What are the most effective medications for ankylosing spondylitis. How do biologics work in treating ankylosing spondylitis. What are the potential risks and side effects of biologic medications. How do NSAIDs, steroids, and DMARDs compare to biologics in treating ankylosing spondylitis. What are the latest advancements in ankylosing spondylitis treatment.

Understanding Ankylosing Spondylitis and Its Treatment Options

Ankylosing spondylitis (AS) is a chronic inflammatory condition that primarily affects the spine and sacroiliac joints. For many individuals living with this condition, finding effective treatment is crucial for managing pain, reducing inflammation, and maintaining mobility. This article delves into the various medication options available for AS, with a particular focus on biologic therapies.

The Role of Inflammation in Ankylosing Spondylitis

Inflammation plays a central role in the progression of ankylosing spondylitis. It causes pain, stiffness, and can lead to structural changes in the spine over time. Understanding this process is key to comprehending how different medications work to alleviate symptoms and potentially slow disease progression.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): The First Line of Defense

NSAIDs are often the initial treatment approach for individuals with ankylosing spondylitis. These medications work by reducing inflammation and alleviating pain. They can be divided into three main categories:

• Over-the-counter NSAIDs (e.g., aspirin, ibuprofen, naproxen)
• Prescription NSAIDs (stronger doses of OTC medications)
• COX-2 inhibitors (e.g., celecoxib, sold as Celebrex)

Are NSAIDs sufficient for managing ankylosing spondylitis in all patients? While NSAIDs can be effective for many individuals, especially those with mild to moderate symptoms, some patients may require more potent medications to control their condition adequately.

Biologics: A Game-Changer in Ankylosing Spondylitis Treatment

Biologic medications have revolutionized the treatment of ankylosing spondylitis for many patients. These drugs work by targeting specific components of the immune system involved in the inflammatory process. Biologics can offer several benefits for AS patients:

• Slowing disease progression
• Treating peripheral joint pain
• Alleviating spinal arthritis pain

How do biologics differ from traditional medications? Unlike conventional drugs, biologics are derived from living organisms and are designed to target specific pathways in the immune system. This targeted approach can lead to more effective symptom control with potentially fewer side effects compared to broad-spectrum immunosuppressants.

FDA-Approved Biologics for Ankylosing Spondylitis

Currently, there are six FDA-approved biologic medications for the treatment of ankylosing spondylitis:

1. Etanercept (Enbrel)
2. Infliximab (Remicade)
3. Adalimumab (Humira)
4. Golimumab (Simponi)
5. Certolizumab (Cimzia)
6. Secukinumab (Cosentyx)

These medications fall into two main categories: TNF inhibitors (the first five on the list) and interleukin inhibitors (secukinumab). Each works slightly differently to modulate the immune response and reduce inflammation.

Administration and Dosing of Biologic Medications

Biologic medications for ankylosing spondylitis are administered via injection or infusion. The frequency and method of administration can vary significantly depending on the specific drug and individual patient needs.

How often do patients need to take biologic medications? The dosing schedule can range from once a week to once every six weeks, depending on the medication. For example:

• Etanercept may be administered weekly
• Adalimumab is typically given every two weeks
• Infliximab infusions might be scheduled every six to eight weeks

It’s crucial for patients to work closely with their healthcare providers to determine the most appropriate dosing regimen based on their individual response to treatment and any potential side effects.

Potential Risks and Side Effects of Biologic Therapies

While biologics can be highly effective in managing ankylosing spondylitis, they do come with potential risks and side effects. The most significant concern is an increased susceptibility to infections due to the suppression of the immune system.

What are the most common side effects of biologic medications? Some patients may experience:

• Injection site reactions
• Upper respiratory infections
• Headaches
• Nausea
• Fatigue

More serious but rare side effects can include an increased risk of certain cancers, particularly lymphoma, and the reactivation of latent tuberculosis. It’s essential for patients to undergo thorough screening before starting biologic therapy and to be monitored regularly during treatment.

Emerging Therapies: Oral Biologics and JAK Inhibitors

The landscape of ankylosing spondylitis treatment is continually evolving, with researchers exploring new therapeutic options. One promising area of research is the development of oral biologic medications, specifically Janus kinase (JAK) inhibitors.

What are JAK inhibitors, and how do they differ from traditional biologics? JAK inhibitors are small molecule drugs that work inside cells to block specific signaling pathways involved in inflammation. Unlike traditional biologics, which are large protein molecules that must be injected or infused, JAK inhibitors can be taken orally.

In 2016, the FDA approved tofacitinib citrate (XelJanz), a JAK inhibitor, for the treatment of rheumatoid arthritis. While not yet approved for ankylosing spondylitis, some experts believe JAK inhibitors may prove effective in treating AS and other autoimmune conditions.

The Future of Ankylosing Spondylitis Treatment

As research continues, we may see more targeted therapies developed for ankylosing spondylitis. These could include:

• New biologic targets beyond TNF and interleukin inhibition
• Combination therapies that leverage multiple mechanisms of action
• Personalized medicine approaches based on genetic markers or biomarkers

The goal of these advancements is to provide more effective treatments with fewer side effects, ultimately improving the quality of life for individuals living with ankylosing spondylitis.

Complementary Treatment Options: Steroids and DMARDs

While biologics have become a mainstay in the treatment of ankylosing spondylitis, other medication classes still play important roles in managing the condition.

Steroids in Ankylosing Spondylitis Management

Steroids can be valuable in certain situations for AS patients. They are primarily used in two ways:

1. To control painful eye symptoms associated with AS
2. As localized injections into painful joints

Why aren’t oral steroids commonly used for ankylosing spondylitis? Oral steroids, such as prednisone, are rarely prescribed for AS due to their long-term side effects and limited efficacy in managing the disease’s primary symptoms. However, short courses of oral steroids may be used in some cases of severe flares.

Disease-Modifying Antirheumatic Drugs (DMARDs)

DMARDs, including methotrexate and sulfasalazine, may be prescribed to AS patients who experience peripheral joint pain, such as in the knees, hips, or ankles. These medications can help reduce inflammation and slow joint damage in these areas.

Are DMARDs effective for all types of pain associated with ankylosing spondylitis? DMARDs are generally not effective in treating axial joint pain, which includes pain in the neck, back, and sacroiliac joints. For this reason, they are typically reserved for patients with significant peripheral joint involvement.

Tailoring Treatment Plans for Individual Patients

The treatment of ankylosing spondylitis is not a one-size-fits-all approach. Healthcare providers must consider various factors when developing a treatment plan, including:

• The severity and location of symptoms
• The presence of extra-articular manifestations (e.g., uveitis, inflammatory bowel disease)
• The patient’s overall health and comorbidities
• Potential drug interactions with other medications
• The patient’s preferences and lifestyle considerations

How do doctors determine the most appropriate treatment for each patient? This process typically involves a thorough assessment of the patient’s condition, including physical examinations, imaging studies, and laboratory tests. Doctors may start with NSAIDs and progress to more potent medications if symptoms are not adequately controlled.

The Importance of Monitoring and Adjusting Treatment

Regular follow-up appointments are crucial for patients with ankylosing spondylitis. During these visits, healthcare providers can:

• Assess the effectiveness of current treatments
• Monitor for any side effects or complications
• Adjust medication dosages as needed
• Consider adding or switching medications if the response is suboptimal

Patients should be encouraged to communicate openly with their healthcare team about their symptoms, concerns, and any changes in their condition. This collaborative approach can lead to better outcomes and improved quality of life.

The Role of Non-Pharmacological Interventions

While medications play a crucial role in managing ankylosing spondylitis, they are most effective when combined with non-pharmacological interventions. These complementary approaches can help improve overall health, maintain flexibility, and reduce the burden of symptoms.

Exercise and Physical Therapy

Regular exercise is essential for individuals with ankylosing spondylitis. It can help:

• Maintain flexibility and range of motion
• Strengthen muscles that support the spine
• Improve posture and reduce pain
• Enhance overall cardiovascular health

What types of exercises are most beneficial for ankylosing spondylitis patients? Low-impact activities such as swimming, cycling, and yoga can be particularly helpful. Working with a physical therapist to develop a tailored exercise program is often recommended.

Lifestyle Modifications

Certain lifestyle changes can complement medical treatments and help manage ankylosing spondylitis symptoms:

• Maintaining good posture
• Using proper ergonomics at work and home
• Quitting smoking, which can exacerbate symptoms and increase cardiovascular risk
• Managing stress through relaxation techniques or mindfulness practices
• Adhering to a healthy, anti-inflammatory diet

These non-pharmacological interventions, when combined with appropriate medication, can significantly improve outcomes for individuals living with ankylosing spondylitis.

The Importance of Patient Education and Support

Living with a chronic condition like ankylosing spondylitis can be challenging. Patient education and support play crucial roles in achieving optimal treatment outcomes and maintaining a good quality of life.

Understanding the Disease and Treatment Options

Patients who are well-informed about their condition are better equipped to:

• Recognize early signs of flares or complications
• Make informed decisions about their treatment options
• Adhere to their medication regimens and follow-up appointments
• Communicate effectively with their healthcare team

How can patients stay informed about the latest developments in ankylosing spondylitis treatment? Reliable sources of information include reputable medical websites, patient advocacy organizations, and educational materials provided by healthcare professionals.

The Value of Support Networks

Support networks can be invaluable for individuals living with ankylosing spondylitis. These may include:

• Support groups (in-person or online)
• Patient mentoring programs
• Family and friends who understand the challenges of the condition
• Mental health professionals who can help with the psychological aspects of living with a chronic illness

Engaging with these support systems can help patients cope with the emotional and practical challenges of managing ankylosing spondylitis, leading to better overall outcomes and quality of life.

Ankylosing Spondylitis Medications | Arthritis-health

Watch: Ankylosing Spondylitis Video

Many people who have ankylosing spondylitis take medications to help reduce the inflammation that causes pain and stiffness. What type of medication a doctor recommends will depend on the person’s symptoms and their severity.

There are four types of medications commonly used to treat ankylosing spondylitis: Nonsteroidal anti-inflammatory drugs (NSAIDs), biologics, steroids, and DMARDs. Like all medications, these drugs can cause side effects or interact with other medications. Patients are advised to discuss any drug therapy plan with their health care professional and report side effects.

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Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs are often the first line of defense against ankylosing spondylitis pain. NSAIDs is a broad category of medications that includes:

1. Over the counter NSAIDs, such as aspirin, ibuprofen, and naproxen.
2. Prescriptions NSAIDs, which have the same ingredients as over-counter-medications but are packaged in stronger doses.
3. COX-2 inhibitors, sometimes called coxibs, which are available only by prescription. Celecoxib, sold as Celebrex, is a COX-2 inhibitor.

See Pain Medications for Arthritis Pain Relief

Biologics

Biologic medications suppress immune system activity, thereby decreasing ankylosing spondylitis disease activity and symptoms. In some people, biologic drugs called TNF-inhibitors (TNF-blockers) as well as certain interleukin (IL) inhibitors appear to do one or more of the following:

• Slow the progression of the ankylosing spondylitis
• Treat peripheral joint pain
• Treat spinal arthritis pain

See Biologics: Basic Facts for Patients

Biologic medications are administered with a needle, either injected under the skin or infused into a vein. Exactly how much and how often a medication must be administered varies significantly depending on the drug and the patient. Some ankylosing spondylitis patients may take medication once a week, while others get an infusion once every 6 weeks.

See The Science Behind Biologics

Currently, there are six FDA-approved biologic medications for ankylosing spondylitis:

• Etanercept (Enbrel)
• Infliximab (Remicade)
• Adalimumab (Humira)
• Golimumab (Simponi)
• Certolizumab (Cimzia)
• Secukinumab (Cosentyx)

These biologic medications are expensive. In addition, they carry potential risks and side effects, including possible infections resulting from a suppressed immune system.

See Risks and Side Effects of Biologics

Oral biologics
Researchers are studying a class of drugs called Janus kinase (JAK) inhibitors, which can be taken orally. In 2016, the FDA approved the JAK inhibitor tofacitinib citrate (XelJanz) for rheumatoid arthritis. Some experts believe it may also be effective in treating other autoimmune diseases, including as ankylosing spondylitis.

See Biologics, Biosimilars, and Interchangeable Biosimilars—What is the Difference?

In This Article:

• What Is Ankylosing Spondylitis?

• Ankylosing Spondylitis Causes and Risk Factors

• Ankylosing Spondylitis Symptoms

• Complications of Severe Ankylosing Spondylitis

• Ankylosing Spondylitis Diagnosis

• Ankylosing Spondylitis Treatment

• Ankylosing Spondylitis Medications

• Ankylosing Spondylitis Surgery

• Ankylosing Spondylitis Video

Steroids

Steroids may be used to control painful eye symptoms or injected into painful joints. Oral steroids, such as oral prednisone, are rarely used to treatment AS or other spondyloarthropathies.

See Cortisone Injections (Steroid Injections)

Disease-modifying antirheumatic drugs (DMARDs)

DMARDs, such as methotrexate and sulfasalazine, may be prescribed to people whose ankylosing spondylitis causes peripheral joint pain, such as pain in the knees, hips or ankles. DMARDs are not effective in treating pain doctors call axial joint pain, including pain in the neck, back, and sacroiliac joint.

¹
Disease Modifying Anti Rheumatic Drugs (DMARDS). National Ankylosing Spondylitis Society. http://nass.co.uk/about-as/living-well-with-as/medication-for-as/disease-modifying-anti-rheumatic-drugs-dmards/

See Sacroiliac Joint Pain and Inflammation

DMARD side effects may include but are not limited to headaches, abdominal bloating, and nausea/vomiting. Patients can develop bone marrow suppression and/or liver toxicity, so it is important for doctors to regularly monitor patient’s blood samples.

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Medications May Change Over Time

Most newly-diagnosed patients are started on NSAID medications. If symptoms are not alleviated within a reasonable window of time, or if the case is severe, the doctor may recommend using another type of medication, usually a biologic. Over months or years, a medication may become less effective or cause unacceptable side effects, and a new medication can be prescribed.

Dr. Judith Frank is a rheumatologist and internal medicine physician. She has been practicing for nearly 30 years, specializing in osteoarthritis, rheumatoid arthritis, gout, and lupus. She completed her Doctor of Medicine degree, residency, and fellowship training from Rush University.

• 1
  Disease Modifying Anti Rheumatic Drugs (DMARDS). National Ankylosing Spondylitis Society. http://nass.co.uk/about-as/living-well-with-as/medication-for-as/disease-modifying-anti-rheumatic-drugs-dmards/

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Treating Ankylosing Spondylitis With Biologics

In this Article

Your doctor may prescribe certain treatments, like nonsteroidal anti-inflammatory drugs and physical therapy, to help your ankylosing spondylitis. But everyone is different: What works for someone else might not work for you. If this happens, your doctor will most likely recommend that you try a new class of drugs known as biologics.

“These are amazing drugs that have really revolutionized how we treat this disease,” says Yale Medicine rheumatologist Deborah Desir, MD.

Though they won’t magically cure your ankylosing spondylitis, they can help slow the disease’s progression and make symptoms more manageable.

How Do Biologics Work?

Biologics stop the damaging inflammation that happens with ankylosing spondylitis.

“They’re genetically engineered proteins that target cytokines, specific molecules in your immune system,” says Lianne Gensler, MD, director of the University of California San Francisco’s Ankylosing Spondylitis Clinic.

Cytokines activate inflammation throughout your body, which keeps your immune system on its toes to fight off invaders. But if they go into overdrive, they can trigger inflammatory diseases such as ankylosing spondylitis.

There are two main classes of biologics used to treat ankylosing spondylitis:

Tumor necrosis factor alpha (TNF-α) inhibitors. These were the first approved in 2003. They work not only to ease joint inflammation, but related inflammation in the gut and eyes as well. There are five approved for ankylosing spondylitis:

• Adalimumab (Humira)
• Certolizumab (Cimzia)
• Entanercept (Enbrel)
• Golimumab (Simponi)
• Infliximab (Remicade)

IL-17 inhibitors. Two are FDA-approved for ankylosing spondylitis: ixekizumab (Taltz) and secukinumab (Cosentyx). They target different cytokines than the TNF inhibitors. They’re often used in people whose ankylosing spondylitis didn’t respond to several of the TNF medications.

Who Should Take Biologics?

While biologics are very effective, they’re not for everyone.

“These drugs are very powerful, but they also suppress the immune system, which means you’re more vulnerable to infection,” Gensler says. Because of this, most doctors hold off using them right away.

When you’re newly diagnosed with ankylosis spondylitis, your doctor will most likely start you on a course of nonsteroidal anti-inflammatory drugs (NSAIDS). These include over-the-counter versions such as ibuprofen, as well as prescription-strength drugs like celecoxib (Celebrex).

“These drugs are the most common ones we use, and for good reason: a huge percentage of patients are able to get control of their symptoms on them,” Desir says.

They’ll also prescribe physical therapy to help ward off the “frozen” spine and general stiffness that can occur with ankylosis spondylitis.

The downside of NSAIDs is that to stay symptom-free, most people need very high doses. Over time, this can lead to side effects such as stomach bleeding and higher risk of heart attack or stroke.

“We’re most worried about these side effects in older adults, since they are the ones who are already at risk for these diseases. But for a younger patient in their 20s or 30s newly diagnosed with the condition, that’s much less of a concern,” Gensler says. “We don’t have long-term safety data on biologics yet beyond about 2 decades, so it’s still unknown what the effects of these drugs would be on patients who are on them for most of their lives. That’s why we’d prefer to start with an NSAID, and then escalate if need be.”

In general, Gensler says you should consider a biologic if:

• You’ve tried a course of NSAIDs and physical therapy for a few weeks and are still bothered by symptoms.
• Your X-rays already show that you have a lot of damage to your sacroiliac joints, the joints that connect your spine to your pelvic bone.
• You’ve already lived with ankylosis spondylitis for a long time.

It can sometimes take up to 10 years for people to be diagnosed with this condition.

“Sometimes patients come in for the very first visit in extreme pain and very disabled, and they say that their quality of life is terrible and they’d do anything to get it back to where they can function again,” Gensler says.

What Should I Expect When I Take a Biologic?

If you and your doctor agree biologics are the next step, they’ll test you for tuberculous first.

“Some people have what’s known as latent TB, where the bacteria live silently in their lungs,” Desir says. “Since these drugs suppress your immune system, the TB can ‘wake up’ and cause an actual infection.”

All biologic treatments leave you more prone to infection, especially upper respiratory infections such as colds, flu, or COVID-19. To stay healthy, you should:

• Wash your hands often
• Avoid or wear a mask in crowded areas, enclosed spaces, public transportation, and childcare facilities
• Keep up to date on all your vaccines, including the flu and COVID-19 vaccines.

Some biologics are given at home via self-injection, and others are given through an IV in your doctor’s office. You may notice some pain, redness, and swelling. You can use antihistamines and an over-the-counter pain reliver such as acetaminophen to treat discomfort.

If you’re on the fence about trying a biologic, Gensler suggests giving it a 3-month trial.

“I stress to (people) that this does not have to be a lifetime commitment. They can always go off of the biologic and return to their original medications,” she says. “But oftentimes, after a few months, people are shocked at how much better they feel. They’ve suffered for so long they’ve just accepted their symptoms as normal. But thanks to biologics, it doesn’t have to be that way anymore.”

© 2022 WebMD, LLC. All rights reserved.

Photo Credit: KATERYNA KON / SCIENCE PHOTO LIBRARY/ Getty Images

SOURCES:

Deborah Desir, MD, associate professor of clinical medicine, Yale School of Medicine.

Lianne Gensler, MD, director, University of California San Francisco’s ankylosing spondylitis clinic.

UptoDate: “Patient education: Axial spondyloarthritis, including ankylosing spondylitis (Beyond the Basics).”

Spondylitis Association of America: “Medications Used to Treat Ankylosing Spondylitis and Related Diseases. ”

Arthritis Foundation: “Biologics.”

American Journal of Managed Care: “Epidemiology of Axial Spondyloarthritis.”

Annals of Rheumatic Diseases: “Diagnosis journey of patients with ankylosing spondylitis in the united states.”       

Modern principles of therapy for ankylosing spondylitis | Kimova A.M.

The article presents modern principles of therapy for ankylosing spondylitis

For citation. Kimova A.M. Modern principles of therapy for ankylosing spondylitis // RMJ. 2015. No 25. S. 1499–1503.

Ankylosing spondylitis (AS) (Bekhterev’s disease, Strümpel-Marie-Bekhterev’s disease) is a chronic inflammatory disease of the spine (spondylitis), sacroiliac joints (sacroiliitis), often peripheral joints (arthritis), enthesis (enthesitis), in some cases – eyes (uveitis), cardiovascular system – aortic root (aortitis), other internal organs.
This disease was known in ancient Egypt. The first descriptions of AS in foreign literature were made by A. Strümpel (1884) and P. Marie (1898) and were regarded as a variant of chronic articular rheumatism [1]. In the domestic literature, priority is given to V.M. Bekhterev, although the clinical picture of patients with “stiffness of the spine”, described by Bekhterev, differed from the classical AS clinic. However, V.M. Bekhterev drew great attention to the problem of AS, which served as an impetus for the study of AS and other spondyloarthritis [2].

Classification modified New York criteria for the diagnosis of AS (1984):
1. Pain and stiffness in the lower back – more than 3 months, decreasing after exercise and aggravated at rest.
2. Limitation of movements in the lumbar spine in the sagittal and frontal planes.
3. Decreased chest excursion (compared to normal values ​​for gender and age).
4. Bilateral sacroiliitis 2-4 stages or unilateral sacroiliitis 3-4 stages.
The diagnosis of definite AS is established in the presence of radiological and at least 1 clinical criterion [3].
The disease can begin in childhood, but the peak falls on the 3rd decade (usually no later than 40 years). Men get sick 2-3 times more often than women. In more than 90% of cases, the genetic marker HLA-B27 is detected. Despite the fact that the clinical picture of AS was described half a century ago, the diagnosis of AS is established, on average, 7–10 years after the onset of the first manifestations. This is due to a number of reasons such as:
– variety of the clinical picture at the onset of the disease;
– non-vertebral lesions, in connection with which patients turn to various specialists;
– slow development of radiographic signs of sacroiliitis, which are of decisive importance;
– spontaneous long-term remissions in the first years of the disease;
– absence of immunological markers;
– non-permanent increase in ESR and CRP in the first months and years of AS;
– lack of sufficient knowledge about the debut of AS among doctors of other specialties.
The clinical picture of AS does not depend on gender and the presence of HLA-B27. In about 25% of cases, the disease appears in childhood. Not always AS begins with spondylitis or sacroiliitis.

Variants of disease onset

Spinal injury
Damage to the spine usually begins with the sacroiliac joints with a gradual transition to the overlying sections. Sacroiliitis is manifested by intermittent pain in the buttocks, radiating to the gluteal folds, along the back of the thigh, to the inguinal region. Gradually, the pain increases, becomes bilateral. Inflammatory pain in the lower back is also characteristic of the early stage of the disease, for the diagnosis of which the following criteria have been developed:
– age of onset of pain – earlier than 40 years;
– gradually increasing current;
– reduction of pain after exercise;
– lack of improvement at rest;
– night pain.
Pain is considered inflammatory if 4 out of 5 signs are present. With AS, all parts of the spine are involved in the process. The disease often occurs under the guise of lumbosacral sciatica. With damage to the thoracic spine, costovertebral joints, there is pain in the chest, sometimes girdle character. The pain is aggravated by coughing, taking a deep breath, turning. The defeat of the costovertebral joints helps to reduce the excursion of the chest, which further leads to a decrease in the vital capacity of the lungs. The defeat of the cervical spine occurs at a later date and leads to a decrease in the volume of movement of the head and neck. Cervical spondylitis may be accompanied by symptoms of discirculatory encephalopathy. Pain in the spine reflexively causes muscle spasm, which leads to limited mobility of the spine. In the early stages of the disease, the limitation of the range of motion in the spine is due to inflammation and reflex spasm of the muscles against the background of pain; at the stage of advanced clinical manifestations, movements are limited due to ossification of the spine. Over time, as a result of an inflammatory lesion of the spine, changes in posture occur that are characteristic of AS: the posture of the “beggar”, the posture of the “proud”.

Peripheral joint disease
Peripheral arthritis is noted throughout the disease in more than half of patients and begins mainly with the joints of the lower extremities. The most commonly affected are the hip, knee, ankle joints, less often the temporomandibular, metatarsophalangeal, and shoulder joints. Peripheral arthritis of any localization is a serious problem due to severe pain, as well as due to the destruction of the articular surfaces and dysfunction. The most unfavorable in terms of prognosis is coxitis, often bilateral. It often develops in patients who fell ill in childhood [8]. Peripheral arthritis in AS is often associated with enthesitis.

Enthesites
Inflammation of entheses in AS is natural. In AS, enthesitis is manifested by pain during movement, in which the corresponding tendon is involved, soreness, and sometimes swelling of the area of ​​enthesis. Enthesitis usually appears in the heel, elbow, knee, shoulder and hip joints. The underlying bone (osteitis) is involved in the inflammatory process, which leads to the development of erosions and further ossification and excessive bone formation. These phenomena underlie the appearance of peculiar radiographic changes characteristic of AS: extra-articular bone erosion, subchondral osteosclerosis, bone proliferation (“spurs”) and periostitis. In AS, extraskeletal lesions are observed: uveitis, changes in the aorta and heart, kidney damage.

Uveitis
The frequency of uveitis in systemic rheumatic diseases ranges from 25 to 50%. Uveitis is the most common extraskeletal manifestation of AS; it can be a manifestation and for a long time the only manifestation of the disease. Uveitis begins acutely and lasts up to 3 months, has a recurrent character, can affect all parts of the uveal tract. Both eyes can be involved alternately in the process. Patients have pain in the eye, photophobia, lacrimation, conjunctival hyperemia. The development of complications leads to a decrease in vision and blindness at a young, working age. Blindness and low vision can account for 10 to 35% of eye diseases [9].

Damage to the heart and aorta
Damage to the heart and aorta determines the prognosis of the disease and the tactics of therapeutic measures. It is known that there is no relationship between activity and severity of damage to the musculoskeletal system. Despite the fact that damage to the cardiovascular system often proceeds subclinically, damage to the aorta and aortic valves is found in 24–100% of cases on section [4, 11].
Early diagnosis of AS allows avoiding unnecessary examinations and protecting patients from improper therapy, including surgical manipulations, orienting the patient to the systematic use of non-steroidal anti-inflammatory drugs (NSAIDs), and in case of an unfavorable prognosis of AS, prescribing tumor necrosis factor inhibitors (anti- TNF-therapy) at an early stage. Training in physiotherapy exercises and a healthy lifestyle contributes to a more favorable outcome of AS.

Treatment of AS
It should be based on the clinical signs of the disease present at the time of examination (vertebral, articular, enthesis symptoms), their severity, the presence of prognosis indicators: disease activity / inflammation, functionality / disability, structural damage, involvement of the hip joints, spinal deformity, general clinical status (age , gender, comorbidities and therapy), patient expectations and preferences. The management of a patient with AS requires a mandatory combination of non-pharmacological and pharmacological methods of treatment.

Non-drug treatments
Non-drug methods of treatment include daily performance of a set of physical exercises aimed at maintaining a sufficient range of motion in the spine and large joints, strengthening skeletal muscles [12]; breathing exercises, back massage, physiotherapeutic procedures with various anti-inflammatory ointments in the form of phonophoresis, balneotherapy: radon and hydrogen sulfide baths. The functional state of the spine in people who regularly engage in exercise therapy and muscle training is better than in patients who neglect exercise for one reason or another. Non-pharmacological methods for AS may include educational programs – schools for patients. They can be done both individually and in groups. Non-pharmacological treatments for AS are only of secondary importance.

Pharmacological treatments
Pharmacological methods of treatment combine drugs from several groups: NSAIDs, muscle relaxants, corticosteroids, anti-TNF therapy.
NSAIDs
Despite the long history of the use of NSAIDs in the practice of rheumatology, in the current EULAR/ASAS recommendations, they are still first-line drugs in the treatment of AS, since they are distinguished by a unique combination of analgesic, anti-inflammatory, and antipyretic effects [5]. The long-term use and high efficacy of NSAIDs in relation to inflammatory pain raises the question of their ability to have not only symptomatic, but also disease-modifying effects, i. e., slowing radiographic progression. A recent observation by A. Wanders et al. confirmed that NSAIDs can slow down radiological progression (ossification) in the spine. According to this study, it turned out that the average values ​​of radiological changes were significantly less in patients who took NSAIDs constantly, and not on demand. However, it has not been established what influences the slowing down of spinal ossification: the suppression of active inflammation or the direct effect of NSAIDs on bone tissue – the suppression of osteoblast activity. According to morphological studies, inflammation in the area of ​​enthesis and bone (osteitis) in AS continues throughout the entire disease and does not tend to completely subside even when ankylosing of the spine or joint occurs, which is the basis for long-term use of this group of drugs. After establishing the diagnosis of AS (regardless of the stage of the disease), NSAIDs should be administered to the patient immediately. AS is the only rheumatological disease in which long-term use of NSAIDs is pathogenetically justified, highly effective and has no alternative, except for TNF-a inhibitors. The first goal of prescribing NSAIDs is to relieve pain. This is usually achieved within 2 weeks. If the main symptoms of the disease are night pain in the spine and morning stiffness, then it is desirable to prescribe prolonged forms of drugs. Sometimes, to eliminate pain and morning stiffness, a sequential change of 2-3 drugs is necessary.
The most effective drugs for the treatment of AS are the classic (standard) drugs: diclofenac, indomethacin, ketoprofen, naproxen. However, the frequency of adverse reactions in this group of drugs, especially with long-term use, which is required in the treatment of AS, makes preference for selective COX-2 inhibitors. In turn, moderately selective (meloxicam, nimesulide, nabumetone, etodolac) and highly selective (celecoxib, valdecoxib, etoricoxib, lumirocoxib) stand out among the latter. The choice of drug should be based on an analysis of the advantages and disadvantages of various groups of NSAIDs, taking into account the presence of analgesic, anti-inflammatory effects in combination with good tolerability (safety in relation to the gastrointestinal tract (GIT) and the cardiovascular system). In Russia, many experts consider nimesulide (Nise) to be a drug with these properties. The advantages of this drug are also noted by many world experts. In an article dedicated to the 25th anniversary of the use of nimesulide in Italy, C. Mattia et al. pointed to the obvious predominance of the positive qualities of this drug [6]. These conclusions are confirmed by clinical studies of scientists from NIIR them. V.A. Nasonova – A.E. Karateev et al. Retrospective analysis of the incidence of complications from the gastrointestinal tract, cardiovascular system and liver in patients admitted to the NIIR from 2007 to 2008 and taking nimesulide at a dose of 200 mg for at least 12 months. before admission, showed that in addition to effective analgesic, anti-inflammatory properties, the drug Nise has good tolerance. Nimesulide has proven to be an effective pain reliever. It has high bioavailability – within 30 minutes after oral administration, a significant concentration of the drug in the blood is reached, which is at least 25% of the maximum. The full analgesic and anti-inflammatory effect of nimesulide occurs 1-3 hours after administration.
As is known, the pharmacological action of all NSAIDs is associated with the blockade of COX-2, and the gastrointestinal complications associated with their use are mainly determined by the suppression of COX-1 activity in the gastrointestinal mucosa. But COX-1 is also involved in the development of inflammation, and therefore a local decrease in its activity in the area of ​​damage should be considered as a positive factor. Nimesulide has such an effect – it only slightly affects the “structural” COX-1 of the gastric mucosa, but significantly reduces the effects of this enzyme in the area of ​​inflammation. Recently, the question of the central effects of NSAIDs associated with their ability to penetrate the tissue of the central nervous system and influence the development of a number of links in the pathogenesis of chronic pain associated with the activation of the central pain system (the phenomenon of “central sensitization”) has been actively discussed. Nimesulide obviously has such an effect, which is confirmed by the data of experimental and clinical studies. There is good reason to believe that nimesulide has a number of pharmacological effects independent of class-specific effects on COX-2. In particular, it suppresses the hyperproduction of the main pro-inflammatory cytokines (interleukin-6, TNF-a), reduces the activity of metalloproteinases.
The effectiveness of nimesulide for the relief of acute and chronic pain in rheumatic diseases (RD) is confirmed by a series of clinical trials. Thus, there is evidence of its use in postoperative pain relief. In acute rheumatic inflammation of the periarticular soft tissues – enthesitis, bursitis and tendonitis, it demonstrates a good therapeutic effect, comparable or more pronounced than the effect of high doses of “traditional” NSAIDs – diclofenac and naproxen. In particular, W. Wober et al. conducted a study in which 122 patients with subacromial bursitis and tendonitis took nimesulide 200 mg/day or diclofenac 150 mg/day for 14 days. At the same time, a “good” or “excellent” response to treatment was somewhat more often observed in persons taking nimesulide – 82.3%, compared with 78.0% in the diclofenac group. A subjective assessment of the tolerance of the drugs used showed an even more pronounced advantage of nimesulide: 96.8% of patients rated its tolerability as “good” or “excellent”, while only 72.9% gave a similar assessment to diclofenac [14].
Nimesulide is effective for acute low back pain (LBP). According to a clinical trial conducted by Finnish scientists, nimesulide at a dose of 100 mg 2 times a day was superior to ibuprofen at a dose of 600 mg 3 times a day, both in terms of the severity of the analgesic effect and in restoring the function of the spine. By the 10th day of therapy, the use of nimesulide provided an improvement in functional activity by more than 2 times. This makes nimesulide (Nise) very attractive for the treatment of pain in Bechterew’s disease.
One of the most valuable advantages of nimesulide for clinical practice is its good gastrointestinal tolerance. After all, it is the development of the pathology of the digestive system, which is one of the class-specific complications of NSAIDs, that is one of the main parameters that determine the risk-benefit ratio for this class of painkillers.
The risk of liver complications when using nimesulide (Nise) is not higher than that of “traditional” NSAIDs. An analysis of the available literature data and clinical studies shows that the negative dynamics of laboratory biochemical parameters, indicating the development of liver pathology, is observed with the use of nimesulide with the same frequency as with other NSAIDs. When analyzing reports of hepatotoxic reactions, it turned out that the total number of reports when using diclofenac was 990, ibuprofen – 590, and nimesulide – only 152. Most importantly, a life-threatening pathology – liver failure was recorded by WHO in 21 patients who received diclofenac, and in 32 patients who received ibuprofen. Against the background of taking nimesulide, this complication was noted only in 4 cases. It becomes clear that complications from the liver when using nimesulide are extremely rare, and their absolute number in comparison with other popular NSAIDs is very small.
In 2013, the absence of specific hepatotoxicity of nimesulide was confirmed by another population-based study. S. Gulmez et al. studied the causes of acute liver failure in 9479 people included in the list in need of emergency liver transplantation (European Union, 2005–2007). NSAIDs were the etiological factor of this potentially fatal complication in 40 cases, paracetamol – in 192. The relative risk (RR) of acute liver failure for different drugs is different. According to the results of the study, nimesulide was less dangerous than paracetamol and ibuprofen, and actually equal to such drugs as diclofenac and ketoprofen. In Russia, not a single case of severe hepatotoxic reactions has been described [7].
An important factor contributing to the popularity of nimesulide among other drugs of this drug group is its low cost, which makes it affordable for the vast majority of the inhabitants of our country. After all, the main consumers of NSAIDs are patients suffering from chronic diseases of the joints and spine, elderly people with low income.
In addition to standard forms for oral administration, a preparation for local use is also presented – Nise gel containing 1% of the active substance. Local forms of NSAIDs are a useful and safe agent that can be used for adjuvant therapy both when applied to the skin and in the form of phonophoresis with an ointment on the painful area [13].
Glucocorticosteroids (GCS)
For the treatment of AS, systemic use of corticosteroids is not recommended. But these drugs are effective as local therapy for peripheral arthritis in recurrent synovitis. The effectiveness of HA in the treatment of AS is beyond doubt, but they are less effective in the treatment of enthesitis (apparently due to the lower concentration of the active substance in the avascular zone of enthesis). In these cases, local injections of corticosteroids into the enthesis zone are highly effective.
Muscle relaxants
It is known that pain in the spine is accompanied by muscle spasm, the presence of which in turn exacerbates pain and spasm. It has been established that the simultaneous use of NSAIDs and muscle relaxants reduces back pain and also helps to maintain spinal mobility [7].
DMARDs
Synthetic DMARDs: sulfasalazine, methotrexate, leflunomide are not recommended in the treatment of axial forms of AS due to inefficiency. But in peripheral arthritis, this group of drugs is used with a positive effect, which is recommended to be evaluated no earlier than after 3 months. Sulfasalazine is taken in a daily dose of 2-3 g. The use of methotrexate, depending on the effectiveness, toxicity, can be at a dose of 10 to 15-20 mg per week and must be accompanied by folic acid intake, excluding the day of methotrexate intake. In case of intolerance to methotrexate, the patient may be prescribed Arava. The latter is taken at 20 mg/day after a 3-day induction dose of 100 mg/day for 3 days.
Genetically engineered biological products (GIBPs)
Recently, significant progress has been made in the treatment of diseases of the joints and spine due to the use of GEBP. The high efficiency of this group of drugs has been confirmed by numerous studies and long-term use in medical practice. In AS, these drugs provide a distinct reduction in pain and inflammation in the spine, joints, and entheses. Approved drugs for the treatment of AS include infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. A fundamental difference in the effectiveness of these drugs in relation to the effect on the main symptoms (pain, stiffness, enthesitis, peripheral arthritis) has not been established. Treatment with GIBD should be started if there is no effect in the treatment of both NSAIDs and NSAIDs in combination with DMARDs (sulfasalazine at a maximum dose of 3 g / day) for 3 months. The effect of TNF-a inhibitors on uveitis (as opposed to the effects on the spine and peripheral arthritis) has been little studied. A group of employees of the NIIR them. V.A. Nasonova (A.A. Godzenko, A.G. Bochkova, Sh.F. Erdes et al.) studied the effect of TNF-a inhibitors: infliximab, adalimumab, and etanercept on the frequency of uveitis attacks in patients with AS. As a result of the study, it was found that TNF-a inhibitors effectively affect uveitis in patients with AS. The three drugs studied (infliximab, adalimumab, etanercept) significantly reduced the incidence of uveitis exacerbations compared to standard anti-inflammatory therapy. The criteria for evaluating response to treatment are a global assessment of the patient’s well-being using a 100-mm visual analog scale (VAS), pain in the spine using the VAS, a functional assessment of the patient (BASFI), and an assessment of inflammation using the BASDAI questionnaire [1, 10].

Surgery
In cases of involvement in the process of the hip joints with the development of coxitis and subsequent functional disorders in patients, arthroplasty of the hip joint can be performed. Spinal surgery (corrective osteotomy) may be performed if necessary.
Despite significant progress in the treatment of AS in recent years, many unresolved problems remain: monitoring of patients, the immunogenicity of GEBAs and their impact on the efficacy and safety of therapy, etc. This leaves the tactics of managing and treating patients with AS in the focus of scientists and physicians.

Treatment of ankylosing spondylitis in Israel

Treatment of ankylosing spondylitis in Israel is carried out by experienced doctors who have all the necessary knowledge and practical skills to effectively reduce symptoms, prevent the progression of the disease, improve the quality of life of patients through the use of the latest biotherapy, effective pharmaceuticals , physiotherapy and surgical techniques.

30%

diagnoses made in the CIS countries are refuted in the clinic Ichilov Complex

100%

high-precision diagnostic program

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– one-hour support in Russian 1 Diagnosis of AS

Methods of treatment of Bechterew’s disease in Israel

Bechterew’s disease (ankylosing spondylitis, AS) is a type of arthritis characterized by inflammation of the joints of the spine, the typical foci of inflammation are the lumbar joints, paravertebral soft tissues, often the disease spreads to the shoulder, hip joints, leads to impaired vision and bowel function.

The true cause of this pathology has not yet been revealed, scientists believe that genetic and environmental factors play an important role in the development of AS, the vast majority of patients with Bechterew’s disease have a specific leukocyte antigen HLA-B27, which indicates a possible autoimmune the nature of the disease.

There is currently no method that can completely cure ankylosing spondylitis, but the doctors of our clinic have techniques that can significantly alleviate the symptoms of the disease, improve the patient’s quality of life and prevent serious complications.

Drug therapy

Pharmacological drugs are used to reduce symptoms – relieve pain, reduce inflammation, improve freedom of movement. The drugs that are used in the treatment of AS include drugs from two groups – non-steroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs.

The first group includes drugs that provide analgesia and anti-inflammatory effects, the second group includes drugs that have a specific effect on certain biological processes and can lead to a slowdown in the progression of AS. Often, disease-modifying antirheumatic drugs are used to treat patients who have inflammation of the hips, knees, elbows, and wrists (peripheral arthritis). Also, certain therapeutic results can be achieved by local injections of corticosteroid drugs.

Biotherapy

Biological drugs from three groups are currently used for the treatment of ankylosing spondylitis – tumor necrosis factor TNF inhibitors, anti-interleukin-6 inhibitors and interleukin-17 inhibitors. Tumor necrosis factor is a special protein compound involved in all inflammatory processes (especially those of an acute nature). By inhibiting this protein, our doctors prevent its destructive effect on bone and cartilage tissues. Anti-interleukin-6 and interleukin-17 are also endogenous proteins that regulate inflammation in the body. By suppressing their biosynthesis, our doctors reduce joint inflammation. Thus, patients with Bechterew’s disease have very high levels of interleukin-17 in the blood, so the suppression of its synthesis plays a significant role in the treatment of patients who, for whatever reason, are not recommended drugs from the TNF inhibitor group.

Physiotherapy

Physiotherapy is used as an aid to reduce pain in the back, neck, knees and shoulders. In our clinic, such types of physiotherapy as various low-intensity aerobic exercises, transcutaneous electromyostimulation (exposure to nerves with electric current for the treatment of chronic pain syndrome), and thermotherapy (various types of heating) are widely used.

Good means of reducing the symptoms of the disease are acupuncture, Swedish massage, deep tissue massage. Education of patients with ankylosing spondylitis so-called. The “Alexander Technique” (a method developed by the Austrian actor Frederik Matthias Alexander) helps them move more comfortably and efficiently later in life, maintaining a more stable body position.

Surgical methods

Surgical approaches to treatment are used only in especially severe cases, most patients with ankylosing spondylitis do not require surgery. Surgical techniques include operations to replace joints and correct spinal deformities: a popular method of surgical treatment is arthroplasty — replacement of the hip and knee joints with artificial implants. This helps to improve the quality of life of the patient, significantly improve his mobility.

Many patients with Bechterew’s disease develop spinal deformities (kyphosis), and in such a pronounced form that the patient can hardly look forward or into the eyes of the interlocutor. Added to this are difficulties in eating, pain in the cervical spine, instability of gait. Such patients are shown surgical treatment of curvature of the spine, during which the vertebrae of the cervical spine are fixed in a vertical position so that the patient can easily look forward. This approach has one drawback – the vertebrae are fixed with metal fasteners and grow together with each other, which leads to a decrease in mobility in the cervical region.

• Joint arthroplasty

Diagnosis of AS

Diagnosis of patients with suspected AS in the center of Ichilov Complex takes only a few days, during which time the patient receives an accurate diagnosis and a planned treatment program.

First day — consultation

On the first day, the patient, together with the curator-translator accompanying him, go to the clinic, where he is consulted by a leading specialist (the curator first meets the patient at the airport and helps to stay at the hotel for the time of diagnosis). The doctor examines the patient, draws attention to the symptoms of Bechterew’s disease and prescribes the necessary studies.

The second day is a complex of diagnostics

The second day is devoted to the passage of a full complex of diagnostics, which may include various studies.

• Radiographic examinations – the study of the condition of the joints using x-rays. At the same time, signs of AS are indicated by the presence of erosion and sclerosis of the joints. The disadvantages of the method include the impossibility of its use for the early diagnosis of Bechterew’s disease – the signs that make it possible to draw conclusions about the presence of spondyloarthritis from an x-ray image appear only a few years after the onset of the disease.
• Magnetic resonance imaging can compensate for the shortcomings of most radiographic methods and detect changes in the structure of the joints at an earlier stage of the disease, while saving the patient from excessive radiation exposure to the body.
• Blood test – during periods of exacerbations of the disease, many patients with Bechterew’s disease have an increased concentration of C-reactive protein in the blood and an increase in the erythrocyte sedimentation rate.
• Genetic tests – one of the most characteristic signs of the development of Bechterew’s disease is an increase in the level of the HLA-B27 gene, this feature is noted in 80-90% of patients with ankylosing spondylitis.
• The BASDAI test is a study based on the calculation of the index of the same name. The BASDAI index is compiled on the basis of the patient’s answers to 6 questions regarding the main symptoms of Bechterew’s disease (presence of fatigue, back pain, joint pain, severity and duration of morning stiffness, etc. ). Subjectively assessing the severity of each of these symptoms on a 10-point scale, the patient allows the rheumatologist to predict the effectiveness of different types of therapy for the disease.

Third day – planning the treatment program

Having received the results of the diagnosis, the leading specialist makes the final diagnosis and plans the treatment program. Each item is selected individually, taking into account the severity of the inflammatory process. The patient himself can take part in planning the stages of treatment. In addition to receiving full information about their diagnosis and participation in the selection of types of treatment, patients of all Israeli clinics are guaranteed the right to use a “second opinion” at the legislative level – an assessment of the chosen treatment tactics by an independent medical specialist.

• Magnetic Resonance Imaging (MRI)

Treatment of ankylosing spondylitis in Israel – prices our clinics.

In the vast majority of cases, the cost of treatment in Israeli medical centers saves up to 25-45% compared to clinics in the European Union and the United States.

Advantages of ankylosing spondylitis treatment in the center Ichilov Complex

In addition to the affordable price, the treatment of this disease in our center has other advantages.

• The doctors of the center are experienced specialists who have undergone many years of training and specialization in the treatment of Bechterew’s disease. Many of them are internationally known, conduct their own research in this area and publish their results in leading scientific medical publications.
• Clinic Ichilov The complex is equipped with the latest diagnostic equipment that allows to detect spondylitis at the earliest possible stages, predict the success of a particular type of therapy and clearly monitor the dynamics of treatment.
• For the treatment of ankylosing spondylitis, our center uses modern and highly effective methods to stop or at least significantly alleviate the inflammatory process, stop the pain syndrome, and correct spinal column deformities.