Authors: Ruperto N, Hanrahan L, Alarcón G, Belmont H, Brey R, Brunetta P, Buyon J, Costner M, Cronin M, Dooley M, Filocamo G, Fiorentino D, Fortin P, Franks A Jr, Gilkeson G, Ginzler E, Gordon C, Grossman J, Isenberg D, Kalunian K, Petri M, Sammaritano L, Sánchez-Guerrero J, Sontheimer R, Strand V, Urowitz M, von Feldt J, Werth V, and Merrill J. (2010). Lupus epub ahead of print.
What is the topic?
Lupus is a chronic autoimmune disorder characterized by unpredictable disease flares and remissions. However, there has never been community-wide agreement on how to define clinical flares in lupus patients. Various clinical trials have used different definitions of flare, making it hard to compare results or interpret outcomes. Specific problems were identified with current flare measurements, including the fact that minor worsening could cross thresholds defining severe disease and that patients with significant worsening of disease might not be treated as aggressively as the definitions required. To address this problem, the Lupus Foundation of America convened an international working group to obtain a consensus definition of disease flare in lupus to facilitate new drug development and help physicians characterize lupus with standard, agreed-upon language.
What did the researchers hope to learn?
The researchers hoped to create an internationally agreed-upon definition of a lupus flare that would have practical applications for clinical trial designs.
Who was studied?
This study involved several surveys of an international group of experts in lupus as well as face-to-face workshops.
How was the study conducted?
With help from the Paediatric Rheumatology International Trials Organization (PRINTO), three web-based surveys were conducted, using a scientific method called the Delphi method for pulling together a range of opinions and helping a group sort through the opinions and rank the degree of agreement for each one. Participants included 120 lupus experts from 11 countries, representing universities, government agencies, and the drug development industries. The areas of expertise included rheumatology (adult and pediatric), dermatology, immunology, nephrology, neurology, pulmonology, epidemiology, and statistics.
What did the researchers find?
12 preliminary definitions were drafted during the survey process, and refined through the agreement process. During a final face-to-face workshop, majority agreement was obtained for the following definition: “A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment.”
What were the limitations of the study?
Some Delphi survey response rates were below the optimal cut-off of 70% acceptance of definitions for a lupus flare.
What do the results mean for you?
This definition of lupus flare underscores the need to see a significant change in order to consider a patient to be flaring, suggesting that measurements that define flare simply by clinical thresholds are inadequate. The absolute requirement for a change of treatment in order to define a significant worsening of disease was voted down. This may have an important impact on interpreting changes in patients during clinical trials.