There are a number of different types and classes of medications used in the treatment of ankylosing spondylitis and related diseases. Note that different people respond to different medications with varying levels of effectiveness. Thus, it may take time to find the most effective course of treatment.
NSAIDs are the most commonly used class of medication for the treatment of pain and stiffness associated with spondyloarthritis. Ibuprofen, for instance, is a generic NSAID and is found in over-the-counter pain relievers such as Advil and Motrin.
Sometimes, high doses of NSAIDs are needed to maintain relief from the symptoms of ankylosing spondylitis and related diseases. This can pose a problem because NSAIDs can cause significant side effects, especially in the gastrointestinal tract (stomach, intestines, etc.). NSAIDs can cause reduced amounts of protective mucus in the stomach, which can result in stomach irritation. Over time, this can lead to heartburn, gastritis, and possibly ulcers and even bleeding. People can take other medications (such as antacids) to neutralize or prevent the production of excess stomach acid, help coat and protect the stomach (such as Carafate), or restore the lost mucus (such as Cytotec).
There may also be an increased risk of heart attack or stroke associated with NSAIDs, especially in people with a history of heart diseases.
A different class of NSAIDs known as COX-2 inhibitors (or COXIBs) seem to reduce the risk of gastrointestinal complications associated with traditional NSAID therapy. Celebrex (Celecoxib) is still being used to treat spondyloarthritis. Others, such as Vioxx, were pulled from the market in 2004 because of the high rate of heart attacks caused by the drug.
Although NSAIDs are commonly the first line of medications used to treat ankylosing spondylitis and related diseases, sometimes they aren’t enough to control the symptoms. It is important to note, however, that it may take several weeks for some NSAIDs to show positive results. If you are considering changing medications, remember to ask your doctor about the potential benefits and side effects before you and your doctor decide whether a change in treatment is right for you.
In severe cases of ankylosing spondylitis or related disease, NSAIDs may only be partially effective or the side effects too severe to continue their use. In this case, a doctor may prescribe one of the following medications.
Sulfasalazine is one medication that can be helpful to some people with severe disease. It is known to effectively control not only pain and joint swelling from arthritis of the small joints, but also the intestinal lesions in inflammatory bowel disease. It comes in tablet form and is taken orally. Sulfasalazine is generally not utilized for spinal arthritis.
Side effects are relatively infrequent, but can include headaches, abdominal bloating, nausea, and oral ulcers. Rarely, someone being prescribed this medication can develop bone marrow suppression, which is why it is important for your doctor to regularly monitor your blood count.
Originally developed to treat cancer, this chemotherapy drug is widely used and often very effective for the treatment of rheumatoid arthritis. When prescribed for treating symptoms of spondyloarthritis, it is given in smaller doses and is generally not utilized for spinal arthritis. Methotrexate can either be taken via a self-injectable shot or orally in tablet form. When taking methotrexate, it is also necessary to take the vitamin folic acid in order to help suppress some of the possible side effects, including oral ulcers and nausea. Because of other potential serious side effects, frequent monitoring of blood counts and liver function are required. Methotrexate is strongly contraindicated in pregnant women, as it has caused birth defects and death in unborn babies.
While corticosteroids such as prednisone can be effective in relieving inflammation, the side effects of long-term use of systemic corticosteroids (which impact the entire body) can be very severe. As such, experts strongly recommend against using oral or injectable systemic corticosteroids. In contrast, local injections into inflamed joints (which do not impact the entire body) are acceptable, and can provide temporary relief of the pain caused by arthritis or bursitis.
Biologic medications are made from living organisms. The material they are made from can come from many sources, including humans, animals, and microorganisms such as bacteria or yeast.
The tumor necrosis factor alpha (TNF-α) inhibitors were the first biologic medications to have shown great promise in treating spondyloarthritis, with the first TNF inhibitor – Enbrel – being approved in 2003. These medications have been shown to be highly effective in treating not only the arthritis of the joints, but also the inflammation in the gut and eyes, as well as the spinal arthritis associated with ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), and related diseases.
A serious and well-known complication of the TNF inhibitors is an increased frequency of infections, along with a reduced ability to fight infections, including tuberculosis. Thus, a TB test is required before starting any of the TNF therapies. There is also a slightly increased risk of certain cancers associated with TNF inhibitors, such as lymphoma (most notably in children and teens) and skin cancers.
It should be noted that each TNF inhibitor/biologic medication works in a slightly different manner. Thus, if one does not have a positive effect, another one might.
The following TNF inhibitors are currently approved for forms of spondyloarthritis: Enbrel, Humira, Remicade, Simponi, and Cimzia.
IL-17 inhibitors are another class of biologic medications approved for spondyloarthritis. There are currently two IL-17 inhibitors approved by the FDA for forms of spondyloarthritis – specifically for ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), and psoriatic arthritis (PsA). Cosentyx (secukinumab) was approved for AS and PsA in January of 2016, and Taltz (ixekizumab) was approved for PsA in December of 2017, and for AS in August of 2019. Both were approved for nr-axSpA in June of 2020.
Both IL-17 and TNF-α are inflammatory cytokines (cell signaling molecules) that, as the name implies, signal to activate inflammation throughout the body, modulating or altering the immune system response. Inflammatory cytokines play an important role; however, when there is an overabundance of these, as has been described in inflammatory disease, they can cause harm to the body if left unchecked.
IL-17 and TNF-α cytokines signal to specific immune cells directing them to activate inflammation, with each cytokine being responsible for signaling to a different set of cells. IL-17 and TNF inhibitor medications work by targeting their respective cytokines, obstructing their signaling pathways, and by this mechanism seek to reduce inflammation. Since IL-17 inhibitors target different cytokines than the TNF inhibitors, the hope is that this newer class of biologic medications will help those who haven’t responded well to the TNF inhibitors, or are not able to tolerate them.
IL-17 inhibitors carry similar risks of infections, and reduced ability to fight infections as the TNF inhibitors. They have also shown in clinical trials to exacerbate inflammatory bowel disease in patients who have it, as well as bring on new cases of inflammatory bowel disease.
Ustekinumab (Stelara) works similarly to the IL-17 inhibitor, but targets different cytokines: IL-12 and IL-23. Stelara was approved in 2013 for psoriatic arthritis. Stelara also carries increased risks of infections, and reduced ability to fight infections, as well as a slightly increased risk of certain cancers.
Janus kinase (JAK) inhibitors, also known as JAKi, are the latest class of synthetic (non-biologic) disease-modifying anti-rheumatic drugs (DMARDs) that have been proven effective in the treatment of multiple forms of arthritis, including psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA). These medications are taken orally as pills, as opposed to biologics, which are injectable.
JAK inhibitors specifically target the JAK family of enzymes, namely JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), each of which are involved in the initiation of the signal for a cell to make more than 60 different cytokines and growth factors.
Unlike biologics, which inhibit the effects of one single cytokine, JAKi can block the effects of multiple cytokines that are implicated in the pathogenesis (development) of many immune-mediated rheumatic diseases, including AS. They have a shorter half-life compared to biologics, meaning they are active in the body for less time, which means if they are discontinued, any side effects will disappear in a quicker fashion.
Two JAKi are FDA-approved for ankylosing spondylitis (AS) and for psoriatic arthritis (PsA): tofacitinib (Xeljanz or Xeljanz XR) and upadacitinib (Rinvoq). Upadacitinib is also approved for non-radiographic axial spondyloarthritis (nr-axSpA).
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