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Thread: refused cytoxan for rituxan

  1. #1
    Join Date
    May 2006
    san francisco
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    Default refused cytoxan for rituxan

    I was diagnosed with lupus when I turned 18, four years ago. I started on prednisone and then added cellcept and was recently told that I need further therapy. The doctors said the protocol is to recieve cytoxan but that rituxan is also being experimented with for lupus nephritiis.
    I made the decision to go with the rituxan to my doctors disapproval who says it hasn't been tested thouroughly. Has anyone had an experience with either of these drugs?
    I don't know if I did the right thing :?:

  2. #2
    Join Date
    Nov 2001
    Victorville, California
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    Rituximab (Rituxan) is a monoclonal antibody approved for use in certain types of CD20-positive non-Hodgkin's lymphomas. CD20 is primarily expressed on immature and mature B cells but not on plasma cells or T cells; thus, rituximab may be less immunosuppressive than other treatment regimens. B cells are essential to the development of systemic lupus erythematosus (SLE). The chimeric monoclonal antibody rituximab depletes B cells by targeting the pan-B-cell surface marker CD20. Preliminary experience with this agent in SLE and other autoimmune diseases has been encouraging.
    Here is an article that I found:
    "After rituximab received Food and Drug Administration approval for lymphoma, several investigators began trying it in uncontrolled series of patients with a variety of autoimmune diseases. The hope was not only that the drug might be therapeutically effective, but also that through monitoring its use we would learn a great deal about the role of B cells in the pathogenesis of these conditions. Encouraging anecdotal reports have appeared for a potential response to rituximab of patients with rheumatoid arthritis, polymyositis/dermatomyositis, idiopathic thrombocytopenia purpura, essential mixed cryoglobulinemia, hemolytic anemia, myasthenia gravis, Wegener's granulomatosis, and IgM-mediated neuropathy, as well as patients with SLE . This approach has recently received a major impetus from the preliminary report of substantial efficacy in a controlled trial in rheumatoid arthritis.

    So what about SLE? A published experience with six patients looked promising, as did a few individual anecdotes . A phase I trial from Looney and colleagues showed improvement in certain subgroups in a post hoc analysis. Our own phase I trial also has examples of patients who have improved clinically and who have decreased steroid usage after treatment (unpublished data). The safety profile has so far been good, as would have been predicted from the extensive experience (over 300,000 patients) in individuals with B-cell malignancies, although it must not be forgotten that rare cases of severe, fatal infusion reactions have been reported . Surprisingly, many of the SLE patients developed human antichimeric antibody responses, perhaps in part because they did not receive the full therapeutic dose in the early dose-escalation period of the protocols.

    At this point, it is essential that controlled trials be conducted to determine for certain whether rituximab has a clinically useful therapeutic effect in SLE. If efficacy could be established for one particular manifestation, such as renal disease or skin disease, or on the basis of overall disease scores, it would add an important additional drug to our approach to SLE in general. If rituximab permitted substantially lower use of steroids or cytotoxics, particularly cyclophosphamide, it would be a significant advance in patient safety.

    What can we expect with rituximab treatment of SLE? The data so far indicate that autoantibodies, such as anti-DNA, are not suppressed. This is in distinction to what has been seen in the rheumatoid population, where both rheumatoid factors and anticyclic citrullinated peptide antibodies decreased. Anecdotally, skin and musculoskeletal manifestations may have been particularly responsive. All of the phase I trials and case reports have so far been short term. If rituximab can be shown to be effective, how will it be appropriately used? Perhaps in conjunction with cytotoxic or steroid therapy, as in the rheumatoid arthritis trial? What about repeat dosing? Will human antichimeric antibody (HACA) development be avoided by full dosing and by combination with cytotoxic agents, in parallel with the experience with infliximab? If HACA do appear, will they either cause increased complications, such as infusion reactions, or will they dampen the effect of treatment or even retreatment by blocking binding of rituximab to CD20 or by changing pharmacokinetics? In most patients treated with rituximab, the B cells return to the peripheral blood starting about 6 months after treatment. Will the return of B cells signal a recrudescence of clinical disease? When should patients be retreated, and at what doses and for how long? If prolonged B-cell suppression is necessary to maintain clinical control, will this eventually lead to an immunosuppressed state with a high risk for pyogenic infections? Will it be possible to combine rituximab with other biologicals that interfere with, for example, T cell–B cell collaboration, in order to achieve greater clinical benefit with less risk? Once efficacy is established in a controlled setting, all of these questions will have to be addressed either by additional trials or by collective experience.

    From a more theoretical point of view, a major issue revolves around the role of CD20+ B cells in the pathogenesis of disease. If the key cells to target are the autoantibody forming cells themselves, then the effectiveness of rituximab would depend on the extent of persistence of the CD20 marker in this population, and the longevity of those antibody forming cells that do not express CD20 [29]. If rituximab successfully could deplete the CD20+ precursors of CD20- antibody forming cells, then these cells would not be replaced when they die off. Another issue is what the B-cell repertoire will look like when it returns, and what aspects of the disease are indeed B-cell dependent."

    Given the variety of mouse models of SLE, and the fidelity with which they reproduce the spectrum of autoantibodies seen in SLE, it is unfortunate that no method currently exists to deplete B cells from mature, diseased animals as efficiently as rituximab depletes B cells in humans. If it were possible to model this therapeutic approach in mice, then we could get preliminary answers to many of the questions raised, and design our therapeutic approaches more logically. Although our and other laboratories are trying to develop this modality in mice, for the present it remains important that the trials to demonstrate safety and efficacy of rituximab in SLE, as well as in other autoimmune diseases, be accompanied by incisive studies of B-cell function and T-cell function that will provide insights into the disease mechanism and into the therapeutic potential of B-cell depletion."


  3. #3
    Join Date
    Jun 2006
    Thanked 17 Times in 13 Posts


    starlove I've been on both cytoxan and rituxan. When I was first diagnosed and needed treatment for the lupus nephritis 16 years ago I was treated with cytoxan over a period of 6 years. I have recently had a flare and after my kidney biopsy in Janurary I went back on cytoxan with the addition of Rituxan. I had 500mg of cytoxan IV every other week for 6 treatments and Rituxan 680mg (based on weight) IV every week for 4 treatments. The aggressive treatment I had all those years ago with the cytoxan per my nephrologist said that it has saved my kidneys. The cytoxan also helped to put my lupus in remission and I was in remission for 9 years until last year. I belive cytoxan is a good drug. Doing both I think is important in my opinion but you need to talk that over with your nephrologist and you personally need to feel comfortable with it. I too am on cellcept and prednisone. I hope this helps you. Health and Happiness to you!

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