Treatment Efficacy and Clinical Burden in Nonradiographic Axial Spondyloarthritis vs Ankylosing Spondylitis

Human body radiograph of spine
Human body radiograph of spine
New research compared treatment efficacy by drug class and clinical and humanistic burdens of nr-axSpA with those of AS.

Nonradiographic axial spondyloarthritis (nr-axSpA) was associated with lower C-reactive protein (CRP) levels than ankylosing spondylitis (AS), but had similar clinical and humanistic burdens and response to tumor necrosis factor (TNF) inhibitor treatment, according to a study published in Seminars in Arthritis and Rheumatism.

“Nr-axSpA can be seen as an early form of AS, before inflammation has yet caused visible structural damage to the bone on x-rays,” Joachim Sieper, MD, of Charité, Campus Benjamin Franklin, Berlin, told Rheumatology Advisor. “Because this is a rather new concept, it was important to compare the two stages of the disease.”

The characteristics, treatment, and clinical burden of AS are well established. Nr-axSpA, however, was only classified in recent years in the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria. As a result, the clinical burden and optimal treatment strategies of nr-axSpA are currently under investigation.

Dr Sieper and colleagues performed a systematic literature review that included 50 studies from 2010 to 2015 to compare the burdens and treatment efficacy of antirheumatic drugs in nr-axSpA vs AS.

Compared with patients with AS, patients with nr-axSpA had lower CRP levels, less structural damage, and less functional impairment. However, disease activity and health-related quality of life scores were similar.

“Most of the clinical and laboratory parameters are the same for the two diseases,” Dr Sieper noted. “A major difference is that a higher percentage of AS patients is male and have CRP positivity, probably because both male sex and CRP positivity are risk factors for progressing from nr-axSpA to AS more rapidly.”

The efficacy of TNF inhibitors for nr-axSpA and AS was similar, but rates of TNF inhibitor use were significantly lower for nr-axSpA. Nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and glucocorticoids were used with equal frequency among the two disease states.

TNF inhibitors for nr-axSpA were only recently approved in Europe but not in the United States, which may explain the lower rates of TNF inhibitor use in nr-axSpA than in AS.

“In order to enable timely treatment of nr-axSpA patients, a specified indication is necessary in clinical practice to avoid off-label prescription or issues with insurance coverage,” the authors wrote. “Several ongoing clinical trials are investigating the efficacy of [TNF inhibitors] in maintaining clinical remission in nr-axSpA.”

Summary and Clinical Applicability

nr-axSpA, which may be considered an early form of AS, has only been classified in recent years; consequently, the burdens associated with nr-axSpA and the most effective treatment strategies are largely unknown. In this literature review, Dr Sieper and colleagues compared treatment efficacy by drug class and clinical and humanistic burdens of nr-axSpA with those of AS.

While laboratory and radiographic differences existed between nr-axSpA and AS, the clinical and humanistic burdens were comparable. In addition, TNF inhibitors appeared to be equally effective in both disease states.

“Whether nr-axSpA is regarded as an early form of AS or as a distinct disease entity, it represents an important subgroup of axSpA,” the authors wrote. “Ongoing clinical trials may provide the required evidence for a specified indication for TNFα inhibitors, important to prevent off-label use. Further research is crucial to better understand the disease spectrum and predictors of progression.”

Study Limitations

  • Only 13 studies evaluated the use of TNF inhibitors in nr-axSpA vs AS; of these, only 6 were randomized controlled trials

  • Health-related quality of life was assessed in only 4 studies, of which 3 were observational studies


This study was funded by Merck & Co., Inc.

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Sieper J, Hu X, Black CM, et al. Systematic review of clinical, humanistic, and economic outcome comparisons between radiographic and non-radiographic axial spondyloarthritis [published online September 13, 2016]. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2016.09.002 

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