical progressive erosive-destructive polyarthritis and extra-articular manifestations. RA is associated with a high risk of cardiovascular events, osteoporotic fractures, early disability and premature mortality of patients. Only timely diagnosis and early active treatment of patients with RA can improve the prognosis and outcomes of the disease.
The course of the disease consists of several successive stages: early, advanced and late, each of them has its own clinical features and approaches to therapy.
Basic principles of RA therapy ("Treat to target" or "Treatment to achieve the goal"):
1. Achieving remission (DAS28 (total index (includes a simplified score of 28 joints), allows multiple assessment of RA activity and can be used to monitor its activity in daily practice)<2,6) или как минимум низкой активности заболевания (DAS28 <3,2).
2. Early active therapy with basic anti-inflammatory drugs (DMARDs), primarily methotrexate (MT), no later than the first 3 months. from the onset of the disease.
3. Treatment should be as active as possible, with a rapid MT dose escalation and subsequent change (if necessary) in the treatment regimen within 3 months. until remission (or low activity) of the disease is achieved.
4. Careful monitoring of changes in disease activity and correction of therapy at least 1 time in 3 months. or monthly in patients with high and moderate RA activity.
5. In case of insufficient effectiveness of standard therapy for DMARDs, the appointment of genetically engineered biological drugs (GIBP) is indicated.
6. The definition of therapy tactics should be agreed with the patient.
To poor prognostic factors (FNP) in patients with RA include:
- young age;
- female;
- high titers of rheumatoid factor (RF) and / or antibodies to cyclic citrulline peptide (ACCP);
- erosive process in the joints according to X-ray examination or magnetic resonance imaging (MRI);
– increased levels of acute phase indicators: erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP);
– high disease activity according to DAS28, SDAI (Simplified Disease Activity Index) or CDAI (Clinical Disease Activity Index);
- extra-articular manifestations (Sjögren's syndrome, lung damage, etc.).
Evaluation of the effectiveness of treatment RA according to the criteria of the European Antirheumatic League (EULAR) is presented in Table 1. The generally accepted method for assessing the activity of RA is the calculation of the DAS28 index, which can be automatically generated on the website www.das-score.nl.
Criteria for the effectiveness of RA therapy:
good clinical response (≈ ACR 70) (American College of Rheumatology criteria);
low disease activity (DAS28 ≤ 3.2) or remission (DAS28 ≤ 2.6);
improvement in function (HAQ (Health Assessment Questionare, a health status questionnaire that assesses the functional abilities of patients with RA)<1,5) и качества жизни;
prevention of degradation progression:
- slowing down the growth of radiological indices (Sharp, Larsen);
- the absence of new erosions;
- stabilization or improvement of the condition according to MRI.
In patients in remission for more than 1 year after discontinuation of glucocorticosteroids (GCS), consideration should be given to discontinuing treatment with GEBAs, especially if they were used in combination with DMARDs. The choice of patients is important in determining treatment tactics.

Let us consider individual clinical situations and approaches to therapy in RA.

I. Patient with newly diagnosed early RA
The early stage of RA is a conditionally isolated, clinical and pathogenetic stage of the disease with an active synovitis duration of up to 1 year, characterized by a predominance of exudative changes in the affected joints, a frequent atypical course, and a good response to treatment. The definition of the concept of "early RA" is associated with the prevailing ideas about the pathogenesis of the disease and the need for early active therapy for RA. Early RA can debut as undifferentiated arthritis, which requires dynamic monitoring of patients and a thorough differential diagnostic search. At the early stage of RA, the most informative are the diagnostic criteria of the American and European rheumatological communities proposed in 2010 (Table 2).

The diagnosis of RA can be established with a total score of at least 6 points.
It has been proven that adequate basic therapy at an early stage of RA can prevent structural damage, which contributes to the preservation of the functional activity of patients and improves long-term prognosis. DMARDs must be prescribed no later than 3 months. from the onset of RA with rapid dose escalation to achieve optimal effect (DAS<2,4) и последующей заменой препарата в течение 3–6 мес. при его неэффективности . Терапию БПВП следует продолжать даже при снижении активности заболевания и достижении ремиссии.
First-line DMARDs include MT, leflunomide (LF), and sulfasalazine (SS) (Table 3), as they have been shown to be effective in preventing destructive joint changes (Evidence A). Second-line drugs (hydroxychloroquine, gold preparations, etc.) are used when first-line drugs are ineffective or in combination with them.
MT is the “gold standard” for active RA therapy. If necessary, the appointment of MT at a dose> 15 mg / week. it is recommended to use the parenteral route of administration (in / m or s / c). Also, in order to minimize side effects, it is necessary to prescribe folic acid 1 mg / day (5 mg / week), excluding the days of taking MT.

The main strategies for the treatment of early RA (Fig. 1) :
1. MT monotherapy followed by replacement with other DMARDs (LF, SS) after 3–6 months. in case of inefficiency or poor tolerability).
2. Combined basic therapy, including in combination with a high dose of GC. Combinations of DMARDs are used both in the first row (MT + SS or MT + LF) and in the second row (MT + Plaquenil), etc.
3. Combination therapy with synthetic DMARDs + GEBAs (primarily inhibitors of tumor necrosis factor (TNF) with high RA activity persisting > 3–6 months, as well as in the presence of FNP. For example, MT 25 mg / week + Infliximab 3 mg / day kg of body weight.

II. Patient with advanced RA not responding to conventional DMARDs
An advanced stage of RA is a disease with clearly expressed symptoms and a disease duration of more than 1 year. The articular syndrome has a persistent, symmetrical and polyarticular character with a predominant lesion of the joints of the hands and feet, signs of high or moderate laboratory activity, RF seropositivity, and an erosive process in the joints according to radiography are revealed. If the diagnosis is established for the first time, then the patient management strategy is the same as in early RA. In the case of already conducted treatment with an insufficient effect or intolerance to synthetic DMARDs (both in the form of monotherapy and in their combined use), as well as the presence of FNP, GEBAs are prescribed (Fig. 2). The use of GIBP allows the most selective effect on individual links in the immunopathogenesis of RA and significantly improves the condition of patients with RA who are resistant to standard DMARDs and GCs. It has been established that the combination of traditional DMARDs with GEBA is more effective than monotherapy.
The appointment of GIBP is shown:
– with long-term (> 3–6 months) high RA activity;
- high disease activity< 3 мес., только при наличии у больных ФНП.
TNF-α inhibitors are the first-line drugs among GEBDs. Other GEBAs are prescribed to RA patients with an inadequate response to TNF-α blockers or when they cannot be used (Table 4).

Contraindications to the appointment of GEBA: lack of treatment with one or more DMARDs (primarily MT) at a full therapeutic dose; relief of exacerbations; severe infectious diseases (sepsis, septic arthritis, pyelonephritis, osteomyelitis, tuberculosis and fungal infections, human immunodeficiency virus), malignant neoplasms; pregnancy and lactation.

III. Patient with late RA and osteoporotic fractures
The late stage of RA is defined as the stage of irreversible structural changes (deformities, subluxations) of the joints with a disease duration of > 2 years, with or without pronounced signs of active inflammation (Fig. 3). The steady progression of the disease leads to the formation of various types of subluxations and contractures of the joints, in connection with which the role of rehabilitation and orthopedic measures increases.

The development of osteoporosis (OP) and associated fractures is one of the most severe complications of RA, which determines the unfavorable course and prognosis of the disease. The frequency of osteoporotic fractures among patients with RA is 1.5–2.5 times higher than in the general population. It is assumed that the development of OP and articular destruction in RA has common pathogenetic mechanisms, which are based on cytokine-dependent activation of osteoclastogenesis, leading to increased bone resorption. The development of AP in RA is determined by many general and specific risk factors associated with the disease and treatment.
RA-associated risk factors for OP and fractures:
- the activity of the inflammatory process,
- X-ray stage
– severity of functional disorders (HAQ > 1.25),
- duration of illness
- intake of GC,
- high risk of falls.
In patients with RA, glucocorticosteroids increase the risk of vertebral fractures by 4–5 times and double the risk of hip fractures. It has been proven that there is no safe dose of HA. It should also be remembered that the development of fractures in patients receiving GC occurs at higher values ​​of tissue mineral density (BMD) than in primary OP, so anti-osteoporotic therapy should be started at T-criterion values< -1,5 стандартного отклонения от референсных значений.
The management program for patients with RA and osteoporotic fractures includes control of RA activity, correction of modifiable risk factors for OP and fractures, prevention of falls, anti-osteoporotic therapy, diet and exercise. All patients with RA need to calculate the absolute risk of fractures (FRAX-algorithm) (fracture risk assessment tool, 10-year absolute risk of fracture - a WHO fracture risk assessment tool) and prophylactic administration of calcium and vitamin D preparations. Anti-osteoporotic therapy is prescribed without taking into account BMD data. in patients aged 65 years and older with a history of fractures with minimal trauma. Bisphosphonates (BP) and antibodies to RANKL (nuclear factor kappa beta activator receptor ligand) with antiresorptive action are the first-line drugs in the treatment of OP in RA patients (Table 5). The attractiveness of BP in RA lies in the fact that, according to experimental studies, they can have a beneficial effect on the course of the disease. It has been established that BPs are able to inhibit the synthesis of pro-inflammatory cytokines and the development of bone erosions in RA. In patients with early arthritis, BP in combination with MT effectively prevents the development of bone destruction.

IV. Elderly patient with RA and NSAID gastropathy
RA in the elderly is characterized by an active, rapidly progressive course, a high level of comorbidity, and poor outcomes. Of particular importance in the structure of comorbid conditions in RA are cardiovascular and gastrointestinal pathologies. According to numerous studies, cardiovascular morbidity and mortality in RA patients is 2–4 times higher than in the general population, which dictates the need for timely identification and correction of cardiovascular risk factors.
Recommendations for reducing cardiovascular risk in patients with RA:
ASA should be taken ≥2 hours before taking non-steroidal anti-inflammatory drugs (NSAIDs).
Do not use NSAIDs for 3-6 months. after an acute cardiovascular event or procedure.
Monitor blood pressure regularly.
Use NSAIDs at low doses with a short half-life (avoid extended-release NSAIDs).
NSAID-gastropathy is one of the most common complications of long-term use of NSAIDs, manifested as an erosive or ulcerative lesion of the upper gastrointestinal tract (GIT) (mainly antrum and prepyloric stomach). Taking NSAIDs does not affect the progression of RA, however, it allows better control of the symptoms of the disease during the treatment of DMARDs and GEBAs. NSAID-associated risk factors for gastrointestinal and cardiovascular complications are presented in Table 6.
EULAR experts have developed a "calculator" for the individual selection of NSAIDs, depending on the presence of risk factors for the gastrointestinal tract and the cardiovascular system. NSAIDs with the lowest cardiovascular risk include naproxen, celecoxib, ketoprofen, low-dose ibuprofen (<1200 мг/сут). Основные лекарственные средства, которые используют для лечения НПВП-индуцированных гастропатий, - ингибиторы протонной помпы (ИПП), Н2-блокаторы и мизопростол (синтетический аналог ПГ Е2). Алгоритмы выбора НПВП у больных РА с учетом гастроинтестинального и сердечно-сосудистого риска представлены в таблице 7 .
Not so long ago, a new generation of NSAIDs appeared that increase the activity of nitric oxide (NO) in the gastric mucosa (NO-NSAIDs). As is known, NO has gastroprotective properties: it stimulates the secretion of mucus, bicarbonate, improves microcirculation, inhibits the adhesion of leukocytes to the endothelium, which determines the pharmacological advantages of this group of NSAIDs. One of the representatives of NO-NSAIDs is the drug Nizilat (amtolmetin guacil), which, along with high analgesic and anti-inflammatory activity, has gastroprotective properties. In randomized clinical trials, a lower frequency and severity of damage to the gastric mucosa after the use of amtolmetin guacil were demonstrated compared with those of other non-selective NSAIDs (diclofenac, indomethacin, piroxicam), with comparable anti-inflammatory and analgesic efficacy. A comparative study of amtolmetin guacil 1200 mg/day and celecoxib 400 mg/day in patients with RA showed equivalent efficacy and safety of the drugs. The therapeutic dose of amtolmetin guacil (Nayzilat) is 600 mg 2 times / day on an empty stomach, maintenance - 600 mg / day.

Conclusion
RA is a heterogeneous disease, the outcomes of which are largely determined by the timely diagnosis of the disease and the right treatment tactics. Early stage RA, especially the first 3 months. from the onset of the disease, are most favorable for effective basic therapy. The basis for the management of patients with RA is careful monitoring of disease activity (at least 1 time / 3 months) with subsequent correction of therapy if necessary. The choice of therapy is determined by the stage of RA, disease activity, the presence of FNP, coexisting comorbid conditions, and the effectiveness of previous treatment.

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Rheumatoid arthritis is a severe autoimmune disease of the joints. Clinical recommendations for diagnosis, treatment, rehabilitation and prevention.

Rheumatoid arthritis is a rheumatic autoimmune disease, the causes of which remain unknown to modern medicine.

Pathology is manifested by chronic erosive arthritis and systemic damage to internal organs.

All this often causes early disability and shortened life expectancy of patients.

RA diagnoses according to the ICD-10 classification:

Consider what rheumatoid arthritis is, clinical guidelines for its diagnosis and treatment.

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The main thing in the article

The manifestation of the disease is variable. Most often, it begins with polyarthritis, in more rare cases, the signs of arthritis can be mild, but the following symptoms predominate:

• pain and stiffness in the joints,
• deterioration in general condition;
• weakness, fatigue;
• weight loss;
• temperature rise to subfebrile values;
• swollen lymph nodes.

All this may precede clinically pronounced joint damage.

• skin;
• muscle corset;
• bronchopulmonary system;
• of cardio-vascular system;
• urinary system;
• endocrine system.

Assessment of the patient's appearance allows you to identify:

1. Deficiency in body weight.
2. Hyperhidrosis.
3. Generalized amyotrophy.
4. Inflammation of the mucous membrane of the eyes.
5. Lymphadenitis, lymphadenopathy.
6. Skin pathologies - rheumatoid nodules, thickening, hypotrophy.
7. Digital arteritis, sometimes with the development of gangrene of the fingers.
8. Microinfarcts in the area of ​​the nail bed.

Rheumatoid arthritis is characterized by symmetrical multiple lesions of the small joints of the feet and hands.

With an acute onset and active inflammation, periarticular osteoporosis and single cysts are detected within a month from the onset of the pathological process, while multiple cysts, narrowing of the joint spaces and single erosions are detected only after 3-6 months from the onset of the disease, especially in the absence of therapeutic measures.

It is not recommended to take basic anti-inflammatory drugs in patients with RA who have previously had non-melanoma skin cancer or have a history of solid tumors. Genetically engineered biological preparations in this case should be used with great care.

It is also undesirable to take hydroxychloroquine, sulfasalazine, rituximab, TNF-a inhibitors in patients with rheumatoid arthritis with a history of lymphoproliferative diseases - chronic lymphocytic leukemia, hairy cell leukemia, extramedullary tumors, etc. Other DMARDs and genetically engineered biologics are prescribed to such patients with caution.

Side effects of treatment with genetically engineered biological drugs

GEBA therapy is a fairly safe method of treatment, although in some cases various adverse (up to severe) reactions are possible that require careful monitoring - systemic immune reactions, hypersensitivity reactions (including anaphylaxis), severe infections (including latent tuberculosis infection), as well as local reactions with subcutaneous administration of the drug.

☆ Standard for Primary Health Care for Rheumatoid Arthritis. Medical measures for diagnosing a disease in the Consilium System.

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Treatment tactics after achieving remission

A gradual, carefully controlled dose reduction or withdrawal of GIBAs is possible if a stable remission is achieved after the withdrawal of glucocorticoids or if they continue to be taken at a dose of less than 5 mg per day.

Cancellation of genetically engineered drugs is more likely in patients with early RF/ACCP-negative rheumatoid arthritis.

In some cases, against the background of the cancellation or reduction of the dosage of genetically engineered biological products, the patient develops an exacerbation, which requires immediate re-appointment of the same or other GEBDs.

As a rule, this measure leads to a rapid suppression of inflammation activity in most patients.

An exacerbation against the background of discontinuation of GEBAs or a decrease in their dose most often develops with an advanced RF/ACCP-positive variant of rheumatoid arthritis.

The attending physician should consider reducing the dose or discontinuing standard DMARDs when long-term stable remission is achieved after completion of treatment with genetically engineered drugs.

In patients with an advanced form of the disease, the abolition of basic drugs usually provokes an exacerbation, and therefore is not recommended.

Surgery

Surgical treatment of rheumatoid arthritis is carried out in a traumatological and orthopedic hospital.

Indications for it:

1. Synovitis resistant to drug treatment.
2. Joint deformities, violation of their functions.
3. Chronic pain syndrome.

Types of surgical treatment:

• arthroscopic and open synovectomy;
• debridement;
• osteotomy;
• osteoplasty;
• joint arthroplasty.

Surgical intervention leads to an improvement in the functional abilities of the patient in the medium term.

In the perioperative period, patients with rheumatoid arthritis are treated with cytostatics, in particular, methotrexate.

Its cancellation can provoke an exacerbation of RA in the postoperative period and significantly worsen the results of the intervention. A contraindication to the use of methotrexate is only the presence of severe renal pathologies in the patient.

Before surgery, treatment with genetically engineered biological products is interrupted for a time depending on their pharmacokinetic properties.

The term for stopping treatment depends on:

• half-life of drugs - 3-5 times longer than their half-life;
• individual characteristics of the patient;
• the nature of the upcoming operation.

Therapy is resumed if there is no information about the presence of infection, and the surgical wound surface heals and is in a satisfactory condition.

Hormone therapy continues in the postoperative period at the same dosage. On the day of surgery, a patient with rheumatoid arthritis is shown the appointment of replacement therapy (in / in the infusion of hydrocortisone 25-100 mg or 6-MPRED - 5-30 mg, depending on the severity of the intervention).