EULAR 2018 Review

Effect of upadacitinib on patient-reported outcomes in RA
Strand, et al. presented two posters on patient-reported outcomes (PROs) with
upadacitinib in the SELECT-NEXT and SELECT BEYOND studies. A total of 661 patients
with active RA and an inadequate response to csDMARD were included in the analysis of
PROs in SELECT-NEXT. Treatment with upadacitinib 15 mg or 30 mg daily for 12 weeks
resulted in significant and clinically meaningful improvements in physical function, pain,
fatigue, morning stiffness, QoL and work instability. Numbers Needed to Treat (NNT) with
upadacitinib ranged from 4 to 8 patients [#0254]. A total of 498 patients with active RA and
an inadequate response to bDMARDs were included in the analysis of SELECT-BEYOND.
Compared with placebo at Week 12, upadacitinib-treated patients reported higher
responses that were statistically significant and clinically meaningful for HAQ-DI, PtGA
pain, pain, duration and severity of morning stiffness and SF-36 Physical Component
Summary (PCS). NNT with upadacitinib ranged from four to eight patients in this difficultto-treat
cohort [#0255].
Tofacitinib efficacy and safety in RA
Fleischmann and colleagues presented a post hoc analysis of the ORAL Strategy study
describing the impact of background glucocorticoids on the safety and efficacy of tofacitinib
(with and without MTX) and adalimumab with MTX. Patients with RA were randomised
1:1:1 to receive tofacitinib 5 mg BID, tofacitinib 5 mg BID plus MTX, or SC adalimumab 40
mg (every other week) plus MTX. In the cohort of 1146 patients who were randomised and
treated, efficacy endpoints (ACR50 response rate, LDA, remission rates, change in HAQ-
DI score) were generally similar for each treatment group when stratified by glucocorticoid
use. Unexpectedly, glucocorticoid use did not appear to be associated with higher rates of
AEs, discontinuations due to AEs, serious infection events, and SAEs [#0247].
Cumulative probability plots showing clinical and functional efficacy across treatments for
patients with RA in the ORAL Strategy study were presented by Takeuchi, et al. The
proportion of patients who achieved responses of ACR20, ACR50 and ACR70 was similar
for tofacitinib 5 mg BID plus MTX, and adalimumab SC 40 mg (every other week) plus
MTX every other week but was numerically smaller for tofacitinib 5 mg BID monotherapy.
Reductions from baseline in HAQ-DI were similar across treatment groups, although a
slightly higher proportion of patients who received tofacitinib monotherapy reported an
increase in HAQ-DI compared with other treatments. These data are consistent with the
primary ORAL Strategy findings [#0252].
Wiesenhutter examined the utility of various disease activity measures (DAMs) for clinical
decision making during implementation of a treat-to-target (T2T) strategy, following the
initiation of tofacitinib (n=39) and TNFis (n=40). Patients at a rheumatology clinic
underwent disease activity measure (DAM) assessments, which included conventional
clinical assessments, DAS28CRP, and the CDAI, as well as the ultrasound power Doppler
joint count (UPDJC) and multi-biomarker disease activity score (MBDA). Patients
underwent regular assessments, and if found to have inadequate control, changes were
made in their clinical regimen and reassessment was performed 3 to 6 months later. All of
the DAMs resulted in significant clinical responses with the exception that following the
initiation of tofacitinib, the MBDA did not result in clinically significant improvement. When
individual biomarkers from the MBDA were analysed, TNFi therapy led to significant
reduction in 6 of 12 biomarkers (IL-6, TNF-R1, TNF-R2, MMP-2, SSA and CRP), whereas