THU0219 The Infliximab Dose Increase is Not Correlated with Clinical Improvement in RA Patients
Authors: M. T. López-Casla, D. Pascual-Salcedo, C. Plasencia, P. Alcozer, S. García-Carazo, G. Bonilla, A. Villalba, D. Peiteado, F. Arribas, E. Martín-Mola, A. Balsa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The anti-TNF therapy is an effective treatment in RA patients, however a considerable percentage of patients develop clinical inefficacy (primary or secondary); part of which can be explained by the development of antibodies to infliximab (ATI). In some patients, a dose increase is often used to achieve a clinical improvement, mainly in patients with secondary inefficacy. However, there is no evidence that demonstrates if dose escalation is a good therapeutic option. <h3>Objectives</h3> To assess whether increasing the infliximab (Ifx) dose is an effective therapeutic option in RA patients who develop clinical inefficacy. <h3>Methods</h3> The present study included 36 RA patients treated since 2000 with Ifx at La Paz University Hospital, in whom a Ifx dose increase was implemented due to inefficacy [23/36 (64%) primary non-responders and 13/36 (36%) secondary non-responders]. All patients started to receive Ifx at 3 mg/kg i.v. at standard schedule. A therapeutic increase was defined as: Ifx dose higher than 3 mg/kg i.v. (until maximum of 5 mg/kg) or interval time between infusion 6-7 weeks. The clinical activity was measured by the Disease Activity Score 28 (DAS28) at baseline, before starting the dose escalation, at 6 months and at 1 year after the dose increase. The drug and ATI levels were measured by a capture and bridging ELISA, respectively. Statistical analysis was made using SPSS system 11.0. <h3>Results</h3> Thirty one out of 36 patients (86.1%) were female, with a mean age of 58±13.6 years. The disease duration was 19.2±10.5 years and the time under Ifx therapy was 6.6±3.8 years. Most patients received concomittant therapy with DMARDs [15 (41.7%) methotrexate, 22 (41.7%) other DMARDs and 8 (22.2%) in monotherapy] and 13 (38.2%) received prednisone. All patients were active (DAS28) at baseline and before starting the dose increase (5.4±1.0 at baseline and 4.2±1.2 just before dose escalation). ATI were detected in 13/34 (38.2%) patients at the moment of decision to increase (in 2 patients ATI were already present in the first available sample) and only 2 (5.5%) patients became negative after dose increase. The Ifx increment did not produce significant improvement in clinical activity (DAS28) in RA patients, independently on ATI status [ATI-negative: 4.25±1.4 at pre-increase vs 3.9 ±1.0 at 6 months after increase (p=0.311) and 4.04±1.1 vs 4.03 ±1.3 at 1 year after increase (p=0.970); ATI-positive: 4.09±0.9 at pre-increase vs 4.1±1.3 at 6 months after increase (p=0.945) 3.7 ±0.7 vs 3.0±0.8 at 1 year after increase (p=0.110)]. A total of 26 (76.5%) patients discontinued the Ifx therapy, not identifying differences between ATI-positive patients (15/21, 71.4%) and ATI-negative patients (11/13, 84.6%), p=0.378. <h3>Conclusions</h3> Infliximab dose escalation does not seem to be an effective therapeutic option in RA patients who develop primary and secondary inefficacy. Further studies are necessary to confirm these results. <h3>Disclosure of Interest</h3> None Declared