Background/Purpose:Little data exists on how physicians weigh benefit-risk tradeoffs of drugs, despite the impact on prescribing decisions. Biologic rheumatoid arthritis (RA) treatments can yield substantial benefits for patients, but can be associated with potentially serious, life-threatening risks. The aim of this study was to examine rheumatologists’ preferences when weighing potential benefits and potential risks of biologic RA therapies. Method:US rheumatologists treating 10 or more RA patients monthly completed a web-enabled survey with a series of treatment-choice questions. These questions required choosing between two hypothetical RA treatments with differing levels of efficacy (defined as reduction in difficulty doing activities of daily living) and five potential treatment-related risks: annual risks of pneumonia, pneumocystis and progressive multifocal leukoencephalopathy (PML); 5-year risk of lymphoma; and risk of post-injection/-infusion anaphylaxis. An index of the importance of each treatment attribute was estimated using a mixed-logit choice model. The results of the model were used to calculate the maximum level of each risk rheumatologists considered acceptable to achieve different improvements in patients’ functioning. Result: 190 rheumatologists completed the survey. The majority (77%) was male and in private practice (84%). Most (70%) had been in practice for at least 10 years. Rheumatologists were willing to accept increases in treatment-related risks to improve a patients’ ability to do daily activities. The most important risk was annual PML, followed in order of decreasing importance by 5-year risk of lymphoma, risk of post-injection/-infusion anaphylaxis, annual risk of pneumocystis, and annual risk of pneumonia. The maximum level of treatment-related risks that rheumatologists would accept for reduced limitations on daily activities from moderate to mild or from mild to none are presented in Table 1. Rheumatologists were consistently more willing to accept greater risks for greater benefits (improving RA from moderate to mild). Serious but rare risks such as PML, lymphoma and anaphylaxis were much less tolerated than more common risks with significant morbidity and mortality. Conclusion: Rheumatologists do not place uniform importance on different potential treatment-related risks. In order to reduce the impact of RA on patients’ ability to conduct daily activities, rheumatologists appear willing to accept levels of treatment-related greater than those levels reported in the literature. PML was more unacceptable than we anticipated relative to risks such as lymphoma and pneumocystis that are associated with substantial morbidity, mortality and much greater frequency. Table1. Maximum percentage-point treatment-related risk rheumatologists would accept for different improvements in limitations on daily activities.
Maximum Acceptable Risk for an Improvement in daily limitations from
Moderate to Mild
Mild to None
Annual risk of PML
5-year risk of lymphoma
Risk of anaphylaxis after each injection or infusion
Annual risk of pneumocystis
Annual risk of pneumonia
Disclosure: A. B. Hauber, None; J. T. Cross, Genentech Inc., 3 ; D. E. Yocum, I own stock in Roche, 9 ; F. R. Johnson, None; J. C. Yang, None; I. Villaneuva, Genentech Employee, 3 ; P. P. Katz, Genentech and Biogen IDEC Inc., 5 .