ACR Congress Review 2019

In summary, individually, high baseline levels of key inflammatory serum cytokines, as well as the
presence of a low sICAM1/CXCL13 ratio, were each indicative of positive outcomes in bDMARD-IR RA
patients treated with filgotinib [46*].
Finally, Taylor and colleagues presented results of an RNA sequencing study that examined the value of
baseline gene expression for predicting therapeutic response to filgotinib in patients from FINCH2.
Baseline Rodriguez-Carrio IFN signature score showed no significant association with Week 12 clinical
response (P>0.05 for all comparisons). In contrast, the baseline FINCH2-derived composite IFN-based
signature was significantly associated with an increase of DAS28-CRP after 12 weeks (P=0.0026),
independent of treatment. The composite IFN-based signature score was significantly associated with a
filgotinib-specific improvement in DAS28-CRP (100 mg, P=0.0045; 200 mg, P=0.0005) and ACR-N
responses (100 mg, P=0.036) after 12 weeks. The authors concluded that IFN signalling alone is not
sufficient to predict response to MTX in a bDMARD experienced population. However, an expanded
FINCH2-derived composite IFN signature demonstrated a treatment-specific significant association at
Week 12 [2012].
Effect of filgotinib on cholesteryl ester transfer protein levels in RA patients
Di Paolo and colleagues presented findings on the in vitro profiles of JAKis as evaluated using human
cell-based assays and pharmacokinetic-pharmacodynamic models. Filgotinib 100 and 200 mg resulted
in lower calculated cellular inhibition than the other JAKis at clinical exposures. Notably, filgotinib 100 mg
and 200 mg were calculated to reduce cholesteryl ester transfer protein (CETP) expression by 17.3%
and 27.4%, respectively. Baricitinib, tofacitinib, and upadacitinib did not alter CETP levels. These results
provide a potential mechanistic link to the observed reduction of CETP concentration and activity
following filgotinib treatment, and the associated observed reduction in LDL:HDL in RA patients [59*].
Peficitinib
Interim results of peficitinib a long-term open-label extension study
Takeuchi and colleagues presented the interim results of a long-term open-label extension study of
peficitinib (NCT01638013) conducted in Japan, Korea and Taiwan. Patients who had previously
completed Phase 2b or Phase 3 studies (RAJ1/3/4) received oral peficitinib (50, 100 or 150 mg) once
daily. Starting dose was 100 mg (RAJ3/4) or 50 mg (RAJ1). Doses could be increased to 150 mg/day or
reduced (from 100 mg/day or 150 mg/day) to 50 mg/day according to clinical response and safety
assessment, as judged by the investigator. A total of 843 patients received peficitinib (RAJ1, n=201;
RAJ3, n=225; RAJ4, n=417) with a mean treatment exposure of 22.7 months. During long-term
treatment, ACR20 responses were maintained from baseline for patients receiving maximum doses of
100/150 mg/day and were improved then maintained in patients receiving maximum doses of
50 mg/day. ACR components and DAS28-CRP also demonstrated continuous improvements from the
baselines of preceding studies. TEAEs were reported in 89.8% of patients and were primarily grade 1/2
in severity; the most common were nasopharyngitis, RA and herpes zoster. Rates of AEs of special
interest (serious infections, herpes zoster-related disease and malignancies) were greater for patients
from RAJ3/4 than RAJ1. There was no evidence to support a trend towards increasing incidence
rate/100 patient years with treatment duration. One death during and one death after the study were
considered probably and possibly related to study drug, respectively. The authors concluded that no
additional safety concerns were observed with longer term administration of peficitinib in RA patients,
and efficacy was maintained for the study duration [508].
*Chairman’s Pick