EULAR 2018 Review

monocytes to differentiate into dendritic cells translated into a functional impairment of
phagocytic ability. NOX5 protein expression was significantly decreased in pre-treated Mo-
DC from PsA patients, and to a lesser extent in cells from RA patients. The authors
proposed that inhibition of Mo-DC development by tofacitinib may alter migration of DC to
the joint and subsequent activation of the immune response [#0046].
Post hoc analyses of baricitinib Phase 3 studies
Hepatic safety in patients with RA who received isoniazid (INH) for latent TB (LTBI) was
reported by Hsieh et al. In this post hoc analysis of data from 3 Phase 3 baricitinib studies
(n=2516 patients; RA-BEAM, RA BUILD, RA BEACON), 246 patients reported LTBI and
169 had confirmed laboratory data and received INH as LTBI treatment. The percentage of
patients with greater than one times the ULN levels of ALT was numerically higher in
patients in the INH group versus no INH, and was consistent across placebo, baricitinib
and adalimumab treatment groups. No treatment interruptions or discontinuations were
reported in INH users in the baricitinib or adalimumab groups. The authors concluded that
the data do not suggest an increased hepatic safety risk in patients receiving baricitinib
and INH concomitantly [#0098].
A post hoc analysis of the RA-BEAM and RA-BEGIN studies in patients with RA was
reported by de Vlam, et al. The analysis showed that controlling disease activity by
achieving LDA or remission increases the chance to regain normal physical function and
relieve pain, independent of treatment (baricitinib monotherapy, baricitinib plus MTX or
adalimumab). The data from RA-BEAM may indicate that achieving no/limited pain at
Week 12 may be more likely with baricitinib compared with adalimumab, when achieving
remission (83% versus 73%) [#0258].
Pope and colleagues reported a post hoc analysis of RA-BEAM. The authors showed that
reductions in pain and fatigue were associated with improvements in regular daily
activities, presenteeism and work productivity, with patients who reported lower levels of
fatigue and pain tending to experience greater improvements compared with patients with
higher levels of pain and fatigue. When patients achieved a minimal level of pain (pain
VAS ≤10 mm), similar improvements in presenteeism and work productivity were observed
regardless of fatigue level. Similar results were observed between treatment groups
[#0240].
Phase 1 pharmacokinetic studies with upadacitinib in volunteers with renal impairment
Mohamed, et al. reported results from a Phase 1 study that examined the
pharmacokinetics of upadacitinib in 24 volunteers with either normal renal function or mild,
moderate or severe renal impairment. In participants with mild, moderate and severe
hepatic impairment, point estimates for plasma exposure ratios following a single 15 mg
dose were 1.18, 1.33 and 1.44 for AUC and 1.06, 1.11 and 1.14 for maximum plasma
concentration, relative to participants with normal renal function. The authors concluded
that renal impairment has only limited effect upon upadacitinib pharmacokinetics, with
mean plasma exposure in participants with severe renal impairment within 44% of that
observed in patients with normal renal impairment [#0479].