SLICC PIs: Dr. Ian Bruce, Dr. John G. Hanly, Dr. Murray Urowitz, Dr. Susan Manzi, Dr. Ann Clarke, Dr.Vern Farewell

Studies of Damage in the SLICC Inception Cohort

New Investigators: Dr. Aidan O’Keefe (Post-doctoral statistician) University of Cambridge and Dr. Jayne Little (Clinical MPhil Fellow) University of Manchester Funding Source: Human Genome Sciences / Glaxo Smith Kline, UCB and National Institute for Health Research (UK)

Long-term damage is an important outcome in SLE patients. We aimed at studying damage accrual over the early years of follow-up in recently diagnosed patients to assess the rate of accrual and factors that determine the development and progression of damage in patients from the SLICC Inception Cohort. As glucocorticoids (GC) are an important driver of future damage we also have started to study GC use across our centres with the aim of exploring factors associated with GC use, especially if there are any temporal trends in GC use and to what extent physician-related factors may influence use.

We included 1722 patients in this analysis. Over the entire study period, 81.3% patients received oral GCs and 26.3% received parenteral GCs at some point. GC use was strongly associated with treatment center, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis.

Regarding damage, patients with damage at enrolment were significantly more likely to have further worsening of the SDI at each follow-up visit. Multivariate multistate models for transitions from no damage to damage and increase(s) in pre-existing damage were comparable; age, USA African race/ethnicity, SLEDAI score, steroid use and hypertension were all associated with increasing damage. For transition from SDI 0 to >=1, male gender (Relative Transition Rates [95%CI]: 1.48 [1.06, 2.07]) and USA Caucasian race/ethnicity (1.63 [1.08, 2.46]) were also associated with damage; while patients of Asian race/ethnicity had lower rates of new damage (0.60 [0.39, 0.93]). Increase in pre-existing damage was also reduced in patients taking antimalarials (0.63 [0.44, 0.89]). Each point increase in SDI score was associated with an increased risk of death (41 deaths) (HR [95%CI]: 1.46 [1.18, 1.81]).

GCs remain a cornerstone in SLE management and there have been no significant changes in their use over the last 10-15 years. Whilst patient and disease factors contribute to the variation in GC use, between center differences suggest that physician-related factors also contribute.

We have also shown that damage is an important stratification factor as it predicts future damage accrual and mortality. We have identified a number of potentially modifiable risk factors for damage accrual including GC use. These observations are important as they emphasize the need for evidence-based treatment algorithms to inform a more standardized approach GC use in SLE. They also show that an integrated intervention strategy to address key factors that drive damage, may improve long-term outcomes in SLE patients.


References:

  • 1.Bruce IN, O’Keeffe AG, Farewell V, Hanly JG, Manzi S, Su L, Gladman DD, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Gordon C, Wallace DJ, Clarke AE, Bernatsky S, Ginzler EM, Isenberg DA, Rahman A, Merrill JT, Alarcón GS, Fessler BJ, Fortin PR, Petri M, Steinsson K, Dooley MA, Khamashta MA, Ramsey-Goldman R, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven RF, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Urowitz MB. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Ann Rheum Dis. 2015; 74:1706-13.
  • 2.Little J, Parker B, Lunt M, Hanly JG, Urowitz MB, Clarke AE, Romero-Diaz J, Gordon C, Bae SC, Bernatsky S, Wallace DJ, Merrill JT, Buyon J, Isenberg DA, Rahman A, Ginzler EM, Petri M, Dooley MA, Fortin P, Gladman DD, Steinsson K, Ramsey-Goldman R, Khamashta MA, Aranow C, Mackay M, Alarcón GS, Manzi S, Nived O, Jönsen A, Zoma AA, van Vollenhoven RF, Ramos-Casals M, Ruiz-Irastorza G, Lim SS, Kalunian KC, Inanc M, Kamen DL, Peschken CA, Jacobsen S, Askanase A, Sanchez-Guerrero J, Bruce IN. Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort. Rheumatology In press

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