Less Damage Accrual in Lupus Linked to Remission, Low Disease Activity

In patients with systemic lupus erythematosus (SLE), remission off-treatment and on-treatment, low disease activity Toronto cohort (LDA-TC), and modified lupus low disease activity state (mLLDAS) are all associated with a lower likelihood of damage accrual. Results of the study were published in Annals of the Rheumatic Diseases.

With the researchers sought to establish the independent effect of different definitions of remission and LDA on damage accrual in patients with SLE. They proposed remission off-treatment and on-treatment, LDA-TC, and LLDAS as targets in the treatment of SLE.

Data between 1999 and 2011 were obtained from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, which is a multinational, multiethnic, longitudinal inception cohort that comprises patients recently diagnosed with SLE from 33 centers in Asia, Europe, and North America. 

A total of 1652 participants were enrolled in the study (88.6% women, n=1464). The median participant age at diagnosis was 34.2±13.4 years, and the mean baseline duration of disease was 5.6±4.2 months. The mean follow-up of all participants was 7.7±4.8 years, with a mean of 7.5±4.8 visits per patient; a total of 12,236 follow-up visits were included.

Individuals who had at least 2 annual evaluations from the SLICC cohort were investigated. Overall, 5 mutually exclusive disease activity states were defined:

1. Remission off-treatment was defined as clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K score of 0 without prednisone or immunosuppressive agents;
2. Remission on-treatment was defined as cSLEDAI-2K score of 0 with prednisone 5 mg/day or less and/or maintenance immunosuppressive agents;
3. LDA-TC was defined as cSLEDAI-2K score of 2 or lower without prednisone or immunosuppressive agents;
4. mLLDAS was defined as cSLEDAI-2K score of 4 with no activity in major organ systems, no new disease activity, prednisone 7.5 mg/day or less and/or maintenance immunosuppressive agents; and
5. Active disease activity was defined as all other visits.

Antimalarial agents were permitted in all individuals. At each annual visit, disease activity (ie, the percentage of time that participants were in a specific state since cohort entry) was measured with use of the cSLEDAI-2K score, damage accrual was established with use of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and the average doses of all medications were recorded.

Overall, 762 participants experienced an increase in SDI score of at least1 during follow-up. The SDI increased in 1267 visits — by 1 point in 992 patients, by 2 points in 194 patients, by 3 points in 61 patients, by 4 points in 16 patients, and by 5 points in 4 patients. A total of 2555 of the visits were classified as remission off-treatment, 2419 as remission on-treatment, 556 as LDA-TC, 680 as mLLDAS, and 6026  as active.

Per multivariable analysis, being in remission off-treatment, remission on-treatment, LDA-TC, and mLLDAS (per 25% increase in time spent in a specified state vs the active state) all were predictive of a lower likelihood of damage accrual. Results of the analysis are shown:

• Remission off-treatment (incidence rate ratio [IRR], 0.75, 95% CI, 0.70- 0.81);
• Remission on-treatment (IRR, 0.68, 95% CI, 0.62-0.75);
• LDA-TC (IRR, 0.79, 95% CI, 0.68-0.92); and
• mLLDAS (IRR, 0.76, 95% CI, 0.65-0.89).

Some limitations of the study should be noted. Because the Physician Global Assessment score was not included in the SLICC cohort, the researchers could not use the original definition of remission and LLDAS. It remains unknown whether achievement of remission or LLDAS is related to the underlying disease or to the use of more aggressive treatment.

The study authors conclude, “This study reinforces the relevance of remission off-treatment and on-treatment, LDA-TC and LLDAS as potential targets in the management of patients with SLE.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Ugarte-Gil MF, Hanly J, Urowitz M, et al. Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Ann Rheum Dis. Published online August 9, 2022. doi:10.1136/ard-2022-222487