A. Current status of treatment of ankylosing spondylitis
Ankylosing spondylitis is an autoimmune disease of unknown etiology. Although there is no specific cure, the condition of the majority of patients can be well controlled through systematic and standardized treatment, which can reduce or even avoid the occurrence of disability.
The goals of treatment for ankylosing spondylitis are
① Relief of signs and symptoms – Eliminate or minimize symptoms such as back pain, morning stiffness and fatigue.
② Restoration of function – To maximize the restoration of physical functions such as spinal mobility, social mobility and work capacity.
③ Prevent joint damage – To prevent new bone formation, bone destruction, bony ankylosis and spinal deformation in patients with involvement of the hip, shoulder, mid-shaft and peripheral joints.
④ To improve patients’ quality of life-including socioeconomic factors, work, medical retirement, and retirement.
⑤ Preventing complications of spinal disorders-preventing spinal fractures and flexion contractures, especially in the cervical spine.
Third, the treatment options and principles of ankylosing spondylitis
There is no cure for AS. However, with timely diagnosis and appropriate treatment, patients can achieve symptom control and improve prognosis. Non-pharmacological, pharmacological and surgical treatment should be used to relieve pain and stiffness, control or reduce inflammation, maintain good posture, prevent deformation of the spine or joints, and correct deformed joints if necessary, in order to improve and enhance the quality of life of patients.
1.Non-pharmacological treatment
① Education of patients and their families about the disease is an indispensable part of the overall treatment plan, which helps patients to actively participate in treatment and cooperate with physicians. The long-term plan should also include the patient’s psychosocial and rehabilitation needs.
② Patients should be counseled to exercise reasonably and consistently to obtain and maintain the best position of the spinal joints, strengthen the paravertebral muscles and increase lung capacity; swimming is one of the good and effective adjuncts to treatment.
③ Standing should try to maintain the posture of chest up, abdomen and eyes flat in front, and sitting should also keep the chest upright. One should sleep on a hard bed and take more supine positions to avoid positions that promote flexion deformity. Pillows should be short and should be discontinued once upper thoracic or cervical spine involvement occurs.
④ Select the necessary physical therapy for painful or inflamed joints or other soft tissues.
⑤ Smokers are advised to quit smoking; patient smoking is one of the risk factors for poor functional prognosis.
2.Medication
(1) Non-steroidal anti-inflammatory drugs (NSAIDs)
This class of drugs can rapidly improve patients’ low back pain and morning stiffness, reduce joint swelling and pain and increase range of motion, and is preferred for symptomatic treatment in both early and late stage AS patients. There is a wide range of anti-inflammatory drugs, but their efficacy in AS is generally comparable.
The most common adverse effects of NSAIDs are gastrointestinal discomfort and a few ulcers; other less common are cardiovascular diseases such as hypertension, which may be accompanied by headache, dizziness, liver and kidney damage, hematocrit, edema and allergic reactions. The physician should choose one anti-inflammatory drug for each patient. The use of two or more anti-inflammatory drugs at the same time will not increase the efficacy, but will increase the adverse drug reactions and even have serious consequences. Regardless of the NSAID used, in order to not only achieve symptomatic improvement but also to delay or control progression, it is usually recommended to continue using the appropriate drug at the therapeutic dose for a longer period of time. To assess the effectiveness of a particular NSAID, the same dose should be used consistently and regularly for at least two weeks. If a drug is not effective for 2-4 weeks, it should be switched to another anti-inflammatory drug of a different class. Adverse drug reactions should always be monitored and adjusted promptly during the course of drug administration.
(2) Biological agents
Mainly anti-tumor necrosis factor-α antagonists, the imported ones include.
① Etanercept (Etanercept);
② Infliximab;
③ Adalimumab.
Domestic ones include.
①Ixepro;
②Qiangk.
These drugs have been evaluated in a number of randomized double-blind placebo-controlled trials for the treatment of AS, with an overall efficiency of about 50%-75% (see “Standardized Treatment of Rheumatoid Arthritis” for application methods).
Antitumor necrosis factor-alpha antagonists are recommended for continued use if they are effective for 6 to 12 weeks. Patients who are dissatisfied with or cannot tolerate one of the antitumor necrosis factor-alpha antagonists may have a better outcome with another agent. However, their long-term efficacy and effect on axial joint x-ray lesions in AS remain to be studied. Studies suggest that patients who initially respond well appear to sustain efficacy for at least two years. The use of anti-tumor necrosis factor-alpha antagonists may also reduce the frequency of recurrences of uveitis. Although they recommend only for patients with “definitive” AS according to classification criteria, some studies suggest that for patients with AS who lack typical clinical radiological changes and do not meet the diagnostic criteria for AS (i.e., meet the “probable” or SpA criteria of the AS classification criteria) Patients with AS who do not meet the diagnostic criteria for AS (i.e., meet the “probable” or SpA criteria for AS classification) may also be treated with antitumor necrosis factor antagonists in the following cases: moderately severe active spinal lesions despite treatment with NSAIDs; or ‘moderately severe active peripheral arthritis despite the use of NSAIDs and one other disease-controlling agent.
The most significant adverse reactions to TNF-α antagonists are infusion reactions or point-of-injection reactions, ranging from nausea, headache, pruritus, and dizziness to hypotension, dyspnea, and chest pain. Other adverse reactions were an increased chance of infection, including common respiratory tract infections and opportunistic infections (e.g., tuberculosis), but did not reach statistical significance compared with placebo. Pretreatment screening for tuberculosis significantly reduces the incidence of tuberculosis associated with TNF-α antagonist therapy and is now routine. Exacerbations of demyelinating disease, lupus-like syndrome, and congestive heart failure have also been reported, but the incidence is low. Routine blood and urine tests and liver and kidney function should be reviewed regularly during drug administration.
(3) Salicyclovir
This product can improve joint pain, swelling and stiffness in AS, and reduce serum IgA levels and other laboratory activity indicators, especially for improving peripheral arthritis in AS patients. To date, there is a lack of evidence on the therapeutic effect of this product on the mesial joint lesions of AS and on the prognosis of the disease. The usual recommended dosage is 2.0g/day in 2 to 3 oral doses. Increasing the dose to 3.0g/d increases the efficacy but also increases the number of adverse effects. The onset of action of this product is slow, usually 4-6 weeks after dosing. To increase patient tolerability, the dose is usually started at 0.25g 3 times a day and then increased by 0.25g weekly until 1.0g twice a day. The dose and duration of treatment may be adjusted according to the condition or the patient’s response to treatment and maintained for 1 to 3 years. To compensate for the slow onset of action of salazosulfapyridine and its weak anti-inflammatory effect, a fast-acting anti-inflammatory drug is usually used in combination with it. Adverse reactions include gastrointestinal symptoms, rash, hematocrit, headache, dizziness, and reduced spermatozoa and abnormal morphology in men (recoverable with discontinuation). It is contraindicated in patients with sulfa allergy.
(4) Glucocorticoids
Oral or intravenous systemic corticosteroids are generally not recommended for the treatment of AS because of their side effects and inability to stop the course of AS. Intractable tendon terminal disease and persistent synovitis may respond well to topical corticosteroid therapy. Uveitis can be better controlled by pupil dilation and hormonal spotting of the eye. Refractory iritis may require systemic hormone or immunosuppressive therapy. Intra-articular injections of glucocorticoids may be used for intractable peripheral joint (e.g., knee) effusions that do not respond well to systemic medications, but repeated injections should be given at 3- to 4-week intervals, usually no more than 2 to 3 times/year. Similarly, CT-guided intra-sacroiliac joint steroid injections may be an option for patients with intractable sacroiliac joint pain. Tendon terminal disease similar to heel pain can also be treated with local steroid injections.
(5) Other medications
Thalidomide has been used in some men with refractory AS and has shown significant improvement in clinical symptoms, blood sedimentation and C-reactive protein. The initial dose is 50 mg/d, and the dose is increased by 50 mg every 10 days to 200 mg/d, and 300 mg/d has been used overseas. Insufficient dose is ineffective, and the symptoms are likely to recur rapidly after discontinuation of the drug. The adverse effects of this product include drowsiness, thirst, decreased blood cells, increased liver enzymes, microscopic hematuria and tingling sensation at the fingertips. Therefore, patients who choose this treatment should be closely monitored, and blood and urine tests should be performed weekly at the beginning of the drug, and liver and kidney functions should be checked every 2 to 4 weeks. Regular neurological examinations should be performed for long-term users to detect possible peripheral neuritis. Methotrexate and anti-rheumatic botanicals (see “Standardized treatment of rheumatoid arthritis”) can be used for patients with peripheral joint involvement in AS who lack efficacy of the above treatments, but their efficacy in medial joint lesions is uncertain and needs further study.
(6) Surgical treatment
Joint space narrowing, ankylosis and deformity caused by hip joint involvement are the main causes of disability in this disease. In order to improve the joint function and quality of life of patients, artificial total hip replacement is the best choice. The majority of patients have their joint pain controlled, some have normal or near-normal function, and 90% of the life expectancy of the replaced joint is more than 10 years.