Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study

Adv Rheumatol. 2024 May 8;64(1):38. doi: 10.1186/s42358-024-00366-y.

Abstract

Background: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.

Methods: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.

Results: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.

Conclusions: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Keywords: Anti-malarials; Autoimmune diseases; Cohort study; Immunosuppressants; SLEDAI; Systemic lupus erythematosus.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimalarials* / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Azathioprine* / therapeutic use
  • Calcineurin Inhibitors / therapeutic use
  • Cohort Studies
  • Female
  • Glucocorticoids* / therapeutic use
  • Humans
  • Hydroxychloroquine* / therapeutic use
  • Immunosuppressive Agents* / therapeutic use
  • Leflunomide / therapeutic use
  • Logistic Models
  • Lupus Erythematosus, Systemic* / drug therapy
  • Male
  • Methotrexate* / therapeutic use
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Prednisolone* / therapeutic use
  • Propensity Score
  • Severity of Illness Index
  • Standard of Care*
  • Symptom Flare Up
  • Tacrolimus / therapeutic use
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Hydroxychloroquine
  • Glucocorticoids
  • Azathioprine
  • Prednisolone
  • Methotrexate
  • Antimalarials
  • Mycophenolic Acid
  • Leflunomide
  • Calcineurin Inhibitors
  • Tacrolimus
  • Antirheumatic Agents