Spondyloarthropathies: Anti-tumor Necrosis Factor-alpha Agents
Spondyloarthropathies: Anti-tumor Necrosis Factor-alpha Agents
Objective. Anti-TNF-α agents are remarkably effective in the treatment of SpAs. However, 30% of patients withdraw from anti-TNF-α agents yearly because of inadequate efficacy or side effects. The objective of this study was to assess in current practice the response to a second and a third anti-TNF-α.
Methods. Retrospectively, all records of patients who had received at least two anti-TNF-α agents have been studied. For axial forms, treatment was considered effective if 3 months after switching the patient had a favourable expert opinion or showed an improvement in BASDAI of at least 2 on a scale of 0–10 or an improvement of 50% (BASDAI 50). For peripheral forms, the treatment was considered effective if the patient had a favourable expert opinion or if a clinical improvement of >30% of the swollen and tender joint counts was established. The reasons for switching were: (i) primary non-responder; (ii) loss of efficacy; and (iii) occurrence of side effects. To identify response predictor factors bivariate analysis was performed.
Results. Three hundred and seventy-seven patients under anti-TNF-α agents were treated and 99 patients had received at least two anti-TNF-α agents. Twenty-eight of these 99 patients had been treated with three anti-TNF-α agents. Following the failure of a first anti-TNF-α, the response to a second agent was satisfactory in 80.8%. Patients who had received a third anti-TNF-α following failure of the first two also showed a satisfactory response in 82.1%. The reason for switching from the first or second agent was not predictive of the response.
Conclusion. In the event of failure or intolerance to anti-TNF-α in the treatment of SpAs, performing a first or second switch produces a satisfactory therapeutic response.
The concept of SpAs encompasses a range of diseases with common characteristics. It includes AS, PsA, articular manifestations of IBDs (SP/IBDs), ReA, juvenile spondylitis and uSpA. Conventional DMARDs have limited effectiveness on axial manifestations. For peripheral forms, conventional DMARDS have demonstrated potential effectiveness particularly in PsA.
The advent of TNF-α inhibitors (anti-TNF-α) has improved the management of patients with SpA. Many randomized, placebo-controlled clinical trials have demonstrated the efficacy of anti-TNF-α in the treatment of AS and PsA. The efficacy of these therapies has also been demonstrated in uSpAs and in SP/IBD. Three anti-TNF-α are currently used in the treatment of SpA: etanercept, adalimumab and infliximab. Most of the data have shown that infliximab, etanercept and adalimumab have comparable safety and efficacy profiles. In the absence of comparative head-to-head trials, there is no hierarchy recommended for the first prescription of anti-TNF-α.
Although anti-TNF-α have a dramatic effect on the treatment of SpA, almost 30% of the patients will have to discontinue their treatment prematurely due to loss of efficacy or side effects. For those patients for whom a first anti-TNF-α fails, the alternative is a switch, corresponding to the introduction of a new anti-TNF-α. In RA, experience of switching anti-TNF-α is now substantial. In the case of failure of a first anti-TNF-α, the introduction of a new agent permitted a satisfactory response to be obtained in most situations. But if switching to a second anti-TNF-α has been found to be efficient in 64–68%, the lack of efficacy of two anti-TNF-α, due to a primary non-responder, is predictive of ineffectiveness of the third anti-TNF-α. Data regarding the use of this strategy in the management of SpA are limited. Delaunay et al. were the first to publish a preliminary study involving only 15 patients. These patients were unresponsive or intolerant to infliximab and etanercept was administered. Cantini et al. reported in a prospective and observational study the efficacy and safety of etanercept in 23 AS patients who were unresponsive or intolerant to infliximab. Conti et al. also conducted a prospective and observational study involving the switching of anti-TNF-α in 23 patients. Coates et al. conducted a retrospective study on 16 SpA patients followed up for 2 years. All these authors found a satisfactory clinical response with a second anti-TNF-α.
The aim of this study was to determine in a large cohort of patients the response to a second anti-TNF-α after the unsuccessful administration of a first anti-TNF-α in patients with SpA. The study data were drawn from 'real-life' clinical situations. We also analysed whether the response to the second agent was determined by the reason for switching. Finally, we completed our analysis by studying patients who had received a third anti-TNF-α after the failure of the first two.
Abstract and Introduction
Abstract
Objective. Anti-TNF-α agents are remarkably effective in the treatment of SpAs. However, 30% of patients withdraw from anti-TNF-α agents yearly because of inadequate efficacy or side effects. The objective of this study was to assess in current practice the response to a second and a third anti-TNF-α.
Methods. Retrospectively, all records of patients who had received at least two anti-TNF-α agents have been studied. For axial forms, treatment was considered effective if 3 months after switching the patient had a favourable expert opinion or showed an improvement in BASDAI of at least 2 on a scale of 0–10 or an improvement of 50% (BASDAI 50). For peripheral forms, the treatment was considered effective if the patient had a favourable expert opinion or if a clinical improvement of >30% of the swollen and tender joint counts was established. The reasons for switching were: (i) primary non-responder; (ii) loss of efficacy; and (iii) occurrence of side effects. To identify response predictor factors bivariate analysis was performed.
Results. Three hundred and seventy-seven patients under anti-TNF-α agents were treated and 99 patients had received at least two anti-TNF-α agents. Twenty-eight of these 99 patients had been treated with three anti-TNF-α agents. Following the failure of a first anti-TNF-α, the response to a second agent was satisfactory in 80.8%. Patients who had received a third anti-TNF-α following failure of the first two also showed a satisfactory response in 82.1%. The reason for switching from the first or second agent was not predictive of the response.
Conclusion. In the event of failure or intolerance to anti-TNF-α in the treatment of SpAs, performing a first or second switch produces a satisfactory therapeutic response.
Introduction
The concept of SpAs encompasses a range of diseases with common characteristics. It includes AS, PsA, articular manifestations of IBDs (SP/IBDs), ReA, juvenile spondylitis and uSpA. Conventional DMARDs have limited effectiveness on axial manifestations. For peripheral forms, conventional DMARDS have demonstrated potential effectiveness particularly in PsA.
The advent of TNF-α inhibitors (anti-TNF-α) has improved the management of patients with SpA. Many randomized, placebo-controlled clinical trials have demonstrated the efficacy of anti-TNF-α in the treatment of AS and PsA. The efficacy of these therapies has also been demonstrated in uSpAs and in SP/IBD. Three anti-TNF-α are currently used in the treatment of SpA: etanercept, adalimumab and infliximab. Most of the data have shown that infliximab, etanercept and adalimumab have comparable safety and efficacy profiles. In the absence of comparative head-to-head trials, there is no hierarchy recommended for the first prescription of anti-TNF-α.
Although anti-TNF-α have a dramatic effect on the treatment of SpA, almost 30% of the patients will have to discontinue their treatment prematurely due to loss of efficacy or side effects. For those patients for whom a first anti-TNF-α fails, the alternative is a switch, corresponding to the introduction of a new anti-TNF-α. In RA, experience of switching anti-TNF-α is now substantial. In the case of failure of a first anti-TNF-α, the introduction of a new agent permitted a satisfactory response to be obtained in most situations. But if switching to a second anti-TNF-α has been found to be efficient in 64–68%, the lack of efficacy of two anti-TNF-α, due to a primary non-responder, is predictive of ineffectiveness of the third anti-TNF-α. Data regarding the use of this strategy in the management of SpA are limited. Delaunay et al. were the first to publish a preliminary study involving only 15 patients. These patients were unresponsive or intolerant to infliximab and etanercept was administered. Cantini et al. reported in a prospective and observational study the efficacy and safety of etanercept in 23 AS patients who were unresponsive or intolerant to infliximab. Conti et al. also conducted a prospective and observational study involving the switching of anti-TNF-α in 23 patients. Coates et al. conducted a retrospective study on 16 SpA patients followed up for 2 years. All these authors found a satisfactory clinical response with a second anti-TNF-α.
The aim of this study was to determine in a large cohort of patients the response to a second anti-TNF-α after the unsuccessful administration of a first anti-TNF-α in patients with SpA. The study data were drawn from 'real-life' clinical situations. We also analysed whether the response to the second agent was determined by the reason for switching. Finally, we completed our analysis by studying patients who had received a third anti-TNF-α after the failure of the first two.