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Figure Legends
Figure 1. Exposure-response relationship of AUCeff based on filgotinib and GS-829845 against ACR and DAS28 (CRP) responses at Week 12 in subjects with RA in pooled Phase 2 and Phase 3 studies. The analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies DARWIN 1, DARWIN 2, FINCH 1, FINCH 2, and FINCH 3, and had at least 1 nonmissing PK parameter of interest. Each symbol represents the proportion of subjects achieving the ACR response with the vertical line showing the 95% confidence interval within each group based on the Clopper-Pearson method. Circles show ACR20, triangles show ACR50, and squares show ACR70 in the left panel. Hollow circles show DAS28 ≤ 3.2 and hollow triangles show DAS28 < 2.6 in the right panel. Shaded areas with blue stripes show median (dashed vertical line) and fifth and 95th percentiles (dotted vertical lines) of AUCeff for filgotinib 200 mg once daily in Phase 2 and Phase 3 subjects with RA; shaded areas with pink cross pattern show median (dashed vertical line) and fifth and 95th percentiles (dotted vertical lines) of AUCeff for filgotinib 100 mg once daily in Phase 2 and Phase 3 subjects with RA. AUCeff is based on the population PK‑predicted exposure in Phase 2 and Phase 3 subjects with rheumatoid arthritis receiving filgotinib.
Figure 2.Exposure-response relationship of AUCeff based on filgotinib and GS-829845 against ACR and das28 (CRP) responses at Week 24 in subjects with RA in pooled Phase 2 and Phase 3 studies. The analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies DARWIN 1, DARWIN 2, FINCH 1, FINCH 2, and FINCH 3, and had at least 1 nonmissing PK parameter of interest. Each symbol represents the proportion of subjects achieving the ACR response with the vertical line showing the 95% confidence interval within each group based on the Clopper-Pearson method. Circles show ACR20, triangles show ACR50, and squares show ACR70 in the left panel. Hollow circles show DAS28 ≤ 3.2 and hollow triangles show DAS28 < 2.6 in the right panel. Shaded areas with blue stripes show median (dashed vertical line) and fifth and 95th percentiles (dotted vertical lines) of AUCeff for filgotinib 200 mg once daily in Phase 2 and Phase 3 subjects with RA; shaded areas with pink cross pattern show median (dashed vertical line) and fifth and 95th percentiles (dotted vertical lines) of AUCeff for filgotinib 100 mg once daily in Phase 2 and Phase 3 subjects with RA. AUCeff is based on the population PK‑predicted exposure in Phase 2 and Phase 3 subjects with rheumatoid arthritis receiving filgotinib.
Figure 3.Boxplot of AUCeff in subjects who achieved and did not achieve ACR20/50/70 and DAS28 (CRP) responses in pooled Phase 2 and Phase 3 studies. PK/PD analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies FINCH 1, 2, 3, and had at least 1 nonmissing PK parameter of interest. For each box, the bottom and top edges are located at the sample 25th (Q1) and 75th (Q3) percentiles, respectively; the center horizontal line is drawn at the 50th percentile (median); and outliners (beyond 1.5 × the interquartile range) are displayed as small squares. ACR and DAS28 responses at Week 12 are shown in the upper panel and ACR and DAS28 responses at Week 24 are shown in the lower panel.
Figure 4. Filgotinib AUC0-24 by the 5 most frequent TEAEs in subjects with RA up to Week 52 data. The analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies FINCH 1, FINCH 2 FINCH 3, DARWIN 1, DARWIN 2, DARWIN 3, and had at least 1 nonmissing PK parameter of interest. For each box, the bottom and top edges are located at the sample 25th (Q1) and 75th (Q3) percentiles, respectively; the center horizontal line is drawn at the 50th percentile (median); and outliners (beyond 1.5 × the interquartile range) are displayed as small squares. AUC0-24 is the population PK-predicted exposure in Phase 2and Phase 3 subjects with rheumatoid arthritis receiving filgotinib.
Figure 5. GS-829845 AUC0-24 by the 5 most frequent TEAEs in subjects with RA up to Week 52 data. The analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies FINCH 1, FINCH 2 FINCH 3, DARWIN 1, DARWIN 2, DARWIN 3, and had at least 1 nonmissing PK parameter of interest. For each box, the bottom and top edges are located at the sample 25th (Q1) and 75th (Q3) percentiles, respectively; the center horizontal line is drawn at the 50th percentile (median); and outliners (beyond 1.5 × the interquartile range) are displayed as small squares. AUC0-24 is the population PK-predicted exposure in Phase 2and Phase 3 subjects with rheumatoid arthritis receiving filgotinib.
Figure 6. Filgotinib AUC0-24 by the 5 most frequent Grade 3/4 laboratory abnormalities in subjects with RA. The analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies FINCH 1, FINCH 2 FINCH 3, DARWIN 1, DARWIN 2, DARWIN 3 and had at least 1 nonmissing PK parameter of interest. For each box, the bottom and top edges are located at the sample 25th (Q1) and 75th (Q3) percentiles, respectively; the center horizontal line is drawn at the 50th percentile (median); and outliners (beyond 1.5 × the interquartile range) are displayed as small squares. AUC0-24 is the population PK-predicted exposure in Phase 2 and Phase 3 subjects with rheumatoid arthritis receiving filgotinib.
Figure 7.GS-829845 AUC0-24 by the 5 most frequent Grade 3/4 laboratory abnormalities in subjects with RA. The analysis set includes subjects with RA who were enrolled/randomized, received at least 1 dose of filgotinib in studies FINCH 1, FINCH 2 FINCH 3, DARWIN 1, DARWIN 2, DARWIN 3, and had at least 1 nonmissing PK parameter of interest. For each box, the bottom and top edges are located at the sample 25th (Q1) and 75th (Q3) percentiles, respectively; the center horizontal line is drawn at the 50th percentile (median); and outliners (beyond 1.5 × the interquartile range) are displayed as small squares. AUC0-24 is the population PK-predicted exposure in Phase 2 and Phase 3 subjects with rheumatoid arthritis receiving filgotinib.