Blanco, Paola, MD

Shah, Hiral N, MD

Shah, Shashin, MD

Sullivan, Matthew, DO

English

Lehigh Valley Health Network: LVHN Scholarly Works

Lehigh Valley Health NetworkLVHN Scholarly WorksDepartment of MedicineAttempted Salvage Therapy Through Initiation ofVedolizumab as an Inpatient in Two Patients withRefractory Active Ulcerative ColitisMatthew Sullivan DOLehigh Valley Health Network, Matthew.Sullivan@lvhn.orgPaola Blanco MDLehigh Valley Health Network, Paola_G.Blanco@lvhn.orgShashin Shah MDLehigh Valley Health Network, Shashin.Shah@lvhn.orgHiral N. Shah MDLehigh Valley Health Network, hiral_n.shah@lvhn.orgFollow this and additional works at: http://scholarlyworks.lvhn.org/medicinePart of the Gastroenterology Commons, and the Medical Sciences CommonsThis Poster is brought to you for free and open access by LVHN Scholarly Works. It has been accepted for inclusion in LVHN Scholarly Works by anauthorized administrator. For more information, please contact LibraryServices@lvhn.org.Published In/Presented AtSullivan, M., Blanco, P., Shah, S., Shah, H. (October 2015). Attempted Salvage Therapy Through Initiation of Vedolizumab as an Inpatientin Two Patients with Refractory Active Ulcerative Colitis. Poster presented at: American College of Gastroenterology Annual ScientificMeeting, Honolulu, HI.Sullivan, M., Blanco, P., Shah, S., Shah, H. (2016, April 26). Attempted Salvage Therapy Through Initiation of Vedolizumab as an Inpatientin Two Patients with Refractory Active Ulcerative Colitis. Poster presented at LVHN Department of Medicine Research Day, LehighValley Health Network, Allentown, PA.A 40 Year-Old Male1Department of Internal Medicine, 2Department of Gastroenterology and Hepatology, Lehigh Valley Health Network, Allentown, PennsylvaniaAttempted Salvage Therapy Through Initiation of Vedolizumab as an Inpatient in Two Patients with Refractory Active Ulcerative ColitisMatthew J. Sullivan, DO1, Paola Blanco, MD2, Shashin Shah, MD2, and Hiral Shah, MD2Background•	 	Ulcerative	colitis	(UC)	is	a	chronic	inflammatory	bowel	disease	which	can	cause	bloody	diarrhea,	abdominal	cramps,	and	fatigue.1•	 	Disease	severity	in	UC	is	measured	using	multiple	scoring	systems	such	as	the	Mayo	Clinic	score	which	takes	into	account	stool	frequency,	rectal	bleeding,	endoscopic	appearance,	and	a	global	assessment.		A	higher	score	correlates	with	more	severe	disease	and	the	maximum	score	is	12.2		The	Inflammatory	Bowel	Disease	Questionnaire	(IBDQ)	which	considers	social	and	emotional	factors	is	used	as	well.3•	 	Severe	acute	UC	is	defined	as	≥6	stools	per	day,	tachycardia,	anemia,	and	elevated	erythrocyte	sedimentation	rate.		Between	18-25%	of	UC	patients	will	experience	an	episode	of	severe	acute	UC	and	20-30%	of	these	patients	will	require	colectomy.4•	 	The	management	of	UC	has	changed	greatly	due	to	the	introduction	of	tumor	necrosis	factor-alpha	(TNF-α)	antagonists	such	as	adalimumab	and	infliximab.	However,	there	is	a	subset	of	patients	with	moderate	to	severe	disease	who	are	refractory	or	intolerant	to	these	medications.	It	is	also	thought	that	30-40%	of	patients	will	lose	response	to	TNF	antagonists	over	time.5•	 	Vedolizumab	is	a	recombinant	humanized	IgG1	monoclonal	antibody	which	binds	α4β7	integrin	resulting	in	a	“gut	selective”	anti-inflammatory	effect	by	inhibiting	interaction	with	mucosal	addressin-cell	adhesion	molecule	1	(MAdCAM-1)	and	therefore	preventing	migration	of	leukocytes.1,6•	 	Clinical	trials,	such	as	GEMINI	I,	have	shown	vedolizumab	to	be	effective	as	both	induction	and	maintenance	therapy	for	UC.1		•	 	Induction	dosing	is	a	300mg	infusion	given	over	30	minutes	at	weeks	0,	2,	and	6	followed	by	maintenance	infusions	every	8	weeks	thereafter.		It	is	indicated	for	adults	with	moderate	to	severe	active	UC	who	have	had	an	inadequate	response	with,	lost	response	to,	or	were	intolerant	to	a	TNF-α	blocker.7Discussion:© 2015 Lehigh Valley Health NetworkReferences:1.	 	Feagan	BG,	Rutgeerts	P,	Sands	BE,	et	al.	Vedolizumab	as	Induction	and	Maintenance	Therapy	for	Ulcerative	Colitis.	N	Engl	J	Med.	2013	Aug	22;369:699-710.2.	 	Rutgeerts	P,	Sandborn	WJ,	Feagan	BG,	et	al.	Infliximab	for	Induction	and	Maintenance	Therapy	for	Ulcerative	Colitis.	N	Engl	J	Med.	2005	Dec	8;353:2462-2476.	3.	 	Han	SW,	McColl	E,	Steen	N,	et	al.	The	Inflammatory	Bowel	Disease	Questionnaire:	A	Valid	and	Reliable	Measure	in	Ulcerative	Colitis	Patients	in	the	North	East	of	England.	Scand	J	Gastroenterol.	1998	Sep;33(9):961-966.4.	 	Bitton	A,	Buie	D,	Enns	R,	et	al.	Treatment	of	Hospitalized	Adult	Patients	With	Severe	Ulcerative	Colitis:	Toronto	Consensus	Statements.	Am	J	Gastroenterol.	2012;107:179-194.5.	 	Gilroy	L	and	Allen	PB.	Is	there	a	role	for	vedolizumab	in	the	treatment	of	ulcerative	colitis	and	Crohn’s	disease?	Clin	Exp	Gastroenterol.	2014	May	22;7:163-172.•	 	Clinical	trials	have	established	that	vedolizumab	is	safe	and	effective	in	patients	with	moderate	to	severe	UC,	including	those	who	have	previously	failed	TNF	antagonist	therapy.		This	has	lead	to	FDA	approval	in	this	cohort	of	patients.•	 	In	an	early	trial	of	MLN02,	the	precursor	of	vedolizumab,1	181	adults	with	active	UC	demonstrated	a	clinical	remission	rate	of	33%	by	six	weeks	following	vedolizumab	infusions	at	days	1	and	29.	However,	patients	in	this	study	were	naïve	to	TNF	antagonists	and	those	with	severe	disease	were	excluded.8	•	 	GEMINI	I	expanded	on	this	study	and	validated	effectiveness	of	vedolizumab	over	placebo	for	both	induction	and	maintenance	as	measured	by	reduction	in	Mayo	Clinic	and	IBDQ	scores,	mucosal	healing,	fecal	calprotectin	levels,9	and	decreased	concomitant	glucocorticoid	requirements.		This	study	enrolled	patients	with	previous	unsuccessful	treatment	with	glucocorticoids,	immunosuppressive	medications,	or	TNF	antagonists,	and	71.5%	of	enrolled	patients	were	continued	on	glucocorticoids	and/or	immunosuppressants	during	the	trial.1			•	 	GEMINI	I	also	looked	at	vedolizumab	concentrations	during	treatment	and	found	that	both	every	4	week	and	every	8	week	dosing	regimens	resulted	in	>95%	saturation	of	α4β7	integrin	on	targeted	T	cells.1•	 	Our	patients	were	initiated	on	vedolizumab	as	inpatients	during	severe	acute	colitis	for	attempted	salvage	therapy	after	failing	TNF	antagonists	and	neither	was	able	to	avoid	surgery.•	 	One	of	the	listed	limitations	of	GEMINI	I	was	that	it	“was	not	designed	to	identify	the	time	of	the	maximal	effect	of	vedolizumab	as	induction	therapy.”		Also,	the	number	of	patients	with	previous	TNF	antagonist	use	was	only	40%	and	those	who	received	a	TNF	antagonist	within	60	days	were	ineligible	for	enrollment.1•	 	Further	studies	of	vedolizumab	are	required	in	the	setting	of	severe	acute	colitis	when	glucocorticoids	and/or	TNF	antagonists	have	failed;	where	it	has	great	potential	benefit	to	disease	control	and	patient	quality	of	life.…progressed	from	mild	ulcerative	proctitis	to	pancolitis	over	the	course	of	a	few	months	with	worsening	abdominal	pain,	bloody	diarrhea,	and	intolerance	to	oral	intake.		He	previously	received	the	induction	dose	of	infliximab	without	significant	improvement	to	his	symptoms	and	had	already	been	referred	to	colorectal	surgery	to	discuss	surgical	options.		As	his	symptoms	progressed	he	was	admitted	for	generalized	weakness	and	malnutrition	and	reported	up	to	18	stools	per	day.		Colonoscopy	revealed	severe	diffuse	inflammation	consistent	with	active	UC	(Image	1).		Due	to	the	severity	of	his	disease	it	was	decided	to	initiate	the	patient	on	vedolizumab	during	his	inpatient	stay.		His	Mayo	Clinic	score	at	that	time	was	≥11.		Unfortunately,	he	did	not	respond	and	required	total	colectomy	during	this	hospitalization.A 75 Year-Old Female…with	a	three	year	history	of	UC	was	admitted	with	increased	stool	frequency	and	bloody	bowel	movements	shortly	after	completing	a	steroid	taper.		She	had	been	initiated	on	infliximab	at	the	time	of	her	diagnosis	but	this	had	been	discontinued	due	to	intolerance	and	was	being	treated	with	mesalamine	at	time	of	admission.		Colonoscopy	revealed	severe	pancolitis	with	mucosal	edema,	friability,	and	spontaneous	oozing	(Image	2).		She	was	evaluated	by	colorectal	surgery,	but	her	preference	was	to	avoid	surgery	and	the	decision	was	made	to	initiate	vedolizumab.		At	this	point	her	Mayo	Clinic	score	was	≥9.		She	received	her	first	dose	as	an	inpatient	and	stabilized	enough	to	allow	discharge.		However,	she	was	soon	readmitted	with	worsening	symptoms	and	required	total	colectomy	with	end	ileostomy.Acknowledgements:Victoria	Loven,	MD	for	providing	biopsy	images.6.	 	Bickston	SJ,	Behm	BW,	Tsoulis	DJ,	et	al.	Vedolizumab	for	induction	and	maintenance	of	remission	in	ulcerative	colitis.	Cochrane	Database	Syst	Rev.	2014	Aug	8;8:CD007571.7.	 	Takeda	Pharmaceuticals	U.S.A.,	Inc.	Indications.	Entyvio.	https://www.entyviohcp.com/.	Accessed	16	Sept	2015.	8.	 	Feagan	BG,	Greenberg	GR,	Wild	G,	et	al.	Treatment	of	Ulcerative	Colitis	with	a	Humanized	Antibody	to	the	α4β7	Integrin.	N	Engl	J	Med.	2005	June	16;352:2499-2507.9.	 	Wagner	M,	Peterson	CGB,	Ridefelt	P,	et	al.	Fecal	markers	of	inflammation	used	as	surrogate	markers	for	treatment	outcome	in	relapsing	inflammatory	bowel	disease.	World	J	Gastroenterol.	2008	Sep	28;14(36):5584-5589.Image 1. Colonoscopy	revealing	continuous,	diffuse	inflammation	consistent	with	severe	ulcerative	colitis.Image 3. Colon	biopsy	demonstrating	crypt	destruction	and	loss	with	expansion	of	the	lamina	propria	by	inflammatory	cells	and	surface	ulceration.Image 2. Colonoscopy	exhibiting	severe	mucosal	changes	of	ulcerative	colitis	including	friability,	mucus,	and	circumferential	edema	with	oozing.Image 4. Colon	biopsy	demonstrating	crypt	destruction	with	expansion	of	the	lamina	propria	by	inflammatory	cells	and	surface	ulceration.

Attempted Salvage Therapy Through Initiation of Vedolizumab as an Inpatient in Two Patients with Refractory Active Ulcerative Colitis

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Attempted Salvage Therapy Through Initiation of Vedolizumab as an Inpatient in Two Patients with Refractory Active Ulcerative Colitis

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