Evaluating Organ Systems in Lupus


LFA-REAL offers a straight-forward evaluation for lupus-affected organ systems, a study shows.

Capturing disease activity in lupus can be challenging. As a multisystem autoimmune disease, it is a complex and unpredictable disease that can make diagnosis challenging.

Researchers led by Anca Askanase, M.D., of Columbia University Medical Center, conducted a preliminary test of LFA-REAL (Lupus Foundation of America-Rapid Evaluation of Activity in Lupus) as a possible measure for systemic lupus erythematosus (SLE) disease activity. Their findings appear in Lupus Science & Medicine.

They found strong correlations between the test and existing lupus disease activity measures such as the SLE Disease Activity Index (SLEDAI), the British Isles Lupus Assessment Group Index (BILAG 2004) and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Physician’s Global Assessment (SS-PGA).

Dr. Askanase told Rheumatology Network that making quick and accurate disease evaluation easier for everyone involved in lupus care will have far-reaching positive implications. 

“The more we understand how to improve disease measurements, the more likely we are to obtain improved outcomes and move toward treating targets in lupus,” she said. “We can target remission as opposed to ‘as good as it gets.’ We’ll achieve better outcomes in lupus, including longer life expectancy and having a better quality of life.”  

Existing SLE disease measures

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Existing tests vary in detail and data. SLEDAI, for example, includes 24 common manifestations measured in a point system to measure disease severity. The BILAG 2004 Index measures nine organ systems with 97 descriptors that are scored as "not present, improving, same, worse, new or recurrence" in the past month. The scores are calculated into a complex algorithm that matches the descriptions to the organ. SS-PGA is a 100 mm scale to assess a patient's overall disease activity from 0-3 range with 1 for mild disease actvity and two for moderate disease activity.

None of the measures are perfect. SLEDAI, for example, was not designed to detect worsening condition. In this case, if the minimal definition is met, it receives the same numerical weight regardless of its severity. 

Neither the SELENA SLEDAI Flare Index or the SRI-50 (improvement index) addresses the fact that patients with severe disease cannot often be differentiated from patients with mild disease. However, BILAG does differentiate mild, moderate and severe activity, but doesn’t always score them clearly. It’s a complicated measure to learn, the researchers wrote.

SS-PGA is simple and intuitive, “but its compression of a broad spectrum of moderate to severe disease severity into a small region of the scale can be problematic in accurately evaluating disease progress, particularly when multiple organs are involved.”

“These outcome measures are still frequently misunderstood and scored incorrectly, even by experienced clinical trialists,” researchers stated in the article.

LFA-REAL has been designed to be “efficient but a scalable SLE disease activity measure” for use as both a reliable outcome measure in both clinical practice and trials.

“We believe that this system can be learnt by a clinician skilled in the care of lupus patients within minutes, and in practice it can be scored rapidly for most patients. Since it is constructed as an expanded version of PGA (based on completing a separate SS-PGA for each active organ system), it is designed to be sensitive to change and allow for precise and accurate measurement of disease severity and treatment progress,” the researchers wrote. “A tool that can be used in both clinical trials and practice would allow practicing clinicians to more easily interpret, evaluate and apply the findings from clinical trials.”


The study results

Of 91 SLE patients with mild to severe disease activity, their median SLEDAI score was 4.0 (range 0–28) and BILAG score 8.0 (0–32). The median SS-PGA was 38 mm (4–92) versus the total REAL 50 mm (0–268), which expands in range by additive organ scores. The median SS-PGA score of this group was 66 mm (50–92) versus median REAL score of 100 mm (59–268). The total REAL scores correlated with SLEDAI, BILAG and SSPGA (correlation coefficient=0.816, 0.933 and 0.903, respectively; p<0.001 for all). Inpidual LFA-REAL organ scores for musculoskeletal and mucocutaneous also correlated with corresponding BILAG domain scores (correlation coefficient=0.925 and 0.934, p<0.001).


In this Q&A, Rheumatology Network spoke with Dr. Askanase to learn more about LFA-REAL.

Q: Why were you interested in studying a new lupus assessment tool’s efficacy?

A: A big problem in lupus drug development - and a big problem in lupus assessment in everyday practices - is the lack of simple, versatile tools that work for both trials and practice. The same tool should be complete enough for use in everyday practice, accurate enough for trials, and easy for doctors to understand the results. It also must have quantitative data for assessments, as well as progress evaluation. This means we need a simple tool that moves from research to practice and back again. 


Q: Why is a simplified tool important, and what makes this one better?

A: For a very long time, the assessment for progress in lupus has primarily been based on physician assessment and evaluation. Increasingly, assessments are needed to fully grasp the lupus activity picture. We need to have both physician and patient assessment options of a program come together. Physicians are taught how to evaluate lupus and how to separate damage from activity and emotional issues. We’re also expecting patients to provide an accurate assessment of one or the other. But, lupus is complicated. That’s our job as physicians taking care of patients - we’re supposed to guide them on giving us the information we’re looking for on activity, chronicity, and emotional issues. The piece this instrument tries to address is the need to reconcile the physician and patient impressions of disease progress and disease changes. So, ultimately, we have both - assessment areas that evaluate the same parts of disease activity in the same way and areas where there’s pergence.


Q: How are the physician and patient assessments different?

A: For the physician, arthritis is a marker of joint pain, swelling, and stiffness. For the patient, these are also very important issues. But, it’s never explained to them these are items they should think about in evaluating joint symptom severity. That’s part of what we’re trying to do with the patient-reported outcomes piece with the new instrument. The paper we’re referring to is only evaluating the clinician-reported outcome. The development of the patient-reported piece is in progress, as is the full evaluation of the program. 

Historically, physician and patient disease-activity and progress evaluation have been discordant. They are discordant in mild disease, according to physicians, and those with severe disease. Because of this, there’s the thought doctors need a better design for getting a bigger disease picture. And, patient reports have been mostly ignored or side-tracked. Unless we understand disease activity and disease improvement must reconcile for patient and physician, we’ll never have excellent therapeutics with good, long-term lupus outcomes.  


Q: Overall, how will this assessment be a better option for the provider?

A: For the physician, it allows for a graded assessment of each organ system in a very intuitive and clinically-based way, making the assessment process a lot easier. For example, SLEDAI gives two points for a rash. It might be a couple of dots on the face or a small area on the neck or chest. It could be the whole body covered in a rash. Understanding the variability and the full extent of how much this impacts the patient is critical. We’re trying to enable the physician to give us a graded assessment – a non-yes or no answer. We’re looking for the full-spectrum analysis for skin, arthritis, lung and heart involvement, for kidney and for hematological involvements. This instrument gives us a graded assessment of all the organ systems. It’s intuitive and simple, but it also allows for the capture of disease complexity.


Q: What could be the challenges to using this assessment?

A: Doctors caring for lupus patients have historically avoided assessment. I think, regardless of simplicity, we’ll have a bit of a hard time getting people to use it regularly. Ultimately, payers are going to dictate what we do. If payers require quantitative measurements for biologics and expensive immuno-suppressant reimbursement, that will lead to fastest implementation. Alternatively, we’re well placed and working with LFA on the final instrument validation. It will broaden the education of physicians and patients, and it will allow for the tool to be disseminated and adopted quickly. 


Q: What are the next steps?

A: The plan is for a consensus conference to present the tool and get buy-in. We will present the data we have, hopefully convincing people to use it before they’re forced to because payers will ask for quantitative over qualitative data.


Anca Askanase, Xiaoqing Li, Avery Pong, et al. "Preliminary test of the LFA rapid evaluation of activity in lupus (LFA-REAL): an efficient outcome measure correlates with validated instruments,"

Lupus Science and Medicine

. Published online March 4, 2015. DOI:10.1136/lupus-2014-000075  

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