Infliximab in Ankylosing Spondylitis
Infliximab in Ankylosing Spondylitis
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.
Infliximab, a chimeric monoclonal antibody to TNF-α, showed efficacy for ankylosing spondylitis (AS) in a randomised, placebo-controlled trial in which 61.2% of the patients were responders at 24 weeks. Although methotrexate (MTX) is often used for patients with predominantly peripheral AS and those with psoriatic arthritis, the few attempts to treat predominantly axial disease were disappointing. Haibel et al. studied 20 patients with AS who received MTX 15 to 20 mg/week subcutaneously and found no difference in Assessment in Ankylosing Spondylitis 20% improvement criteria (ASAS 20) scores before and 16 weeks after treatment. Until now, MTX has been evaluated in only three small, randomised, controlled trials, and a Cochrane review concluded that there was insufficient evidence to support the use of MTX for AS with predominantly axial symptoms.
Data comparing infliximab with and without MTX treatment in AS are sparse and conflicting. Pérez-Guijo et al. found a greater reduction in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores with infliximab + MTX treatment than with infliximab alone, whereas Breban et al. found no statistically significant difference between patients who did or did not receive MTX in a subset of AS patients receiving treatment with infliximab by an on-demand strategy. However, in the latter study, patients receiving MTX showed a better response and fewer reactions to infusions than did patients not receiving MTX, although the results were not statistically significant. Currently, regarding TNF-α antagonist therapy for patients with AS or psoriatic arthritis, the French Society for Rheumatology recommendations suggest that there is insufficient evidence for concomitant disease-modifying antirheumatic drugs improving the effectiveness of TNF-α antagonist therapy.
To date, no study has used infliximab exposure as an end point to compare treatment with the combination of infliximab and MTX with infliximab alone in AS with predominantly axial symptoms. Indeed, if such a combination increases exposure to infliximab, it should improve response and may be recommended in clinical practice. In the present study, we compared the individual exposure to infliximab of AS patients with predominantly axial symptoms receiving infliximab alone or infliximab and MTX combined.
Abstract and Introduction
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.
Introduction
Infliximab, a chimeric monoclonal antibody to TNF-α, showed efficacy for ankylosing spondylitis (AS) in a randomised, placebo-controlled trial in which 61.2% of the patients were responders at 24 weeks. Although methotrexate (MTX) is often used for patients with predominantly peripheral AS and those with psoriatic arthritis, the few attempts to treat predominantly axial disease were disappointing. Haibel et al. studied 20 patients with AS who received MTX 15 to 20 mg/week subcutaneously and found no difference in Assessment in Ankylosing Spondylitis 20% improvement criteria (ASAS 20) scores before and 16 weeks after treatment. Until now, MTX has been evaluated in only three small, randomised, controlled trials, and a Cochrane review concluded that there was insufficient evidence to support the use of MTX for AS with predominantly axial symptoms.
Data comparing infliximab with and without MTX treatment in AS are sparse and conflicting. Pérez-Guijo et al. found a greater reduction in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores with infliximab + MTX treatment than with infliximab alone, whereas Breban et al. found no statistically significant difference between patients who did or did not receive MTX in a subset of AS patients receiving treatment with infliximab by an on-demand strategy. However, in the latter study, patients receiving MTX showed a better response and fewer reactions to infusions than did patients not receiving MTX, although the results were not statistically significant. Currently, regarding TNF-α antagonist therapy for patients with AS or psoriatic arthritis, the French Society for Rheumatology recommendations suggest that there is insufficient evidence for concomitant disease-modifying antirheumatic drugs improving the effectiveness of TNF-α antagonist therapy.
To date, no study has used infliximab exposure as an end point to compare treatment with the combination of infliximab and MTX with infliximab alone in AS with predominantly axial symptoms. Indeed, if such a combination increases exposure to infliximab, it should improve response and may be recommended in clinical practice. In the present study, we compared the individual exposure to infliximab of AS patients with predominantly axial symptoms receiving infliximab alone or infliximab and MTX combined.
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