Systemic Lupus Erythematosus @ ACR
Flares and Disease Activity in Systemic Lupus Erythematosus
Although the definition of flares in systemic lupus erythematosus (SLE) is clear according to available guidelines, the identification and evaluation of flares in clinical practice can be challenging. Approaches to diagnosing and reducing flares and evaluating disease activity in SLE were major topics of discussion at the recent ACR Convergence 2024 meeting.
Following these presentations, featured expert George C. Tsokos, MD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Tsokos are presented here.
For patients with SLE, there are methods that are used to identify flares in clinical studies, and there are other more practical methods that are used to identify flares in clinical practice. In clinical studies, flares are identified when a patient’s score increases by a certain number of points on an objective measurement tool such as the SLE Disease Activity Index (SLEDAI). Several abstracts presented at ACR Convergence 2024, including those by Anca D. Askanase, MD, MPH, et al (abstract 0629), Patti Katz, PhD, et al (abstract 2170), and Melissa Munroe, MD, PhD, et al (abstract 0623), highlighted the usefulness of both patient-reported outcomes and clinician-assessed measurement tools to evaluate disease activity.
Conversely, in clinical practice, the identification of flares is often based on clinical judgment. In clinical practice, objective measurements such as the SLEDAI may be used to monitor disease activity over time, but it is not the patient’s SLEDAI scores that drive management decisions; rather, it should be the intensity of the disease manifestations.
When patients with SLE come to you for their follow-up, you should go through all the possible manifestations. Some of them will tell you, “Doctor, this joint never bothered me before, but it bothers me now.” Then you do laboratory work, and the findings will also guide your determination of whether there is disease activity flaring. And finally, at the end of this process, you make a determination of whether you should intensify or change treatment or whether you should not do anything but wait and just follow the patient.
In the future, this approach of using clinical judgment may also be combined with looking at objective measures of potential disease activity, such as type I interferon status and the presence of anti-C1q antibodies, as was reported at ACR Convergence 2024 in abstracts 1497 and 1488. One particularly interesting study presented at the meeting integrated proteomics, artificial intelligence, and clinical signs to develop a tool to monitor disease activity (abstract 2379). This model indicated utility in helping to identify flares, and that is a good thing. I like this approach.
Determining high vs low disease activity should also incorporate clinical judgment, and the intensity of a patient’s disease manifestations should inform how aggressively one approaches treatment. If a patient has a very high intensity of disease manifestation coming from 1 organ, you would likely be aggressive in treating this individual. If a patient has a high intensity of manifestations coming from multiple domains or organs, then you would be even a little more aggressive in treatment—regardless of what the patient’s SLEDAI score tells you—because of the individual patient presentation. For example, if somebody has mild arthritis with 1 inflamed joint, you would likely stratify it as low disease activity. If a patient has chest pain but you cannot detect any fluid in the lungs or heart, then you may also call this low disease activity. However, if a follow-up echocardiogram or chest x-ray detects fluid, then you would likely stratify it as high disease activity. For blood manifestations, if a patient has mild thrombocytopenia, you may consider it low disease activity. However, if their platelet count decreases to less than 20×103/mL, you would call it a severe flare, and it would require more attention. Finally, if you have a patient with mild arthritis, mild chest pain, and low platelet counts, you would certainly need to treat that individual. However, if the manifestations from these domains are not severe, you may not treat them very aggressively.
Deciding on which treatment to use when a patient’s disease activity increases depends on the disease severity and what treatment the patient is already taking, whether that is steroids, mycophenolate mofetil, voclosporin, and so on. Multiple algorithms are available, and every doctor uses them differently. Although there are general guidelines, all the algorithms should be personalized to the patient you have in front of you. Different aspects of the efficacies of some of the drugs used to reduce flares and disease activity in SLE were confirmed in studies by Marta Mosca, MD, PhD, and colleagues (abstract 2402), Megan Clowse, MD, MPH, and colleagues (abstract L16), and Edward Vital, MD, and colleagues (abstract 1492) presented at ACR Convergence 2024.
Arora S, Isenberg DA, Castrejon I. Measures of adult systemic lupus erythematosus: disease activity and damage. Arthritis Care Res (Hoboken). 2020;72(suppl 10):27-46. doi:10.1002/acr.24221
Askanase A, Vital E, Meier O, et al. Evaluating the concordance between SRI4 and BICLA using placebo data from randomized controlled trials of patients with active systemic lupus erythematosus [abstract 0629]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Chen L, Deng O, Cong R, et al. Causal proteomics-assisted machine learning model enhances flare risk prediction in systemic lupus erythematosus [abstract 2379]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Clowse M, Isenberg D, Merrill J, et al. Dapirolizumab pegol demonstrated significant improvement in systemic lupus erythematosus disease activity: efficacy and safety results of a phase 3 trial [abstract L16]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Gonzalez-Trevino M, Hetrick M, Sanchez-Rodriguez A, Duarte-Garcia A, Tebo A. Clinical utility and performance of anti-C1q antibodies for systemic lupus erythematosus: comparative analysis of three different assays [abstract 1488]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Katz P, Eudy A, Patterson S, et al. Preliminary evaluation of a patient-reported version for the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI): the Systemic Lupus Erythematosus Disease Activity Questionnaire (SLEDAQ) [abstract 2170]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Morand EF, Fernandez-Ruiz R, Blazer A, Niewold TB. Advances in the management of systemic lupus erythematosus. BMJ. 2023;383:e073980. doi:10.1136/bmj-2022-073980
Mosca M, Costenbader K, Merrill J, et al. Belimumab reduces disease flares versus placebo in adults with early active systemic lupus erythematosus: results of a large integrated analysis [abstract 2402]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Munroe M, DeFreese D, Holloway A, et al. Select patient reported outcome measure domains enhance immune mediator based indexes that inform flare risk and disease activity in systemic lupus erythematosus [abstract 0623]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Schilirò D, Silvagni E, Ciribè B, et al. Systemic lupus erythematosus: one year in review 2024. Clin Exp Rheumatol. 2024;42(3):583-592. doi:10.55563/clinexprheumatol/mnvmvo
Smith J, Garcia LPW, Bonilla D, et al. Type I interferon status and clinical manifestations in a large cohort of patients with systemic lupus erythematosus [abstract 1497]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
Vital E, Furie R, Morand E, Bruce I, Knagenhjelm J, Lindholm C. Timing of SLEDAI-2K item improvements during the first year of intravenous anifrolumab treatment of moderate to severe SLE [abstract 1492]. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.
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