Drug survival and causes of discontinuation of the first anti-TNF in ankylosing spondylitis compared with rheumatoid arthritis: analysis from BIOBADABRASIL

Abstract

Treatment survival with biological therapy may be influenced by many factors, and it seems to be different among various rheumatic diseases and biological agents. The goal of the study was to compare the drug survival and the causes of discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years following the introduction of the first treatment. Gender, age, disease duration, disease activity, comorbidities, and concomitant therapies were assessed. A total of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n = 504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n = 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was 63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was 47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p ≤ 0.001). Patients with RA discontinued anti-TNF more than patients with AS when adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31). Female patients who were also corticosteroid users, but not of advanced age, have shown lower survival for both diseases (log-rank, p ≤ 0.001). The discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of discontinuation were ineffectiveness and adverse event in both diseases. AS patients have better drug survival adjusted to gender, age, and corticosteroid. This results appear to be related to the disease mechanism.

Retention rates of adalimumab, etanercept, and infliximab as first‐ or second‐line biotherapies for spondyloarthritis patients in daily practice in Auvergne (France)

“…The discontinuation rate for inefficacy and adverse effects was the same in the Swedish and Brazilian registries, whereas the Czech registry recorded adverse effects as the most common cause of drug discontinuation. 4,14,15 Although we found our discontinuation rate due to undesirable effects to be relatively low compared to that of other registries, it was nevertheless close to that observed in the NOR-DMARD registry (8.5%). 8 Retention of the initial anti-TNF treatment was superior in patients exhibiting severe biological inflammatory syndromes, consistent with the data of the Danish and Czech registries, as well as an Italian multicenter study, yet contrasting with the findings of a Swedish and French study.…”

“…Median follow up was 26 (9-57) months (12 months for the first anti-TNF, 7 [5][6][7][8][9][10][11][12][13][14][15][16][17][18] for the second). In total, 103 patients (34.3%) discontinued their initial anti-TNF treatment.…”

“…However, these registries more often address rheumatoid arthritis than axSpA. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] While retention rates for anti-TNFs have been investigated using several patient registries, their follow-up duration did not typically exceed 8 years. 4,5 Young age, male gender and presence of inflammatory syndrome appeared predictive of retention in most, ALthough not all cases.…”

Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis

“…Evidence on the relative efficacy and safety of these medications is indirect and incomplete because no randomized controlled trials (RCTs) directly compare two or more TNF antagonists in RA patients [2]. Lack of efficacy and adverse effects are the most common reasons for discontinuing TNF antagonists [3–9], and therefore discontinuation risk is a good measure of the benefit-harm balance of these medications [10]. Hence, comparison of discontinuation risk of different TNF antagonists can help in treatment decisions, especially selection of an individual medication.…”

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

“…Global registers of biological treatment show that a lower proportion of patients with ankylosing spondylitis compared to patients with RA discontinue TNF inhibitor treatment. In the BiobadaBrasil registry, the mean drug survival in patients with ankylosing spondylitis was 63.08 months and in patients with RA was 47.5 months, with an adjusted hazard ratio (adjHR) of discontinuation of 1.6 (95% confidence interval [CI], 1.14‐2.31) for RA vs ankylosing spondylitis . In the Norwegian Antirheumatic Drug Register trial, the 1‐year retention rate was 77.5% vs 65.4% for ankylosing spondylitis vs RA, with an adjHR for treatment termination of 0.66 (95%CI, 0.47‐0.92) for ankylosing spondylitis vs RA .…”