Circulating concentration of infliximab and response to treatment in ankylosing spondylitis: results from a randomized control study.

OBJECTIVE: A minority of patients with ankylosing spondylitis (AS) fail to respond to infliximab treatment. This study compared the circulating infliximab concentration and the presence of clinical symptoms in patients continuously treated with infliximab or after treatment interruption. METHODS: Patients with active AS were randomly assigned at week 0 to receive infliximab either at weeks 4, 6, 10, and then every 6 weeks (continuous treatment), or at weeks 4, 6, and 10 and then upon symptom recurrence (on-demand treatment). The circulating concentration of infliximab was determined early during treatment and at weeks 46 and 52 for the continuous treatment group or upon relapse for the on-demand group. Response in the continuous treatment group was defined at week 58 using the ASsessment in AS International Working Group Criteria for 20% improvement. RESULTS: Among the 93 patients in the continuous treatment group, treatment failure was not associated with a low circulating concentration of infliximab, either during early treatment or at 1 year. Eleven (39.2%) of the 28 nonresponders had an infliximab concentration of >10 microg/ml at week 52, whereas 9 (13.8%) of the 65 responders had an infliximab concentration of <1 microg/ml. In the on-demand group, the infliximab concentration at relapse closely correlated with the time to relapse. However, 24 (36.9%) of 65 patients had a resurgence of clinical symptoms at an infliximab concentration of >10 microg/ml, whereas 25 patients (38.4%) had a relapse at an infliximab concentration of <0.5 microg/ml. CONCLUSION: Responsiveness to infliximab treatment is highly heterogeneous among individuals with AS, and this parameter overcomes the circulating infliximab concentration to explain treatment success or failure.

Maintenance of infliximab treatment in ankylosing spondylitis: results of a one-year randomized controlled trial comparing systematic versus on-demand treatment.

OBJECTIVE: Continuous treatment with the anti-tumor necrosis factor alpha (anti-TNFalpha) antibody infliximab is efficacious in ankylosing spondylitis (AS), whereas treatment discontinuation results in disease relapse, with variable delay. This study was undertaken to compare the efficacy of continuous treatment with infliximab with that of a treatment regimen adapted to symptom recurrence. Methotrexate (MTX) in combination with infliximab was also tested. METHODS: Patients with active AS were randomly assigned at week 0 to receive infliximab every 6 weeks (continuous treatment) or upon symptom recurrence (on-demand treatment), following infusions at weeks 4, 6, and 10. Patients in the on-demand group were randomly assigned to receive either MTX in combination with infliximab or infliximab alone. Patients were monitored for 1 year. The primary end point was the proportion of patients who met the ASsessment in AS International Working Group criteria for 20% improvement (ASAS20) at week 58. RESULTS: Of 247 patients, 124 were assigned to receive infliximab every 6 weeks and 123 to receive on-demand treatment. Among the latter, 62 received MTX, and 61 received infliximab alone. A greater proportion of patients receiving infliximab every 6 weeks fulfilled ASAS20 response criteria at week 58 than did patients receiving on-demand treatment (75% versus 46%; P<0.0001). Patients in the continuous treatment group received more infliximab infusions after week 10 than did those in the on-demand group (mean+/-SD 5.8+/-2.2 versus 3.5+/-2; P<0.0001). Addition of MTX did not significantly affect the proportion of patients with an ASAS20 response at week 58, nor the number of infliximab infusions administered. CONCLUSION: These findings indicate that continuous treatment of AS with infliximab is more efficacious than on-demand treatment, and that the addition of MTX to infliximab provides no significant benefit.

[State of unmet medical needs in France in 2006: necessity of reinforcing research effort]. / Besoins médicaux non couverts en France en 2006: l'effort de recherche doit être poursuivi.

Leem (French Pharmaceutical Companies) realized an inventory of unmet medical needs in 2006 in France for 12 pathologies. All of them are considered as national public health priorities by the law of August 9th, 2004. Allied to the epidemiological projections, analyses concerned various stages and/or pathology forms, impact of guidelines in clinical practice, therapeutic strategies, marketed therapeutics and pharmacological products in an advanced phase of clinical development. With more than 100 products listed in clinical phase III or pre-registration/marketed for those pathologies, French Pharmaceutical Companies contribute, quasi exclusively, to the development of innovative pharmaceutical products to answer unmet medical needs. This study illustrates the necessity of French Government to support therapeutic innovation led by Pharmaceutical Companies in France.