Background The anti-TNF agents prevents joint destruction, and brought drastic change on rheumatoid arthritis treatment, but some patients have to discontinue these drugs due to inadequate response. In Infliximab (IFX) standard dose (3mg/kg every 8 weeks) in particular, the loss of efficacy sometimes occurs. To maintain the effect, we can use dose escalation of IFX or shortening the infusion interval, and also use combination therapy of both methods.
Objectives To investigate the continuity and effectiveness of 3 dose modulation methods using multi-center registry for the treatment of RA with biologics in Japan (Tsurumai Biologics Communications registry;TBCR) (Kojima et al 2012, Mordern Rheumatology).
Methods There are 603 cases treated with Infliximab among 2,072 registration of TBCR. Of these, 85 were received interval-shortening (7 weeks or less) and 64 were intensified by dose-escalation (more than 100 mg), while 51 were treated with both strategy (table 1). Drug survival of three strategies was examined using Kaplan-Meier survival analysis defined the time until discontinuation and treatment responses at last observation or last observation carried forward (LOCF) based on DAS28CRP4 were compared between each groups by one-way ANOVA.
Results Of 85 in interval-shortening group, 22 cases discontinued due to inadequate response, and 13 cases were stopped IFX due to adverse events at LOCF, and Of 64 in dose escalation group, 24 cases discontinued due to inadequate response and 8 cases stopped IFX due to adverse events. In combination group, 51 cases were treated with both dose escalation and shortening the interval, 11 cases discontinued due to inadequate response and 3 cases discontinued due to adverse events. DAS28CRP4 at the time just before interval-shortening was 4.38, just after treatment was 3.56 and at the last obsevation was 3.42, while 4.02, 3.64, 3.51 in dose-increasing group, and 4.11, 3.71, .3.34 in combination group respectively. All groups improved DAS28CRP4 significantly, and maintained significantly in interval-shortening group and combination group at LOCF(P<0.005). A combination group was significantly higher in the continuity that assumed effect invalidity Primary end-point for dose-increasing group (Log-rank test; p=0.001) (figure 1). Assumed IFX discontinuation Primary end-point, a combination group was significantly higher in the continuity for dose-increasing group (Log-rank test; p=0.003) (figure 2). There was no significant difference in the dropout rate for adverse events between each group (figure 3).
Conclusions Occurring the loss of efficacy for IFX, we can have a choice dose escalation or interval-shortening. Additionaly we would suggest that combination therapy which is able to overcome the absolute lack of the drug and the rise of the clearance of the drug was the most favorable method.
Disclosure of Interest K. Funahashi: None Declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer., N. Takahashi: None Declared, D. Kato: None Declared, Y. Hattori: None Declared, M. Hanabayashi: None Declared, N. Ishiguro: None Declared