ACR Congress Review 2019

Enhancing knowledge of the clinical importance of cytokine signalling
The Cytokine Signalling Forum
www.cytokinesignalling.com
ACR 2019
Conference Highlights

ACR 2019
Conference Highlights
Chairman’s Welcome
Dear CSF Member,
Welcome to this year’s selection of ACR abstracts on cytokine signalling agents and my ‘Chairman’s picks’.
As in previous years, there continued to be an intense focus on the Janus kinase (JAK) inhibitors, with late stage trial results
from filgotinib, peficitinib and newly approved upadacitinib – as well as a host of real-world and trial data for the more
established baricitinib and tofacitinib.
The largest number of trial abstracts concern upadacitinib. Key among them are the 48-week data from SELECT
MONOTHERAPY [513], SELECT-EARLY [928] and 60-week data from SELECT BEYOND [518], and SELECT NEXT [538].
There is an interesting study analysing the clinical and functional outcomes of switching between upadacitinib and
adalimumab following initial non-response [2907] and another looking into structural joint damage inhibition with upadacitinib
monotherapy and combination use [547].
For filgotinib, Combe et al and Westhovens et al presented data from the FINCH trials [506; 927], whilst Takeuchi et al
presented data on the inhibition of joint destruction with peficitinib in combination with methotrexate [507].
There is new clinical data for both tofacitinib and baricitinib – with a phase 3 study assessing disease trajectories in baricitinib
patients [1350], and a look at MTX-withdrawal in patients taking the extended-release formulation of tofacitinib [1412].
Real-world studies examined the utility of these two drugs in clinical practice, exploring the impact of time since first
diagnosis on tofacitinib [1484] and an updated baricitinib safety profile with patients exposed for up to 7 years [847].
At this year’s congress there was a focus on safety and patient reported outcomes, with pain relief in patients investigated
for both baricitinib [1407] and tofacitinib [1502]. MACE and VTEs are also in the spotlight with meta analyses across JAK
inhibitors [2358] and data for upadacitinib [846] being presented.
We also saw Phase 2 data from Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib [929]. It will be important to see how
these agents progress over the coming years, and to find out what hope they can offer to patients who fail on current
therapies.
Within the following pages, we share our selection of the congress highlights, including my ‘Chairman’s picks’. As always,
thank you for your continued support, and we hope you enjoyed your time in Atlanta at ACR 2019!
Kind regards,
Prof. Iain McInnes

Highlights from ACR 2019
During the ACR 2019 annual meeting, many presentations and posters reported on cytokine signalling
and related drugs. This document reviews the highlights.
NOVEL TREATMENTS – Clinical Trials
Filgotinib
Filgotinib Phase 3 studies in RA patients – FINCH1 and FINCH3
Combe and colleagues presented the primary outcome results from the Phase 3, double-blind,
active- and placebo-controlled FINCH1 study evaluating filgotinib versus adalimumab or placebo in
patients with active RA and an inadequate response to MTX. The study randomised 1,759 patients, of
whom 1,755 received study drug and were analysed (filgotinib 200 mg QD, n=475; filgotinib 100 mg QD,
n=480; adalimumab 40 mg Q2W, n=325; placebo, n=475). At Week 12, significantly more patients in the
filgotinib 200 mg and 100 mg arms achieved an ACR20 response compared with placebo (76.6%,
69.8% and 49.9%, respectively). Similarly, compared to placebo, more patients receiving filgotinib
achieved ACR50 and ACR70 responses, DAS28-CRP scores ≤3.2 and

corticosteroids, and different classes of DMARDs on filgotinib efficacy as measured by ACR20 and
DAS28(CRP). Of the 448 patients randomised and treated at baseline, 80.4% were female with a mean
age of 56 years and a mean RA duration of 12.4 years. Benefits were observed for filgotinib across
subgroups. Notably, there was an absence of impact of disease duration, seropositivity, disease activity
and concurrent medication use, on the effectiveness of filgotinib [504].
Genovese et al. evaluated the efficacy of filgotinib in FINCH2 based on number and mechanism of
action (MOA) of prior biologics. Prior bDMARD exposure, including the total number and MOA, was well
balanced amongst the 3 treatment arms. Compared with placebo, filgotinib demonstrated improved
clinical outcomes in bDMARD refractory patients. The efficacy observed with filgotinib was maintained
with no significant effects based on the number and MOA of prior bDMARD use, including in patients
with prior exposure to IL-6 inhibitors [517].
A third analysis of FINCH2, which investigated the extent of anaemia, thrombocytopenia and leukopenia,
was also presented by Genovese and colleagues. Overall, haemoglobin levels, platelet, lymphocyte and
neutrophil counts remained consistent throughout the study. At baseline, 28.8%, 0.9%, 2.2% and 5.8%
patients had mild-moderate low levels of haemoglobin, platelet, neutrophil and lymphocyte, respectively,
and 1.1% had severely low levels of lymphocytes. Of the patients with mild-moderate haemoglobin
levels at baseline, 13.1% with filgotinib 200 mg, 9.5% with filgotinib 100 mg, and 7.6% with placebo
achieved normal haemoglobin at Week 24. All patients with baseline mild-moderate low platelets and
neutrophils had normal levels at Week 24, except for one patient with mild neutropenia receiving
filgotinib 100 mg. Of the patients with normal platelet and neutrophil levels at baseline, >94% maintained
normal levels at Week 24 in all treatment groups. The authors summarised that most patients with
normal haemoglobin, platelet, lymphocyte and neutrophil levels at baseline maintained them over 24
weeks of filgotinib treatment. Overall, the results suggest that filgotinib does not increase the incidence
of anaemia, thrombocytopenia or leukopenia in patients who entered the study with active RA despite
prior biologic therapies [2875].
Modulation of disease-associated cytokines with filgotinib
Taylor and colleagues presented three analyses of disease-associated cytokines in the FINCH2 study.
Cytokine profiles were compared with those of 50 demographically matched healthy volunteers in a
transcriptomic and proteomic study of serum samples from 449 patients. Among 28 cytokines evaluated
in baseline RA serum, 18 were significantly different from healthy volunteers. Of these, CXCL13, CCL2,
CCL3, CCL4, IL-18 and osteocalcin reversed toward healthy volunteer phenotype after filgotinib
treatment, whereas only IL-18 reached healthy volunteer levels in placebo-treated patients. The baseline
transcriptional profile of RA patients was enriched with pathways implicated in RA pathology, including
inflammatory responses and IFN, IL-6, TNFα signalling. Reversal of transcriptional profiles was broadly
dose- and time-dependent, with fewer genes differentially expressed from healthy volunteers after 12
weeks of filgotinib versus placebo. In summary, differences in the peripheral molecular profile were
observed between bDMARD-experienced RA patients and healthy volunteers. While an overall trend
toward the non-diseased molecular profile was observed following filgotinib, only a subset of cytokines
and pathways were statistically indistinguishable from healthy volunteers after 12 weeks [45].
Data from a longitudinal study of cytokines in blood and urine samples from FINCH2 RA patients were
also presented. Comparing filgotinib 100 mg to placebo, high baseline serum levels of CCL3, CXCL10,
IL-5, IL-6, IL-18, MMP3, SAA and VCAM1 were individually associated with improved ACR response or
reduction in RA activity (DAS28-CRP) at Week 12. High baseline serum CRP, CXCL13 and VEGFA
levels were also associated with improved response to filgotinib 200 mg. In placebo-treated patients, a
low sICAM1/CXCL13 ratio led to a lower ACR50 response rate than those with a high ratio. In contrast,
in filgotinib-treated patients, a low sICAM1/CXCL13 ratio led to an improved ACR50 response.
*Chairman’s Pick

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

Suppression of joint destruction with peficitinib
A secondary analysis evaluating the suppression of join destruction with peficitinib was presented by
Takeuchi and colleagues. This Phase 3 trial (NCT02305849) examined the efficacy and safety of a
peficitinib-MTX combination in patients with RA who had an inadequate response to MTX. A total of 518
patients were included in the analysis: placebo (n=170), peficitinib 100 mg/day (n=174) and peficitinib
150 mg/day (n=174). Sensitivity analyses showed that the change in mTSS at Week 28 was similar to
the primary analysis result, demonstrating the robustness of the primary analysis. At Week 28, a
significantly greater proportion of patients achieved a change in mTSS of ≤0.5 with both peficitinib 100
and 150 mg/day compared with placebo (67.1% and 72.6% versus 45.8%, respectively; P

treatment with MTX. A total of 1629 patients were randomised to upadacitinib 15 mg QD, placebo, or
adalimumab 40 mg EOW, while continuing stable background MTX. Rescue therapy was offered based
on predefined clinical criteria at Weeks 14 to 26 and all patients receiving placebo who were not rescued
were switched to upadacitinib at Week 26. Between Weeks 14 and 26, 38.7% of patients randomised to
upadacitinib and 48.6% of patients randomised to adalimumab were rescued. At Week 26, and Week
48, significantly more patients in the upadacitinib versus adalimumab group achieved ACR20/50/70, low
disease activity and remission; this was also true for visits between Weeks 26 and 48. Similarly,
improvements in pain and function were significantly greater in the upadacitinib versus adalimumab
group through Week 48. At Week 26, there was significantly less radiographic progression for
upadacitinib versus placebo, which was maintained through Week 48 based on linear extrapolation.
Safety was consistent with observations in the first 26 weeks. The rate of AEs leading to discontinuation
was higher with “any adalimumab” versus “any upadacitinib”, while the rate of herpes zoster was higher
with “any upadacitinib” exposure. In summary, upadacitinib continued to demonstrate superior clinical
and functional responses compared with adalimumab through Week 48 [527].
Sixty-week results from the ongoing extension of the Phase 3 SELECT-NEXT study were presented by
Burmester and colleagues. In SELECT-NEXT, patients with moderately-to-severely active RA and an
inadequate response to csDMARDs received once-daily upadacitinib 15 mg, upadacitinib 30 mg or
placebo for 12 weeks on stable background csDMARDs. At Week 12, the start of the long-term blinded
extension, patients initially randomised to placebo were switched to upadacitinib 15 mg or 30 mg per
pre-specified assignment at baseline. Patients initially assigned to upadacitinib continued their assigned
dose; no dose adjustments were permitted, but adjustments to background RA medications were
permitted from Week 24. Ninety-two percent of patients completed Week 12 and continued onto the
extension. Based on an “As Observed” analysis, for patients who continued on upadacitinib 15 mg
(85%) and upadacitinib 30 mg (81%), clinical and functional outcomes continued to improve or were
maintained through Week 60, with 59% and 56% of patients in these groups achieving
DAS28-CRP

1114 patients were included, of whom 648 received monotherapy in SELECT-MONOTHERAPY and 466
received combination therapy in SELECT-NEXT. In these cohorts of patients with RA and an inadequate
response to MTX, both upadacitinib monotherapy and upadacitinib combination therapy led to significant
improvements in efficacy outcomes versus continued MTX or placebo plus MTX. No significant
differences were observed between upadacitinib monotherapy and upadacitinib combination therapy
across a range of clinical endpoints including ACR20/50/70 responses and measures of LDA and
remission. In addition, improvements in quality of life as measured by HAQ-DI were similar with
upadacitinib monotherapy and combination therapy. The authors concluded that in MTX-IR RA patients,
the efficacy of upadacitinib appears comparable when administered as monotherapy or when given in
combination with MTX [511*].
Kapetanovic and colleagues presented a post-hoc analysis of the SELECT-EARLY study results to
examine the effect of receiving upadacitinib treatment within 3 months of treatment. A total of 270
patients started treatment within 90 days from RA diagnosis (median: 44 days). At Week 24, compared
to MTX, significantly greater proportions of patients receiving upadacitinib 15 or 30 mg monotherapy
achieved efficacy outcomes including ACR20, 50 and 70 responses, DAS28CRP

Individual and composite measures of disease activity in patients with RA treated with upadacitinib or
comparators were presented by van Vollenhoven and colleagues. The analyses included patients who
were MTX naïve (SELECT-EARLY, n=947) or MTX-IR (SELECT-COMPARE, n=1629). Responses at
Week 12 were defined as ≥50% improvement in the 7 components of the ACR response criteria. In
MTX-naïve and MTX-IR patients, treatment responses at 12 weeks occurred in significantly higher
proportions of patients receiving upadacitinib monotherapy versus MTX and upadacitinib plus MTX
versus placebo for all 7 components of the ACR response criteria, and for 5 of 7 ACR components for
upadacitinib plus MTX versus adalimumab plus MTX. Favourable outcomes with upadacitinib treatment
were evident both in composite and individual parameters [523].
Kremer and colleagues presented the comparative efficacy of upadacitinib in combination with MTX
versus upadacitinib in combination with other csDMARDs. Analyses were performed using data from the
SELECT-NEXT and SELECT-BEYOND trials, in which 535 and 410 patients, respectively, received
concomitant MTX (mean dose 17 mg/week), and 124 and 82 patients received non-MTX csDMARDs.
Across all subgroups, the proportion of patients achieving efficacy outcomes was higher with both
upadacitinib doses compared with placebo. There were no significant differences between efficacy
outcomes with upadacitinib in combination with MTX versus upadacitinib in combination with non-MTX
csDMARDs in either patient population; this included ACR20 response as well as LDA and remission
defined by DAS28-CRP and CDAI. In summary, the efficacy of upadacitinib in patients with RA
appeared comparable whether administered in combination with MTX or non-MTX csDMARDs [524*].
Hall and colleagues presented remission rates in patients with RA treated with upadacitinib or
comparators. The analyses included patients who were MTX naïve (SELECT-EARLY, n=945), MTX-IR
(SELECT-COMPARE, n=1629) and bDMARD-IR (SELECT-BEYOND, n=498). At 12 weeks, in
SELECT-EARLY and SELECT-COMPARE, a significantly greater proportion of patients receiving
upadacitinib 15 or 30 mg QD achieved remission by all four definitions versus MTX, placebo or
adalimumab. In SELECT-BEYOND, (a refractory population many of whom had an inadequate response
to multiple bDMARDs), a significantly greater proportion of patients receiving upadacitinib 30 mg
achieved all remission definitions versus placebo within the first 12 weeks and rates of remission further
increased through Week 24 for both dose groups. All disease activity components of each remission
definition were significantly improved in patients receiving upadacitinib compared to MTX or placebo,
and all Boolean components were significantly improved in patients receiving upadacitinib 15 mg
compared with adalimumab [529].
An evaluation of structural joint damage progression through Week 48 in patients with moderately to
severely active RA treated with upadacitinib monotherapy or in combination with MTX was presented by
Peterfy and colleagues. The analysis included patients from SELECT-EARLY (n=945) and
SELECT-COMPARE (n=1629). At Weeks 24/26, upadacitinib as monotherapy and in combination with
background MTX significantly inhibited radiographic progression (measured by mean ΔmTSS) and the
proportion of patients with no radiographic progression versus MTX and placebo, respectively. The
significant inhibition of radiographic progression with upadacitinib was maintained through Week 48
versus MTX in SELECT-EARLY and versus placebo in SELECT-COMPARE. Following the switch of all
placebo patients to upadacitinib in SELECT-COMPARE by Week 26, no further change in mean mTSS
was observed through Week 48. In summary, upadacitinib both as monotherapy, and in combination
with background MTX, was effective in inhibiting the progression of structural joint damage through
Week 48 in MTX-naïve, and MTX-IR patients, respectively [547*].
Fleischmann and colleagues presented outcomes associated with a treatment switch from upadacitinib
to adalimumab and vice-versa among MTX-IR RA patients who were non-responders or partial
responders in a Phase 3 study of upadacitinib 15 mg QD versus placebo or adalimumab 40 mg injection
EOW. Of the 651 and 327 patients randomised to receive upadacitinib and adalimumab, 39% were
switched from upadacitinib to adalimumab and 49% were switched from adalimumab to upadacitinib.
*Chairman’s Pick

At 6 months post-switch, patients switched to adalimumab achieved 69%, 37%, 16% improvements in
ACR20/50/70 responses, and 40% and 21% achieved DAS28-CRP≤3.2 and ≤2.6. Patients switched to
upadacitinib achieved 81%, 56%, 32% improvements in ACR20/50/70, and 56% and 35% achieved
DAS28-CRP≤3.2 and ≤2.6 at 6 months. Mean changes from the original baseline in HAQ-DI were -0.58
and -0.73 for patients switching to adalimumab and upadacitinib, respectively. The proportions of
patients with infection and serious infection through 6 months post-switching appeared consistent with
those observed for adalimumab and upadacitinib during comparable periods. The authors concluded
that patients with initial non-response to either upadacitinib or adalimumab can benefit from switching to
the other therapy [2907*].
Effects of upadacitinib on reverse cholesterol transport
Charles-Schoeman and colleagues presented findings on the effect of upadacitinib treatment on
cholesterol efflux capacity (CEC) and the association of CEC with changes in inflammation and serum
lipids using data from a subset of patients in the BALANCE II and SELECT-NEXT studies. In both
studies, changes in global and ABCA1-dependent CEC, and to a lesser extent non-ABCA1-dependent
CEC, were significantly higher in the upadacitinib-treated group compared with the placebo group. Thus,
upadacitinib treatment was associated with significant improvement in CEC. This effect was observed
even among those demonstrating minimal clinical response (but not in those treated with placebo). The
effect seemed to be primarily driven by ABCA1-dependent cholesterol efflux and is strongly correlated
with a rise in HDL cholesterol as well as reduction in systemic inflammation as measured by change in
CRP levels [510].
Normalisation of key pathobiological pathways in upadacitinib-treated patients
A poster on the mode of action of upadacitinib in patients with RA was presented by Sornasse et al. The
authors used a proteomic approach to evaluate a set of plasma proteins associated with inflammation in
randomly selected plasma samples from patients in the SELECT-NEXT and SELECT-BEYOND studies
(placebo, n=167; upadacitinib 15 mg QD, n=200). Consistent with its selectivity for JAK1, upadacitinib
was found to operate via inhibition of multiple JAK1-dependent upstream pathways that result in the
normalisation of key functional downstream effects associated with the pathobiology of RA, including
T cell and myeloid cell-related pathways. It was also noted that non-JAK signalling pathways were also
normalised, suggesting functional integration of JAK1 with parallel pathogenic signalling in RA effector
cells [522*].
Upadacitinib MOA assessed by genome-wide RNA expression
Lent and colleagues presented a poster on upadacitinib mechanism of action as assessed by
genome-wide RNA expression. Whole blood samples were analysed from a subset of patients from the
SELECT-NEXT study (upadacitinib 15 mg QD, n=99; placebo, n=100). Analysis of the top 100 most
affected transcripts by upadacitinib at Week 2, Week 4, and Week 12 identified modest but highly
significant modulation of a set of genes known to be differentially expressed in RA peripheral blood.
mRNA associated with B and T lymphocytes were increased, while mRNA associated with neutrophils
and monocytes were decreased, likely reflecting (at least in part) changes in leukocyte recirculation.
Pathway analysis demonstrated a broad inhibitory effect by upadacitinib on cytokines associated with
the pathobiology of RA, on intracellular signalling, and on toll-like receptor-pathways. Similarly, pathways
related to both innate and adaptive immune activation, leukocyte movement, phagocytic cell activity, and
leukocyte adhesion were predicted based on mRNA modulation, to be inhibited by upadacitinib.
Reciprocally, pathways associated with the numbers of B, T, and haematopoietic cells were predicted to
be activated by upadacitinib. In summary, upadacitinib normalizes key pathobiological pathways in RA
consistent with its clinical effect [545*].
*Chairman’s Pick

Upadacitinib in axial spondylarthritis
Ismail and colleagues presented a sub-analysis of the SELECT-AXIS I study to explore the relationship
between upadacitinib exposures and several ankylosing spondylitis (AS) efficacy endpoints and safety
parameters to support dose selection for future studies. Upadacitinib plasma exposures in patients with
AS were also compared with those in RA. A total of 187 patients were included (upadacitinib 15 mg QD,
n=93; placebo, n=94). Patients in the active treatment arm had statistically significant higher response
rates for ASAS 40, ASAS 20, and ASAS PR compared to those in the placebo arm. However, within the
single active treatment arm there were no clear exposure-response relationships between increasing
upadacitinib average concentrations and the probability of achieving the evaluated efficacy outcomes,
suggesting the achievement of a plateau in response. With increasing upadacitinib exposure, there was
an increase in the percentage of subjects experiencing decreases of haemoglobin of ≥ 1 g/dL from
baseline, and no upadacitinib exposure-dependent increases in percentage of subjects experiencing
lymphopenia or infection were observed. Upadacitinib plasma concentrations and pharmacokinetic
parameters (drug clearance and volume of distribution) in patients with AS were similar to those
previously observed in subjects with RA in the SELECT-BEYOND and SELECT-NEXT studies. Overall,
the results of this analysis support selection of the upadacitinib 15 mg QD dose for further evaluation in
future AS/axial SpA studies [1492].
BTK inhibitors
Fenebrutinib in RA – Phase 2 results
Cohen and colleagues presented findings from a fenebrutinib Phase 2 study, which enrolled patients
with moderate-to-severe active RA with an inadequate response to either MTX (Cohort 1) or TNF
inhibitors (Cohort 2). Results were presented for cohort 2 TNF-IR patients, who were randomised to
fenebrutinib 200 mg (n=48) or placebo (n=50); the majority of patients (98% and 90%, respectively)
completed the 12-week study. ACR20/50/70 responses in were greater for fenebrutinib versus placebo
(58/25/15% versus 24/12/4%) and generally increased over time, with a plateau of ACR50 after Week 8
for all patients. At Week 12, DAS28-CRP decreased by -1.43 and -2.26 from baseline in the placebo and
fenebrutinib arms, respectively. More patients in the placebo arm (45%) than in the fenebrutinib arm
(22%) reported at least one AE, and no serious AEs were reported. One case of herpes zoster and two
grade 3 chemistry abnormalities (low phosphorous, high uric acid) were reported in the fenebrutinib arm.
There were no clinically significant changes in haematology or immunoglobulin parameters. No Grade 4
or 5 abnormalities were reported. No deaths or malignancies were reported. In summary, fenebrutinib
demonstrated higher efficacy rates across disease activity measures versus placebo at Week 12 in the
TNF-IR population and the safety profile was acceptable [929*].
New agents
PF-06650833 in RA: Phase 2b results
Danto and colleagues presented Phase 2b study results for PF-06650833, a highly selective, small
molecule, reversible IRAK4 inhibitor in development for RA treatment. Patients with moderately to
severely active ACPA-positive RA and an inadequate response to methotrexate were randomised to
12 weeks’ dosing with PF-06650833 20 mg, 60 mg, 200 mg, 400 mg modified-release tablets QD,
tofacitinib 5 mg BID, or placebo. Overall, 269 patients were randomised and treated (PF-06650833,
n=187; tofacitinib, n=43; placebo, n=39). Mean change from baseline in Week 12 SDAI was significantly
higher in the PF-06650833 arms versus placebo (P≤0.005) and in the 200 mg and 400 mg groups
(sensitivity analysis; P

from baseline in DAS28-4(CRP) versus placebo was observed in PF-06650833 60 mg, 200 mg, and
400 mg QD groups at Week 12 (P

Safety, efficacy and PROs with a tofacitinib modified-release formulation in RA
Results of the open-label phase of the ORAL Shift study were presented by Cohen and colleagues. This
Phase 3b/4 study compared the efficacy and safety of tofacitinib modified-release 11 mg QD with and
without MTX in patients with RA who had achieved LDA with tofacitinib and MTX. Patients with
moderate-to-severe RA and an inadequate response to MTX received open-label tofacitinib modifiedrelease
11 mg QD with MTX (tofacitinib + MTX) for 24 weeks. Patients achieving LDA (CDAI≤10) at
week 24 entered the 24-week double-blind MTX withdrawal phase and were randomised 1:1 to receive
tofacitinib modified release 11 mg QD with placebo (tofacitinib monotherapy) or continue tofacitinib
+ MTX. In the open label phase, DAS28-4(ESR) improved with mean changes from baseline of ‐1.96
and -2.67 at Week 12 and Week 24, respectively. Improvements from baseline were observed for all
other efficacy outcomes and PROs at these timepoints. ACR20/50/70 and HAQ-DI response rates, and
LDA and remission rates, improved from Week 12 to Week 24. AEs, SAEs, and discontinuations due to
AEs were reported by 52.2%, 2.9%, and 5.9% of patients, respectively; no deaths were reported. AEs of
special interest each occurred in ≤1% of patients. The authors concluded that efficacy and safety in the
open label phase appeared consistent with that of tofacitinib immediate-release 5 mg BID and with the
double-blind phase of ORAL Shift [1412*].
Strand and colleagues presented SF-36 data from double-blind phase of the ORAL Shift study. A total of
530 patients achieved LDA at Week 24 and were treated in the double-blind phase (tofacitinib
monotherapy: n=264; tofacitinib + MTX: n=266). Mean changes from baseline to Week 24 showed
improvements in SF-36 PCS, MCS, and all domain scores. LSM changes from Week 24 to 36 and 48 in
SF-36 PCS, MCS, and all domain scores (except Role Physical and Bodily Pain at Week 36) were
similar in both treatment arms. These findings reinforce that patients receiving tofacitinib modified
release 11 mg QD plus MTX who achieve LDA, may withdraw MTX up to Week 48 without significant
worsening of PROs [1377].
Tofacitinib efficacy in RA patients with early versus established disease
Takeuchi and colleagues presented findings from a post-hoc analysis of ORAL Strategy evaluating the
efficacy and safety of tofacitinib monotherapy, tofacitinib plus MTX and adalimumab plus MTX, stratified
by baseline RA duration. A total of 241 patients had early RA (≤2 years duration) and 905 patients had
established RA (>2 years duration). ACR50 and ΔDAS28-4(ESR) were generally similar for tofacitinib
monotherapy and tofacitinib plus MTX up to Month 12 in early RA but were significantly greater with
tofacitinib plus MTX in established RA (P

Effect of tofacitinib on the qualitative HDL profile of RA patients
Findings from a study of functional markers of HDL at baseline and 3 months after tofacitinib were
presented by Luissi and colleagues. The study enrolled patients diagnosed with RA per ACR/EULAR
2010 criteria and who started tofacitinib from January 2016 onwards (bDMARD failures, n=18; cDMARD
failures, n=16). At three months of follow up, DAS28 decreased significantly, and TC, C-LDL, HDL-C
and C-non-HDL levels increased significantly. No changes were observed in paraoxon activity or
phenylacetate activity associated with tofacitinib use in the whole cohort; however, sub-analysis on
patients not previously treated with biologic DMARDs showed a significant increase in the activity of
these substrates of PON1. The authors concluded that, on bDMARD naïve patients, treatment with
tofacitinib improved the antioxidant activity of HDL (paroxonase activity), in spite of an increase in the
overall lipoprotein levels [1415].
Impact of switching to tofacitinib
Harnett and colleagues presented findings from a retrospective cohort study, assessing the impact of
TNFi cycling with adalimumab and etanercept versus switching to tofacitinib. A total of 740 patients with
RA who newly started index medication with tofacitinib or select TNFi (adalimumab or etanercept) were
identified from a US claims database. Patients who switched from adalimumab or etanercept to
tofacitinib had higher persistence, effectiveness, and significantly lower change in RA-related costs
compared with patients cycling between adalimumab and etanercept [1426].
Time to discontinue tofacitinib in RA patients
Real-world data from a Canadian observational cohort were presented by Movahedi and colleagues.
The authors examined the discontinuation rate of tofacitinib, with and without concurrent MTX, and with
and without prior biologic use. Among the 131 patients included in the analysis, 53.4% received
tofacitinib without MTX and 46.6% received tofacitinib with MTX. Discontinuation was reported in 33.6%
of all tofacitinib patients with a median survival of 31.3 months and overall retention at 6, 12 and 24
months was 80.5%, 63.1% and 53.5% respectively. Thirty-four percent of patients stopped their
tofacitinib due to non-response/loss of response, 50.0% due to adverse events, and 16% due to other
reasons. Discontinuation due to any reason was borderline significantly lower in the tofacitinib plus MTX
group compared with the tofacitinib without MTX group. There was no significant difference in tofacitinib
discontinuation between the two groups of patients with and without prior biologic use (P=0.77) [1428].
Impact of time since first diagnosis on tofacitinib safety and efficacy in PsA
Nash and colleagues presented a secondary analysis of the Phase 3 OPAL Broaden study to examine
the efficacy and safety of tofacitinib in patients with PsA, stratified by time since first PsA diagnosis.
OPAL Broaden was a 12-month study in which csDMARD-IR patients with active PsA were randomised
to receive tofacitinib 5 or 10 mg BID or placebo. A total of 316 patients were included in the analysis
(

Impact of BMI on tofacitinib safety and efficacy in PsA
A post-hoc analysis on the impact of baseline BMI on tofacitinib efficacy and safety in patients with PsA
was presented by Ritchlin and colleagues. Data were pooled from two placebo-controlled, double-blind,
Phase 3 studies in patients with active PsA and an inadequate response to ≥1 csDMARD (OPAL
Broaden) or to ≥1 TNFi (OPAL Beyond). The analysis included 710 patients of whom 43.8% were obese
(BMI ≥ 30). At baseline, 161 patients had a BMI

etween January 2008 and December 2015. Among 10,442 patients identified, 36.5% swapped to a
non-TNFi drug, most commonly abatacept (54.2%). The remaining 63.5% switched to a cycling regimen
(second TNFi), most commonly adalimumab (41.2%). For subsequent lines of therapy, non-TNFi drugs
were more common. Patients who swapped were significantly older and sicker than those who cycled
(P

Patient-reported outcomes with JAK inhibitors
Upadacitinib
Patient-reported outcomes with upadacitinib in RA
Several posters presented data on PROs with upadacitinib in the Phase 3 SELECT studies.
Fleischmann and colleagues presented a 26-week analysis of PROs with upadacitinib and adalimumab
in the Phase 3 SELECT-COMPARE study. This ongoing Phase 3 study randomised patients with
moderately to severely active RA and inadequate responses to MTX to receive upadacitinib 15 mg QD,
adalimumab 40 mg EOW, or placebo while on background MTX therapy. Patients treated with
upadacitinib or adalimumab reported clinically meaningful changes from baseline in all PtGA, pain VAS,
HAQ, FACIT-F, and duration and severity of AM stiffness at Week 26. Higher proportions of patients
receiving upadacitinib (74% to 84% of patients) continued to have clinically meaningful responses from
Week 12 to 26 than with adalimumab (66% to 70% of patients; all P values

Baricitinib
Pain relief with baricitinib in RA
A post-hoc analysis of pain improvement in the RA-BEAM study was presented by Taylor and
colleagues. A total of 1,305 patients on a stable background of MTX were randomised and received oral
baricitinib 4 mg QD, SC adalimumab 40 mg EOW, or placebo. At Week 12, the percentages of patients
who achieved remission with placebo, adalimumab, and baricitinib, respectively, were 2%, 7%, 8%; for
low disease activity: 15%, 27%, 33%; for moderate disease activity: 33%, 40%, 38%. At all CDAI values,
the estimated change in pain VAS for baricitinib was greater versus placebo and adalimumab. Similar
trends were observed with other disease activity measures. Baricitinib demonstrated greater pain
improvement versus adalimumab and placebo in all disease activity categories. With CDAI/SDAI,
greater differentiation between baricitinib and adalimumab was observed as CDAI/SDAI values
increased. In summary, baricitinib provided additional pain improvement versus placebo and
adalimumab when disease activity was controlled and across all levels of disease activity, as measured
by CDAI, SDAI, DAS28-CRP, or DAS28-ESR at Week 12 [1407*].
Pope and colleagues presented an analysis of data from the RA-BEAM, RA-BUILD, and RA-BEACON
trials to examine pain relief with baricitinib in opioid users and non-opioid users. A pooled analysis of RA
patients from the RA-BEAM (MTX-IR), RA-BUILD (cDMARD-IR) and RA-BEACON (TNF-IR) trials
showed that pain reduction with baricitinib 4 mg was similar between opioid users and non-users and
was observed at all time points. In RA-BEAM, pain reduction with baricitinib 2 mg versus placebo was
similar between opioid users and non-users from Week 12. A significant difference in pain reduction was
not observed for adalimumab versus placebo in the opioid users; whereas, for non-users, a difference in
pain reduction was observed for adalimumab versus placebo at all time points (P

Update on JAK inhibitor safety data
Upadacitinib
Upadacitinib safety in the SELECT clinical program
Findings from an integrated analysis of the upadacitinib safety profile from the SELECT Phase 3 clinical
program were presented in three posters.
Cohen and colleagues presented exposure-adjusted event rates (EAERs) and key safety data. Across
the five Phase 3 trials, 3834 patients received one or more dose of upadacitinib 15 (n=2630) or 30 mg
QD (n=1204). The EAERs of overall SAEs and AEs leading to discontinuation on upadacitinib 15 mg
were comparable to adalimumab; while the rates of both were higher on upadacitinib 30 versus
upadacitinib 15 mg and MTX. Rates of deaths were comparable across the treatment groups. Serious
infection rates were comparable between upadacitinib 15 mg and adalimumab, while higher on
upadacitinib compared with MTX. Rates of herpes zoster were higher in both upadacitinib groups versus
MTX and adalimumab. The rates of serious infections and herpes zoster were higher on upadacitinib 30
versus 15 mg. Rates of VTE, MACE, and malignancy were comparable with that observed in the MTX
and adalimumab groups while also being consistent with reported rates in the RA population [509*].
Choy and colleagues presented an analysis focusing on MACE and VTE. The EAERs of MACE and
VTE in the upadacitinib groups were comparable to placebo, MTX and adalimumab. Approximately 40%
of MACEs and 1 PE event (upadacitinib 15 mg) were fatal. All patients with a MACE or VTE event had
one or more CV risk factors (hypertension, diabetes, dyslipidaemia) or one or more VTE risk factor (prior
history of thrombotic event, obesity, or hypertension) at baseline, respectively. Treatment with
upadacitinib increased the levels of LDL-C and HDL-C, however, their ratio remained constant over time
and there was no association of LDL‐C increases and MACE occurrences. No dose‐response or pattern
of time-to-VTE-onset was observed with either upadacitinib dose [846*].
An integrated, long-term safety analysis of upadacitinib in Japanese patients was presented by
Yamaoka and colleagues. The analysis included a total of 371 Japanese patients who received
upadacitinib 7.5 (n=121), 15 (n=126), or 30 mg QD (n=124) in one of three clinical studies (SELECT-
SUNRISE, SELECT-EARLY or SELECT-MONOTHERAPY). Among the Japanese population, EAERs
were consistently higher in the 30 mg group compared with the 15 mg and 7.5 mg groups. EAERs in the
15 mg and 7.5 mg groups were comparable. In comparison with the global population, EAERs in the 15
mg and 30 mg groups was higher in the Japanese population. The EAER of infections (including herpes
zoster) was also higher in the Japanese population compared with the global population. In contrast,
EAERs of AESI (including malignancies, cardiovascular disorders, hepatic disorders, and laboratory
abnormalities) were comparable between the Japanese and global populations [2407].
Baricitinib
Long-term baricitinib safety in RA
The long-term safety and efficacy profile for baricitinib up to 7 years was presented by Genovese et al.
The analysis included 3770 patients with RA (10,127 patient-years of exposure) from 9 randomised trials
and an ongoing open-label, long-term extension study. No significant differences were seen for
baricitinib 4 mg versus placebo in AEs leading to permanent drug discontinuation, death, malignancy,
serious infection, or MACE. The incidence rate of herpes zoster was significantly higher for baricitinib
4 mg versus placebo (3.8 versus 0.9) and numerically higher for baricitinib 2 mg (3.1). Incidence rates
for DVT/PE were numerically higher in baricitinib 4 mg versus placebo. Malignancy (excluding
*Chairman’s Pick

non-melanoma skin cancer) incidence rates were 0.8 (2 mg) and 1.0 (4 mg; as-randomised analysis). In
summary, baricitinib maintained a safety profile similar to that previously reported and acceptable in the
context of demonstrated efficacy [847*].
Filgotinib
Filgotinib safety in the FINCH programme
Pooled safety data from the double-blind, active and placebo-controlled periods of FINCH 1–3 up to 24
weeks were presented by Winthrop and colleagues. The FINCH studies enrolled patients who had a
diagnosis of RA (2010 ACR/EULAR criteria) and had ≥ 6 swollen joints and ≥ 6 tender joints at both
screening and Day 1. The pooled safety analyses included 3,452 patients across FINCH 1–3, including
2,088 patients who received filgotinib. At Week 24, the frequency of TEAEs was similar between
patients who received filgotinib and those in the control arms. The proportions of patients with TEAEs of
interest were also similar across groups. Overall, the frequency of MACE, herpes zoster virus, DVT and
PE was low, and similar across groups. The incidences of MACE were 0.2% for filgotinib, 0.3% for
adalimumab, and 0.5% for placebo/csDMARD. Additionally, the incidences of DVT/PE were

In the first presentation, the analyses included a total of 1544 tofacitinib (2138.2 patient years) and 7083
bDMARD (9904.9 patient years) initiators. Rates of MACE and serious infection events were similar in
patients starting tofacitinib or bDMARDs for RA. The herpes zoster incidence rate was higher for
tofacitinib versus bDMARDs and hazard ratios (HR) for herpes zoster were significantly increased with
tofacitinib versus bDMARDs (adjusted HR 2.12, 95% CI: 1.22, 3.66). All herpes zoster events were nonserious
with tofacitinib. VTE IRs were similar in both cohorts [2372].
In a second presentation, the authors compared 5-year IRs of malignancy and mortality in a total of 1999
tofacitinib (4505.62 PY) and 6354 bDMARD (16670.84 PY) initiators. RA patients initiating tofacitinib or
bDMARDs had similar rates of total cancer excluding NMSC, NMSC, and death, with adjusted HRs
(95% CI) of 1.04 (0.68, 1.61), 1.02 (0.69, 1.50), and 1.0 (0.62, 1.63), respectively [2874*].
Risk of serious infections with tofacitinib
A poster presenting the comparative incidence rates of serious bacterial, viral or opportunistic infections
in RA patients was presented by Pawar and colleagues. Using data from three US healthcare claims
databases, a total of 123,960 biologic initiators were identified, of which 4.5% were tofacitinib initiators. A
total of 2,958 serious infection events occurred. In the tofacitinib group, the crude IR for serious
infections per 100 person-years ranged from 2.80 (MarketScan) to 7.89 (Medicare). Adjusted HRs
showed higher risk of composite serious infections with tofacitinib compared with abatacept (HR 1.20,
95% CI 1.09-1.31), etanercept (1.27, 1.14-1.42), golimumab (1.35, 1.29-1.40) and tocilizumab (1.46,
1.31-1.63), but similar risk compared to adalimumab, certolizumab and infliximab. Serious bacterial
infection risk was higher in tofacitinib than abatacept (1.15, 1.09-1.21), certolizumab (1.16, 1.10-1.23),
etanercept 1.14 (1.04-1.25) and golimumab (1.21, 1.06-1.39) [2826].
Vinet and colleagues presented results from a study comparing the risk of serious infections in children
born to mothers with chronic inflammatory diseases who used non-TNFi biologics or tofacitinib during
pregnancy, versus unexposed offspring and children exposed to TNFi in utero. The US MarketScan
database was used to identify 16,490 offspring of mothers with RA (4,142), AS (381), PsO/PsA (5,743),
and inflammatory bowel disease (6,731), as well as 164,553 children born to unaffected mothers
matched for age, year of delivery and state of residence. Very few serious infections were detected in
children exposed to non-TNFi biologics or tofacitinib (2 cases [1.9%]: one case was exposed to
tofacitinib, while the other was exposed to abatacept). The percent of serious infections in offspring of
inflammatory disease mothers with no TNFi exposure was 2.1%, while for those with TNFi in utero
exposure, it was 2.3%. In children born to unaffected mothers, the percent of serious infections was
1.6% [1901].
Baricitinib
Post-marketing surveillance of baricitinib safety in RA
A poster presenting baricitinib safety based on post-marketing surveillance data was presented by
Matsuno and colleagues. This interim report summarized registration data including pre-treatment test
rates and AEs. As of August 2018, 1288 patients had been enrolled. Registration data were reported as
follows: women, 81%; mean age, 64 years old; mean RA duration, 12 years; Steinbrocker stage II, 32%;
stage III or IV, 52%; baricitinib 4 mg, 68%; baricitinib 2 mg 32%; MTX use, 57%; corticosteroid use, 51%;
pre-treatment test for tuberculosis, 93%; HBV, 95%; HCV, 93%; and eGFR, 96%. Of 299 AEs collected,
53 were SAEs. SAEs reported in 2 or more patients were pneumonia (n=8), fall (n=4), osteonecrosis
(n=3), herpes zoster (n=2) and interstitial lung disease (n=2). Pulmonary TB (n=1), lymph node TB (n=1)
and DVT (n=1) were also reported as SAEs. Overall, safety findings were consistent with baricitinib’s
known safety profile. These data highlight that care is needed to ensure that all pre-treatment tests are
conducted in all patients [2375].
*Chairman’s Pick

Peficitinib
Peficitinib safety in an Asian population of RA patients
Pooled safety data from four clinical studies of peficitinib in adult patients with active RA were presented
by Takeuchi and colleagues. Two pooled datasets (Phase 3 studies and Phase 2/3 studies) were used
for the analyses. A total of 1052 patients were included in the pooled Phase 2 and 3 studies. Overall
exposure to peficitinib in Phase 2/3 studies was 2336.3 patient-years. Across the 4 studies, there were
3 deaths. In the pooled Phase 3 studies, there were no deaths. The overall incidence of AEs was similar
between the 2 peficitinib groups: 88.5% in the peficitinib 100 mg/day group, 87.7% in the peficitinib
150 mg/day group, and 89.0% in the etanercept group; the incidence of SAEs was 9.4%, 7.6%, and
9.0%, respectively. Among AEs of special interest in the pooled Phase 3 studies, the incidence of
serious infections was 2.9 in patients receiving peficitinib and 2.0 in those receiving etanercept. The
incidence of herpes zoster-related disease was greater in peficitinib groups (5.7) than in placebo (2.3) or
etanercept groups (2.6), and the overall incidence of malignancies (0.6) was similar to that in the
placebo (1.2) and etanercept (0.5) groups. The authors concluded that peficitinib was well tolerated with
no major specific concerns with longer term administration [2403].
JAKi
Short-term risk of MACE or VTE in RA
Results of a meta-analysis of randomised controlled trials (RCTs) to examine the short-term risk of
MACE or VTE in patients with RA initiating a JAKi were presented by Malaurie and colleagues. A total of
30 RCTs were included in the meta-analysis and no statistically significant difference was observed in
MACE or VTE incidences in patients receiving any of the JAKi (baricitinib, decernotinib, filgotinib,
peficitinib, tofacitinib, upadacitinib), compared to the placebo group. A numeric imbalance was observed
in the baricitinib group with 7 VTEs (688 PY) compared with none in the placebo group (452 PY), with
0.01 risk difference, which was not statistically significant. A numeric imbalance was also observed in
the upadacitinib group with 6 VTEs (611 PY) compared to 1 VTE in the placebo group (440 PY), with a
0.01 risk difference, which is not statistically significant. Thus, no statistically significant change was
identified in the short-term risk of MACEs or VTEs in patients with RA initiating a JAKi [2358*].
*Chairman’s Pick

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*Chairman’s Pick

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functional impairment in RA patients with moderate disease activity and an inadequate response to conventional DMARDs. Arthritis
Rheumatol. 2019; 71 (suppl 10):A1439.
Kremer J, Bingham C, Cappelli L, Greenberg J, Geier J, Madsen A, Chen C, Onofrei A, Barr C, Pappas D, Litman H, Dandreo K, Shapiro
A, Connell C, Kavanaugh A. Post-approval comparative safety study of tofacitinib and biologic DMARDS: five‐year results from a US-based
rheumatoid arthritis registry. Arthritis Rheumatol. 2019; 71 (suppl 10):A2372.
Kremer J, Bingham C, Cappelli L, Greenberg J, Madsen A, Geier J, Rivas J, Onofrei A, Barr C, Pappas D, Litman H, Dandreo K, Shapiro A,
Connell C, Kavanaugh A. Comparison of malignancy and mortality rates between tofacitinib and biologic DMARDS in clinical practice: fiveyear
results from a US-based rheumatoid arthritis registry. Arthritis Rheumatol. 2019; 71 (suppl 10):A2874.
*Chairman’s Pick

Kremer J, Van den Bosch F, Rubbert-Roth A, Radominski S, Burmester G, Camp H, Meerwein S, Howard M, Song Y, Zhong S, Combe B.
A comparison of upadacitinib plus methotrexate and upadacitinib plus other csDMARDS in patients with rheumatoid arthritis: an analysis of
two phase 3 studies. Arthritis Rheumatol. 2019; 71 (suppl 10):A524.
Lauper K, Mongin D, Bergstra S, Choquette D, Codreanu C, Elkayam O, Hyrich K, Iannone F, Kristianslund E, Kvien T, Leeb B, Lukina G,
Nordström D, Onen F, Pavelka K, Pombo-Suarez M, Rotar Z, Santos M, Strangfeld A, Courvoisier D, Finckh A. Heterogeneity in the pattern
of use of JAK-inhibitors between countries participating in an international collaboration of registers of rheumatoid arthritis patients (the
JAK-pot study). Arthritis Rheumatol. 2019; 71 (suppl 10):A1420.
Lent S, Sornasse T, Georgantas R, Sokolove J, McInnes I. Molecular analysis of the mode of action of upadacitinib in rheumatoid arthritis
patients: whole blood RNA expression data from the SELECT-NEXT study. Arthritis Rheumatol. 2019; 71 (suppl 10):A545.
Li L, Lu N, Lacaille D, Xie H, Esdaile J, Avina-Zubieta J. Risk of venous thromboembolism in rheumatoid arthritis patients initiating biologic
and non-biologic DMARDs, a population-based study. Arthritis Rheumatol. 2019; 71 (suppl 10):A1894.
Luissi A, Pierini F, Gandino I, Botta E, Brites F, Boero L, Martin M, Meroño T, saez S, Tetzlaff W, Sommerfleck F, Citera G, Rosa J,
Sorroche P, Soriano E. Effect of tofacitinib on the qualitative profile of high density lipoproteins molecules in patients with rheumatoid
arthritis. Arthritis Rheumatol. 2019; 71 (suppl 10):A1415.
Malaurie M, Constantin A, Degboé Y, Ruyssen-Witrand A, Barnetche T. Short-term risk of major adverse cardiovascular events or venous
thrombo-embolic events in patients with rheumatoid arthritis initiating a janus kinase inhibitor: a meta-analysis of randomised controlled
trials. Arthritis Rheumatol. 2019; 71 (suppl 10):A2358.
Matsuno H, Atsumi T, Takei S, Tamura N, Harigai M, Fujii T, Momohara S, Takahashi Y, Narii N, Tsujimoto N, Nishikawa A, Ishii T,
Yamamoto K, Kuwana M, Takagi M. Safety of baricitinib under clinical settings in patients with rheumatoid arthritis, using data from all-case
post-marketing surveillance and spontaneous reports. Arthritis Rheumatol. 2019; 71 (suppl 10):A2375.
Movahedi M, Cesta A, Li X, Keystone E, Bombardier C, Other OBRI Investigators A. Time to discontinuation of tofacitinib in rheumatoid
arthritis patients with and without methotrexate: results from a rheumatoid arthritis cohort. Arthritis Rheumatol. 2019; 71 (suppl 10):A1428.
Nash P, Greenwald M, Lin L, Yu W, Santos Estrella P, Mundayat R, Graham D, Veale D. The impact of time since first diagnosis on the
efficacy and safety of tofacitinib in patients with active psoriatic arthritis. Arthritis Rheumatol. 2019; 71 (suppl 10):A1484.
Pawar A, Desai R, Gautam N, Kim S. Risk of serious infections in tofacitinib versus other biologic drug initiators in patients with rheumatoid
arthritis: a multi-database cohort study. Arthritis Rheumatol. 2019; 71 (suppl 10):A2826.
Peterfy C, Genovese M, Song I, Friedman A, Hall S, Mysler E, Durez P, Baraliakos X, Enejosa J, Shaw T, Li Y, Chen S, Strand V. Inhibition
of structural joint damage with upadacitinib as monotherapy or in combination with methotrexate in patients with rheumatoid arthritis.
Arthritis Rheumatol. 2019; 71 (suppl 10):A547.
Pope J, Lee Y, Curtis J, Mo D, Rooney T, Xie L, Dickson C, Schlichting D, Quebe A, Cardoso A, Simon L, Taylor P. Baricitinib 4 mg and
2 mg once daily reduced pain in both patients who were opioid users and non-users in active rheumatoid arthritis: a post-hoc analysis of
phase 3 trials. Arthritis Rheumatol. 2019; 71 (suppl 10):A1880.
Price L, Pouliot P, Schmitt L. Pre-Biologic Use of janus kinase inhibitors for the treatment of rheumatoid arthritis in the United States.
Arthritis Rheumatol. 2019; 71 (suppl 10):A1445.
Ritchlin C, Ogdie A, Giles J, Gomez-Reino J, Helliwell P, Stockert L, Young P, Joseph W, Mundayat R, Graham D, Woolcott J, Romero A.
Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with psoriatic arthritis. Arthritis Rheumatol. 2019; 71
(suppl 10):A1513.
Smolen J, Emery P, Rigby W, Tanaka Y, Vargas J, Damjanov N, Jain M, Sui Y, Enejosa J, Pangan A, Camp H, Cohen S. Upadacitinib as
monotherapy in patients with rheumatoid arthritis: results at 48 weeks. Arthritis Rheumatol. 2019; 71 (suppl 10):A513
Sornasse T, Sokolove J, McInnes I. Treatment with upadacitinib results in the normalization of key pathobiologic pathways in patients with
rheumatoid arthritis. Arthritis Rheumatol. 2019; 71 (suppl 10):A522.
Strand V, Pope J, Woolcott J, Rivas J, Diehl A, Liu S, Gruben D, Cohen S. MTX withdrawal in patients with RA who achieve low disease
activity with tofacitinib modified-release 11 mg once daily + MTX: An assessment of the impact on the short form-36 patient-reported
outcome. Arthritis Rheumatol. 2019; 71 (suppl 10): A1377.
Strand V, Tundia N, Friedman A, Camp H, Suboticki J, Goldschmidt D, Fernan C, Bergman M. Impact of 24- or 26-week upadacitinib
monotherapy on patient-reported outcomes in patients with moderately to severely active rheumatoid arthritis and no prior use of or an
inadequate response to methotrexate: results from two phase 3 trials. Arthritis Rheumatol. 2019; 71 (suppl 10):A1376.
Takeuchi T, Tanaka Y, Rokuda M, Izutsu H, Kaneko Y, Fukuda M, Kato D. Adverse events of special interest in patients with rheumatoid
arthritis treated with peficitinib in Asian population: pooled safety findings. Arthritis Rheumatol. 2019; 71 (suppl 10):A2403.
Takeuchi T, Tanaka Y, Rokuda M, Izutsu H, Kaneko Y, Fukuda M, Kato D, van der Heijde D. Inhibition of joint destruction in patients with
*Chairman’s Pick

heumatoid arthritis treated with peficitinib in combination with methotrexate: a randomised, double-blind, placebo-controlled trial in Japan.
Arthritis Rheumatol. 2019; 71 (suppl 10):A507.
Takeuchi T, Tanaka Y, Sugiyama N, Iikuni N, Soma K, Shi H, Mysler E, Moots R, Smolen J, Fleischmann R. Efficacy of tofacitinib
monotherapy, tofacitinib with methotrexate and adalimumab with methotrexate in patients with early ( ≤ 2 years) vs established ( > 2 years)
rheumatoid arthritis: a post hoc analysis of data from oral strategy. Arthritis Rheumatol. 2019; 71 (suppl 10):A1413.
Takeuchi T, Tanaka Y, Tanaka S, Kawakami A, Song Y, Chen Y, Rokuda M, Izutsu H, Ushijima S, Kaneko Y, Nakashima Y, Shiomi T,
Yamada E. Longer term safety and efficacy of peficitinib in patients with rheumatoid arthritis after 22.7 months mean treatment exposure:
interim data from a long-term, open-label extension study in Japan, Korea and Taiwan. Arthritis Rheumatol. 2019; 71 (suppl 10):A508.
Taylor P, Downie B, Elboudwarej E, Hawtin R, Mirza A, Liu J. A Composite IFN-based signature is associated with a filgotinib-specific
clinical response in bDMARD-experienced rheumatoid arthritis patients. Arthritis Rheumatol. 2019; 71 (suppl 10):A2012.
Taylor P, Elboudwarej E, Downie B, Hawtin R, Liu J, Mirza A. Key inflammatory biomarkers at baseline are associated with filgotinib
response at week 12 in rheumatoid arthritis patients with inadequate response or intolerance to biologic DMARDs. Arthritis Rheumatol.
2019; 71 (suppl 10):A46.
Taylor P, Elboudwarej E, Downie B, Vestergaard L, Liu J, Mirza A, Hawtin R. bDMARD-experienced filgotinib-treated patient samples
exhibit a partial reversion to the peripheral molecular profile of a demographically matched healthy population. Arthritis Rheumatol. 2019;
71 (suppl 10):A45.
Taylor P, Pope J, Ikeda K, Zhang X, Jia B, Zhang H, Quebe A, Chen Y, Gaich C, Holzkaemper T, Cardoso A, Sebba A. Baricitinib provides
better pain relief across all disease activity levels compared with placebo and adalimumab in rheumatoid arthritis. Arthritis Rheumatol.
2019; 71 (suppl 10):A1407.
van Vollenhoven R, Östör A, Mysler E, Damjanov N, Song I, Song Y, Suboticki J, Strand V. The impact of upadacitinib versus methotrexate
or adalimumab on individual and composite disease measures in patients with rheumatoid arthritis. Arthritis Rheumatol. 2019; 71 (suppl
10):A523.
van Vollenhoven R, Takeuchi T, Pangan A, Friedman A, Chen S, Rischmueller M, Blanco R, Xavier R, Strand V. Monotherapy with
upadacitinib in MTX-naïve patients with rheumatoid arthritis: results at 48 weeks. Arthritis Rheumatol. 2019; 71 (suppl 10):A928.
Vinet E, St-Pierre Y, Moura C, Curtis J, Bernatsky S. Serious infections in offspring exposed in utero to non-TNFi biologics and tofacitinib.
Arthritis Rheumatol. 2019; 71 (suppl 10):A1901.
Weinblatt M, Mysler E, Östör A, Broadwell A, Jeka S, Dunlap K, Suboticki J, Enejosa J, Hendrickson B, Zhong S, Cherny K, Wright G.
Impact of baseline demographics and disease activity on outcomes in patients with rheumatoid arthritis receiving upadacitinib. Arthritis
Rheumatol. 2019; 71 (suppl 10):A516.
Weinblatt M, Thomson G, Chen K, Meerwein S, Schlacher C, Cush J. Clinical responses in patients with inadequate response to
bDMARDS upon treatment with upadacitinib. Arthritis Rheumatol. 2019; 71 (suppl 10):A515.
Westhovens R, Rigby W, van der Heijde D, Ching D, Bartok B, Matzkies F, Yin Z, Guo Y, Tasset C, Sundy J, Mozaffarian N, Messina O,
Landewé R, Atsumi T, Burmester G. Efficacy and safety of filgotinib for patients with rheumatoid arthritis naïve to methotrexate therapy:
FINCH3 primary outcome results. Arthritis Rheumatol. 2019; 71 (suppl 10):A927.
Winthrop K, Genovese M, Combe B, Tanaka Y, Kivitz A, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy J, Keystone E, Westhovens
R, Rigby W, Burmester G. Pooled safety analyses from phase 3 studies of filgotinib in patients with rheumatoid arthritis. Arthritis
Rheumatol. 2019; 71 (suppl 10):A1329.
Yamaoka K, Tanaka Y, Kameda H, Hendrickson B, Meerwein S, Zhang Y, Takeuchi T. The safety profile of upadacitinib in Japanese
patients with rheumatoid arthritis. Arthritis Rheumatol. 2019; 71 (suppl 10):A2407.
*Chairman’s Pick