Etanercept response in patients with rheumatoid arthritis after secondary loss of efficacy of infliximab

Matsuno, Hiroaki

doi:10.1007/s10165-010-0320-8

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…An important problem associated with the use of infliximab, however, is that its efficacy often decreases during prolonged treatment. It has been reported that switching from infliximab to etanercept was effective in RA patients [9,10,13]. Although both these drugs bind to TNF a, etanercept also binds to lymphotoxin-alpha (previously known as TNF-beta) [9]; this explains why the switch can be effective.…”

Section: Discussionmentioning

confidence: 99%

“…However, an important problem associated with the use of infliximab in therapeutic drug regimens is that its efficacy often decreases during prolonged treatment. Some patients who experience treatment failure with their initial agent may benefit from a therapeutic switch from one TNF antagonist to another [9][10][11][12][13]. Indeed, there are now numerous reports that have suggested that initiating therapy with a second anti-TNF a agent in patients who have failed therapy with a first agent may be beneficial.…”

Section: Introductionmentioning

confidence: 99%

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Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab versus etanercept after previous infliximab failure? A retrospective study

et al. 2011

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A retrospective study of 39 rheumatoid arthritis (RA) patients with an inadequate response to infliximab was conducted. The responses of subjects switching from infliximab to tocilizumab (n = 23) were compared to those of subjects switching to etanercept (n = 16). Disease activity was assessed by the Disease Activity Score 28-CRP ([C-reactive protein] DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Twenty-two patients completed 48 weeks of tocilizumab treatment, and 15 patients completed 48 weeks of etanercept treatment. In both treatment groups, 1 patient each discontinued treatment because of lack of efficacy. No serious adverse events occurred during the study, and no patients in either group withdrew due to adverse events. At week 48, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values after switching to either tocilizumab or etanercept, and there was no significant difference in efficacy, as measured by the DAS28-CRP, SDAI, and CDAI, between the two treatment groups (p = 0.12, 0.76, and 0.86, respectively). These results suggest that safety and tolerability were similar for both treatments. A switch from infliximab to either tocilizumab or etanercept in patients with RA who have not responded to infliximab is a feasible, well-tolerated treatment option.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab versus etanercept after previous infliximab failure? A retrospective study

et al. 2011

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“…One is the absence of any clinical response (primary lack of efficacy); the other is the disappearance of an initial favorable response during therapy (secondary loss of efficacy). It has been suggested that switching to an alternative anti-TNFα agent may be less effective in nonresponders who showed a primary lack of efficacy than in those in whom the first anti-TNFα agent was withdrawn due to a secondary loss of efficacy [7–9]. To date, however, we lack reliable guidelines for choosing alternative treatments for individual RA patients who fail to respond to their first anti-TNFα agent [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

Mori¹,

Ueki

2011

Modern Rheumatology

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To characterize primary failure to infliximab and determine the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA), we examined 24 RA patients who had started on infliximab therapy (3 mg/kg) as their first biological agent. Nine of the 24 patients were found to be primary nonresponders, defined as patients who had never achieved a 20% clinical improvement according to the American College of Rheumatology criteria (ACR20) during induction therapy. The remaining 15 patients had achieved an ACR20 response to infliximab, without any relapses, for at least the first 14 weeks. A higher baseline health assessment questionnaire score was markedly associated with primary unresponsiveness to infliximab (p = 0.0005). Six of the 9 primary nonresponders showed rapid clearance of infliximab: their trough concentrations of infliximab were under 1 lg/ml. The other 3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in patients who maintained serum infliximab levels above 1 lg/ml. Human antichimeric antibody was not detected in the rapid-clearance nonresponders. Dose escalation (5 mg/kg) was insufficiently effective. Primary nonresponders to infliximab were started on tocilizumab therapy (8 mg/kg, every 4 weeks), and their responses were assessed after 24 weeks of this second attempt at therapy. All the nonresponders, except for a single rapid-clearance patient, had achieved an ACR20 clinical improvement at the time of assessment. In conclusion, primary nonresponders to infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

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Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

Mori

Ueki

2011

Mod Rheumatol

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To characterize primary failure to infliximab and determine the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA), we examined 24 RA patients who had started on infliximab therapy (3 mg/kg) as their first biological agent. Nine of the 24 patients were found to be primary nonresponders, defined as patients who had never achieved a 20% clinical improvement according to the American College of Rheumatology criteria (ACR20) during induction therapy. The remaining 15 patients had achieved an ACR20 response to infliximab, without any relapses, for at least the first 14 weeks. A higher baseline health assessment questionnaire score was markedly associated with primary unresponsiveness to infliximab (p = 0.0005). Six of the 9 primary nonresponders showed rapid clearance of infliximab: their trough concentrations of infliximab were under 1 μg/ml. The other 3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in patients who maintained serum infliximab levels above 1 μg/ml. Human antichimeric antibody was not detected in the rapid-clearance nonresponders. Dose escalation (5 mg/kg) was insufficiently effective. Primary nonresponders to infliximab were started on tocilizumab therapy (8 mg/kg, every 4 weeks), and their responses were assessed after 24 weeks of this second attempt at therapy. All the nonresponders, except for a single rapid-clearance patient, had achieved an ACR20 clinical improvement at the time of assessment. In conclusion, primary nonresponders to infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

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Etanercept response in patients with rheumatoid arthritis after secondary loss of efficacy of infliximab

Cited by 4 publications

References 16 publications

Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab versus etanercept after previous infliximab failure? A retrospective study

Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab versus etanercept after previous infliximab failure? A retrospective study

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

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