Extended Data Fig. 5: Pro-inflammatory cytokines, bone marrow morphology, and erythrocyte progenitors.

For exploratory endpoints, we report descriptive statistical analyses only. (A) shows the mean change in inflammatory cytokines from baseline at week 24. Data are presented as mean change from baseline ± 95% CI. *NF-κB – set included B2M, CRP, CD40-L, hepcidin, IL-6, IL-12p40, MIP-1 beta, MPIF-1, RANTES, TNFR2, TNF, and VCAM-1. (B) shows the secondary endpoint change in reticulin fibrosis grade (graded according to the WHO classification) by central read at week 24. Percentages are based on the number of patients with bone marrow assessments in the intent-to-treat population at each timepoint; non-evaluable patients are those who are ongoing study treatment and have not yet reached that timepoint or opted out of bone marrow assessment. (C) shows the change in megakaryocytes (CD61 + ) density from baseline in the bone marrow at week 24, overlayed with individual observations. Density assessed by digital pathology. The horizontal line within the boxplot indicates the mean. The lower and upper ends of the box represent the 25th and 75th percentiles, respectively. The boxplot whiskers indicate the Tukey interval. (D) shows examples of immunohistochemistry stainings for megakaryocytes (CD61 + ) representative for observed mean changes of megakaryocyte densities in samples from a single patient randomized to pelabresib–ruxolitinib and a single patient randomized to placebo-ruxolitinib, respectively. There were 117 patients in the pelabresib–ruxolitinib arm and 129 patients in the placebo-ruxolitinib arm with megakaryocyte density data. Immunohistochemistry staining was performed, and digital images analyzed by an automated quantitative cell-specific detection analysis. (E) shows the percentage change in erythrocyte progenitors (CD71+ cells) in the bone marrow according to treatment arm and red blood cell transfusions, overlayed with individual observations. Red blood cell transfusions refer to the number of patients who received any red blood cell transfusion between week 20 and week 24 on treatment. The horizontal line within the boxplots indicates the mean. The lower and upper ends of the box represent the 25th and 75th percentiles, respectively. The boxplot whiskers indicate the Tukey interval. The y-axis encompasses the 99 percentiles of all values. B2M, beta-2 microglobulin; CI, confidence interval; CRP, C-reactive protein; CD40-L, CD40 ligand; IL, interleukin; MIP, macrophage inflammatory protein; MPIF, myeloid progenitor inhibitory factor; NF-κB, Nuclear factor kappa B; RANTES, regulated upon activation, normal T-cell expressed and secreted; TNF, tumor necrosis factor; TNFR, TNF receptor; VCAM, vascular cell adhesion molecule; WHO, World Health Organization.