“Our most important finding is that long-term use of infliximab appears to be safe.”—Bert Vander Cruyssen, MD, PhD
“Our most important finding is that long-term use of infliximab appears to be safe,” said presenter and lead investigator Bert Vander Cruyssen, MD, PhD, post-doctoral fellow at the Ghent University Hospital in Ghent, Belgium. “We saw no new safety issues after 7 years of infiximab treatment, and we found that most safety issues appeared in the first 2 years of infliximab treatment,” he added.Over 500 RA patients in expanded-access program tested long-term infliximab
The investigators evaluated data from an expanded access program in Belgium in which patients with active refractory and erosive rheumatoid arthritis were treated with intravenous infusions of infliximab, in combination with methotrexate.
Between 2000 and 2001, investigators enrolled 511 patients in the program. The subjects showed a median disease duration of 10 years and had failed an average of 3.9 disease modifying anti-rheumatic drugs (DMARDs), including methotrexate monotherapy.
Patients received infliximab treatment at weeks 0, 2, 6 and every 8 weeks after enrollment, with a standard dose of 3 mg/kg. Dose increases with 1 extra vial (100 mg) were an option.
After 7 years, the treating physicians completed a questionnaire regarding efficacy and safety of infliximab therapy, the level of disease activity (DAS28, The Disease Activity Score using 28 joint counts), functional disability (HAQ, Health Assessment Questionnaire) and provided documentation of reasons for infliximab discontinuations.
At 7 years, data for 441 of the 511 original subjects was available for analysis. Four original subjects did not initiate treatment, 17 died and 49 were lost to follow-up. Of the remaining 441 subjects, 160 were still on infliximab treatment at year 7.
Most infliximab problems were in first 2 years of RA treatment
Primary reasons for infliximab discontinuation were lack of efficacy (104), adverse events (107), and elective change of therapy (70). Notably, 50% of treatment discontinuation for safety reasons occurred during the first two years of infliximab therapy. Discontinuation due to inefficacy happened at a steadier rate over the 7-year period.
The researchers reported that mean DAS28 scores of subjects still treated with infliximab at year 7 decreased from 5.7 at baseline to 3.0 at year 4, and remained at that level until year 7. Mean HAQ was 1.07 at year 7.
At year 7, the investigators also found low disease activity (defined as DAS28 < 3.2) in 60.9% of patients, and 45.5% had achieved remission (DAS28 < 2.6).
Translating research into practice: long-term infliximab for RA
“These are very important findings for the practicing rheumatologist,” said Xenophon Baraliakos, MD, senior clinical investigator and staff rheumatologist at Rheumazentrum Ruhrgebiet in Herne, Germany. “These are patients who failed on standard disease modifying anti-rheumatic drugs, or DMARDs, and then began infliximab therapy. One of the big questions about taking this next step treating a patient is not only about efficacy but also about whether it is safe to give this drug to patients for the long-term. And the very good news in this study is that most problems appear in the first 2 years of treatment and the drug safety profile does not worsen with time. So now we can say with much more confidence that long-term treatment with this anti-TNF therapy appears to be safe,” he added.
The authors concluded, “This study describes the 7 year follow-up of a cohort of 511 RA [rheumatoid arthritis] patients with longstanding, refractory disease who were treated with IFX [infliximab] in combination with MTX [methotrexate]. After 7 years, patients who continue to receive IFX experience sustained clinical benefit, as reflected by the maintenance of low DAS and HAQ scores. Long term treatment with IFX appears to be safe: safety issues occurred during the first 2 years of IFX treatment.”
The study was supported by Schering-Plough, Inc.
Reference
1. Vander Cruyssen B, Durez P, Westhovens R, et al. Seven year follow-up of infliximab (IFX) IN rheumatoid arthritis (RA) patients refractory to multiple DMARD treatment: attrition and long-term clinical effect. Presented at: EULAR 2009, Copenhagen, Denmark, June 11, 2009. Poster presentation THU-0181.
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