Long-Term TNFi Use in Axial Spondyloarthritis May Slow Radiographic Progression

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Paras Karmacharya, M.D.

Long-term use of tumor necrosis factor inhibitors (TNFi) may  show radiographic progression benefit in axial spondyloarthritis, say researchers recently writing in Arthritis & Rheumatology.

The treatment goals for axial spondyloarthritis, including ankylosing spondylitis and nonradiographic axial spondyloarthritis, are to control of spinal and peripheral symptoms along with the prevention of radiographic damage. Radiographic progression occurs in 20-45 percent of patients with ankylosing spondylitis after two years and progression is expected to continue, leading to complete fusion of spine in as many as 40 percent of these patients. However, the progression rate is around seven percent after two years in nonradiographic axial spondyloarthritis.

“We aimed to perform a systematic review and meta-analysis on the effect of different therapies on radiographic progression in axial spondyloarthritis,” wrote the authors, led by Paras Karmacharya, M.D., of the Mayo Clinic College of Medicine in Rochester.

The review included studies assessing radiographic progression in axial spondyloarthritis, looking at the particular treatment versus no treatment of interest. A total of 24 studies were included; 18 with TNFis, eight with non-steroidal anti-inflammatory drugs (NSAIDs) and one with secukinumab.

Spinal radiographic progression was not significantly different among TNFi-treated versus biologic naïve populations at two years (mSASSS difference= -0.73, 95% CI -1.52 to 0.12, I2 =28%) and at four years or more years (mSASSS difference= -2.03, 95% CI -4.63 to 0.72, I2 =63%). However, sensitivity analysis limited to studies with low risk of bias showed a significant difference at four years or more (mSASSS difference= -2.17, 95% CI -4.19 to -0.15).

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No significant difference was observed between NSAIDs versus control (mSASSS difference= -0.30, 95% CI =-2.62 to 1.31, I2 =71%), or secukinumab versus biologic naïve (mSASSS difference= -0.34, 95% CI -0.85 to 0.17). There were not enough studies on nonradiographic axial spondyloarthritis or sacroiliac joint progression for analysis.

“Although no significant protective effect of TNFi treatment on spinal radiographic progression of ankylosing spondylitis at two and four years or more was seen, analysis restricted to studies with low risk of bias showed a protective effect at four years or more,” the authors wrote. “Therefore, long-term TNFi exposure might have radiographic progression benefit.”

Assessment of SpondyloArthritis international Society and Outcome Measures in Rheumatology recommend use of modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) for quantitative assessment of axial damage. A change of two mSASSS units in two years or one new syndesmophyte formation in two years is considered as radiographic progression. While radiographic progression is an important predictor of poor functional outcomes in axial spondyloarthritis, treatment is largely symptomatic at present. The current guidelines recommend against introducing an early treat-to-target strategy if any therapy is shown to slow the natural progression of disease, due to a lack of evidence.

The authors recommended further studies to explore the effect of NSAIDs and biologics in patients with early axial spondyloarthritis, with a follow up of longer than four years to see if effects are more pronounced over time

“Lastly, we need more sensitive and reliable measures to document radiographic progression…mSASSS doesn’t include assessment of changes at thoracic spine or posterior elements (facet joints), and cannot assess early damage,” the authors wrote.

REFERENCE

Paras Karmacharya, Ali Duarte‐Garcia,  Maureen Dubreuil, et al. “The Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta‐Analysis.” Arthritis & Rheumatology. January 20, 2020. doi: 10.1002/art.41206