D0356 - Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Rahul Dalal, MD, MPH

Brigham and Women's Hospital
Boston, MA

Rahul Dalal, MD, MPH¹, Kanwal Bains, MBBS¹, Jenna Marcus, BS¹, Emma McClure, BA¹, Jessica R. Allegretti, MD, MPH²
¹Brigham and Women's Hospital, Boston, MA; ²Brigham and Women’s Hospital Crohn’s and Colitis Center, Boston, MA

Introduction: The effectiveness of tofacitinib for pouch-related disorders after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is poorly understood. We conducted a retrospective case series of patients receiving tofacitinib for the treatment of pouch-related disorders.

Methods: This was a retrospective case series of adults prescribed tofacitinib for chronic pouchitis (CP), cuffitis, or Crohn’s-like disease of the pouch (CLDP) at a large academic medical center after 1/1/2015. Patients treated primarily for non-IBD indications were excluded. Electronic health records were manually reviewed for demographics, inflammatory bowel disease (IBD) medication history, pouchoscopy reports, laboratory data, and clinical assessments. The primary outcome was clinical response determined by provider assessment at first clinical follow-up after tofacitinib initiation. Additional outcomes included endoscopic response (determined by endoscopist assessment), tofacitinib discontinuation, need for oral antibiotics or corticosteroids, change in bowel frequency, resolution of rectal bleeding and urgency, IBD hospitalization, need for bowel surgery or ileostomy, and adverse events (AEs).

Results: There were 6 patients who initiated tofacitinib for CP (n=3), cuffitis (n=2), or CLDP (n=1) after IPAA. 5 patients underwent TPC for inflammation and 1 was for dysplasia. All but 1 patient had prior biologic exposures. 3 patients were using antibiotics and 2 were using oral corticosteroids at the time of tofacitinib initiation. Other baseline characteristics are presented in Table 1. Clinical follow-up occurred at a median of 109 days (IQR 49-171 days) after tofacitinib initiation. 1/6 (CP) patients had clinical response. 2/3 patients with post-tofacitinib endoscopic assessments (1/2 CP and 1/1 cuffitis) had endoscopic response at a median of 191 days (IQR 113.5-229 days). All patients ultimately discontinued tofacitinib after a median of 133 days (IQR 95-254 days). Reasons for discontinuation were lack of efficacy (n=3: 1 CP, 2 cuffitis), AEs (n=2: 1 CP, 1 CLDP), and self-discontinuation out of safety concerns (n=1: CP). AEs occurred in 4/6 patients and included infections (C. difficile, pneumonia, candida esophagitis, cytomegalovirus cuffitis, perianal abscess) and dizziness and headaches. Other outcomes are presented in Table 1.

Discussion: The results of this case series do not support the use of tofacitinib for pouch-related disorders. Larger studies are needed to confirm these findings.

Table 1. Baseline characteristics and outcomes
Baseline Characteristics	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6
Pouch phenotype	Chronic pouchitis^a	Chronic pouchitis	Chronic pouchitis	Cuffitis	Cuffitis	Crohn's-like disease of pouch
Age at tofacitinib initiation, y	57	75	61	29	39	50
Sex	Female	Male	Female	Male	Male	Female
Race	Unavailable	White	White	White	Other	White
Ethnicity	Hispanic	Non-Hispanic	Unknown	Non-Hispanic	Non-Hispanic	Unknown
Age at IBD diagnosis, y	45	33	39	25	21	20
Age at colectomy, y	46	60	49	28	24	32
Reason for colectomy	Inflammation	Inflammation	Dysplasia	Inflammation	Inflammation	Inflammation
Initial tofacitinib dose, mg	10	10	20	20	20	20
Dose change, mg	n/a	n/a	n/a	n/a	n/a	10
Current smoking	No	No	No	No	Yes	No
Number of prior biologics	3	1	0	4	2	5
Number of prior anti-TNFs	2	0	0	3	1	1
Prior vedolizumab	No	Yes	No	Yes	Yes	Yes
Current antibiotics	No	Yes	Yes	No	No	Yes
Current oral prednisone or budesonide	Yes	No	No	No	No	Yes
Current immunomodulator	No	No	No	No	No	No
BMI, kg/m²	23.4	22.7	17.6	27.9	29.3	24.6
BMs per 24 hours	5	12	4	12	6	12
Nocturnal BMs	No	Yes	No	Yes	Yes	Yes
Rectal bleeding	No	No	No	Yes	No	No
Urgency	No	Yes	No	Yes	No	No
Fistula	No	No	No	No	No	No
CRP, mg/L^b	13.5	n/a	2.2	4.0	3.5	3.1
Fecal calprotectin, ug/g^b	n/a	134.9	482.1	n/a	54.9	262.0
Albumin, g/dL^b	3.9	3.3	4.5	4.6	4.4	3.6
Pre-tofacitinib pouchoscopy impression	Ulcers in pouch	Mild erythema, congestion, and ulcers in pouch	Mild erythema and friability in J pouch	Mayo 3 cuffitis	Mayo 3 cuffitis	Erythema in j-pouch, superficial ulcers along anastomosis and blind limb, neo-TI strictures, dilated to 12 mm
Outcomes	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6
Clinical response at follow-up^c	Yes	No	No	No	No	No
Post-tofacitinib pouchoscopy impression^d	Ulcers in pouch	Normal pouch	n/a	Mayo 3 cuffitis	n/a	n/a
Endoscopic response	No	Yes	n/a	No	n/a	n/a
Days to discontinuation	2103	294	83	134	131	38
Reason for discontinuation	Patient self-discontinued out of safety concerns	Adverse events	Ineffective	Ineffective	Ineffective	Adverse events
Oral antibiotics or steroids at follow-up	No	No	Yes	Yes	No	Yes
Δ BMs per 24 hours (post-pre) at follow-up	-2	-4	+4	-4	0	0
Resolution of nocturnal BMs	n/a	Yes	n/a	No	No	No
Resolution of rectal bleeding	n/a	n/a	n/a	Yes	n/a	n/a
Resolution of urgency	n/a	No	n/a	No	n/a	n/a
Δ CRP (post-pre), mg/L^e	-6.0	n/a	+0.2	-0.9	-1.1	n/a
Δ Fecal calprotectin (post-pre), ug/g^f	n/a	n/a	n/a	n/a	-10.9	n/a
IBD hospitalization during follow-up^g	Yes	Yes	No	No	No	No
Surgery during follow-up	No	No	No	No	No	No
Adverse event during follow-up	n/a	C. difficile, pneumonia, and candida esophagitis	n/a	Cytomegalovirus cuffitis	Intersphincteric abscess	Dizziness, headaches, fatigue

Table: Table 1. Baseline characteristics and outcomes.
a. This patient had dual indications for tofacitinib: pouchitis and rheumatoid arthritis.
b. The most recent laboratory values available within 6 months prior to tofacitinib initiation were included.
c. Clinical follow-up occurred median of 109 days (IQR 49-171 days) after tofacitinib initiation
d. Pouchoscopy occurred median of 191 days (IQR 113.5-229 days) after tofacitinib initiation.
e. CRP measurements occurred median of 86 days (IQR 41-124 days) after tofacitinib initiation
f. Fecal calprotectin measurement occurred 121 days after tofacitinib initiation.
g. Hospitalization occurred at 303 and 8 days after tofacitinib initiation for patients 1 and 2, respectively.
Abbreviations: TNF = tumor necrosis factor, BMI = body mass index, BM = bowel movement, CRP = C-reactive protein

Disclosures:

Rahul Dalal: Centaur – Consultant. Janssen – Grant/Research Support. Pfizer – Grant/Research Support.

Kanwal Bains indicated no relevant financial relationships.

Jenna Marcus indicated no relevant financial relationships.

Emma McClure indicated no relevant financial relationships.

Jessica Allegretti: Artugen – Consultant. Baccain – Consultant. Bristol Myers Squibb – Consultant, Speaker. Ferring Pharmaceuticals – Consultant. Finch Therapeutics – Consultant, Grant/Research Support. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Grant/Research Support. Morphic – Consultant. Pfizer – Consultant, Grant/Research Support. Seres Therapeutics – Consultant. Servatus – Consultant. Takeda – Consultant.

Rahul Dalal, MD, MPH¹, Kanwal Bains, MBBS¹, Jenna Marcus, BS¹, Emma McClure, BA¹, Jessica R. Allegretti, MD, MPH². D0356 - Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.