Worse response axSpA patients to second TNFi versus first TNFi

It has become common practice to start a second tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) who discontinue their first TNFi [1]. However, evidence on the effectiveness of this strategy in clinical practice has been limited. Moreover, it remains unclear if the reason for discontinuation of the first TNFi influences the response to the second.

Dr Santiago Rodrigues-Manica (Hospital Egas Moniz, Portugal) and colleagues compared the responses to the first and second TNFi and assessed whether the reason for discontinuation of the first TNFi influences the response to the second TNFi. Data was obtained from the Portuguese ReumaPt registry and included  axSpA patients who had discontinued their first TNFi and started a second TNFi and had complete data available on Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline, 3 months, and 6 months for their first TNFi. They were then followed every 6 months up to 12 years.

The primary outcome was the ASDAS clinically important improvement (ASDAS-CII). Secondary outcomes included ASDAS major important improvement (ASDAS-MI); ASDAS low disease activity; ASDAS inactive disease (ASDAS-ID); and BASDAI 50. The reason for discontinuation of the first TNFi was defined as: primary failure (i.e. ASDAS-CII was not achieved at 3 or 6 months); secondary failure (i.e. ASDAS-CII achieved at 3 or 6 months but lost in ≥1 follow-up visit); adverse events; or other (e.g. pregnancy, surgery). The response to the first TNFi at 3 and 6 months was compared with the response to the second TNFi at the same visits, adjusting for age, gender, and C-reactive protein (CRP). The association between the reason for discontinuation of the first TNFi and response to the second TNFi over time was tested using generalised estimating equations (GEE) models, adjusted for age, gender, and CRP. Included in the study were 193 patients with a mean age of 45 years, a median follow-up on the second TNFi of 1.5 years; 53% were male.

Patients had a lower response to the second TNFi compared with the first TNFi according to the primary outcome (i.e. ASDAS-CII) at 3 months (41% vs 51%, respectively) and 6 months (35% vs 56%, respectively). An association was observed between the reason for discontinuation of the first TNFi and response to the second TNFi as defined by the most stringent outcomes (ASDAS-MI and ASDAS-ID), but not for ASDAS-CII. Compared with patients who discontinued their first TNFi due to primary failure, patients were more likely to achieve ASDAS-ID with the second TNFi when they discontinued their first TNFi due to secondary failure (odds ratio 7.3; 95% CI 1.9-27.7), adverse events (odds ratio 9.1; 95% CI 2.5-33.3), or other reasons (odds ratio 7.7; 95% CI 1.6-37.9).

Dr Rodrigues-Manica concluded that axSpA patients showed a worse response to the second TNFi compared with the first TNFi. Patients with secondary failure to the first TNFi have a better response to the second TNFi compared with those discontinuing the first TNFi due to primary failure, particularly for most stringent outcomes (i.e. ASDAS-MI and ASDAS-ID). Further, patients with secondary failure to the first TNFi seem to benefit from treatment with a second TNFi. These findings will have implications for studies designed towards selection of second-line therapy in the setting where more drugs are becoming available for axSpA.

1. Rodrigues-Manica S, et al. FRI0293. EULAR E-Congress, 3-6 June 2020.

 



Posted on 14 August, 202025 March, 2024