Mme Docteur FRANCINE LAUFERON

Bibliographie

• Therapeutic Drug Monitoring of Infliximab in Spondyloarthritis: An Observational Open-Label Study

  2011

  ArticleTher. Drug Monit.

• Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases.

  2011

  ArticleArthritis Research and Therapy

• Infliximab in ankylosing spondylitis: alone or in combination with methotrexate? A pharmacokinetic comparative study.

  2011

  ArticleArthritis Research and Therapy

Source : HAL — archive ouverte CCSD/CNRS (couvre articles, chapitres EMC, communications congrès, thèses).

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Top publications · les plus citées

• 1

  Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases

  Arthritis research & therapy · 2011

  📚 126 citations🎯 RCR 3.97Top 11% NIH🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  Abstract Introduction A proportion of patients receiving infliximab have antibodies toward infliximab (ATI), which are associated with increased risk of infusion reaction and reduced response to treatment. We studied the association of infliximab concentration at treatment initiation and development of ATI as well as the association of the presence of ATI and maintenance of infliximab. Methods All patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving infliximab beginning in December 2005 were retrospectively followed until January 2009 or until infliximab discontinuation. Trough serum infliximab and ATI concentrations were measured at each visit. The patients were separated into two groups: ATIpos if ATI were detected at least once during the follow-up period and ATIneg otherwise. Repeated measures analysis of variance was used to study the association of infliximab concentration at treatment initiation and the development of ATI. Maintenance of infliximab in the two groups was studied by using Kaplan-Meier curves. Results We included 108 patients: 17 with RA and 91 with SpA. ATI were detected in 21 patients (19%). The median time to ATI detection after initiation of infliximab was 3.7 months (1.7 to 26.0 months). For both RA and SpA patients, trough infliximab concentration during the initiation period was significantly lower for ATIpos than ATIneg patients. RA patients showed maintenance of infliximab at a median of 19.5 months (5.0 to 31.0 months) and 12.0 months (2.0 to 24.0 months) for ATIneg and ATIpos groups, respectively (P = 0.08). SpA patients showed infliximab maintenance at a median of 16.0 months (3.0 to 34.0 months) and 9.5 months (3.0 to 39.0 months) for ATIneg and ATIpos groups, respectively (P = 0.20). Among SpA patients, those who were being treated concomitantly with methotrexate had a lower risk of developing ATI than patients not taking methotrexate (0 of 14 patients (0%) vs. 25 of 77 patients (32%); P = 0.03). Conclusions High concentrations of infliximab during treatment initiation reduce the development of ATI, and the absence of ATI may be associated with prolonged maintenance of infliximab. Thus, trough serum infliximab concentration should be monitored early in patients with rheumatic diseases.

• 2

  Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis

  British journal of clinical pharmacology · 2012

  📚 44 citations🎯 RCR 1.56🩺 Clinique🔓 Open Access

  Lire l'abstract Crossref ↓

  WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Infliximab pharmacokinetics in ankylosing spondylitis has been described but using sparce data.• A previous work suggests that infliximab concentrations influence clinical response in ankylosing spondylitis, but the infliximab concentration–effect relationship is not known in this disease.• Methotrexate was shown to influence infliximab pharmacokinetics in rheumatoid arthritis.WHAT THIS STUDY ADDS• This study is the first to describe infliximab pharmacokinetics in ankylosing arthritis using rich data.• The infliximab concentration explains only a small part of interindividual variability in the response of ankylosing arthritis patients.• Contrary to what is observed in rheumatoid arthritis, methotrexate influences neither infliximab pharmacokinetics nor concentration–response relationship in ankylosing spondylitis.AIMSInfliximab, an anti‐tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients.METHODSTwenty‐six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg−1 infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two‐compartment model with first‐order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve.RESULTSA total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day−1 (22%) and intercompartment clearance = 2.3 l day−1. Methotrexate influenced neither pharmacokinetic nor BASDAI variability.CONCLUSIONSUsing the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.

• 3

  Infliximab in ankylosing spondylitis: alone or in combination with methotrexate? A pharmacokinetic comparative study

  Arthritis research & therapy · 2011

  📚 32 citations🎯 RCR 1.07🩺 Clinique🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  Abstract Introduction Methotrexate (MTX) has been shown to modify infliximab pharmacokinetics in rheumatoid arthritis. However, its combination with infliximab in the treatment of ankylosing spondylitis (AS) is not recommended. The objective of this study was to examine the influence of MTX on infliximab exposure in patients with AS. Methods Patients with AS patients who had predominantly axial symptoms were randomised to receive infliximab alone (infusions of 5 mg/kg at weeks 0, 2, 6, 12 and 18) or infliximab combined with MTX (10 mg/week). Infliximab concentrations were measured before and 2 hours after each infusion and at 1, 3, 4, 5, 8, 10, 14 and 18 weeks. We estimated individual cumulative area under the concentration versus time curves (AUC) for infliximab concentration between baseline and week 18 (AUC0-18). Clinical and laboratory evaluations were performed at each visit. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was the primary end point for clinical response. Results Twenty-six patients were included (infliximab group: n = 12, infliximab + MTX group: n = 14), and 507 serum samples were available for measurement of infliximab concentration. The two groups did not differ with regard to AUC0-18 or evolution of BASDAI scores and biomarkers of inflammation. Conclusions The combination of MTX and infliximab does not increase the exposure to infliximab over infliximab alone in patients with AS. Trial registration ClinicalTrials.gov: NCT00507403

Publications scientifiques (5) — classées par pathologie

Source PubMed · Recherche par auteur (homonymes possibles, vérifier l'affiliation).

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