ACR Congress Review 2019

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