OP36 Efficacy and safety of combination induction therapy with guselkumab and golimumab in participants with moderately-to-severely active Ulcerative Colitis: Results through week 12 of a phase 2a randomized, double-blind, active-controlled, parallel-group, multicenter, proof-of-concept study

Abstract

Background Preclinical data from a murine model of acute colitis suggest that dual blockade of interleukin(IL)-23 and TNFα more effectively prevented the development of colonic inflammation than each monotherapy. Guselkumab(GUS), an IL-23p19 subunit antagonist, is being studied in inflammatory bowel disease. Golimumab(GOL), a TNFα antagonist, is approved for ulcerative colitis(UC). The objective of this study was to evaluate the efficacy and safety of combination induction therapy with GUS+GOL vs GUS or GOL alone in adults with moderately-to-severely active UC. Methods 214 patients(pts) naïve to TNFα antagonists and refractory or intolerant to conventional therapy(ie, immunomodulators and/or corticosteroids) were randomly assigned to receive GUS 200mg intravenous(IV) at weeks(wks) 0, 4, and 8(n=71); GOL 200mg subcutaneous(SC) at wk0 then 100mg SC at wks2, 6, and 10(n=72); or combination with GUS 200mg IV+GOL 200mg SC at wk0, GOL 100mg SC at wks2, 6, and 10, and GUS 200mg IV at wks4 and 8(n=71). The primary endpoint was clinical response at wk12; the major secondary endpoint was clinical remission at wk12. Other key endpoints were clinical remission based on the modified Mayo score (mMayo), symptomatic remission, endoscopic improvement, endoscopic normalization, histologic remission, composite histologic-endoscopic endpoints, and biomarker outcomes. Results Baseline disease characteristics were similar among groups(Table 1), however a greater proportion of pts in both monotherapy groups had pancolitis vs the combination group. A greater proportion of pts who received combination therapy achieved clinical response at wk12(83.1%) vs GUS(74.6%) or GOL(61.1%)(Table 2). Similarly, the proportion of pts who achieved clinical remission in the combination group(36.6%) was greater than that of monotherapy groups(21.1% and 22.2%, respectively). Clinical remission by mMayo score, endoscopic improvement, histologic remission, both histologic remission and endoscopic improvement, and biomarker normalization (calprotectin, CRP) rates at wk12 were also greater in the combination group vs GUS or GOL. Percentages of pts with endoscopic normalization and both histologic remission and endoscopic normalization were nearly double with combination therapy vs either monotherapy. Adverse event(AE), serious AE, and infection rates were comparable among treatment groups. One pt receiving combination therapy experienced a serious infection of influenza and sepsis. No deaths, malignancies, or TB cases were reported through wk12. Conclusion Combination induction treatment with GUS+GOL more effectively induced clinical response, clinical remission, and endoscopic improvement at wk12 than either monotherapy alone. AE rates were comparable among the treatment groups.

The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment)

“…The VEGA study (NCT03662542) was a phase 2 induction trial evaluating the combination of an anti-IL-23 (guselkumab) and an anti-TNF (golimumab) in patients with moderately to severely active UC with a history of inadequate response to or failure to conventional therapy. Initial results support both the efficacy and safety of ACT with guselkumab and golimumab 82. A greater proportion of patients receiving combination therapy achieved clinical response (59/71, 83.1%) after 12 weeks compared with monotherapy with either guselkumab (53/71, 74.6%) or golimumab (44/72, 61.1%).…”

Positioning biologics in the treatment of IBD: A practical guide – Which mechanism of action for whom?

“…This 3-arm trial presented as one of the highlights of the recent ECCO congress 2022, compared golimumab (GOL), guselkumab (GUS) and their combined use during induction period of 12 weeks. This showed a significant higher rate of clinical response (83% for combination therapy vs. 75% for GUS (p ​= ​0.215) and 61% for GOL (p ​= ​0.003)) and clinical remission (47% for combination therapy vs. 24% for GUS (p ​= ​0.005) and 25% for GOL (p ​= ​0.007) based on modified Mayo score) without added risks for safety in moderate to severely active UC patients naïve to biologics ( Sands et al., 2022 ).…”

Integrating new and emerging therapies into inflammatory bowel disease clinical practice

“…High quality evidence showing the efficacy of combination therapy is scarce. The VEGA study was a proof-of-concept randomized phase 2 study of patients with UC that showed that the combination of guselkumab and golimumab was better than either drug alone [63 ▪▪ ]. A systematic review by Ahmed et.…”