Long-term Efficacy of Targeted Therapy for Axial Spondyloarthritis

Axial Spondyloarthritis and Targeted Therapy

Axial spondyloarthritis (axSpA) is characterized by chronic inflammation primarily affecting the spine and sacroiliac joints. The disease can manifest in a non-radiographic form, without visible changes on X-rays, or as a radiographic form (ankylosing spondylitis). For patients who do not respond to nonsteroidal anti-inflammatory drugs (NSAIDs), current recommendations suggest therapy with tumor necrosis factor-alpha (TNF-α) inhibitors or interleukin IL-17A inhibitors.

TNF inhibitors, including the recombinant fusion protein etanercept, have shown good short-term efficacy in controlled clinical trials for patients with early axSpA. Long-term efficacy data are primarily available for patients with chronic radiographic forms. However, last year, long-term data were published for a cohort of patients with early disease who participated in a clinical trial comparing the efficacy of sulfasalazine with etanercept (ESTHER).

Methodology and Study Progress

The ESTHER clinical evaluation involved patients with active axSpA (n = 76) who had been diagnosed within the past five years. They were randomized to receive etanercept or sulfasalazine for 48 weeks. If disease remission was achieved after this period, therapy was discontinued, and participants were followed until the end of the second year from study entry. In cases of disease relapse, etanercept was reintroduced and continued until the end of the 10-year duration. Those who did not achieve remission were switched to etanercept and continued with long-term treatment.

Results

Seven patients with non-radiographic and 12 with radiographic axSpA completed the 10-year study extension. Across the entire group, a sustainable clinical response was observed over the 10-year follow-up period. Average BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), and ASDAS (Ankylosing Spondylitis Disease Activity Score) scores improved sharply following treatment initiation and remained favorable, i.e., low, for the entire follow-up period (< 2, and < 2.1 for ASDAS scores), with no differences between the radiographic and non-radiographic forms. At the end of the follow-up, 78.9% of patients were in a state of low disease activity (BASDAI < 3).

Of the original 76 patients, 75% did not complete the 10-year extension. The most common reasons for discontinuing the study were loss of contact (n = 14), insufficient treatment efficacy (n = 13), desire to become pregnant (n = 12), and non-compliance with the therapeutic regimen (n = 5). During the 10-year follow-up, a total of 39 serious adverse events were reported, with 6 considered potentially related to etanercept treatment and 5 leading to treatment discontinuation. No opportunistic infections, tuberculosis cases, or occurrences of solid tumors were observed.

Conclusion

Ten years of etanercept treatment in axSpA patients resulted in long-term clinical response and demonstrated safety consistent with previous observations. Efficacy was comparable between radiographic and non-radiographic forms of the disease. The similar clinical response in both forms indicates that the presence or absence of radiographic sacroiliitis at therapy initiation does not affect the clinical response to TNFi treatment, supporting the concept of axial SpA as a single disease entity.

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Source: Proft F., Weiß A., Torgutalp M. et al. Sustained clinical response and safety of etanercept in patients with early axial spondyloarthritis: 10-year results of the ESTHER trial. Ther Adv Musculoskelet Dis 2021; 13: 1759720X20987700, doi: 10.1177/1759720X20987700.