Background Infliximab (IFX) is a biological agent approved for the treatment of rheumatoid arthritis (RA). RISING study shows the serum concentrations of TNF-α,IFX and IL-6 are related to the curative effect of IFX therapy, however, these parameters are difficult to measure in clinical practice.
Objectives To evaluate the efficacy of intensified infliximab treatment in RA patients resistant to standard regimen, and to elucidate clinical parameters associated with its effectivity.
Methods Among 101 RA patients who received IFX until October 2013 in our hospital, we conducted the intensified IFX therapy, by dose escalation or interval reduction, on 32 patients. Concerning these patients, the initial IFX therapy was not effective within 3 months in 12 patients (primary failure). In the remaining 20 patients, the initial IFX therapy was once effective, nevertheless, later judged as refractory by their attending doctors (secondary failure). We analyzed these patients statistically.
Results Among these 32 patients, the intensified IFX therapy was effective and continued at least for 24 weeks in 16 patients (Group A). IFX was discontinued for unresponsiveness in 16 patients (Group B). In 12 primary failure patients, 7 patients were classified as Group A, and 5 patients were classified as Group B. In secondary failure patients, 9 patients were classified as Group A, and 11 patients were classified as Group B. At the start of the initial IFX therapy, the mean age of Group A was significally younger, compared to Group B (51.8±12.1 years old vs. 65.3±8.9 years old; P<0.05). Moreover, ESR was also significally lower in Group A, compared to Group B (37.3±29.1 mm/hr vs. 58.1±32.2 mm/hr; P<0.05). Through the initial IFX therapy, Group A showed significant decrease of MMP-3, however, Group B showed no significant decrease (Group A: -40.6±17.9 ng/ml; P<0.05/Group B: +6.6±101.5 ng/ml; n.s.). Also, Group A showed significant decrease of RF, although Group B showed no significant decrease (Group A: -60.1±96.1 U/ml; P<0.05/GroupB: -38.8±8.2 U/ml; n.s.). In Group B, 14 patients received other biologics afterward. The following biologics were tocilizumab (TCZ) in 9 patients, abatacept (ABT) in 3 patients, adalimumab (ADA) in 1 patient, and etanercept in 1 patient. An ABT-treated patient and an ADA-treated patient were refractory to the therapy, necessitating switches to TCZ.
Conclusions The response to the intensified IFX therapy is predictable by age and ESR at the start of initial IFX therapy, and the reduction rate of MMP-3 and RF level through the initial IFX therapy. TCZ may be useful for patients unresponsive to the intensified IFX therapy.
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T Takeuchi et al, Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis. Ann. Rheum. Dis. 2011; 70(7):1208-15
T Takeuchi et al,Inhibition of plasma IL-6 in addition to maintenance of an efficacious trough level of infliximab associated with clinical remission in patients with rheumatoid arthritis: analysis of the RISING Study. Ann. Rheum. Dis. 2012; 71(9):1583-5
Disclosure of Interest None declared
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