Briakinumab (Anti-interleukin 12/23p40, ABT874) for Treatment of Crohnʼs Disease (CD) (2010)

Purpose: To evaluate efficacy of briakinumab, an antibody against interleukin 12/23p40, for the induction and maintenance treatment of CD. Methods: 230 patients (pts) with moderately to severely active CD (CDAI 220-400) were randomized 3:1:1 to briakinumab 700 mg (n=139) or 400 mg (n=45), or placebo (pbo; n=46) infusions at Weeks (Wk) 0, 4, and 8. Primary endpoint was clinical remission (CDAI<150) at Wk 6. Pts who responded (decrease from Wk 0 CDAI ≥ 70 points) to induction therapy at Wk 12 were eligible for maintenance therapy. Pts treated with induction briakinumab 400 mg (n=21) or pbo (n=14) who responded at Wk 12 received maintenance treatment with the same therapy at Wk 12, 16, and 20. Pts treated with induction briakinumab 700 mg who responded at Wk 12 were re-randomized to maintenance briakinumab 700 mg (n=21) or 200 mg (n=21), or pbo (n=22) at Wk 12, 16, and 20 and assessed at Wk 24. Secondary end-points included clinical remission at Wk 12 and 24 (among pts responding at Wk 12). Results: Proportion of pts in remission at Wk 6 was 8.7% with pbo, 13.3% with briakinumab 400 mg (p=0.455, CI for difference in proportions = -8.1%, 18.1%) and 17.3% with briakinumab 700 mg (p=0.157, CI=-3.3%, 20.6%). The proportion of pts in remission at Wk 12 was 10.9% with pbo, 28.9% with briakinumab 400 mg (p=0.030, CI=1.8%, 34.9%) and 22.3% with briakinumab 700 mg (p=0.087, CI=-1.7%, 25.0%). Among pts continuing maintenance treatment, the proportion of pts in remission at Wk 24 was 28.6% in pts continuing pbo, 52.4% of pts continuing briakinumab 400 mg (p=0.219), and 57.1% of pts continuing briakinumab 700 mg (p=0.109). Among pts who received induction briakinumab 700 mg and were re-randomized, the proportion of pts in remission at Wk 24 was 47.6% in pts re-randomized to pbo, 42.9% of pts re-randomized to briakinumab 200 mg, and 57.1% of pts re-randomized to briakinumab 700 mg (same pts in preceding sentence who continued briakinumab 700 mg). 173 pts (75.2%) previously received anti-TNF therapy. Subgroup analyses suggested trends towards worse outcome for induction treatment of pts with primary non-response to anti-TNF therapy. During the induction portion of the study, serious adverse events (SAEs) occurred in 4.5% of pts on briakinumab and 8.7% on pbo, including 0.5% with a serious infection on briakinumab and 2.2% with a non-melanoma skin cancer on pbo. During the maintenance portion of the study, SAEs occurred in 2.2% of pts on briakinumab and 7.1% on pbo, including 1.1% with a serious infection on briakinumab. One pt died of respiratory distress failure due to pancreatitis 2 months after last dose of briakinumab. Conclusion: Among pts with moderate to severe CD, briakinumab was not effective for induction or maintenance of remission. Disclosure: Dr Remo Panaccione: Financial Support for Research from: Abbott, Osiris Therapeutics Inc, UCB Inc, Lecture Fee(s) from: Abbott, Centecor Inc, Elan Pharmaceuticals, Inc, Medscape, Consultancy for: Abbott, Axcan Pharma Inc, Biogen/IDEC, Bristol-Myers Squibb, Centocor, Inc, Chemocentryx, Elan Pharmaceuticals, Inc, Ferring Pharmaceuticals Inc, Genetech Inc, UCB Inc Other: Abbott, Axcan Pharma, Centocor Inc, Chemocentryx, Elan Pharmaceuticals, Inc, Genetech Inc, Lippincott Williams & Wilkins, Novartis, PDL BioPharma DrWilliam Sandborn: Financial Support for Research: Abbott Laboratories, Bristol Meyers Squibb, CentocorOrthoBiotech, Genentech, Millennium Pharmaceuticals, Novartis, Pfizer, Shire Pharmaceuticals, UCB Pharma, Warner Chilcott (previously Procter & Gamble) Consultancy: ActoGenix, Abbott Laboratories (fees paid to Mayo), AGI Therapeutics, Albireo, Alfa Wassermann, AM-Pharma, Amgen, Anaphore, Astellas Pharma, Athersys, Atlantic Healthcare Limited, Axcan Pharma, BioBalance Corporation, Celegene, Bristol Meyers Squibb (fees paid to Mayo), Celek Pharmaceuticals, Cellerix, CentocorOrthoBiotech (fees paid to Mayo), Chemocentryix, CoMentis, Cosmo Technologies, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research, Elan Pharmceuticls (fees paid to Mayo), Eli Lilly, Enteromedics, Ferring Pharmaceuticals, Flexion Therapeutics, Funxional Therapeutics Limited, Genentech (fees paid to Mayo), Given Imaging, GlaxoSmithKline, KaloBios Pharmaceuticals, Merck Research Laboratories, Merck Serono, Novo Nordisk, Pfizer (fees paid to Mayo), Procter & Gamble (fees paid to Mayo), Purgenesis Technologies, Regeneron Pharmaceuticals, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough Corporation, Shire Pharmaceuticals (fees paid to Mayo), Sigmoid Pharma, Sitrtis Pharmaceuticals, SLA Pharma, Takeda (fees paid to Mayo), Tillotts Pharma, UCB Pharma (fees paid to Mayo), Vascular Biogenics, Viamet Pharmaceuticals, Wyeth Dr Glenn Gordon: Abbott, Other financial benefit, Speaking and Grant/Research Support Axcan Pharma Inc., Other financial benefit, Grant/Research Support Bristol-Myers Squibb, Other financial benefit, Grant/Research Support Centocor, Other financial benefit, Grant/Research Support Eisai Co.Ltd, Other financial benefit, Grant/Research Support Elan Pharmaceuticals, Inc., Other financial benefit, Speaking Evoke Pharma, Other financial benefit, Grant/Research Support Fleming, Self: Consulting fee, Consulting Luitpold Pharmaceuticals, Other financial benefit, Grant/Research Support Merck and Company, Other financial benefit, Grant/Research Support Procter & Gamble Pharmaceuticals, Other financial benefit, Speaking and Grant/Research Support Prometheus Laboratories, Other financial benefit, Speaking, Consulting and Grant/Research Support Revogenex, Other financial benefit, Grant/Research Support Salix Pharmaceuticals, Other financial benefit, Speaking, Consulting and Grant/Research Support Shire Pharmaceuticals Group, Other financial benefit, Grant/Research Support Takeda Pharmaceutical Company Ltd, Other financial benefit, Speaking and Teaching and Grant/Research Support UCB Pharma, Other financial benefit, Speaking, Consulting and Grant/Research Support Dr Scott Lee:Abbott, Self: Consulting fee, Advisory Committees or Review Panels Abbott, Self: Consulting fee, Grant/Research Support; Abbott, Self: Consulting fee, Speaking and Teaching; Centocor, Inc.,Self: Consulting fee, Advisory Committees or Review Panels; Centocor, Inc., Self: Consulting fee, Grant/Research Support Centocor, Inc., Self: Consulting fee, Speaking and Teaching;Elan Pharmaceuticals, Inc., Self: Grant/Research Support; Millennium Research Group, Self: Salary, Grant/Research Support; Salix Pharmaceuticals, Inc., Self: Salary, Grant/Research Support; UCB, Inc., Self: Consulting fee, Advisory Committees or Review Panels; UCB, Inc., Self: Consulting fee, Grant/Research Support; UCB, Inc., Self: Consulting fee, Speaking and Teaching Dr Alan Safdi: Dr Shahriar Sedghi: Salix Pharmaceuticals, Inc., Other financial benefit, Speaking and Teaching Dr Brian Feagan: Abbott, Self: Consulting fee, Consulting Abbott, Self: Consulting fee, Grant/Research Support Albireo Pharmaceuticals, Self: Consulting fee, Consulting Bristol-Myers Squibb Co., Self: Consulting fee, Grant/Research Support Celgene Corporation, Self: Consulting fee, Advisory Committees or Review Panels Centocor, Inc., Self: Consulting fee, Consulting Centocor, Inc.,Self: Consulting fee, Grant/Research Support Elan Pharmaceuticals, Inc., Self: Consulting fee, Advisory Committees or Review Panels Elan Pharmaceuticals, Inc., Self: Consulting fee, Consulting Funxtional Therapeutics, Self: Consulting fee, Consulting GlaxoSmithKline, Self: Consulting fee, Consulting Merck - consulting fee/speaking Millennium Pharmaceuticals, Self: Consulting fee, Consulting NovoNordisk,Self: Consulting fee, Consulting Ore Pharmaceuticals, Inc., Self: Consulting fee, Consulting Otsuka America Pharmaceutical Inc., Self: Consulting fee, Grant/Research Support Procter & Gamble Pharmaceuticals, Self: Consulting fee, Consulting Prometheus Laboratories Inc., Self: Consulting fee, Consulting Salix Pharmaceuticals, Inc., Self: Consulting fee, Consulting Schering Canada, Self: Consulting fee, Grant/Research Support Schering-Plough Canada Inc, Self:Consulting fee, Consulting Shire Pharmaceuticals Inc., Self: Consulting fee, Consulting Tillotts Pharma, Self: Consulting fee, Advisory Committees or Review Panels UCB Pharma Inc, Self: Consulting fee, Advisory Committees or Review Panels; UCB, Inc., Self: Consulting fee, Consulting UCB, Inc., Self: Consulting fee, Speaking and Teaching Dr Stephen Hanauer: Lecture Fee(s) from: Elan Pharmaceuticals, Consultancy for: Abbott, Millenium Pharma, Novartis Pharmaceuticals, Proctor & Gamble Pharmaceuticals, Prometheus Laboratories Inc Other: Abbott, Amgen, Bristol-Myers Squibb, Caremark, Centocor, CVS/Caremark, Elan Pharmaceuticals, Eli Lilly, Genetech, McNeal Pharma, Millenium Pharma, Proctor & Gamble Pharmaceuticals, Salix Pharmaceuticals Inc, Shire U.S. Inc, Takeda, Warner Chilcotte, Wyeth Pharmaceuticals Ashish Kumar: Employee, Abbott Dr Roberto Carcereri: Employee, Abbott.