Tuesday, January 28, 2014

Rituximab - to extra dose or not - and more problems


Today I’ve read an abstract concerning an extra dose of 1000 mg rituximab.

Vitall, E.M. and colleagues published the following paper: “An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B cell depletion: a randomised controlled trial” (Link: http://ard.bmj.com/content/early/2014/01/17/annrheumdis-2013-204544.abstract). Conclusion: “In rituximab-treated patients with incomplete B cell depletion (predictive of poor response), an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion and clinical responses than placebo with no worsening of safety. Degree of depletion is an important, but modifiable, determinant of response.”

M. Mahevas and colleagues were interested to investigate the following problem: “Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia” (Link: http://www.ncbi.nlm.nih.gov/pubmed/23798363). “The efficacy of two (RTX) regimens: standard therapy of 375 mg/m(2) weekly for 4 weeks vs. a rheumatoid arthritis (RA) regimen of 1,000 mg on days 1 and 15, to treat ITP was compared.” “Tolerance was good and comparable between the two groups. The RA regimen is an effective and safe alternative to the standard regimen to treat adults with ITP.”

And I’d like to point out to a third study, which has been presented at the ACR 2013 Meeting in San Diego [498] by M. Bredemeier and colleagues: A Systematic Review and Meta-Analysis Comparing Low- Versus High-Dose Rituximab For Rheumatoid Arthritis.” Conclusion: “Low-dose RTX has similar effectiveness and met noninferiority criteria for most primary outcomes. Considering the lower cost, it should be the standard RTX regimen for rheumatoid arthritis.”

And I nearly forgot this study, presented at the ACR 2013 Meeting in San Diego [500] by K. Chatzidionysiou and colleagues: “Fixed Versus On-Flare Retreatment With Rituximab In RA—Results From The Cererra Collaboration.” Conclusion: „A fixed retreatment strategy with RTX in RA seems to be more effective than the retreat ‘on-flare’ strategy.”

The studies show that there are still a couple of unresolved problems both in treating RA and ITP, not to mention other entities. Vitall’s study tells us to consider an extra dose, so we need to monitor B-cell depletion, which we usually don’t do in routine treatments. Reimbursement of lab tests differs in different countries. Here in Germany there might be differences in which kind of health care provider is included. Maybe there’s also the problem of an off-label use. But I think we should consider a third dose before switching to another boDMARD.
Mahévas’ study shows us, that even in ITP a less aggressive strategy might also work. And this leads to the study of M. Bredemeier and colleagues. They describe another possible group of patients, who need less rituximab. And the last quoted study favours a fixed strategy instead of an “on-flare” strategy, but doesn’t answer, if a strategy shortly before a flare would succeed. I know the difficulty lies in determinating “shortly before a flare”; but that’s where we rheumatologists come into play.


To sum it up, in treating RA patients with rituximab we might encounter a group that needs a higher dose, a group that needs a standard dose, another one that needs a lower dose, and these groups might be further divided to fixed or variable infusion intervals. No easy task and more studies are needed. 

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