D0355 - Real World Outcomes of Tofacitinib for Ulcerative Colitis at 52 and 78 Weeks

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, Puza Sharma, MD, PhD², Kanwal Bains, MBBS¹, Jordan Pruce, BS¹, Jessica R. Allegretti, MD, MPH³
¹Brigham and Women's Hospital, Boston, MA; ²Pfizer Inc., New York, NY; ³Brigham and Women’s Hospital Crohn’s and Colitis Center, Boston, MA

Introduction: Tofacitinib (tofa) is an oral small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We performed a retrospective cohort study to assess clinical outcomes up to 78 weeks after tofa initiation for UC in a real-world setting.

Methods: This study included adults initiating tofa therapy between 5/1/18-4/1/21 at a large, US academic medical center. Electronic health records were manually reviewed for clinical data. The primary outcome was steroid-free clinical remission (SFCR; i.e. simple clinical colitis activity index <2 or per provider global assessment and no use of oral/IV corticosteroids for >30 days) at 12, 52, and 78 (+/-4) weeks. Secondary outcomes were endoscopic response (decrease in Mayo endoscopic subscore by >1 pt) and remission (Mayo endoscopic subscore 0) at >8 weeks, biochemical response (improvement in elevated C-reactive protein [CRP] or fecal calprotectin [FC] by >25% from baseline) and remission (normalized CRP or FC) at >8 weeks, and dose de-escalation, improvement in arthralgia, colectomy, hospitalization, adverse events (AEs), and treatment discontinuation during follow-up. Continuous data were reported as medians with interquartile range (IQR) due to normality and categorical data were reported as proportions.

Results: 73 patients initiated tofa with median follow-up of 88 weeks (IQR 40.9-151.0 weeks). 60.2% were female, 54.7% had prior exposure to >2 anti-tumor necrosis factor agents, 74.0% had prior exposure to vedolizumab, and 54.7% were receiving concomitant oral/IV steroids (Table 1). Among patients with available data, 31/60 (51.7%) were in SFCR at 78 weeks, 39/47 (83.0%) achieved endoscopic response, and 21/47 (44.7%) achieved endoscopic remission (median time to endoscopy 58.1 weeks, IQR 30.7-103.6 weeks after initiation). Other outcomes are presented in Fig 1A. 31/73 (42.5%) discontinued tofa after a median of 616 days (IQR 286-1057 days) primarily due to non-response (14/31) or colectomy for refractory disease (11/31) and dysplasia (2/31). 15/73 (20.5%) experienced potential AEs during follow-up (Fig 1B), of which 1 (6.7%) required discontinuation (elevated liver enzymes). 38/73 (52.1%) underwent dose de-escalation, among which 18/32 (56.3%) with adequate follow-up were in SFCR at 52 weeks after de-escalation (Fig 1C).

Discussion: In a real-world refractory UC population, tofa was effective for the majority of patients through 78 weeks. Due to a limited sample size, larger real-world studies are needed to corroborate these findings.

Figure: Figure 2. A. Clinical and endoscopic outcomes. Number after SFCR reflects number of weeks. Patients who discontinued therapy due to non-response at earlier endpoints were included in the denominators for later endpoints (i.e. they were considered treatment failures). Denominators for outcomes: SFCR12 n = 71, SFCR52 n = 69, SFCR78 n = 60, endoscopy n = 48, arthralgia n = 23, biochemical n = 30, discontinuation, hospitalization, and adverse events n = 73. Denominators vary due to availability of outcome data. B. Adverse events during all available follow-up. 15 patients reported adverse events, but some reported more than one adverse event (all individual events are included). C. Dose de-escalation outcomes. Dose de-escalation occurred after a median of 36.9 weeks (IQR 20.6-62.3 weeks) from tofacitinib initiation.
Abbreviations: SFCR = steroid-free clinical remission , DVT = deep venous thrombosis

Characteristic	Value
N	73
Female	44 (60%)
Age, y, median (IQR)	41.2 (28.1, 54.0)
UC duration, y, median (IQR)	9.5 (4.4, 15.5)
Race
Caucasian	67 (92%)
Black	0 (0%)
Asian	4 (5%)
Other/Unknown	2 (3%)
Hispanic	0 (0%)
Number of prior anti-TNFs
0	4 (5%)
1	29 (40%)
2	29 (40%)
3	10 (14%)
4	1 (1%)
Prior ustekinumab	8 (11%)
Prior vedolizumab	54 (74%)
Prior 5-ASA	71 (97%)
Current 5-ASA	12 (16%)
Prior immunomodulator	54 (74%)
Current immunomodulator	6 (8%)
Current steroids
Prednisone/methylprednisolone	33 (45%)
Budesonide	7 (10%)
Current oral contraceptive	6 (8%)
Hypertension	19 (26%)
Hyperlipidemia	13 (18%)
Diabetes	7 (10%)
History of coronary artery disease	5 (7%)
History of cerebrovascular accident	1 (1%)
BMI, median (IQR)	25.6 (21.6, 28.9)
Arthralgia at time of initiation	27 (37%)
Endoscopic extent >E1 (i.e. >proctitis)	62 (85%)
Endoscopic severity
None	6 (8%)
Mild	9 (12%)
Moderate	38 (52%)
Severe	20 (27%)
Smoking
Never	59 (81%)
Current	2 (3%)
Former	12 (16%)
Current cannabis use	11 (15%)
Current opioid use	7 (10%)
UC hospitalization within 12 months	19 (26%)
Serum albumin, g/dL, median (IQR)	4.1 (3.8, 4.3)
C-reactive protein, mg/L, median (IQR)	5.1 (1.7, 16.7)
Fecal calprotectin > 120 ug/g	27 (90%)
SCCAI, median (IQR)	5 (3, 8)
Daily bowel movement frequency, median (IQR)	6 (3.5, 10)

Table: Table 1. Baseline characteristics. Albumin, C-reactive protein, fecal calprotectin, SCCAI, and bowel movements were the most recent values available within 3 months prior to drug initiation. The most recent endoscopic data preceding tofacitinib initiation was used: median 19.1 weeks (IQR 6.1-46.1 weeks) prior to tofacitinib initiation.
Abbreviations: IQR = interquartile range, TNF= tumor necrosis factor, ASA = aminosalicylic acid, SCCAI = simple clinical colitis activity index

Disclosures:

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

Puza Sharma: Pfizer – Employee.

Kanwal Bains indicated no relevant financial relationships.

Jordan Pruce 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, Puza Sharma, MD, PhD², Kanwal Bains, MBBS¹, Jordan Pruce, BS¹, Jessica R. Allegretti, MD, MPH³. D0355 - Real World Outcomes of Tofacitinib for Ulcerative Colitis at 52 and 78 Weeks, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.