麻豆传媒

The primary goal of treatment in axial spondyloarthritis (axSpA) is to control the symptoms of pain, stiffness, and fatigue -- ideally to eliminate them or at least to decrease the severity as much as possible, while minimizing the potential adverse events of medications.

"Other goals include to maintain function, prevent complications of spinal disease such as contractures, to minimize symptoms that may occur outside of the musculoskeletal system such as uveitis and aortic valve insufficiency, and to maintain psychosocial function to allow patients to lead as normal a life as possible in the spheres of social participation, ability to work, and to improve overall health status and function," said Dalit Ashany, MD, of the Hospital for Special Surgery in New York City.

First-line treatment is with nonsteroidal anti-inflammatory drugs (NSAIDs), along with physical therapy and exercise. In the most recent iteration of , the American College of Rheumatology (ACR)/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network conditionally recommended continuous treatment with NSAIDs over on-demand use among patients with active disease. However, the authors noted, "the decision to use NSAIDs continuously may vary depending on the severity of symptoms, patient preferences, and comorbidities, particularly gastrointestinal, kidney, and cardiovascular disease." A trial of 4 weeks is generally advised to determine response.

Tumor Necrosis Factor (TNF) Inhibitors

"For many years we only had physical therapy and NSAIDS, but we now have better drugs like biologics that I truly believe have changed the course of disease," said Atul Deodhar, MD, professor of medicine and medical director of rheumatology at the Oregon Health & Science University in Portland. "If you start TNFs early on you are able not only to give the patient very good relief from their common symptoms of pain, fatigue, and stiffness, this also can prevent bony damage and new bone formation," he said.

In the ACR treatment document, the expert panel "strongly recommends treatment with TNF inhibitors." They do not specify which of these agents should be preferred, but comorbidities can influence choices. For example, among patients who have recurrent uveitis, the monoclonal antibodies such as adalimumab (Humira) or infliximab (Remicade) are preferred over the fusion protein etanercept (Enbrel), and for patients with concurrent inflammatory bowel disease (IBD), TNF monoclonal antibodies also are preferred, with the specific medication being chosen in consultation with the patient's gastroenterologist.

Other biologics such as abatacept (Orencia), interleukin (IL)-6 inhibitors, and IL-12/23 inhibitors have not been found to be effective in axSpA.

Newer Agents

"The landscape has dramatically improved over the last 20 years. Prior to the introduction of the TNF inhibitors, there were very few robust treatment options," said Liron Caplan, MD, associate professor at the University of Colorado in Aurora. "Since then we have the TNF inhibitors and two newer classes, the IL-17 inhibitors and JAK inhibitors, which has provided patients with multiple options for managing their condition," he said in an interview.

"However, practically speaking, formularies often dictate the order of medications," he noted.

Secukinumab (Cosentyx) is a monoclonal antibody targeting interleukin (IL)-17A approved in the U.S. and Europe for ankylosing spondylitis (AS), based on the findings of several multicenter phase III trials known as the trials. Participants had disease activity scores and spinal pain ratings of 4 or higher despite maximal tolerated doses of NSAIDs. Patients also could have failed a TNF inhibitor.

In three of four of these studies, significantly greater improvements in clinical signs and symptoms were seen compared with placebo, with benefits persisting through 5 years of treatment. Slowing of radiographic progression also was observed.

While those studies enrolled patients with established radiographic disease, an additional phase III trial referred to as enrolled 555 patients with nonradiographic axSpA, comparing subcutaneous secukinumab with placebo over 52 weeks. Among patients whose regimen included a loading dose, 42% experienced significant improvements of at least 40% on the criteria of the international Assessment of Spondyloarthritis Society (ASAS40) at week 16, as did 40% of those without a loading dose at week 52, versus 29% and 20% of the placebo group at weeks 16 and 52, respectively (P<0.05 for both).

A second IL-17 inhibitor, ixekizumab (Taltz) is also approved for use in AS. In one multicenter phase III trial known as that included 341 patients with active AS, ASAS40 responses at week 16 were seen in approximately 50% of patients receiving ixekizumab compared with fewer than 20% of those receiving placebo.

The ACR recommendations also note that secukinumab or ixekizumab is preferred for patients with active axSpA who have heart failure or demyelinating disease, which are contraindications for TNF inhibitors, and in primary nonresponders to anti-TNF therapy.

The IL-17 inhibitors also are more effective than TNF inhibitors for patients with concurrent psoriasis. "So if patients have psoriasis along with axial involvement, I would use an IL-17 blocker," said Deodhar.

But the ACR recommendations pointed out that secukinumab has been associated with new-onset or an exacerbation of Crohn's disease, with similar risks being suggested for ixekizumab.

Another class of agents now available are the JAK inhibitors such as tofacitinib (Xeljanz), which have the advantage of being orally administered. However, these drugs carry a "black box" warning "regarding increased risk of heart attack, stroke, cancer, and blood clots in certain populations," noted Ashany, who is also assistant professor of medicine at Weill Cornell Medical College. "With this warning patients have to fail TNF inhibitors before JAK inhibitors can be prescribed," she cautioned.

One specific circumstance in which JAK inhibitors is an option is for patients who have coexisting ulcerative colitis and are unable to take a TNF inhibitor. "IL-17 inhibitors have not been shown to be efficacious in inflammatory bowel disease, while tofacitinib is an approved treatment for ulcerative colitis," the ACR panel noted.

"There is some evidence that JAK inhibitors may be beneficial in the treatment of uveitis, but this would not be the first choice until more data are acquired," Ashany said.

An additional concern has been the development of biologic biosimilars. "We strongly recommend continuing treatment with the originator TNF inhibitor over mandated switching to its biosimilar," stated the ACR recommendations. "Medication changes can increase the risk of destabilizing a patient, and the panel judged that additional data were needed to understand the frequency of potential problems and concerns associated with switching patients who were stable on an originator TNF inhibitor to its biosimilar." The panel also noted that there should be "a compelling rationale" for such a change in medications, particularly as the "

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