In 1970s, when I started my career in rheumatology, the clinical trials sparking interest involved thoracic duct drainage, total lymph node irradiation, and plasmapharesis. Despite the extreme nature of these interventions, their efficacy was, in fact, limited. Coupled with emerging data that RA had a mortality rivaling that of certain malignancies, rheumatologists seemed poised for an even more aggressive treatment assault. The analogy with cancer treatment seemed strong as rheumatologists ventured to the use of high dose chemotherapy, broad-spectrum anti-lymphocyte antibodies, and other radical techniques to extirpate pathogenic T cells that were thought to drive the RA fire.
Knowing what havoc cancer treatment can wreak, it seemed inevitable that these approaches would have serious side effects and that more effective therapy would carry the same risk for harm that chemotherapy has in oncology. As an oncologist once told me when I fretted about the scorching toxicity of drugs for leukemia, “You can’t cure cancer with chicken soup.” It seemed that the same would be true for RA.
As a young investigator, I submitted a proposal to the NIH to assess patient acceptance of risk for new RA treatments by performing a standard gamble experiment. Basically, in this proposal, we would ask patients about the chance of death they would accept to get rid of their arthritis. Our question would be phrased as follows. “There is a treatment that can cure your arthritis but it could kill you. What chance of death from this treatment would you accept to be cured?” The other part of the research was to determine the demographic features and other factors (e.g, disease duration or severity) that would influence a patient’s decision.
At that point in history, I estimated that patients with RA would be willing to take less than a 5% chance of death to get cured. Other members of my division gave similar numbers, but the member of our faculty who was then recruiting patients for clinical trials for new RA treatments put the number five times higher. He was right. Indeed, his opinion was in accord with the existing literature indicating that RA patients would accept a 30% chance of dying to get rid of their disease. We never got funded for this grant (What else is new?) so I cannot verify these numbers, but I remain impressed by how bad RA must have been to make patients so desperate for relief.
RA Today: A Different Outlook
Fast-forward thirty years to Paris in 2008. Mission impossible has become mission possible with agents that are well tolerated, easy to administer, and seemingly quite safe, given their efficacy. Indeed, current therapy can lead to remissions rates, stringently defined, of over 50%, and combination therapy can literally stop erosion. Furthermore, as studies presented at EULAR demonstrated, disease modifying antirheumatic drug (DMARD) therapy can prevent the emergence of RA in patients with early signs of synovitis and that, in patients in remission, cessation of DMARDs may be possible.
