Janus kinase (JAK) inhibition with baricitinib in refractory juvenile dermatomyositis

Hanna Kim, Samantha Dill, Michelle O'Brien, Laura Vian, Xiaobai Li, Manuk Manukyan, Minal Jain, Lilian W Adeojo, Jomy George, Maria Perez, Alexei A Grom, Michelle Sutter, Brian M Feldman, Lawrence Yao, Michelle Millwood, April Brundidge, Dominique C Pichard, Edward W Cowen, Yinghui Shi, Shajia Lu, Wanxia Li Tsai, Massimo Gadina, Lisa G Rider, Robert A Colbert, Hanna Kim, Samantha Dill, Michelle O'Brien, Laura Vian, Xiaobai Li, Manuk Manukyan, Minal Jain, Lilian W Adeojo, Jomy George, Maria Perez, Alexei A Grom, Michelle Sutter, Brian M Feldman, Lawrence Yao, Michelle Millwood, April Brundidge, Dominique C Pichard, Edward W Cowen, Yinghui Shi, Shajia Lu, Wanxia Li Tsai, Massimo Gadina, Lisa G Rider, Robert A Colbert

No abstract available

Keywords: cytokines; dermatomyositis; therapeutics.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1.

Change in disease activity and pharmacodynamic markers on baricitinib treatment. *P <0.05; **P <0.01; ‡Clinically relevant minimal improvement; §Clinically relevant moderate improvement; ¶Clinically relevant major improvement; ||Clinical significant improvement in three by week 4 and in the fourth (Patient 3) by week 12.†: This patient had a suspected viral infection around the week 12 visit. ¶: Calculated 95% lower limits which were negative are reset to 0 as drug levels are never negative. The dotted line represents the highest value from healthy controls. A-D. Multiple clinical assessments are shown at baseline (week 0), weeks 4, 8, 12, and 24 with the range of assessment values on the Y-axis. Each color represents a different patient. Clinically relevant improvement in core set measures was based on relative percent change from baseline or a 5 point decrease on CDASI at 24 weeks. P-values were calculated based on linear mixed model analysis of the repeated measures data. At 24 weeks, p-values are FDR adjusted since the 24 week timepoint compared to the baseline is the main analysis interest. At other timepoints, p-values are not adjusted for multiplicity. E: Left panel: Twenty eight-gene IRG (interferon-regulated gene) score shown at baseline (Wk 0) and weeks 4, 8, 12, and 24. Right panel: Serum IP-10 levels at baseline (Wk 0), Wk 4, and Wk 12. Log2 values were analyzed via 2-tailed paired t-test without correction versus baseline. F: Example images of each of the four patients showing the same part of the body at baseline (left) and after 24 weeks (right) for heliotrope and malar rash, dilated and tortuous nailfold capillaries on right second finger, V-sign rash with significant erythema and scale, and violaceous erythema on the lateral thigh and proximal leg. G: Scatter plots with model curves for pSTAT1 by cell type are shown with MFI ratio (IFN-α stimulated divided by un-stimulated) minus 1 versus the peripheral blood drug level. The solid line and light blue band show best-fit curves with 95% predictive intervals, respectively. The table shows IC50 values by cell type calculated based on modeling (estimated) with standard error, and 95% confidence intervals. Wk: week; PGA: Physician Global Activity; Pt: Patient/ Parent; MMT-8: Manual Muscle Testing 8; CDASI: Cutaneous Dermatomyositis Area and Severity Index; IRG: interferon-regulated gene; HC, healthy controls; UL, Upper limit; MFI: median fluorescence intensity; pSTAT: STAT phosphorylation; Stim: Stimulated; Unstim: Unstimulated.