The aim of RA treatment is to control the disease and improve joint function and prognosis. The principles of early treatment, combination of drugs and individualized treatment should be emphasized. Treatment methods include general treatment, drug therapy and surgical and other treatments.
1.General treatment
Emphasize patient education and the concept of holistic and standardized treatment. Appropriate rest, physical therapy, body therapy, topical medication, proper joint activities and muscle exercises play an important role in relieving symptoms and improving joint function.
2.Medication
Commonly used drugs for the treatment of RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), biological agents, glucocorticoids and botanicals.
(1) NSAIDs
These drugs have anti-inflammatory, analgesic, antipyretic and joint swelling effects mainly by inhibiting cyclooxygenase activity and reducing prostaglandin synthesis, and are the most commonly used drugs for RA treatment (see Table 5).
NSAIDs
have an important role in relieving patients’ joint swelling and pain and improving systemic symptoms. Their major adverse effects include gastrointestinal symptoms, hepatic and renal impairment, and a possible increase in cardiovascular adverse events. According to the available evidence-based medical evidence and expert consensus, the following points should be noted in the use of NSAIDs.
① Focus on individualization of the type, dose and dosage form of NSAIDs;
② Use the lowest possible effective dose and short duration of treatment;
③ Generally use one NSAIDs first, and then switch to another one when there is no obvious effect for a few days to a week, avoid taking two or more NSAIDs at the same time;
④ For patients with a history of peptic ulcer, selective COX-2 inhibitors or other NSAIDs plus proton pump inhibitors are recommended;
⑤ The elderly can use NSAIDs with short half-life or smaller doses;
(6) NSAIDs should be used with caution in people at high cardiovascular risk, and acetaminophen or naproxen are recommended if needed;
(7) NSAIDs should be used with caution in patients with renal insufficiency;
⑧ Pay attention to the regular monitoring of blood routine and liver and kidney function.
Topical preparations of NSAIDs (such as diclofenac diethylamine emulsion, capsaicin cream, ketoprofen gel, piroxicam patch, etc.) and botanical creams are useful in relieving joint swelling and pain, and have fewer adverse effects, so their use should be advocated in clinical practice.
(2) DMARDs
DMARDs are anti-rheumatic drugs (DMARDs) that improve the disease. These drugs are slower acting than NSAIDs, and it takes about 1 to 6 months for the clinical symptoms to improve significantly.
Therefore, they are also called slow-acting antirheumatic drugs (SAARDs). These drugs do not have obvious analgesic and anti-inflammatory effects, but can slow down or control the progression of the disease. The early use of DMARDs should be emphasized in patients with RA, and the combination of DMARDs should be considered in patients with severe disease, multiple joint involvement, extra-articular manifestations, or early joint destruction and other poor prognostic factors. DMARDs are commonly used in the treatment of RA.
1) Methotrexate (MTX)
It is effective when given orally, intramuscularly, intra-articularly or intravenously, and is administered once a week. It can be used in combination with other DMARDs if necessary. Commonly used dose is 7.5-20mg/w. Common adverse reactions include nausea, stomatitis, diarrhea, alopecia, rash and hepatic damage, with a few cases of bone marrow suppression and occasional interstitial lung lesions. It is inconclusive whether it causes miscarriage, teratogenesis and affects fertility. Folic acid should be supplemented appropriately and regular blood and liver function checks should be performed during the drug administration.
2) Sulfasalazine (SSZ)
It can be used alone for short duration and mild RA, or in combination with other DMARDs for longer duration and moderate and severe disease. It is generally effective after 4 to 8
SSZ is usually effective after 4-8 weeks. Gradual dose increases from small doses can help reduce adverse effects. The main adverse effects include nausea, vomiting, abdominal pain, diarrhea, skin rash, increased transaminases and decreased spermatozoa, occasionally decreased white blood cells and platelets, and caution in patients with allergy to sulfonamide. Regular blood tests and liver and kidney functions should be performed during the drug administration.
3) Leflunomide (LEF)
The dose is 10-20mg/d orally. It is mainly used for patients with long duration of disease, severe disease and poor prognostic factors. The main adverse effects include diarrhea, pruritus, hypertension, increased liver enzymes, rash, alopecia and decreased white blood cells. It is prohibited for pregnant women because of its teratogenic effect. Blood test and liver function should be checked regularly during the drug administration.
4) Antimalarials
These include hydroxychloroquine and chloroquine. They can be used alone for patients with short duration and mild disease. For severe cases or those with poor prognosis, they should be combined with other DMARDs. These drugs are slow-acting and take 2 to 3 months to work. The dose is hydroxychloroquine 200 mg/d, bid. chloroquine 250 mg/d, qd.
/The former has fewer adverse effects, but the fundus should be checked annually before and during treatment to monitor for possible retinal damage caused by the drug. Chloroquine is less expensive, but ocular damage and cardiac-related adverse reactions (e.g., conduction block) are more common than the former and should be noted.
5) Penicillamine (D-pen)
250-500mg /d orally, can be gradually reduced to maintenance dose of 250mg /d after effect, generally used in patients with mild disease or combined with other DMARDs in severe RA. adverse effects include nausea, anorexia, rash, oral ulcers, loss of smell and liver and kidney damage. Blood and urine routine and liver and kidney function should be checked regularly during treatment.
6) Auranofin
It is an oral gold preparation with an initial dose of 3mg/d, which is increased to 6mg/d after 2 weeks for maintenance treatment. It can be used for different degrees of RA, and should be used in combination with other DMARDs for patients with severe disease.
Combination use. Common adverse reactions include diarrhea, pruritus, stomatitis, liver and kidney damage, leukopenia, and occasionally peripheral neuritis and encephalopathy. Blood and urine routine and liver and kidney function should be checked regularly.
7) Azathioprine (AZA)
Commonly used at a dose of 1-2 mg/(kgqd), usually 100-150 mg/d. Mainly used in patients with severe RA. Adverse effects include nausea, vomiting, alopecia, rash, liver damage, bone marrow suppression, possible damage to the reproductive system, and occasionally teratogenic. Blood tests and liver function should be checked regularly during the drug administration.
8) Cyclosporin A (CysA)
Compared with other immunosuppressants, the main advantage of CysA is that there is little myelosuppression, and it can be used in patients with RA who have severe or long disease duration and poor prognosis. The commonly used dose is 1 to 3 mg/(kgqd). The main adverse effects include hypertension, hepatic and renal toxicity, gastrointestinal reactions, gingival hyperplasia and hypertrichosis. The severity and duration of adverse reactions are related to the dose and blood concentration. Blood test, blood creatinine and blood pressure should be checked during the drug administration.
9) Cyclophosphamide (CYC)
CYC is less commonly used in RA, and may be used in patients with severe disease when remission is difficult with multiple drug therapy. The main adverse effects include gastrointestinal reactions, hair loss, bone marrow suppression, liver damage, hemorrhagic cystitis, and gonadal suppression.
(3) Biologic agents
Biological agents for RA include tumor necrosis factor (TNF)-α antagonists, interleukin-1 (IL-1) and interleukin-6 (IL-6) antagonists, anti-CD20 monoclonal antibodies, and T-cell co-stimulatory signaling inhibitors.
1) TNF-α antagonists
This class of agents mainly includes imported Etanercept, Infliximab and Adalimumab, as well as domestic Lisep and Qiangke. Compared with conventional DMARDs, the main features of TNF-α antagonists are rapid onset of action, significant inhibition of bone destruction, and good overall patient tolerability. The recommended dose and usage of etanercept is 25 mg/dose by subcutaneous injection twice a week or 50 mg/dose once a week. The recommended dose of infliximab for RA is 3 mg/kg/dose once in weeks 0, 2, and 6 and once every 4 to 8 weeks thereafter. The dose of adalimumab for RA is 40 mg/dose by subcutaneous injection every 2 weeks. These agents can have injection site reactions or infusion reactions and may increase the risk of infection and neoplasia, occasionally drug-induced lupus-like syndrome, and demyelinating lesions. Tuberculosis screening should be performed prior to drug administration to exclude active infections and tumors.
2) IL-1 antagonists
Anakinra is the only IL-1 antagonist currently approved for the treatment of RA. The recommended dose is 100 mg/d by subcutaneous injection. The main adverse effects are dose-related injection site reactions and a possible increase in the chance of infection.
3) IL-6 antagonist (Tocilizumab)
It is mainly used in patients with moderate to severe RA and may be effective in patients who do not respond well to TNF-α antagonists. The recommended use is 4 to 10 mg/kg administered by intravenous infusion every 4 weeks. Common adverse effects are infection, gastrointestinal symptoms, rash, and headache.
4) Anti-CD20 monoclonal antibody
The recommended dose and use of rituximab (Rituxiamb) is 500-1000 mg intravenously for the first course of treatment, repeated after two weeks. A second course may be given after 6 to 12 months, depending on the condition. Each injection of rituximab is preceded by an intravenous dose of methylprednisolone given within half an hour. The most common adverse effect is infusion reactions, the incidence and severity of which can be reduced by intravenous glucocorticoid administration. Other adverse reactions include hypertension, rash, pruritus, fever, nausea, arthralgia, etc., and may increase the chance of infection.
5) CTLA4-Ig
Abatacept is used to treat patients with severe disease or poor response to TNF-α antagonists. The recommended doses are 500mg (<60kg), 750mg (60kg-100kg) and 1000mg (>100kg) administered intravenously at week 0, 2 and 4, respectively, and then every 4 weeks depending on the patient’s body weight. The main adverse effects are headache and nausea, and may increase the incidence of infection and tumor.
(4) Glucocorticoids
Glucocorticoids (hormones) can rapidly improve joint pain and systemic symptoms. In patients with severe RA with cardiac, pulmonary or neurological involvement, short-acting hormones can be given in doses that depend on the severity of the disease. Small doses of hormones (prednisone ≤ 7.5 mg/d) are only indicated for a small number of patients with RA. Hormones can be used in the following conditions.
① Severe RA with extra-articular manifestations such as vasculitis;
② Patients with RA who cannot tolerate NSAIDs as a “bridge” treatment;
③ Patients with RA in whom other treatments are not effective;
③ Patients with RA in whom other treatments are not effective; ④ Patients with indications for local hormone therapy (e.g., intra-articular injections).
The principle of hormone therapy for RA is small doses and short courses. The use of hormones must be accompanied by DMARDs, and calcium and vitamin D supplements should be given during hormone therapy to prevent osteoporosis. Hormone injections into the joint cavity are beneficial in reducing arthritic symptoms, but over-frequent puncture of the joint cavity may increase the risk of infection and steroid crystalloid arthritis may occur.
(5) Botanical preparations
1) Radix et Rhizoma
It is effective in relieving joint swelling and pain, but there is a lack of research on whether it slows down joint destruction. Generally, 30-60 mg/d of Radix Polygoni is given in 3 divided doses with meals. The main adverse effect is gonadal suppression, leading to male infertility and female amenorrhea. Other adverse reactions include rash, hyperpigmentation, nail tenderness, hair loss, headache, nausea, vomiting, abdominal pain, diarrhea, bone marrow suppression, elevated liver enzymes, and elevated blood creatinine.
2) Total Paeoniflorin
The usual dose is 600mg, 2-3 times daily. It is effective in reducing joint swelling and pain. Adverse effects are less frequent, mainly abdominal pain, diarrhea, poor appetite, etc.
3) Cyanophylline
20-60mg per dose, taken orally before meals, 3 times daily, can reduce joint swelling and pain. The main adverse reactions include skin itching, rash and leukopenia.
3. Surgical treatment
If the condition of RA patients cannot be controlled after regular medical treatment, surgery can be considered to relieve pain, correct deformity and improve the quality of life. However, surgery cannot cure RA, so drug treatment is still needed after surgery. Commonly used surgeries include synovectomy, artificial joint replacement, joint fusion and soft tissue repair.
(1) Synovectomy
For those who still have obvious joint swelling and synovial thickening after active and regular medical treatment, and whose X-ray shows that the joint space has not disappeared or is not significantly narrowed, synovectomy can be considered to prevent further destruction of articular cartilage, but regular medical treatment is still required after surgery.
(2) Artificial joint replacement
For those whose joint deformity obviously affects the function, who are not treated by internal medicine, and whose X-ray shows the disappearance or obvious narrowing of the joint space, artificial joint replacement can be considered. This surgery can improve the patient’s daily living ability, but there should be standardized drug treatment before and after surgery to achieve the best treatment effect and avoid recurrence.
(3) Joint fusion
With the successful application of artificial joint replacement, joint fusion has been rarely used in recent years, but it is feasible for patients with advanced arthritis, severe joint destruction and joint instability. In addition, arthrofusion can be used as a salvage procedure for failed arthroplasty.
(4) Soft tissue surgery
In addition to joint deformity, atrophy of the joint capsule and surrounding muscles and tendons is also the cause of joint deformity in RA patients. Therefore, joint function can be improved by joint capsule dissection, arthrotomy, tendon release or lengthening, etc. Carpal tunnel syndrome can be treated with transverse carpal ligament dissection and decompression. Bursitis in the shoulder and hip joints requires surgical removal if conservative treatment is ineffective, and N-fossa cysts occasionally require surgical treatment. Rheumatoid nodules are large, have painful symptoms, and can be considered for surgical removal when conservative treatment is ineffective and affects life.
4.Other treatments
In addition to the aforementioned treatments, plasma exchange or immunosorbent therapy can be considered for a small number of patients with poor efficacy of standardized medication, high titer autoantibodies in the serum and significantly increased immunoglobulins. However, the clinical principles of strict control of the indications and the combination of DMARDs should be emphasized. In addition, autologous stem cell transplantation, T-cell vaccine and mesenchymal stem cell therapy may be effective in the remission of RA, but they are only applicable to a small number of patients and require strict control of indications.