Background. Remission and low disease activity (LDA) have recently emerged as key concepts in the management of systemic lupus erythematosus (SLE). The effect of different durations of remission and LDA on SLE outcomes has never been evaluated. Unsolved issues concern the treatment of patients in remission, being the choice and timing of drug tapering until withdrawal still a matter of debate. Aims. To assess the prevalence, duration and predictive effect on damage of remission and LDA in a monocentric cohort of patients with SLE. In addition, to evaluate the rate of immunosuppressant (IS) withdrawal and predictors of subsequent flare and flare-free survival. Patients and methods. Two cohorts were identified: 1) patients diagnosed with SLE between 1990-2009 and seen from 2009 to 2015 for remission and LDA evaluation; 2) patients diagnosed with SLE between 1990-2018, treated with IS over the disease course and seen at least once in 2017 or 2018 for IS withdrawal evaluation. Disease activity was assessed by SLE Disease Activity Index (SLEDAI)-2K and physician global assessment (PGA), flare by SELENA-SLEDAI flare index, and damage by SLICC/ACR Damage Index (SDI). Three levels of remission were defined: complete remission, i.e. no disease activity in corticosteroid- and IS-free patients; clinical remission off-corticosteroids, i.e. serologic active clinical quiescent disease in corticosteroid-free patients; clinical remission on corticosteroids, i.e. clinical quiescent disease with or without serological abnormalities in patients taking prednisone 1-5 mg/day. LDA was defined according to the “lupus low disease activity state” (LLDAS) definition: SLEDAI–2K≤4, no new disease activity, PGA (0–3)≤1, prednisone ≤7.5 mg/day, and well-tolerated IS dosages. Five range of durations of remission and LLDAS were evaluated, i.e. lasting 1, 2, 3, 4, 5 or more consecutive years. The effect of remission and LLDAS on SDI was evaluated by multivariate logistic regression analysis. IS discontinuation was defined as complete withdrawal of any IS. Reasons for discontinuation were classified as remission or poor compliance/intolerance. Predictors of a subsequent flare and flare-free survival were analyzed by multivariate logistic regression and Cox regression analyses, respectively. Results. 293 patients were included in the cohort for remission and LLDAS evaluation: 253 (86.3%) female, mean±SD disease duration 11.1±7.8 years. Among patients achieving 1-year (27, 9.2%), 2-year (47, 16%), 3-year (45, 13.4%), 4-year (26, 8.8%) remission, damage was similar irrespective of the level of remission achieved, whereas among patients achieving ≥5-year remission (113, 38.6%) damage was higher in those in clinical remission on-corticosteroids (p<0.001). At multivariate analysis, ≥2 consecutive year remission was protective against damage [OR (95% CI) 0.228 (0.061–0.850)]. LLDAS lasting 1-, 2-, 3-, 4-, or ≥5-consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%), and 109 (37.2%) patients, respectively. Patients who spent at least 2 consecutive years in were significantly less likely to have an increase in SDI (Odds ratio 0.16, 95% CI 0.06 to 0.42, p<0.001). Among 456 patients seen at least once in 2017-2018, 319 were ever treated with IS (70%). 139 patients (43.5%) discontinued IS, 105 of them (75.5%) due to remission. Among patients who discontinued IS, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (p<0.001). Maintenance therapy with antimalarials (OR 0.24, 95% CI 0.07-0.84, p=0.026) was the strongest protective factor against disease flares. Conclusions. Remission and LLDAS were frequently observed and were protective against damage progression over the follow-up. One third of our patients discontinued ISs during the follow-up. Antimalarial therapy was the strongest protective factor against flare after IS discontinuation
Remissione, low disease activity e sospensione della terapia immunosoppressiva nel lupus eritematoso sistemico. Risultati dalla coorte prospettica di Padova.
ZEN, MARGHERITA
2019
Abstract
Background. Remission and low disease activity (LDA) have recently emerged as key concepts in the management of systemic lupus erythematosus (SLE). The effect of different durations of remission and LDA on SLE outcomes has never been evaluated. Unsolved issues concern the treatment of patients in remission, being the choice and timing of drug tapering until withdrawal still a matter of debate. Aims. To assess the prevalence, duration and predictive effect on damage of remission and LDA in a monocentric cohort of patients with SLE. In addition, to evaluate the rate of immunosuppressant (IS) withdrawal and predictors of subsequent flare and flare-free survival. Patients and methods. Two cohorts were identified: 1) patients diagnosed with SLE between 1990-2009 and seen from 2009 to 2015 for remission and LDA evaluation; 2) patients diagnosed with SLE between 1990-2018, treated with IS over the disease course and seen at least once in 2017 or 2018 for IS withdrawal evaluation. Disease activity was assessed by SLE Disease Activity Index (SLEDAI)-2K and physician global assessment (PGA), flare by SELENA-SLEDAI flare index, and damage by SLICC/ACR Damage Index (SDI). Three levels of remission were defined: complete remission, i.e. no disease activity in corticosteroid- and IS-free patients; clinical remission off-corticosteroids, i.e. serologic active clinical quiescent disease in corticosteroid-free patients; clinical remission on corticosteroids, i.e. clinical quiescent disease with or without serological abnormalities in patients taking prednisone 1-5 mg/day. LDA was defined according to the “lupus low disease activity state” (LLDAS) definition: SLEDAI–2K≤4, no new disease activity, PGA (0–3)≤1, prednisone ≤7.5 mg/day, and well-tolerated IS dosages. Five range of durations of remission and LLDAS were evaluated, i.e. lasting 1, 2, 3, 4, 5 or more consecutive years. The effect of remission and LLDAS on SDI was evaluated by multivariate logistic regression analysis. IS discontinuation was defined as complete withdrawal of any IS. Reasons for discontinuation were classified as remission or poor compliance/intolerance. Predictors of a subsequent flare and flare-free survival were analyzed by multivariate logistic regression and Cox regression analyses, respectively. Results. 293 patients were included in the cohort for remission and LLDAS evaluation: 253 (86.3%) female, mean±SD disease duration 11.1±7.8 years. Among patients achieving 1-year (27, 9.2%), 2-year (47, 16%), 3-year (45, 13.4%), 4-year (26, 8.8%) remission, damage was similar irrespective of the level of remission achieved, whereas among patients achieving ≥5-year remission (113, 38.6%) damage was higher in those in clinical remission on-corticosteroids (p<0.001). At multivariate analysis, ≥2 consecutive year remission was protective against damage [OR (95% CI) 0.228 (0.061–0.850)]. LLDAS lasting 1-, 2-, 3-, 4-, or ≥5-consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%), and 109 (37.2%) patients, respectively. Patients who spent at least 2 consecutive years in were significantly less likely to have an increase in SDI (Odds ratio 0.16, 95% CI 0.06 to 0.42, p<0.001). Among 456 patients seen at least once in 2017-2018, 319 were ever treated with IS (70%). 139 patients (43.5%) discontinued IS, 105 of them (75.5%) due to remission. Among patients who discontinued IS, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (p<0.001). Maintenance therapy with antimalarials (OR 0.24, 95% CI 0.07-0.84, p=0.026) was the strongest protective factor against disease flares. Conclusions. Remission and LLDAS were frequently observed and were protective against damage progression over the follow-up. One third of our patients discontinued ISs during the follow-up. Antimalarial therapy was the strongest protective factor against flare after IS discontinuationFile | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/176393
URN:NBN:IT:UNIPD-176393