Treatment of Ankylosing Spondylitis
The optimal management of ankylosing spondylitis combines both medications and non - drug therapies.
Several different types of AS drugs are available, and decisions about which drug or combination of drugs to use will depend on your particular situation. Your rheumatologist will work with you to develop an individualized treatment plan.
During treatment, make sure that all of your healthcare providers are informed about all of your medications. This includes prescription medications, over-the-counter medications, and dietary supplements. Some products may not be safe to combine with your other medications.
The goals of therapy for AS are to control inflammation, decrease pain, maintain function, and prevent deformity with the fewest side effects. A therapeutic program will include non-drug and drug components.
Non-drug Therapies for Ankylosing Spondylitis
Maintenance of maximum motion of the skeleton, particularly of the entire spine, is a main focus of non-drug therapy for AS. Physical therapy with instruction to do range of motion exercises to maintain function is essential to have a good outcome. Supervised exercises are better than unsupervised exercises in improving pain, stiffness, spinal mobility, and overall well-being in AS patients. In addition, aerobic conditioning activities, such as a stationary bicycle, or walking program, are helpful in maintaining respiratory function and cardiovascular health.
Patient education from health professionals and reliable on-line sources can reinforce important messages involving posture, proper lifting techniques, avoidance of thick sleeping pillows, and the importance of consistent exercise. The correct balance between exercise and rest cannot be overemphasized. Rigorous exercise can exacerbate symptoms. Education about proper nutrition to obtain an ideal weight to minimize stress on weight-bearing joints is also important for an ideal outcome.
Psychological support may be needed for those young patients who realize they have a chronic illness. Some patients believe they are disabled before significant disease manifestations have appeared. Pain, fatigue, joint stiffness can have detrimental effects on interpersonal relationships and work. Learning coping skills are essential to maintain activities of daily living in its many forms.
Drug Therapies for Ankylosing Spondylitis
A wide variety of drug therapies are available for the treatment of AS. The key to success is matching the degree of illness with the corresponding drug. Studies now suggest that treatment with an anti-TNF medication that improves symptoms is associated with radiographic evidence of improved disease.1
Why not treat AS patients with all the drug categories? Each drug category has associated side effects. A patient wants to limit those exposures to a minimum. Essentially, patients want to take the appropriate number of medicines and not one extra.
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs, or aspirin-like drugs possess abilities to decrease pain, fever, and inflammation. They are anti-inflammatory and pain-relieving when given in larger doses long term. In AS, NSAIDs decrease spine stiffness and pain. In a significant number of AS patients, NSAIDs are adequate by themselves to control disease symptoms and improve function. There is also clinical evidence that NSAIDs may slow the calcification of spine structures when taken on a chronic basis. A specific type of NSAID is the cyclo-oxygenase-2 inhibitor. Cyclo-oxygenase -2 enzyme produces cell messengers (cytokines) that initiate and sustain inflammation in tissues. COX-2 inhibitors prevent the production of these cytokines while having no effect on the products of COX-1 enzyme that is necessary for the normal function of the stomach and kidney.
Spasms in spinal muscles in AS patients cause pain and limitation of motion. The addition of a muscle relaxant to a NSAID helps decrease muscle pain and tightness. The most common side effect of muscle relaxants is sleepiness. Taking the medicine early in the evening can minimize the possibility of tiredness.
Disease-Modifying Agents (DMARDs)
DMARDs are drugs that work more slowly than NSAIDs but have the capability of modifying the progression of disease. These drugs have greater benefit in rheumatoid arthritis. DMARDs do not have a beneficial effect on spinal disease. Some benefit may exist for arthritis of peripheral joints like the shoulders and hips. Examples of DMARDs include sulfasalazine, methotrexate, and leflunomide.
Anti-Tumor Necrosis Factor Inhibitors (TNFi)
Cell messenger or cytokines, are released by cells to initiate a variety of functions. An inflammatory cytokine, TNF is associated with the clinical manifestations of AS. TNF is associated with fatigue, joint swelling, stiffness, and pain. A decrease in the production of TNF, or removal from the blood stream can result in a decrease in disease-associated complaints. However, the total removal of TNF can be associated with an increased risk of infection. The goal of therapy is to obtain a physiologic level of TNF.
The results from an analyses in 2020 study suggest long-term treatment for patients with AS of 4 years or longer with anti-TNF therapy can have a significant impact on the progression of their illness as evidenced by radiographic improvement of their disease.1
There are a number of ANTI-TNF therapies available for the treatment of AS including:
- Enbrel (entarnercept) is a soluble receptor for TNF injected weekly.
- Humira (adalimumab) is a fully human anti-TNF monoclonal antibody administered by injection every 2 weeks.
- Simponi (golimumab) is a fully human anti-TNF monoclonal antibody that is injected monthly.
- Cimzia (certolizumab) is an anti-TNF partial antibody connected to polyethylene gycol that prolongs the effect of the antibody that is injected every 4 weeks
- Remicade (infliximab) is a monoclonal directed against TNF that is administered intravenously every 4 to 8 weeks.
The effectiveness of the TNF therapies shows no benefit of one agent compared to another. The use of specific agents in individuals is based on personal preference related to injections versus infusion and frequency of dosing.
Side effects associated with the use of TNF inhibitors include the activation of latent tuberculosis and increased risk of viral and bacterial infections. If infections occur, the infection is treated and the TNF therapy stopped until the infection is resolved. An increased risk of malignancy has been reported. However the degree of this increase which is reported to be small and is undergoing active evaluation.
Interleukin-17 is a protein produced by immune cells that functions as a messenger between cells playing an important role in inflammation and the symptoms associated with AS, including morning stiffness, limited spine motion, and overall fatigue. Antibodies that target the IL-17 pathways are used for the treatment of several conditions in which the IL-17 pathway has a role, including AS, psoriasis and psoriatic arthritis, IL-17 therapies available for the treatment of AS include
- Cosentyx (secukinumab) is an anti-IL-17 monoclonal antibody that blocks the effects of IL-17 leading to an improvement in IL-17 associated symptoms.
- Taltz (ixekisumab) is an anti IL-17 monoclonal antibody that blocks the effects of IL-17.
These agents can be effective in those individuals who have failed one or more TNF inhibitors. Factors that identify those individuals who are more responsive to one class of biologic agent versus another are being investigated but are not available for clinical use at this time.
Side effects associated with the use of IL-17 inhibitors include an increased risk of infections. Another very small risk is the development or worsening of inflammatory bowel disease.
Otezla (apremilast) The expectation is that if an agent is good for one form of a specific form of a spondyloarthritis like psoriatic arthritis, it must be good for all of them. Unfortunately, that is not always the case. Sometimes the benefits of a specific therapy are limited to a specific form of the illness. That is the case with Otezla which has been shown to be effective in psoriatic arthritis.
A phase-3 clinical trial in 490 patients with AS compared Otezla to placebo over a 6 year period. No significant differences in radiographic changes were noted among the study groups. More adverse reactions including diarrhea, nausea, and headaches were noted with Otezla. The lack of effectiveness in AS patients relates to the inhibitory effect of Otezla (a phosphodiesterase 4 inhibitor) on interleukin-23 which is not an important factor in the development and progression of AS.
Nonradiographic spondyloarthritis (nr-axSpA)
Not all patients who have axSpA have plain x-ray changes in the sacroiliac joints. These patients have clinical symptoms of inflammatory back pain and are HLA-B27 positive, but do not have definitive plain x-ray alterations in the sacroiliac joints. Magnetic resonance imaging of the sacroiliac joints is needed to identify the presence of inflammation in the form of bone marrow edema. These individuals do not meet criteria for AS but do have an inflammatory arthritis of the spine. These patients have non-radiographic spondyloarthritis. Questions remain regarding whether nr-SpA is AS in its earliest form but is a disease independent of AS. This question will be answered over time since these designations have only been defined since the advent of MRI. Longitudinal studies will need to be completed to know the answer to this question.
Taltz is an interleukin -17 and f inhibitor (Il-17). Ixekizumab is already approved for the treatment of AS. Based upon the results of the phase 3 COAST-X trial which demonstrated efficacy of 30% of NR-SPA patients versus 13% placebo patients at 52 weeks, the Food and Drug Administration (FDA) approved ixekizumab for the treatment of NR-SPA. Currently, the only other biologic agent approved for the treatment of NR-SPA is the anti-tumor necrosis factor (TNF) inhibitor, certolizumab (Cimzia). The approval of ixekizumab allows physicians to choose between biologics with different mechanisms of action if one form of therapy is ineffective.
Surgical Therapies for Ankylosing Spondylitis
Surgical therapies for AS are more commonly used for the peripheral joints than for the spine. At times the spine can become so brittles that it will fracture. The neck is the most common location for this fracture. Stabilization of the spine is necessary to prevent damage to the spinal cord.
Peripheral joints can be damaged to the degree of requiring a replacement. The hips and shoulders are the most commonly affected peripheral joints. The decision about joint replacement must be done in the setting of spine involvement and how the replacement will result in improved function.
- Overview of Ankylosing Spondylitis
- Diagnosing Ankylosing Spondylitis
- Treatment & Management of Ankylosing Spondylitis
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- Karmacharya P et al. The Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis. Arthritis Rheum doi: 10.1002/ART.41206
- Taylor PC. Et al. a phase III randomized study of apremilast, an oral phosphodiesterase 4 inhibitor, for active ankylosing spondylitis. J Rheumatol 2021 Feb 15;jrheum.201088.doi: 10.3899/jrheum 201088