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(A)
IRG (8 genes) versus non response (
∆
DAS28)
(B)
IRG (3 genes) versus non response (
∆
DAS28)
1.0
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.0
0.0
0.0
0.2
0.4
1-Specificity
0.6
0.8
1.0
0.0
0.2
0.4
1-Specificity
0.6
0.8
1.0
(C)
IRG (8 genes) versus non response (EULAR)
(D)
IRG (3 genes) versus non response (EULAR)
1.0
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.0
0.0
0.0
0.2
0.4
1-Specificity
0.6
0.8
1.0
0.0
0.2
0.4
1-Specificity
0.6
0.8
1.0
FIGURE 3.5
Receiver operating characteristics (ROC) curves for the IFN response genes as predictor for non-
response upon rituximab treatment in the RA validation cohort (N = 26). (A) AUC (0.82) for the eight IFN response
gene set based on ΔDAS28 response criteria, (B) AUC (0.87) for the three IFN response gene set based on ΔDAS28
response criteria, (C) AUC (0.78) for the eight IFN response gene set based on EULAR response criteria (responders
and intermediate responders vs. non-responders) and (D) AUC (0.83) for the three IFN response gene set based on
EULAR response criteria (responders and intermediate responders versus non-responders). On the y axis sensitiv-
ity and on the x axis 1-specificity is indicated. AUC, area under the curve; DAS28, 28 joints disease activity score;
EULAR, European League against Rheumatism; IRG, interferon response gene; RTX, rituximab.
(Adapted with per-
mission from Raterman et al.
[50]
.)
3.4.4 A Type I Interferon Signature as a Pharmacodynamic Marker of Anti-
CD20 mAb Therapy in Patients with RA
Vosslamber and colleagues studied the pharmacological effects of rituximab in RA and
observed a difference in the expression of IFN type I genes during rituximab treatment that
distinguishes responders from non-responders (
Fig. 3.6
)
[53,54]
. Responders exhibited an
increase in IFN response activity after three months' treatment with rituximab, whereas the
IFN response activity remained stable during treatment in the non-responders. This means
that good responders have a low or absent IFN response activity at baseline and develop
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