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Objective.To examine the role of disease activity on organ damage over 5 years in patients with active systemic lupus erythematosus (SLE) despite standard of care.Methods.This analysis of the University of Toronto Lupus Clinic cohort assessed organ damage [measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] in patients with active SLE [SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 6], using Cox proportional time-independent hazard models. Subgroup analyses were conducted in patients with SLEDAI-2K 6 or 7, 8 or 9, and ≥ 10 at baseline, and in the overall study population by steroid dose at study entry (< 7.5 vs ≥ 7.5 mg/day).Results.Among the overall study population (n = 649), SDI progression was observed in 209 (32.2%) patients over the 5-year follow-up period. Mean SDI change in patients with a score > 0 was generally consistent across all SLEDAI-2K subgroups. Multivariable analyses identified age at study start (HR 1.03, P< 0.0001), steroid dose (HR 2.03, P< 0.0001), immunosuppressants (HR 1.44, P= 0.021), and SLEDAI-2K (subgroup analyses HR 1.64–2.03, P= 0.0017 to < 0.0001) as the greatest risk factors for SDI progression, while a study start date after the year 2000 had a protective effect on SDI progression compared with a start date prior to the year 2000 (HR 0.65, P= 0.0004).Conclusion.Patients within the higher SLEDAI-2K subgroups at study entry or receiving high doses of steroids were more likely to have organ damage progression.

Background: Patients with systemic lupus erythematosus (SLE) have substantial unmet medical need. Baricitinib is a Janus kinase (JAK)1 and 2 inhibitor that was shown to have therapeutic benefit in patients with SLE in a phase II clinical trial. The purpose of this study was to evaluate the median change from baseline in conventional serologic biomarkers in subgroups and the overall population of baricitinib-treated patients with SLE, and the SLE Responder Index-4 (SRI-4) response by normalization of anti-dsDNA. Methods: Data were assessed from the phase II trial I4V-MC-JAHH (NCT02708095). The median change from baseline in anti-dsDNA, IgG, and other conventional serologic markers was evaluated over time in patients who had elevated levels of markers at baseline, and in all patients for IgG. Median change from baseline for baricitinib treatments were compared with placebo. Among patients who were anti-dsDNA positive at baseline, SRI-4 responder rate was compared for those who stayed positive or achieved normal levels by week 24. Results: Significant decreases of anti-dsDNA antibodies were observed in response to baricitinib 2 mg and 4 mg compared to placebo beginning at weeks 2 (baricitinib 2 mg = − 14.3 IU/mL, placebo = 0.1 IU/mL) and 4 (baricitinib 4 mg = − 17.9 IU/mL, placebo = 0.02 IU/mL), respectively, continuing through week 24 (baricitinib 2 mg = − 29.6 IU/mL, baricitinib 4 mg = − 15.1 IU/mL, placebo=3.0 IU/mL). Significant reductions from baseline of IgG levels were found for baricitinib 4 mg-treated patients compared to placebo at weeks 12 (baricitinib 4 mg = − 0.65 g/L, placebo = 0.09 g/L) and 24 (baricitinib 4 mg = − 0.60 g/L, placebo = − 0.04 g/L). For patients who were anti-dsDNA positive at baseline, no relationship between achieving SRI-4 responder and normalization of anti-dsDNA was observed by week 24. Conclusions: Baricitinib treatment resulted in a rapid and sustained significant decrease in anti-dsDNA antibodies compared to placebo among those with positive anti-dsDNA antibodies at baseline, as well as a significant decrease in IgG levels in the 4 mg group at weeks 12 and 24. These data suggest that baricitinib may influence B cell activity in SLE. Further studies are needed to evaluate if reductions in anti-dsDNA levels with baricitinib treatment reflect the impact of baricitinib on B cell activity. Trial registration: NCT02708095.