Less than a year ago, the American College of Rheumatology in conjunction with other groups such as the Spondyloarthritis Research and Treatment Network published recommendations for the treatment of ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA), but there have been new developments since then, and likely even more to come.
In the recommendations, the authors stated: “The goals of treatment of AS and nonradiographic axial SpA are to reduce symptoms, maintain spinal flexibility and normal posture, reduce functional limitations, maintain work ability, and decrease disease complications.”
In an interview with MedPage Today, the lead author, Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., added: “In my opinion, the most important aspect of the recommendations is that they focus on providing recommendations for treatment decisions for specific clinical situations, based on the type of patient and the treatment history.
“For example, the recommendations address what treatment should be considered for a patient with active AS who has not responded to the first tumor necrosis factor [TNF] inhibitor used. This approach, using common clinical situations, makes the recommendations directly applicable to practice.”
The 2015 Recommendations
The recommendations were based on a systematic literature review through 2014, formulation of clinical questions to be addressed, and reviewing and rating the evidence. The authors cautioned that the guidelines are meant to apply to typical patients, rather than exceptional cases, and that treatment decisions should always involve education of the patient regarding anticipated benefits and potential harms.
Regarding the various categories of recommendations as stated in the document, strong recommendations were those that would be agreed to by “almost all informed patients,” while conditional recommendations were those that would be chosen by most informed patients, although a minority would not. Recommendations that are conditionally against the treatment are those that would not be chosen by most informed patients, and those that were strongly against, should not be used.
The recommendations initially addressed pharmacologic treatment of patients with active AS, with a strong recommendation for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and a conditional recommendation in favor of continuous rather than on-demand use. No particular NSAID was specified as preferable. Rather, “choice of NSAID should be based on consideration of the patient’s past history of NSAID use, risk factors for adverse effects, and co-morbidities.”
The authors also strongly recommended using TNF inhibitors for patients who had a lack of response or intolerance to at least two NSAIDs. Overall, the guidelines did not favor any specific TNF inhibitor, although they noted that infliximab (Remicade) or adalimumab (Humira) would be preferable for patients who also have inflammatory bowel disease or recurrent iritis.
For patients whose AS remained active despite treatment with a TNF inhibitor, the conditional recommendation is for using a different TNF inhibitor, because of insufficient data at the time of writing the document to support the use of the available non-TNF biologic agents.
The guidelines strongly recommended against the use of systemic glucocorticoids in active AS, although a short course with rapid tapering might be useful in circumstances such as a flare of accompanying peripheral arthritis. Local injections of glucocorticoids could be given to patients with enthesitis or active peripheral arthritis.
For patients with stable AS, which was defined as “asymptomatic or causing symptoms that were bothersome but at an acceptable level as reported by the patient” for at least 6 months, the authors conditionally recommended on-demand rather than continuous NSAID use. In addition, for patients with stable AS being treated with NSAIDs plus TNF inhibitors, there was a conditional recommendation for ongoing treatment with the anti-TNF agent alone.
Other aspects of the recommendations included treatment with physical therapy (strong recommendation) and back exercises (conditional recommendation), as well as total hip arthroplasty for those with advanced arthritis of the hip (strong recommendation).
For patients with nonradiographic axial SpA, the document noted that the literature was sparse and so advised that the same approach should be used as for AS, with the exception of a conditional rather than a strong recommendation favoring the use of TNF inhibitors for NSAID nonresponders.
After the Guidelines
The approval of the interleukin-17A inhibitor secukinumab (Cosentyx) for AS shortly after the publication of the recommendations broadened the treatment options, but as yet there has been little guidance as to where in the treatment paradigm this agent will fit.
When the panel was considering the treatment options, the full paper reporting on the two double-blind MEASURE studies of secukinumab had not yet been published. “The guidelines were excellent, but they quickly became obsolete by the time they were in print,” commented one of the coauthors, Atul Deodhar, MD, of Oregon Health & Science University in Portland.
The availability of secukinumab has increased the focus on the question of what should be done if a patient fails on a first TNF inhibitor, he told MedPage Today. “What we don’t know is whether we should try another anti-TNF or change to secukinumab. No such study has been done to compare.”
Switching to another TNF inhibitor can work, but there is no good evidence as yet whether changing to secukinumab would be more effective, Deodhar noted. “The usual expert opinion would be to try at least two TNF inhibitors before changing.”
It is also important to consider whether the patient experienced primary or secondary failure to TNF inhibition. “Primary failure would be if you give etanercept [Enbrel] and they have absolutely no response, whereas usually with secondary failure, the patient initially says ‘Wow, this is fantastic,’ but after a year or two it’s not working so well. These are the people who do respond to a second TNF inhibitor. With primary failure, I would try secukinumab,” Deodhar said.
There also are other potential agents in development for AS, such as the interleukin-12/23 blocker ustekinumab (Stelara), which is approved for Crohn’s disease and is currently in clinical trials for AS, and the JAK inhibitor tofacitinib (Xeljanz). “And I’m sure the other companies that are making JAK inhibitors will be in this space very quickly,” he said.
Ward said that discussions have begun to update the recommendations to incorporate new evidence since the last literature review and include newly approved medications — “But this work has not yet begun.”