TY - JOUR
T1 - Baricitinib decreases anti-dsDNA in patients with systemic lupus erythematosus
T2 - results from a phase II double-blind, randomized, placebo-controlled trial
AU - Dörner, Thomas
AU - van Vollenhoven, Ronald F.
AU - Doria, Andrea
AU - Jia, Bochao
AU - Ross Terres, Jorge A.
AU - Silk, Maria E.
AU - de Bono, Stephanie
AU - Fischer, Peter
AU - Wallace, Daniel J.
N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This study was sponsored by Eli Lilly and Company, under license from Incyte Corporation. Funding Information: We would like to thank the patients and investigators who participated in the study. Eli Lilly and Company or its representatives provided data, laboratory, and site monitoring services. Writing assistance was provided by Conor McVeigh, PhD, of Eli Lilly and Company. This work has in part been published at the following scientific conference: European League Against Rheumatism (EULAR) 2021 Annual Meeting (Dörner et al. , Ann Rheum Dis , volume 80, supplement 1, year 2021, page 588) and ACR convergence 2021 (Dörner T, Van Vollenhaven R, Doria A, Jia B, Fantini D, Terres J, Silk M, de Bono S, Fischer P, Wallace D. Arthritis Rheumatol. 2021; 73 (suppl 10)). EULAR Abstract Archive (sparx-ip.net ) Dörner T, Van Vollenhaven R, Doria A, Jia B, Fantini D, Terres J, Silk M, de Bono S, Fischer P, Wallace D. Baricitinib Decreases Anti-dsDNA and IgG Antibodies in Adults with Systemic Lupus Erythematosus from a Phase 2 Double-Blind, Randomized, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/baricitinib-decreases-anti-dsdna-and-igg-antibodies-in-adults-with-systemic-lupus-erythematosus-from-a-phase-2-double-blind-randomized-placebo-controlled-trial/. Accessed March 12, 2022. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - Baricitinib
KW - Cytokines
KW - JAK inhibitor
KW - Systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=85130123106&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13075-022-02794-x
DO - https://doi.org/10.1186/s13075-022-02794-x
M3 - Article
C2 - 35578304
SN - 1478-6354
VL - 24
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 112
ER -