Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis
Carter1, John D., Sebba2, Anthony I., Albritton1, Nancy L., Osorio1, Angie H., Pfeiffer2, Ginger L., Valeriano1, Joanne, Vasey1, Frank B.
The administration of 100mg of methylprednisolone intravenously (IV) ½ hour prior to rituximab decreases the incidence and severity of acute infusion reactions (AIRs). However, the recommended pretreatment with IV methylprednisolone adds considerable time to the medication administration protocol; it also conveys potential risk. We present preliminary results of an assessment of oral prednisone as a pretreatment to rituximab.
This is a 6-month open-label assessment of 40mg of oral prednisone given ½ hour prior to rituximab as a prophylaxis against acute infusion reactions in patients with rheumatoid arthritis (RA). Subjects are ages 1880 and are either methotrexate (MTX) or TNF-antagonist inadequate responders. All subjects have to be on concomitant methotrexate. Standard safety and laboratory exclusions applied. All subjects were treated with 40mg of oral prednisone ½ hour prior to their rituximab infusions. Rituximab was administered as per the standard RA protocol; i.e. 1000mg IV twice at days #1 and #15. The primary endpoint is AIRs in the first 24 hours after the initiation of their day #1 infusion. The severity, timing, and treatment (including rituximab dose modifications) of any AIRs are also recorded. Secondary endpoints include AIRs during the 24 hours following the day #15 infusion and any adverse events experienced during the 6 month study; efficacy measures (DAS-28 and HAQ-DI) were also followed as secondary endpoints.
32 subjects have been screened and 27 subjects qualified. Baseline demographics include 25 females and 2 males, with 22/27 (81%) Caucasians, 4 (15%) Hispanics, and 1 other. The subjects mean age was 52.9 years (range 2980) and disease duration was 10.7 years (range 140). The average MTX dose is 15.1mg weekly and 16/27 (59%) have failed previous anti-TNF therapy (average number of TNF-antagonists used was 1.5). 12/27 (44%) subjects were on glucocorticoids at baseline with an average dose of 6.3mg prednisone daily; 18/27 (67%) subjects were seropositive. The mean DAS28 at screening was 5.48 and their HAQ-DI was 1.38. Regarding the primary endpoint, 7/27 (26%) of the subjects had AIRs within 24 hours of their day #1 infusion; 6 were mild in severity and 1 was moderate. There were only 3 (11%) AIRs within 24 hours of their day #15 infusion; all were mild. None of the AIRs required drug discontinuation. Of the 13 subjects who have completed the entire 6 months of the study, 8 (62%) experienced an AE at some point during the trial. There were 2 SAE's (a-fib and asthma) deemed not to be study-drug related. The DAS28 and HAQ-DI all improved significantly at weeks 8, 16, and 26 compared to baseline.
Historical controls demonstrate that 2733% of RA subjects experience AIRs with their first rituximab infusion. Our data suggest a smaller dose of oral prednisone is an effective alternative to IV methylprednisolone as a pretreatment for rituximab in patients with RA.
To cite this abstract, please use the following information:
Carter, John D., Sebba, Anthony I., Albritton, Nancy L., Osorio, Angie H., Pfeiffer, Ginger L., Valeriano, Joanne, et al; A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1693