another view

I will not argue for methotrexate, but I think it is important to state that the real reason to do this type of immunosuppressant therapy (if done right) is that it is an attempt to “reset” the immune system–in the strongest words to make a cure. Immunoglobulin and plasmapheresis really address the symptoms of the disease, not the disease itself. Chemotherapy drugs, rituxan, stem cell transplant all try to affect the cells that cause inflammation. So it is understandable to try to do this. The problem is that no one knows how it is best to do it because the disease is different in different people and it is hard to know precisely how the underlying disease is affected rather than the inflammatory manifestations and symptoms of it.

In the study that was done before and mentioned by Selahsmom, Methotrexate did not work to lower the dose of IV IgG used, but the arguements made were that the dose of methotrexate (a maximum dose of 15 after an eight week dose escalation) was low for other immune diseases and that the duration of therapy was too short (total therapy of only 40 weeks, 32 weeks being at the “maximum” dose) to see an effect. Also the criteria for “working” was not so good as seem in a high number of “responses” in the placebo arm–probably an indication of the complexity and waxing/waning of CIDP and of difficulty in setting a mark for response (since it is hard to distinguish what is ongoing disease and what is previous damage). So the conclusion was that methetrexate might work, but that it needs a differently designed study to determine this–particularly with more important ways to say if it worked.

Regarding dosing, 2.5 mg of methotrexate is a tiny, tiny dose. Tiny babies with leukemia get a much higher dose. For the older teens with leukemia that I help to care for where I work, many get up to 20 pills a week (up to 50 mg) along with other chemotherapy. The smallest dose for an immune system disease that I saw was 7.5 mg/week. Methotrexate works through the folic acid pathway. Giving folic acid helps reduce toxicity, but it also reduces efficacy (by reversing the effect of methotrexate). Because cancer is fatal if not well treated, oncologists never give folic acid with methotrexate. Rheumatologic illnesses are not as life-threatening and so rheumatologists may give folic acid with methotrexate to limit side effects, but it also limits the chance of the medicine working since you are giving the active agent and its reversal agent together. Anyone getting weekly methotrexate should have periodic liver tests. Your husband’s dose was so small that it should not really affect liver or disease. They may not have checked liver studies because the dose was so small or because the potential additive effect on the liver was not recognized enough.

My suggestion is that you write your questions about the goal of treatment, the plans for dose optimization and for toxicity monitoring and ask that they be addressed and also that you request one person to be your husband’s main neurologist to make a consistent plan and to ensure that this is optimally carried out. Be very emphatic that this needs to happen. Chemotherapy can be very dangerous–it is toxic. It can also be very beneficial, but the doctor ordering it has to be knowledgable about dose and what to what out for. Again, giving too little is bad not so much from toxicity, but because other effective therapy is not being given, more things are being done to the patient, and there may be long term effects even if there are not short term toxicities.
WithHope