Efficacy and safety of golimumab 52-week maintenance therapy in Japanese patients with moderate to severely active ulcerative colitis: a phase 3, double-blind, randomized, placebo-controlled study-(PURSUIT-J study)

Abstract

BackgroundThe global phase 3 studies of golimumab [PURSUIT-SC and PURSUIT-maintenance (M)], an anti-tumor necrosis factor-α (anti-TNFα) antibody, have demonstrated clinical efficacy and safety as induction and maintenance therapies in patients with moderate to severely active ulcerative colitis (UC). This study aimed to evaluate the efficacy and safety of golimumab as maintenance therapy in the Japanese population. MethodsIn this phase 3, double-blind (DB), placebo-controlled, parallel group, randomized withdrawal study, 144 Japanese patients with moderately to severely active UC received golimumab doses of 200 mg (at week 0) and 100 mg (at week 2) subcutaneously during the 6-week open-label induction phase. Patients who responded to golimumab induction therapy entered the DB maintenance (M) phase and were randomized (1:1) to receive 100 mg of golimumab subcutaneous injection (SC) or placebo every 4 weeks for 52 weeks. The primary endpoint was clinical response through M-week 54; secondary endpoints included clinical remission and mucosal healing at M-week 30 and 54.ResultsAmong induction responders, more patients on golimumab treatment (56.3%) maintained clinical response through M-week 54 versus the placebo group (19.4%). At both M-week 30 and 54, 50% golimumab-treated patients achieved clinical remission versus the placebo group (6.5%) and a higher proportion of patients on golimumab (59.4%) experienced mucosal healing than the placebo group (16.1%). Incidence of treatment-emergent adverse events was 96.9% in the golimumab group and 71% in the placebo group. Overall, the efficacy and safety results in this study were comparable with those observed in global studies.ConclusionsGolimumab SC treatment maintained clinical efficacy through week 54 among induction responders, and no new safety signals were observed in the patients with moderate to severely active UC.Clinical Trial Registration: The study is registered at ClinicalTrials.gov NCT01863771.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-017-1326-1) contains supplementary material, which is available to authorized users.

Systematic review with network meta‐analysis: comparative assessment of tofacitinib and biological therapies for moderate‐to‐severe ulcerative colitis

“…The current work extends our previously published systematic review and network meta‐analysis, which searched for data through December 2013, by adding one more treatment comparator in the network (ie tofacitinib) and using a much broader evidence base (ie 3 more RCTs of biologics published after 2014 and 4 RCTs of tofacitinib), and provides updated evidence to inform patient management decisions.…”

“…Figure summarises the evidence search and selection process. Thirteen full‐text publications reported the results of 19 eligible studies (ACT 1; ACT 2; ULTRA 1, ITT‐A3; ULTRA 1, ITT‐E; ULTRA 2; Study A3921063; GEMINI 1, induction; GEMINI 1, maintenance; PURSUIT‐SC, phase 3; PURSUIT‐SC, phase 2; PURSUIT‐SC, phase 2 additional; PURSUIT‐M; Suzuki et al. ; Jiang et al.…”

Systematic review with network meta‐analysis: first‐ and second‐line pharmacotherapy for moderate‐severe ulcerative colitis

“…From a total 1866 unique studies identified using our search strategy, we included 12 RCTs of first‐line agents (in biologic‐naïve patients), (ACT 1 and 2, Jiang et al, NCT01551290, ULTRA 1 and 2, Suzuki et al, PURSUIT, GEMINI I, OCTAVE 1 and 2) and 4 of second‐line agents (in patients with prior anti‐TNF exposure), in patients with moderate‐severe ulcerative colitis (ULTRA 2, GEMINI I, OCTAVE 1 and 2). Trials of infliximab (ACT 1 and 2, Jiang et al, NCT01551290,), adalimumab (ULTRA 2, Suzuki et al) and vedolizumab (GEMINI I) also reported outcomes on maintenance therapy, within the same publication; PURSUIT‐M, PURSUIT‐J and OCTAVE‐SUSTAIN reported outcomes for maintenance therapy with for golimumab and tofacitinib respectively . The schematic diagram of study selection is shown in Figure S1 and available direct comparisons and network of trials are shown in Figure and (and Figure S2A and S2B).…”

Systematic review with network meta‐analysis: the impact of medical interventions for moderate‐to‐severe ulcerative colitis on health‐related quality of life

“…Through the selection process presented in flow diagram in Figure , we identified 38 records corresponding to 16 randomised placebo‐controlled trials (4728 patients) (Table S2). Two studies (NCT01551290, PURSUIT‐J) provided incomplete data on HRQL outcomes and could not be included in the meta‐analysis. Thirteen trials assessed impact on HRQL during induction therapy with infliximab (n = 3, ACT1, ACT2, Probert 2003), adalimumab (n = 3, ULTRA 1, ULTRA 2, Suzuki 2014), golimumab (n = 3, PURSUIT‐SC [phase 2, phase 2 additional, phase 3]), vedolizumab (n = 1, GEMINI 1) and tofacitinib (n = 3, Sandborn 2012, OCTAVE 1, OCTAVE 2).…”

“…Through the selection process presented in flow diagram in Figure 1, we identified 38 records corresponding to 16 randomised placebo-controlled trials (4728 patients) (Table S2). Two studies (NCT01551290, PURSUIT-J) 25,26 provided incomplete data on HRQL outcomes and could not be included in the meta-analysis. Thirteen trials assessed impact on HRQL during induction therapy with infliximab (n = 3, ACT1, 27 ACT2, 27 (Table S3).…”