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OP28 The effect of guselkumab induction therapy on early clinical outcome measures in patients with Moderately to Severely Active Crohn’s Disease: Results from the phase 2 GALAXI 1 study

Danese, S.(1);Sandborn, W.J.(2);Feagan, B.G.(3);Weisel, K.(4);Gonzalez, S.(4);Frustaci, M.E.(4);Yang, Z.(4);Johanns, J.(4);Germinaro, M.(4);Afzali, A.(5);Andrews, J.M.(6);D’Haens, G.(7);Hisamatsu, T.(8);Panaccione, R.(9);Reinisch, W.(10);Rubin, D.T.(11);Sands, B.E.(12);Panes, J.(13)

(1)Humanitas Research Hospital, Inflammatory Bowel Diseases Center, Milan, Italy;(2)University of California San Diego, Health Sciences- Gastroenterology, La Jolla- California, United States;(3)Robarts Clinical Trials-Western University, Gastroenterology, London- Ontario, Canada;(4)Janssen Research & Development- LLC, Immunology, Spring House- Pennsylvania, United States;(5)Ohio State University Wexner Medical Center, Gastroenterology, Columbus Ohio, United States;(6)Royal Adelaide Hospital & University of Adelaide, Dept of Gastroenterology and Hepatology, Adelaide- South Australia, Australia;(7)Amsterdam UMC, Gastroenterology, Amsterdam, The Netherlands;(8)Kyorin University, Gastroenterology and Hepatology, Tokyo, Japan;(9)University of Calgary, Gastroenterology & Hepatology, Calgary- Alberta, Canada;(10)Medical University of Vienna, Division of Gastroenterology and Hepatology, Vienna, Austria;(11)University of Chicago Medicine Inflammatory Bowel Disease Center, Gastroenterology, Chicago- Illinois, United States;(12)Icahn School of Medicine at Mount Sinai, Gastroenterology, New York- New York, United States;(13)Hospital Clínic de Barcelona- IDIBAPS- CIBERehd, Gastroenterology, Barcelona, Spain GALAXI 1 Investigators

Background

Guselkumab (GUS), an IL-23 antagonist, is being investigated for the treatment of IBD. GALAXI 1 is a ph2, double-blind, PBO-controlled study in pts with moderately to severely active CD with inadequate response or intolerance to conventional therapies (corticosteroid, immunosuppressant) and/or biologics (TNF antagonist, vedolizumab). Here we report early clinical outcome measures during induction with GUS vs PBO.

Methods

Pts with moderate to severe CD (CDAI score 220-450) were randomized 1:1:1:1:1 to GUS 200, 600 or 1200mg IV at Wks 0, 4, 8; ustekinumab (UST) ~6mg/kg IV at Wk 0 and 90mg SC at Wk8; or PBO IV. Clinical remission (CDAI score<150), clinical response (≥100-point reduction from baseline in CDAI score or CDAI score<150), and clinical-biomarker response (clinical response and ≥50% reduction from baseline in CRP or fecal calprotectin) were evaluated at Wks 4, 8 and 12 for pooled GUS arms vs PBO. UST was a reference arm.

Results

Two hundred fifty pts were evaluated; about 50% failed previous biologic therapy. Baseline demographics and disease characteristics were generally similar among treatment groups (mean CD duration, 8.8yr; mean CDAI, 306.2; median CRP, 5.4mg/L; median fecal calprotectin, 594.0mg/kg). At Wk4, clinical remission was achieved in 20.0% of GUS-treated pts compared with 11.8% of PBO-treated pts. A greater proportion of GUS-treated pts achieved clinical remission compared with PBO-treated pts at Wk8 (42.0% vs 15.7%) and Wk12 (54.0% vs 15.7%). Similarly, within each subgroup of pts who failed biologic therapy(BIO-failures) or conventional therapy(CON-failures), GUS-treated pts achieved a higher rate of clinical remission at Wks 4, 8 and 12 compared with PBO (Fig 1). The proportion of pts who achieved clinical response and clinical-biomarker response was also higher at Wks 4, 8 and 12 among GUS-treated pts compared with PBO-treated pts. From Wks 4 to 8 to 12, the proportion of GUS-treated pts in clinical response increased from 44.0% to 56.0% to 66.0%, respectively, and the proportion in clinical-biomarker response increased from 26.0% to 43.3% to 48.0%. In contrast, the proportion of PBO-treated pts who achieved clinical response and clinical-biomarker response remained stable or decreased from Wks 4 to 8 to 12: 25.5% to 25.5% to 23.5% and 13.7% to 9.8% to 7.8%, respectively (Fig 2).

Conclusion

In pts with moderately to severely active CD, induction treatment with GUS combined treatments versus PBO resulted in higher rates of overall clinical remission, clinical-biomarker response, and clinical response as early as Wk4. This continued to increase through Wk12 with treatment. The early trend for achievement of clinical remission was also evident in sub-groups of pts who failed biologic or conventional therapy.

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