Patients with axial spondyloarthritis (axSpA) with secondary vs primary failure to their first tumor necrosis factor inhibitor (TNFi) have a better response to the second TNFi, according to study results published in Arthritis Research & Therapy.

The aim of the current study was to compare the efficacy of TNFis as first- and second-line therapy and determine whether the reason to discontinue the first TNFi affected response to the second TNFi in patients with axSpA.

The prospective multicenter cohort study included adult patients with axSpA from the Rheumatic Diseases Portuguese Register who discontinued their first TNFi for any reason and started a second TNFi between June 2008 and May 2018. All participants completed data on Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline and 3 and 6 months after starting their first TNFi. The primary outcome was the ASDAS clinically important improvement (ASDAS-CII), defined as a decrease of ≥1.1 units of the ASDAS score from baseline.

The reason for discontinuation of the first TNFi was classified as follows: primary failure, defined as no achievement of ASDAS-CII at 3 or 6 months of treatment; secondary failure, if ASDAS-CII was achieved at 3 or 6 months but was lost in ≥1 subsequent visit; an adverse event; and other reasons, such as pregnancy or surgery.


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Using binomial generalized estimating equation, the researchers examined the association between the reason for discontinuation of the first TNFi and response to the second TNFi in up to 10 years of follow-up.

Of 346 eligible patients with axSpA, 193 (mean age, 45 years; 53% men) with available data for ASDAS at baseline and 3 and 6 months for their first TNFi were included. There were no significant differences in most baseline characteristics across the reason for discontinuation of the first TNFi. The ASDAS data for the first and second TNFi were available for 96 patients at baseline and 3 months and for 79 patients at baseline and 6 months. The adjusted response rate to the second vs first TNFi was lower, including lower ASDAS-CII at 3 (41% vs 51%, respectively) and 6 months (35% vs 56%, respectively).

No association was documented between the reason for discontinuation of the first TNFi and response to the second TNFi according to the ASDAS-CII definition. However, using the most stringent outcomes, including inactive disease, revealed significant differences. Compared with patients who discontinued their first TNFi due to primary failure, the likelihood to achieve ASDAS-inactive disease with the second TNFi was higher for patients who discontinued their first TNFi due to secondary failure (odds ratio [OR], 7.3; 95% CI, 1.9-27.7), adverse events (OR, 9.1; 95% CI, 2.5-33.3), or other reasons (OR, 7.7; 95% CI, 1.6-37.9).

The study had several limitations, including potential residual confounders, small sample size, and missing data on nonpharmacologic interventions.

“[R]esponse to a second TNFi is worse than the response to a first TNFi, especially among patients [who] never responded in the first place to this class of drugs,” the researchers concluded.

Disclosure: This clinical trial was supported by Merck Sharp & Dohme Corp. Please see the original reference for a full list of authors’ disclosures.

Reference

Manica SR, Sepriano A, Pimentel-Santos F, et al. Effectiveness of switching between TNF inhibitors in patients with axial spondyloarthritis: is the reason to switch relevant? Arthritis Res Ther. 2020;22(1):195.