Growing up in the 1950s, I used to play a game called “Telephone” at parties. In this game, you whispered something to the person next to you, and he or she in turn passed it on until we had gone around the room. We then compared what was originally said to what the last person heard. The outcome was never accurate and often hilarious. For example, after “To be or not to be” was passed to 20 people, it became “Don’t tread on me.”
Because telephones—even Dick Tracy’s wrist phone and Maxwell Smart’s shoe phone—are technologically passé, today the game would more properly be titled “World Wide Web.” But life in the 21st century seems to be a bit less innocent than the game I played as a child. Today, it often seems that information, as presented on the Internet (or even in textbooks), is not only distorted during transmission but is deliberately twisted during amplification. Moreover, corruption of information is not confined to politics but seems to have spread to medical information as well.
Clarifying the Methotrexate Message
Rheumatologists have been particularly victimized by the Web-based distortion of knowledge about our most oft-used drug. In preparing a journal supplement devoted to methotrexate, my co-editors, Vika Furer and Ted Pincus, wrote a scathing article on the amazingly bad information contained in widely read sources on the use of low-dose methotrexate in the treatment of rheumatic and other inflammatory diseases. It became clear to us that most textbooks of pharmacology and even medicine simply copy the discussion of methotrexate toxicity and drug interactions from the sections devoted to chemotherapeutic uses of the drug at doses that are 10- to 100-fold higher than those used to treat rheumatoid arthritis (RA) (grams/week versus low milligrams/week). Indeed, my co-editor and every other practicing rheumatologist is fully aware of this problem. I am sure that most rheumatologists spend a remarkable amount of quality telephone time with patients’ pharmacists who are convinced by their online data sources that methotrexate cannot be given with a nonsteroidal antiinflammatory drug (NSAID) in the treatment of RA.
Not having examined my own electronic drug information sources previously, I looked up methotrexate using the Medscape App on my phone and iPad. First, I looked up the dose of the drug and was informed that for RA, one should use no more than 20 mg/wk because of “increased risk of bone marrow suppression.” The fact that, in most people, bioavailability is the major factor limiting dosage was not mentioned. When I looked up drug interactions, I noticed that, in addition to the warnings associated with use of methotrexate with every NSAID ever developed, there were also notices of relative contraindications for every biologic in common use to treat RA or psoriasis.
For all of these agents, there was a warning that the biologic (fill in your favorite) “… and methotrexate both increase immunosuppressive effects; risk of infection. High likelihood serious or life-threatening interaction. Contraindicated unless benefits outweigh risks and no alternatives available.” Nearly every study on biological agents ever published indicates that the benefits of combining a biologic with methotrexate always outweigh the risks. More importantly, for infliximab, the Food and Drug Administration–approved labeling states, “Remicade, used in combination with methotrexate, can reduce signs and symptoms, help stop further joint damage, and improve physical function in patients with moderately to severely active RA.”
This particular finding raises a number of questions, such as, “Who writes this stuff?” The authorship of these online resources is never clear. Is the information in all of the other databases as bad or worse? Is it possible that the information in these databases regarding the use, dose, toxicity, or drug interactions of all other drugs is of equally dubious veracity? Finally, might this disinformation campaign be deliberate?
In my more paranoid moments, I have even imagined that there is a conspiracy of drug companies trying to diminish the use of methotrexate in the treatment of rheumatic diseases by terminally irritating rheumatologists who prescribe the bulk of it so that we go directly to more expensive biologic agents as first-line drugs. In my alternative paranoid universe, I also imagine that malpractice lawyers are trying to develop the factual bases for a new round of malpractice suits because rheumatologists don’t get sued often enough.
How do we end the nightmare? I propose that we stop the pain using the power of the cloud by posting ratings of drug and disease databases on the ACR website. If that doesn’t work, we can HAQ into the offending database and change the entry. Failing that, we can even be old fashioned and use the telephone to provide the correct information. This time we will shout instead of whisper.
Dr. Cronstein is Paul R. Esserman Professor of Medicine at New York University School of Medicine, in New York City.
