SAT0169 No evidence that concomitant glucocorticoid therapy affects efficacy and safety of tocilizumab monotherapy in rheumatoid arthritis clinical trials

Abstract

Background:For rheumatoid arthritis (RA) patients included in clinical trials, background treatment with glucocorticoids (GCs) is quite common (40–60%), but their potential contribution to efficacy and safety of the disease modifying anti-rheumatic drug (DMARD) tested in that trial has rarely been evaluated.Objectives:To establish whether a stable GC dose at baseline and during the study contributed to the efficacy and safety of TCZ monotherapy initiated in RA patients in 4 TCZ RCTs. In addition, to investigate the same issue in the comparator arms of these trials, in which adalimumab (ADA) or methotrexate (MTX) was initiated.Methods:Data from 4 randomized controlled double-blind trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with TCZ monotherapy arms was analysed in this post hoc analysis [1–4]. Study participants were MTX-naïve, intolerant or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR). Because of differences between the studies in region, and baseline RA duration and disease severity, analyses were done separately for each study. Stable GC dose at baseline was allowed and was to be continued unchanged during the first 24 weeks. Analyses of covariance (ANCOVA) of change from baseline to Week 24 in CDAI and DAS28 and logistic regression analyses at Week 24 for CDAI remission and ACR50 were performed. Repeated measures analyses using all visits up to week 24 were also done. Incidence rates of serious adverse events (SAEs) were assessed by GC use.Table 1Disease Activities at week 24 of GC Users versus non-GC Users per Treatment per StudyResults:Baseline characteristics were mostly comparable between GC users and non-GC users in each treatment arm for each study. The adjusted differences (95% CIs) of CDAI change at week 24 between GC and non-GC users in TCZ arms of AMBITION, FUNCTION, ACT-RAY and ADACTA were -1.4 (-4.8, 2.1), 0.8 (-2.5, 4.1), 1.2 (-4.0, 6.3) and -4.2 (-9.7, 1.4), respectively (table 1). CDAI remission rates, ACR50 response rates and DAS28 score changes at 24 weeks neither were significantly different between GC users and non-GC users in the TCZ arms, nor in the MTX and ADA arms (table 1). Repeated measures analyses to week 24 showed no significant differences in DAS28 or CDAI. Statistically significant predictors for the various clinical outcomes included baseline CDAI, baseline DAS28, age, sex, RA duration and region. A numerically higher but not significantly different SAE rate was seen in the GC-arms of all four trials, compared to the non-GC-arms.Conclusions:No evidence was found that GC treatment at baseline and continued at a stable dose affects either clinical efficacy or safety over 24 weeks of TCZ, MTX, or ADA monotherapy initiated at baseline in RA clinical trials.References[1]Jones G, et al. Ann Rheum Dis2010;69:88–96.[2]Dougados M, et al. Ann Rheum Dis2013;72:43–50.[3]Gabay C, et al. Lancet2013;381:1541–50[4]Burmester GR, et al. Ann Rheum Dis2017;76:1279–84.Disclosure of Interest:M. Safy Grant/research support from: Research grant from AZ, J. Jacobs: None de...

Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis

“…In the only similar study of another targeted DMARD published to date, pooled data from six clinical trials of tofacitinib in RA found no significant effect on the efficacy of tofacitinib in patients with GC use compared with patients without GC use, with some slight differences between patients with and without concomitant csDMARD use [6]. Consistent with the findings of the current evaluation, an analysis of pooled data from four clinical trials of TCZ-IV in patients with RA found no evidence that concomitant GC therapy affected the proportion of patients who achieved DAS28-ESR–defined remission [21]. Although concomitant GC use did not appear to affect the efficacy of TCZ-SC, a slight numerical trend toward better control of disease activity by DAS28-ESR composite score was observed with GC use in patients who received TCZ-SC monotherapy, but this trend was not visible in the TCZ-SC + csDMARD subgroups, possibly due to overlapping effects of csDMARDs and GCs.…”

“…Potential effects of concomitant medications used to treat comorbid conditions were not evaluated. Despite a large sample size in the phase 4 setting, the population of the common-framework TOZURA study programme was likely less heterogeneous than the populations of pooled analyses of multiple clinical trials [6,21].…”

Safety and Efficacy of Baricitinib in Patients Receiving Conventional Synthetic Disease-Modifying Antirheumatic Drugs or Corticosteroids

“…As in our study, in patients who used glucocorticoids through baseline and then with tofacitinib during the phase 3 studies, their post hoc analysis found that the concomitant use of the glucocorticoids did not appear to affect clinical efficacy [ 7 ]. A study of glucocorticoids taken with tocilizumab during RA trials also found no evidence that concomitant glucocorticoid therapy affected efficacy and safety [ 8 ].…”

Glucocorticoids in rheumatoid arthritis: current status and future studies

“…Moreover, in an analysis presented at the 2018 ACR meeting but not yet published of pooled data from four RCTs (AMBITION, ACT-RAY, ADACTA and FUNCTION) on intravenous tocilizumab (TCZ), concomitant GC therapy had no impact on the clinical efficacy of TCZ at 24 weeks 42. The authors assessed patients in the comparator arms: the clinical response of patients receiving adalimumab as well as those initiating MTX was not affected by the use of GCs.…”