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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