The heterogeneous nature of systemic lupus erythematosus (SLE) makes assessing disease activity a complex exercise.¹ The limbic spoke to Professor Mandana Nikpour, Rheumatologist at Royal Prince Alfred Hospital in Sydney, about the clinical utility of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K),² how to interpret scores, and other clinical considerations required to help ensure a comprehensive patient assessment.

What is the purpose of the SLEDAI-2K?

Prof Nikpour: The SLEDAI-2K is a tool used to measure disease activity in SLE, a condition that can affect multiple organs. It helps to identify active disease in specific organ systems, which is crucial for determining treatable or reversible aspects of the disease, as opposed to irreversible damage. The scoring system consists of a list of 24 items – 16 clinical and 8 laboratory results – that reflect disease activity.^3,4 Each item relies on either clinical judgement or laboratory tests. For example, joint inflammation is assessed through physical examination, while urinary abnormalities require laboratory analysis. Clinicians must also attribute observed abnormalities to lupus activity, distinguishing them from other potential causes like infections. This comprehensive approach ensures accurate assessment and management of SLE.

What does the SLEDAI-2K measure?

Prof Nikpour: The SLEDAI-2K measures disease activity across various organ systems, weighting them based on severity. It includes 24 items, with the highest scores assigned to severe manifestations such as seizures, psychosis, and vasculitis.³ Nervous system descriptors and vascular issues score eight points each.³ Musculoskeletal involvement, including arthritis and myositis score four points each, kidney involvement with urinary abnormalities score up to 16 points collectively.³ Mucocutaneous symptoms such as rash and ulcers score two points each, and heart and lung involvement, such as pleurisy and pericarditis, also score two points each.³ Lower scoring items include serological activity (low complement, raised anti-DNA) and fever, each scoring 1-2 points. The SLEDAI-2K does not cover all possible SLE manifestations, such as gastrointestinal activity, but it includes the most common ones. 

What is the clinical utility of the SLEDAI-2K? 

Prof Nikpour: The SLEDAI-2K is a valuable tool for rheumatologists to quantify the total burden of disease activity in SLE across multiple organ systems. It helps to identify which organs are affected and the extent of disease activity, which can be used to guide treatment decisions. Patients with high disease activity may require treatment adjustments to control inflammation. So, the tool is not only useful for documenting disease status but also for informing therapeutic strategies. 

How are scores from the SLEDAI-2K interpreted and what do these scores mean for patients?  

Prof Nikpour: The SLEDAI-2K scores are interpreted to assess the level of disease activity in SLE. A score of 0 indicates no disease activity. Scores of 1-4 suggest low disease activity, which might include joint involvement only or serologic activity only (low complement and/or raised anti-DNA). Scores between 5-10 indicate moderate disease activity, while scores above 10 reflect high disease activity, signifying severe organ involvement or multiple organ systems affected. The overall burden of disease activity, represented by the total score, along with the specific organs affected, helps tailor treatment decisions. Higher scores necessitate more aggressive management to control inflammation and prevent organ damage.

What other scoring systems can clinicians use to complement the SLEDAI-2K to ensure a comprehensive patient assessment?

Prof Nikpour: Two scoring systems that can complement the SLEDAI-2K are the British Isles Lupus Assessment Group (BILAG) index and the Physician Global Assessment (PGA). The BILAG index is more comprehensive than the SLEDAI-2K, capturing a wider range of organ manifestations (97 items in the 9 different organs/systems) and providing a nuanced grading of disease activity (lack of activity, mild activity, moderate activity, and severe illness).^4,5 However, the BILAG is more complex to apply at the point of care. The PGA offers a global impression of disease activity on a scale from 0–3, allowing for a more granular assessment.⁵ For example, while the SLEDAI-2K might score a low platelet count as just one point, the PGA can reflect the clinician’s concern about a markedly low platelet count by assigning a higher score, indicating the need for more intense treatment. No one instrument captures the complexity of disease activity in SLE, but combining these tools, for example the SLEDAI-2K with the PGA, can provide a more holistic view of disease activity.

What are some of the pitfalls and considerations of the SLEDAI-2K?

Prof Nikpour: The SLEDAI-2K has several advantages, including simplicity and ease of use at the point of care. However, it has limitations. One pitfall is that it requires complete resolution of an activity item to no longer score it, which may not reflect partial improvements.⁶ Additionally, it does not cover every possible lupus manifestation, though it includes the most common features. Some severe manifestations, like pleurisy and pericarditis, score low, potentially underestimating disease severity. Despite these limitations, the SLEDAI-2K remains robust and has been effectively used in clinical trials.⁶ Patient-reported outcomes such as quality of life are also important, but may not always correlate with measurable disease activity, and are not captured by the SLEDAI-2K.

What is low level disease activity state (LLDAS) in SLE and how is it related to the SLEDAI-2K?

Prof Nikpour: To qualify for treatment with the biologic anifrolumab, which has recently been listed on the PBS,⁷ patients require a SLEDAI-2K score of ≥10. However, the measure of whether a patient has responded to treatment is based on attainment of LLDAS. LLDAS is defined by a SLEDAI-2K score of four or less, with no activity in any of the major organ systems – so you cannot have nervous system activity or nephritis or pleuropericarditis or vasculitis.⁴ Additionally, the PGA should be a score of one or less on a scale of 0–3, indicating at most, mild disease activity.⁴ Patients must also have successfully tapered prednisolone to 7.5 mg/day or less. Achieving LLDAS indicates reduced disease activity and a response to treatment. It also indicates that the medications prescribed to achieve LLDAS had a successful glucocorticoid sparing effect, which is important for minimising the long-term side effects of steroids.

How can clinicians access the SLEDAI-2K?

Prof Nikpour: The SLEDAI-2K tool is widely available online. One version of the tool can be accessed here, titled Lupus Low Disease Activity State Calculator.

Disclosure

This article has been developed independently by the limbic and is supported by a non-restrictive educational grant from AstraZeneca. Treatment decisions based on these data are the responsibility of the prescribing physician.

References

1. Mikdashi J, et al. Arthritis Res Ther. 2015;17(1):183
2. Lin A, et al. Front Lupus. 2024;2:1442013
3. MDApp. SLEDAI-2K Calculator. Available at https://www.mdapp.co/sledai-2k-calculator-systemic-lupus-erythematosus-disease-activity-index-2000-628/ [Accessed 10th October 2024]
4. Arora S, et al. Arthritis Care Res (Hoboken). 2020;72 Suppl 10:27-46
5. Suszek D, et al. Reumatologia. 2024;62(3):187-195
6. Kalunian KC, et al. Rheumatology (Oxford). 2018;57(1):125-133
7. The Pharmaceutical Benefits Scheme. ANIFROLUMAB. Available at: www.pbs.gov.au  [Accessed October 2024]