Ankylosing spondylitis is known as the “undead cancer” because of the physical disability that results when patients are not treated regularly. However, early diagnosis, long-term treatment, and regular follow-up can lead to a “disease-free” state, where a small amount of medication can be used to keep the disease stable, non-progressive, and non-disabling, and to “live with the disease and dance with the wolves.
Some patients refer to ankylosing spondylitis (AS) as an “incurable cancer”, implying that it is incurable.
The term “undead cancer” refers to patients with ankylosing spondylitis who, in the absence of formal treatment, suffer from physical disabilities that can seriously affect their lives and work. However, in fact, early diagnosis, early treatment, long-term treatment and regular follow-up can achieve a “disease-free” state, i.e., the application of a small amount of medication can keep the disease stable, non-progressive and non-disabling, and achieve “living with the disease, dancing with the wolves”.
Many doctors emphasize exercise for their patients. Why is exercise so important for AS patients?
The importance of exercise is indeed no less than that of medication, and like rheumatoid arthritis and other diseases, the more you exercise, the better AS is. Often patients, once this disease is discovered, are off school and bedridden, which is a fundamental mistake. Exercise relieves symptoms, prevents spinal and joint disability, builds muscle strength, increases lung capacity, and improves quality of life.
It has been shown that after 6 months of exercise can also significantly improve self-confidence and joint flexibility and improve joint function. However, it is important to emphasize that exercise should be done carefully and without interruption.
Is the exercise program, intensity and duration, different for patients with ankylosis who have progressed to different stages of the disease?
Yes, the exercise program, intensity and duration vary with the duration of the disease and the site of involvement. If the disease is long and there is a hunchback, flat spine, and limited chest expansion, back exercises and chest expansion exercises should be emphasized, and because of poor spinal mobility and easy combination of osteoporosis, impact strenuous exercises should be avoided.
Patients with shorter disease duration and better joint and spinal mobility can do some recreational exercises, such as radio gymnastics, swimming and Tai Chi. However, it is important to note that swimming should not be done in cool water, but in warm water, such as hot springs. There are special spas abroad for patients to use. And playing tai chi can improve the flexibility and agility of joints.
Regarding the continuity of exercise is more important than the intensity level of exercise, in general, moderate intensity exercise (2-4 hours/week) is more desirable than no exercise and high intensity exercise (>10 hours/week). At least 5 times a week for at least 30 minutes each time.
Once ankylosis is diagnosed, is there a certain posture that patients should be aware of when sitting, standing, sleeping, etc.?
Sitting, standing and sleeping postures are indeed important. First of all, it is important to keep the body upright, avoid long-term bending and flexion, do not adopt a posture for a long time, and change the position appropriately to maintain the normal physiological curvature of the spine and prevent spinal deformity.
Second, try to sleep on a hard bed, using supine or prone position, avoid side lying, especially the flexion of the leg side lying position. Although the flexion position can reduce pain, but easy to lead to spinal hunchback deformity. If there is cervical spine involvement, the pillow should be low or go to the pillow to lie flat to prevent cervical spine reverse arch deformity. If a pillow is used, it should be as low as possible to maintain a normal forward arch without increasing the posterior protrusion of the upper thoracic vertebrae.
Again, when standing, head up, chest up, abdomen, if necessary, can stand with back against the wall to maintain good posture.
When sitting, you should straighten your back against a hard chair, keep your upper body straight, bend your hips and knees 90 degrees, avoid sitting on low benches and sofas, and avoid bending too long to cause spinal deformities.
There is a saying that ankylosis patients should have their height measured regularly, what is the significance of this?
Regular height measurement enables early detection of spinal curvature, as well as compression fractures due to osteoporosis, which can be treated early.
What are the main drugs available for the treatment of ankylosing spondylitis and can you give an overall description?
The main types of drugs are as follows.
① Non-steroidal anti-inflammatory drugs: first-line drugs that relieve pain and morning stiffness, improve function and mobility, and may slow the progression of imaging in patients. They need to be used continuously for those with active and symptomatic disease, with attention to the risk of gastrointestinal, cardiovascular and renal side effects.
②Relief anti-rheumatic drugs: including lorazepam, methotrexate, thalidomide, leflunomide, etc. It can stop the disease progression to improve the prognosis.
③Biological agents: the most used are anti-tumor necrosis factor antagonists, which have good anti-inflammatory effects and can rapidly control the disease activity and stop the disease progression. Commonly used TNF inhibitors include the imported Enzyme (etanercept), classical gram (infliximab), Xumel (adalimumab), and the domestic Ixep and Qiangke.
④Glucocorticoids: If there is no extra-articular spinal comorbidity such as ophthalmia, systemic oral use is not recommended, but intra-articular injection or tendon end injection can be given as soon as possible to relieve local inflammation and reduce local pain.
⑤ Analgesics: For patients with residual pain after failure of the above drug therapy, contraindication or poor tolerance, paracetamol and opioids can be considered for pain management.
Patients generally call non-steroidal anti-inflammatory drugs as painkillers, is this only used to relieve pain?
NSAIDs, which have anti-inflammatory and pain-relieving effects, are the first-line drugs for ankylosing spondylitis. It is not just for pain relief, but also has anti-inflammatory effects that can effectively relieve back pain and morning stiffness in AS patients, improve function and mobility, and even delay the imaging progression of spinal lesions.
Can NSAIDs be taken when it hurts and not when it doesn’t? Or should they be taken consistently throughout the year?
Whether to take them continuously or intermittently is controversial and generally depends on the type and stage of the disease and adverse drug reactions. For patients with predominantly medial joint involvement, long-term continuous use may be recommended; while for patients with predominantly peripheral joint involvement, it may be used on an as-needed basis after controlling the disease; if the patient is a patient with advanced AS with medial joint involvement, complete fusion of the spine and sacroiliac joints, and normal inflammatory indexes, long-term use is not required. In addition, they are used with caution in elderly patients and in patients with peptic ulcers.
There are many different kinds of these drugs, such as aminoglycoside, diclofenac sodium, celecoxib, meloxicam, etc. Do they all have the same effect? Can they be substituted for each other? Or is it necessary to change the medication when some kind of effect is not good?
All of them are NSAIDs with the same mechanism of action, but with different efficacy and side effects. The actual anti-inflammatory is the elimination of sterile inflammation, not bacterial infectious inflammation.
Aminoglycoside and diclofenac sodium are traditional NSAIDs, while meloxicam is a propensity cyclooxygenase-2 inhibitor and celecoxib is a specific cyclooxygenase-2 inhibitor.
Overall, aminoglycoside and diclofenac sodium are somewhat more effective, but also have more side effects, especially gastrointestinal adverse effects (ulcers, bleeding, etc.). Celecoxib is slightly less effective, but has fewer gastrointestinal complications.
In general, for a certain NSAID, if the efficacy is not good after 1-2 weeks of continuous full dose, it can be replaced by other NSAIDs with different chemical structure. The efficacy and side effects of each NSAID vary greatly with the individual.
Many patients worry that taking too many of these drugs will hurt their stomachs, so how should they weigh the pros and cons?
These drugs do have certain gastrointestinal adverse reactions, a few cause ulcers, bleeding and even perforation, it is necessary to weigh the pros and cons.
For young patients without underlying diseases such as gastrointestinal tract, traditional NSAIDs can be chosen; while for those with upper gastrointestinal bleeding or other gastrointestinal events, selective cyclooxygenase-2 inhibitors and gastric mucosal protectors and acid suppressants can be used, and for those with H. pylori infection, gastroenterology can be used for root cause treatment if possible.
However, no matter which NSAID is used, patients need to be observed for black stools and gastrointestinal discomfort and have regular stool routine checks.
Which patients need to apply salazosulfapyridine? What is its role in ankylosing spondylitis?
Sulfasalazine is the most widely used second-line drug for the treatment of ankylosing spondylitis. It is mainly indicated for patients with ankylosing spondylitis with peripheral arthritis to improve peripheral joint symptoms; secondly, it is effective against iritis, a complication of ankylosing spondylitis; it is also effective against co-infections of the intestinal tract (more than 60% of AS patients have intestinal inflammation), inhibiting microorganisms in the intestinal tract and improving the condition.
Is it true that salazosulfapyridine may have a spermicidal effect in men?
The side effects of salazosulfapyridine include spermopenia in men, but it is generally reversible and can be recovered within a few months after stopping the drug, so there is nothing to worry about.
Is methotrexate also more commonly used?
Methotrexate is more widely used in rheumatoid arthritis and is also used quite a bit in ankylosing spondylitis. Small open studies have confirmed that methotrexate can be used in patients with predominantly peripheral arthritis. Methotrexate can be used alone or in combination with other drugs such as salazosulfapyridine for those with hip joint involvement.
There are several points to note with methotrexate: observe for side effects such as mouth ulcers, fever, anorexia and dyspnea, etc. Once they occur, you need to consult a doctor and have your liver and kidney functions and blood and urine routines tested; it is prohibited for patients with existing poor liver and kidney functions or active hepatitis B virus infection; adding folic acid can reduce the side effects of the drug, usually about 10 mg after taking methotrexate for 2 days a week.
Is it true that only a few patients may need to apply glucocorticoids?
Yes, hormones are not routinely used, especially not in large doses for long-term oral use. Only a few patients use hormones, and mainly intra-articular puncture injections; systemic oral hormones are mainly used for acute iritis and pulmonary involvement, while intra-articular injections are mainly suitable for refractory severe arthritis with only 1-2 refractory to NSAIDs; there is generally no indication for systemic hormone use in the type with mid-axis involvement.
Is it possible that some patients will be treated with halofluoromide? What is the role of this drug?
Leflunomide works similarly to methotrexate and is used primarily in patients with peripheral joint involvement. Its most common side effects are the possibility of liver damage, and high blood pressure or gastrointestinal discomfort.
Some patients do experience a transient increase in aminotransferases, so liver function needs to be reviewed regularly before and after dosing. If transaminases are within 2 times the normal value, add hepatoprotective drugs for observation; at 2-3 times the normal value, reduce the dosage by half and add hepatoprotective drugs and recheck after 1-2 weeks; if transaminases continue to rise or are still maintained, discontinue the drug. Resume use after discontinuation will be determined by the patient’s condition.
Which patients need thalidomide (Response Stop)?
Thalidomide is Response Stop. This drug was first used to treat vomiting in pregnant women and was withdrawn from the market for a time due to the fetal seal limb incident, but later studies found that this drug has an inhibitory effect on TNF and anti-vascular proliferation, and is now widely used in the treatment of many diseases, including multiple myeloma, leprosy, leukoaraiosis, ankylosing spondylitis, etc.
For patients with slightly more severe AS (not necessarily refractory), whether of the peripheral arthritis type or the mid-axis involvement type, Response Stop can be used to improve pain and morning stiffness, and may be better in combination with salazosulfapyridine. There is also the fact that many patients can add Reactive Stop orally after using biologics to prevent recurrence of the disease.
Dafabet Online: What is the rationale for biologics in the treatment of ankylosing spondylitis?
Biologics include anti-TNF (tumor necrosis factor) inhibitors, IL-6 inhibitors, etc. Currently, the biologics used to treat ankylosing spondylitis are mainly anti-TNF inhibitors. The main principle of treatment is that many pro-inflammatory factors are elevated in AS patients, among which tumor necrosis factor-alpha plays an important role in the pathogenesis of AS. TNF inhibitors achieve anti-inflammatory effects by binding to TNF-alpha and blocking its binding to the receptor.
What are the side effects of biological agents? Can it also cause tumors?
Side effects of biologics include local injection reactions, allergies, secondary infections, tumors and demyelinating lesions. Biologics are contraindicated in people with active infections and should be monitored for side effects such as various infections during treatment. Biologics have a slightly increased risk of inducing lymphoma, but the risk of solid tumors is still controversial. Therefore, patients with a history of malignancy or family history of malignancy should be used with caution and weigh the pros and cons, and if the condition requires that they must be used, it is best to use them for a short period of time at a reduced dose.
Do biologics need to be injected for life? Or can we stop using them after a period of injection?
No. Biologics are drugs that treat both the symptoms and the root cause of the disease, control inflammation quickly, and delay the formation of fatty deposits and bone redundancy in imaging for a long period of time, so we advocate using them for as long as possible, usually more than 3-6 months. The effect of treatment.
Will there be a relapse after stopping the drug?
If the biologic agent is stopped quickly, relapse will definitely occur, which requires gradual reduction of dose to maintain consolidation, or adding other oral medications to prevent relapse.
Do I have to be tested for TB and hepatitis B before using biologics? Why?
Yes, it is necessary to check for potential tuberculosis and hepatitis B before using biologics. Because our country is a big country of hepatitis and tuberculosis, anti-TNF agents can lower the body’s resistance and make the previously inactive tuberculosis or hepatitis active, leading to chronic HBV infection and serious complications such as tuberculosis dissemination, extrapulmonary tuberculosis and fulminant hepatitis. Therefore, screening for the risk of underlying TB is required.
There are domestic and imported biologics, what is the difference between the two?
There is indeed a difference between domestic and imported biologics, with imported drugs including Enzyme (etanercept), Classic (infliximab) and Xumilat (adalimumab); and domestic drugs including Ixab and Qiangk, which are analogues of etanercept. These drugs are divided into approximately two major classes, namely anti-TNF fusion protein class and monoclonal antibody class, according to the strength and nature of their action.
Imported drugs have been on the market abroad for a longer period of time, with more research on efficacy and safety, but are relatively expensive; domestic drugs made after imported drugs (Enzyme) have been on the market for a shorter period of time, are relatively inexpensive, and are included in the medical insurance category in some provinces and municipalities.
There are no head-to-head studies comparing the efficacy and side effects of imported and domestic drugs, and patients need to choose with their family’s financial situation and different diseases.
For Wegener’s granulomatosis, inflammatory bowel disease and leukoaraiosis with eye involvement, monoclonal antibiotics are better, while for patients with low resistance and previous contraindications such as tuberculosis or other infections that are currently well controlled and necessitate the use of biologics, fusion proteins are better to prevent further reduction in resistance.
What is the approximate cost of biologics?
Currently, the domestic biological agent, ECP, is usually about 900 dollars for one shot and 2 times a week; the other domestic drug, Qiangk, is about 700 fast for one shot and also twice a week.
Imported biologic Enzyme, playing once is about 2,500 yuan, also twice a week; Xiomel, playing once is about 7,600 yuan, but playing once every two weeks. The class gram playing once is about 13,200 yuan, but the interval of injection is gradually extended, respectively 0, 2, 6, 8, that is, after the first injection, the second injection at an interval of 2 weeks, after which the third injection at an interval of 6 weeks. But the longest interval does not exceed 8-12 weeks.
Dafu Online: After talking about so many drugs above, what is the general principle when choosing a specific drug?
Non-steroidal anti-inflammatory drugs are still the first-line drugs for the treatment of AS, and they are used in full amount and in full course, and the effect is not good enough to change to another non-steroidal anti-inflammatory drug; patients with mainly peripheral arthritis involvement can be treated with non-steroidal anti-inflammatory drugs combined with salazosulfapyridine, and intra-articular injection of hormones can be used for those with persistent arthritis.
If two consecutive NSAIDs are not effective after adequate treatment and the patient has high disease activity (duration ≥ 4 weeks; BASDAI ≥ 4), biologic therapy may be considered for initiation. Biologic agents are interchangeable. If the patient continues to complain of pain or is intolerant to these treatments, acetaminophen and opioid analgesics may be administered.
Will my doctor recommend injections of biologics after multiple oral medications have failed?
Biologics may be recommended for patients who have failed to respond to multiple oral medications. However, in fact, the indications for biologics are not limited to these patients in whom multiple oral medications have failed. Biologics may also be applied if the patient has active disease lasting ≥ 4 weeks; BASDAI ≥ 4, and if the following treatments have failed.
(i) All patients: who have received at least two successive NSAIDs with inadequate results after adequate treatment.
(ii) Patients with a predominantly mid-axis type: treatment with drugs that inhibit progression (referred to as DMARD-type drugs) is not mandatory before starting anti-TNF biologics.
(iii) Patients with peripheral arthritis: poor efficacy of at least one local hormonal therapy and poor efficacy of adequate treatment with one DMARDs, such as salazosulfapyridine.
(iv) Patients with attachment site inflammation: poor local efficacy. All of these patients can be treated with biologics if their economic situation allows.
If biologics are not available due to economic factors, is it possible to control the disease with long-term oral medication?
If biologics are not available due to economic factors, long-term oral medication can also control the disease. However, oral medications are relatively slow to take effect, and it may take longer to achieve clinical remission. It is important to monitor the side effects of oral medications during long-term use.
Since most patients with ankylosing spondylitis are young, does the use of these medications affect pregnancy? Does it affect men and women differently?
There is a lack of clinical data and laboratory evidence on the effects of NSAIDs on pregnancy and the fetus. No teratogenic effects have been found for these drugs, although indomethacin can inhibit labor and can cause premature atresia of the ductus arteriosus, and some NSAIDs may cause impaired fetal kidney function.
It is usually recommended to discontinue these medications several weeks before pregnancy. If this is not possible, a drug with a shorter half-life, such as Lapsone, can be taken during the first 32 weeks of pregnancy and discontinued after the seventh month of pregnancy.
Male patients taking salazosulfapyridine can develop oligospermia, which can lead to reduced fertility. However, clinical data show that no significant adverse effects have been observed in female patients taking salazosulfapyridine during pregnancy. If the condition requires maintenance treatment, salbutamol can be discontinued during pregnancy.
Methotrexate requires discontinuation of the drug 3 months or more before conception.
Leflunomide needs to be discontinued 2 years prior to planned pregnancy, and in the event of an unplanned pregnancy, elimination of its metabolites can be rapid with bilirubicin.
Glucocorticoids, because they are administered by local intra-articular injection, have little effect on pregnancy.
Biologics are contraindicated for pregnant and lactating women, and pregnancy is usually possible about 1 month after discontinuation of the drug.
Drs. Online: Does AS require lifelong medication? Is it true that some patients become stable after the age of 40 and do not need to take medication?
In cases where the disease is difficult to control and there are no toxic side effects of the medication, it is best to take the medication for life, at least 2 years. However, some patients can remain stable for a long time in the absence of obvious triggers such as intestinal and urinary tract infections. However, there are no statistics on whether the specific age is 40 years or other ages. Generally, after a number of years of regular treatment, the disease is stable for a long period of time, and discontinuation of the drug and follow-up observation can be attempted. However, in the case of a specific patient, the discontinuation of the drugs needs to be assessed individually, taking into account the situation of each individual.
Do I need to return to the hospital for regular review after applying these drugs? Why?
On the one hand, it is necessary to understand the efficacy of the medication and decide to further maintain the treatment or change the treatment plan; on the other hand, it is necessary to monitor the side effects of the medication and to detect the adverse reactions of the medication and deal with them in a timely manner.
What are the general tests that patients need?
In the review, C-reactive protein, erythrocyte sedimentation rate and other indicators reflecting the activity of the disease should be improved, and blood routine, liver and kidney function should be checked to clarify whether there are any adverse drug reactions, and if necessary, sacroiliac joint, spine plain film or MRI should be reviewed to clarify the progress. In addition, depending on the patient’s condition, such as whether hepatitis B or tuberculosis is combined, or whether fever occurs during the follow-up, it is necessary to improve the relevant examinations to ensure the safety of the medication and to detect and deal with the comorbidities at an early stage.
What is the frequency of review?
The interval of review is not fixed. When the disease is active, the review should be done more frequently, usually once every two weeks or once a month. After the disease has stabilized and the side effects of the medication are gone, the interval can be extended to 1-3 months, but preferably not more than six months. Patients on long-term stable medication should be checked at least once every six months.
At what point does the patient progress to the point where surgical treatment is required?
The indications for surgical treatment are.
① Total hip arthroplasty for patients with AS whose imaging suggests structural destruction with refractory pain or loss of function.
(ii) corrective spinal osteotomy can be performed for patients with severe deformities of the spine with limited movement.
(iii) Patients with acute vertebral fractures need to be consulted by a spine surgeon and treated surgically if necessary.
Is it possible to avoid surgery through long-term strict medication and exercise?
Long-term strict medication and exercise can enable patients to maintain good joint function, slow down the progression of the disease, avoid joint deformity and spinal ankylosis, and avoid surgery.