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

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Date
2022Author(s)
Ugarte-Gil, M.F.
Hanly, J.
Urowitz, M.
Gordon, C.
Bae, S.-C.
Romero-Diaz, J.
Sanchez-Guerrero, J.
Bernatsky, S.
Clarke, A.E.
Wallace, D.J.
Isenberg, D.A.
Rahman, A.
Merrill, J.T.
Fortin, P.R.
Gladman, D.D.
Bruce, I.N.
Petri, M.
Ginzler, E.M.
Dooley, M.A.
Ramsey-Goldman, R.
Manzi, S.
Jönsen, A.
Van Vollenhoven, R.F.
Aranow, C.
MacKay, M.
Ruiz-Irastorza, G.
Lim, S.
Inanc, M.
Kalunian, K.
Jacobsen, Sø.
Peschken, C.
Kamen, D.L.
Askanase, A.
Pons-Estel, B.A.
Alarcón, G.S.
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Objective To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. Methods Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. Results There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). Conclusions Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.
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