Why do autoimmune drugs, such as methotrexate, work in some patients but not others with the same condition?

Why do autoimmune drugs, such as methotrexate, work in some patients but not others with the same condition?

Unfortunately, non-response to drugs used to treat autoimmune conditions is not uncommon. Methotrexate is only effective in 30-50% of patients who try it. Efficacy of a drug in each patient is determined by a variety of factors. Although patients can be diagnosed as having the same autoimmune condition, they can experience vastly different symptoms, possible due to different underlying mechanisms.

The heterogeneity (diversity) within diseases like RA is becoming clearer. More evidence supports that the diagnosis likely encompasses a number of genetically-related diseases that share joint inflammation as the presenting feature, rather than a singular disorder. Subtle differences will also exist in the underlying immunological etiopathologies (the causes and effects of a disease). Current treatment strategies are designed to standardize treatment across patient groups which superficially appear similar but might have very different disease processes. Factors that may influence/explain different underlying mechanisms in the same disease include genetic makeup, gender, hormone levels, and environmental factors like whether or not a patient is a smoker.

Although numerous drugs are available to treat these conditions, a great deal of work is needed in order to more accurately predict which patients will respond to a specific drug. This is why many researchers are focused on elucidating the different underlying mechanisms that occur in the same autoimmune condition. Approaching autoimmune treatment on an individual patient level will likely involve clinical, genetic, immunological, and currently unknown factors to inform treatment choice. Improved accuracy in predicting response will ensure patients do not suffer a lengthy period of trial and error, unnecessary pain and the risk of permanent damage. It is hoped that in time we will be able to assign patients to subcategories within the same disease classification and this will help to get them on a drug they will respond to, better controlling each individual’s disease.

Article Author
Arthritis National Research Foundation

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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