Table 2

Proposed matrix for application of the SLE-specific disease modification criteria in clinical trials and clinical practice

Disease Modification definition categoryInterim timepoints for assessment of disease modification POTENTIAL in clinical trials (vs standard therapy alone) and clinical practice (no comparison)Disease modification CONFIRMED
Outcomes year 1Outcomes years 2–5Outcomes
year >5
Extra renalMinimising disease activity with minimal treatment-associated toxicity
AND
Slowing/Preventing organ damage progression

  • Significant reduction in disease activity measured using a validated tool (ie, SELENA-SLEDAI, BILAG, SRI-4)

  • Significant reduction in severe flare measured using a validated tool (ie, SFI or BILAG)

  • Reduction in use of steroids* and/or immunosuppressants

  • Sustained improvement in multiple organ domains/no worsening in multiple organ domains

  • Prevention of severe flares

  • Continued reduction in use of steroids* and/or immunosuppressants

No change in SDI or delayed progression
RenalMinimising disease activity with minimal treatment-associated toxicity
AND
Slowing/Preventing organ damage progression

  • Significant improvement in uPCR or kidney activity index via biopsy

  • Significant reduction in renal flare

  • Minimise eGFR decline (ie, ≤30%)

  • Reduction in use of steroids* and/or immunosuppressants

  • Sustained improvement in uPCR or no worsening in kidney chronicity index via biopsy

  • Prevention of renal flares

  • Minimise further decline in eGFR (ie, <30%)

  • Continued reduction in steroids* and/or immunosuppressants

No change in SDI or delayed progression

  • *≤7.5 mg/day per 2019 EULAR SLE treatment guidelines and LLDAS;36 64 ≤5 mg/day per DORIS remission definition.63

  • BILAG, British Isles Lupus Assessment Group; DORIS, Definitions Of Remission In SLE; eGFR, estimated glomerular filtration rate; EULAR, European Alliance of Associations for Rheumatology; GC, glucocorticoid; LLDAS, Lupus Low Disease Activity State; SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SELENA, Safety of Estrogens in Lupus Erythematosus National Assessment; SFI, SELENA-SLEDAI Flare Index; SLEDAI, SLE Disease Activity Index; SRI-4, SLE Responder Index-4; uPCR, urinary protein-creatinine ratio.