P0692 - Efficacy of JAK Inhibitors in Patients With Inflammatory Bowel Disease

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Murad Qirem, MD

Saint Michael's Medical Center
Newark, NJ

Murad Qirem, MD¹, Yashwitha Sai Pulakurthi, MBBS², Wajeeha Aiman, MBBS³, Amaar Ahmad, MD³, Arwa Battah, MD³, Dema Shamoon, MD⁴, Yatinder Bains, MD⁴
¹Saint Michael's Medical Center, Newark, NJ; ²New York Medical College-Saint Michael's Medical Center, Newark, NJ; ³Saint Michael's Medical Center, Newark, NJ; ⁴Saint Michael's Medical Center, New York Medical College, Newark, NJ

Introduction: Janus kinase (JAK) pathways have been implicated in the pathogenesis of inflammatory bowel diseases (IBD) and are now used as targets for therapy.bIn this systematic review, the efficacy of the JAK inhibitors tofacitinib, upadacitinib, filgotinib, ivarmacitinib and peficitinib in patients with ulcerative colitis (UC) and Crohn's disease (CD) will be assessed.

Methods: We followed PRISMA Guidelines and a literature search was performed on PubMed with mesh terms, ‘’inflammatory bowel disease’’ “IBD” “janus kinase inhibitors” and “JAK inhibitors” from the inception of data until 06/02/2023. We screened 753 articles and included 9 randomised clinical trials (RCT, N =6974), measuring the efficacy of JAK inhibitor based regimens in IBD. We extracted data for clinical response (CR), clinical remission, endoscopic response (ER), and endoscopic remission.

Results: In total and equal to 6974 total patients. Ivarmacitinib was only studied in ulcerative colitis showed clinical response (CR) in 67 patients out of 123 in comparison to placebo which showed CR in 11-41.

In a phase 3 trial of Upadacitinib in crohns disease showed CR in 361 patients out of 674, in comparison to placebo which showed CR in 113 patients out of 347 in the induction phase. In the maintenance phase, it showed CR in 157 patients out of 337, while placebo showed CR in 25 out of 165. It also showed endoscopic response in 271 patients out of 674 in comparison to placebo in 29 patients out of 347.

In another phase 3 trial on ulcerative colitis patients, Upadacitinib showed CR in 488 out of 664 in comparison to placebo in 86 patients out of 332 during induction phase. Maintenance phase showed CR in 180 patients out of 302 as compared to placebo in 28 out of 149. ER in 267 patients out of 664 in comparison to placebo 25 patients out of 332.

Peficitinib showed CR in 87 patients out of 176 patients in comparison to placebo 17 out of 47 patients. ER in 57 patients out of 176 in comparison to placebo 8 out of 43

Filgotinib showed Clinical remission in 168 patients 1069, in comparison to placebo 31 out of 279. In another phase 2 study showed clinical response in 77 patients out of 130 in comparison to placebo in 8 patients out of 44.

Tofacatinib showed CR in 521 patients out of 905 patients in comparison to placebo 72 out of 234 patients in the induction phase. The maintenance phases are mentioned in table 1.

Discussion: The use of JAK inhibitors in IBD have shown significant efficacy in comparison to placebo.

Author, year	Population	Drug, Dose, Frequency	N	Clinical Response	Clinical Remission	Endoscopic Response	Endoscopic Remission
Chen et. Al. 2023	Ulcerative Colitis	ivarmacitinib 8 mg once daily	41	46.30%	22.00%	NA	NA
		ivarmacitinib 4 mg twice daily	41	46.30%	24.40%
		ivarmacitinib 4 mg once daily	41	43.90%	24.40%
		Placebo	41	26.80%	4.90%
Loftus. et. Al. 2023	Crohn’s Disease	45 mg of upadacitinib once daily	350	56.60%	49.50%	45.50%	28.90%
		placebo once daily	176	37.30%	29.10%	13.10%	7.40%
		45 mg of upadacitinib once daily	324	50.50%	38.90%	34.60%	19.10%
		placebo once daily	171	27.50%	21.10%	3.50%	2.30%
		15 mg of upadacitinib once daily	169	51.20%	37.30%	27.60%	NA
		30 mg of upadacitinib once daily	168	41.40%	47.60%	40.10%	NA
		placebo once daily	165	15.20%	15.10%	7.30%	NA
Sandborn et. Al. 2020	Ulcerative Colitis	upadacitinib 7.5 mg once daily	47	29.80%	8.50%	14.90%	NA
		upadacitinib 15 mg once daily	49	44.90%	14.30%	30.60%
		upadacitinib 30 mg once daily	52	44.20%	13.50%	26.90%
		upadacitinib 45 mg once daily	56	50.00%	19.60%	35.70%
		placebo once daily	46	13%	0.00%	2.20%
Danese 2022	ulcerative colitis	upadacitinib 45 mg once daily	319	73%	26%	36%	14%
		placebo once daily	155	27%	5.00%	7%	1%
		upadacitinib 45 mg once daily	345	74%	33%	44%	18%
		placebo once daily	177	25%	4.00%	8%	2%
		upadacitinib 15 mg once daily	148	63%	42%	49%	24%
		upadacitinib 30 mg once daily	154	56.60%	52.00%	62%	26%
		placebo once daily	149	19%	12%	14%	6%
Feagan 2021	ulcerative colitis	Filgotinib 100mg	277	NA	19.1	NA	5.80%
		Filgotinib 200mg	245	NA	26.10%	NA	12.20%
		placebo	137	NA	15.30%	NA	3.60%
		Filgotinib 100mg	285	NA	9.5	NA	2.10%
		Filgotinib 200mg	262	NA	11.50%	NA	3.40%
		placebo	142	NA	7.20%	NA	2.10%
		Filgotinib 100mg	179	NA	23.80%	NA	13.40%
		placebo	91	NA	13.50%	NA	7.90%
		Filgotinib 200mg	202	NA	132%	NA	15.60%
		placebo	99	NA	11.20%	NA	6.10%
Vermeire 2017	Crohn’s Disease	Filgotinib 200 mg once a day	130	59%	47%	25%	14%
Vermeire 2017	Crohn’s Disease	Placebo once a day	44	18%	23%	14%	7%
Sands 2018	Ulcerative Colitis	peficitinib 25mg once daily	44	34.10%	15.90%	20.50%	11.40%
		peficitinib 75mg once daily	44	54.50%	15.90%	29.50%	15.90%
		peficitinib 150mg once daily	44	54.50%	15.90%	45.50%	11.40%
		peficitinib 75mg twice daily	44	54.50%	15.90%	36.40%	22.70%
		placebo	43	39.50%	7.00%	18.60%	2.30%
Sandborn et. Al. 2017	Ulcerative Colitis	Tofacitinib 10mg twice daily	476	week 8 9.9%	18.50%	NA	6.70%
		Placebo	122	week 8 2.8%	8.20%	NA	1.60%
		Tofacitinib 10mg twice daily	429	week 8 55%	16.80%	NA	7%
		Placebo	112	week 28.6%	3.60%	NA	1.80%
Sandborn et. Al. 2014	Ulcerative Colitis	Tofacitinib 1 mg twice daily	36	Response 70* - 36.1% Response 100^ - 30.6%	30.60%	NA	NA
		Tofacitinib 5 mg twice daily	34	Response 70 - 57.6% Response 100 - 45.5%	14.30%	NA	NA
		Tofacitinib 10 mg twice daily	35	Response 70 - 45.7% Response 100 - 37.1%	14.30%	NA	NA
		Placebo twice daily	34	Response 70 - 47.1% Response 100 - 29.4%	20.60%	NA	NA

Table: Table 1

Disclosures:

Murad Qirem indicated no relevant financial relationships.

Yashwitha Sai Pulakurthi indicated no relevant financial relationships.

Wajeeha Aiman indicated no relevant financial relationships.

Amaar Ahmad indicated no relevant financial relationships.

Arwa Battah indicated no relevant financial relationships.

Dema Shamoon indicated no relevant financial relationships.

Yatinder Bains indicated no relevant financial relationships.

Murad Qirem, MD¹, Yashwitha Sai Pulakurthi, MBBS², Wajeeha Aiman, MBBS³, Amaar Ahmad, MD³, Arwa Battah, MD³, Dema Shamoon, MD⁴, Yatinder Bains, MD⁴. P0692 - Efficacy of JAK Inhibitors in Patients With Inflammatory Bowel Disease, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.