Golimumab Therapy in Ulcerative Colitis

Won Moon

doi:10.4166/kjg.2016.67.2.64

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Moon: Golimumab Therapy in Ulcerative Colitis

Review Article

Korean J Gastroenterol 2016;67(2):64-73.

Published online: 4 October 2016

DOI: https://doi.org/10.4166/kjg.2016.67.2.64

Golimumab Therapy in Ulcerative Colitis

Won Moon

Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea

Correspondence to: Won Moon, Department of Internal Medicine, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 49267, Korea. Tel: +82-51-990-5207, Fax: +82-51-990-3005, E-mail: moonone70@hanmail.net

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF- agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis.

Keywords: Ulcerative colitis, Tumor necrosis factoralpha, Infliximab, Adalimumab, Golimumab

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Fig. 1.

The Program of Ulcerative Colitis Research Studies Utilizing and Investigational Treatment (PURSUIT)-IV, PURSUIT-S, and PURSUIT-M. GLM, golimumab.

Table 1.

Approvals of Anti-TNF- Agents for Moderate to Severe Ulcerative Colitis by FDA, EMA, and KFDA

Agents	Year of approval
Agents	EMA	FDA	KFDA
Infliximab	February 2006	September 2005	May 2007
Adalimumab	March 2012	September 2012	August 2012
Golimumab	September 2013	May 2013	May 2014

TNF-, tumor necrosis factor alpha; FDA, US Food and Drug Administration; EMA, European Medicines Agency; KFDA, Korea Food and Drug Administration.

Table 2.

Results of the PURSUIT-IV Study of Golimumab

Placebo vs. golimumab	p-value
Placebo vs. golimumab	Clinical response (week 6)	Clinical remission (week 6)
Golimumab 1 mg/kg	0.467	0.832
Golimumab 2 mg/kg	0.081	0.370
Golimumab 4 mg/kg	0.145	0.702

PURSUIT-IV, the Program of Ulcerative Colitis Research Studies Utilizing and Investigational Treatment-Intravenous.

Table 3.

Safty Summary of the PURSUIT-IV Study of Golimumab

	SAE (%)	AE (%)
Placebo	3.90	19.48
Golimumab 1 mg/kg	3.17	20.63
Golimumab 2 mg/kg Golimumab 4 mg/kg	4.05 3.95	20.27 11.84

PURSUIT-IV, the Program of Ulcerative Colitis Research Studies Utilizing and Investigational Treatment-Intravenous; SAE, serious adverse events; AE, adverse events.

Table 4.

Results from the PURSUIT-SC Study on Golimumab

	Placebo	Golimumab 200 mg/100 mg	Golimumab 400 mg/200 mg
Clinical response (%)	30.3	51.0 (p＜0.0001)	54.9 (p＜0.0001)
Clinical remission (%)	6.4	17.8 (p＜0.0001)	17.9 (p＜0.0001)
Mucosal healing (%)	28.7	42.3 (p=0.0014)	45.1 (p=0.0001)
Change from baseline in IBDQ	14.8±31.25	27.0±33.72 (p＜0.0001)	26.9±34.28 (p＜0.0001)

Clinical Response: decrease from baseline in total Mayo score of at least 30% and 3 points, accompanied by either a rectal bleeding subscore 0 or 1 or a decrease from baseline of at least 1 point in rectal bleeding subscore. Clinical remission: total Mayo score lower than 2 points, with no subscore greater than 1. Mucosal healing, Mayo endoscopic subscore of 0 or 1.

PURSUIT-SC, the Program of Ulcerative Colitis Research Studies Utilizing and Investigational Treatment-Subcutaneous; IBDQ, Inflammatory Bowel Disease Quality of Life Questionnaire.

Table 5.

Results from the PURSUIT-M Study on Golimumab

	Placebo	Golimumab 50 mg	Golimumab 100 mg
Sustained clinical response (%)	31.2	47.0 (p=0.010)	49.7 (p＜0.001)
Sustained clinical remission (%) Sustained mucosal healing (%)	15.6 26.6	23.2 (p=0.122) 41.7 (p=0.11)	27.8 (p=0.004) 42.4 (p=0.002)
Sustained steroid free response (%)	20.7	38.5 (p=0.026)	38.5 (p=0.026)

Sustained clinical response: maintenance of clinical response through week 54 among golimumab induction responders. Sustained clinical remission: clinical remission at both week 30 and 54. Sustained mucosal healing: mucosal healing at both week 30 and 54. Sustained steroid-free response: corticosteroid-free clinical remission at week 54 among patients receiving concomitant corticosteroids at baseline.

PURSUIT-M, the Program of Ulcerative Colitis Research Studies Utilizing and Investigational Treatment-Maintenance.

Table 6.

Safety Summary of Golimumab-treated Patients (PURSUIT-M)

	Placebo (n=156)	Golimumab (mg)		Dose adjustment (mg)			All golimumab (n=384)
	Placebo (n=156)	50(n=154)	100(n=154)	Placebo-100(n=76)	50–100(n=25)	100–200(n=14)	All golimumab (n=384)
≥1 AE	103 (66.0)	112 (72.7)	113 (73.4)	54 (71.1)	16 (64.0)	9 (64.3)	285 (74.2)
Frequent AEs
Ulcerative Colitis	29 (18.6)	27 (17.5)	24 (15.6)	13 (17.1)	4 (16.0)	1 (7.1)	69 (18.0)
Nasopharyngitis	11 (7.1)	14 (9.1)	21 (13.6)	7 (9.2)	4 (16.0)	3 (21.4)	46 (12.0)
Headache	14 (9.0)	12 (7.8)	12 (7.8)	8 (10.5)	2 (8.0)	1 (7.1)	35 (9.1)
Arthralgia	12 (7.7)	11 (7.1)	8 (5.2)	7 (9.2)	0 (0.0)	1 (7.1)	27 (7.0)
Upper respiratory tract infection	4 (2.6)	8 (5.2)	9 (5.8)	6 (7.9)	3 (12.0)	1 (7.1)	26 (6.8)
Abdominal pain	4 (2.6)	11 (7.1)	11 (7.1)	3 (3.9)	2 (8.0)	0 (0.0)	26 (6.8)
Rash	3 (1.9)	9 (5.8)	7 (4.5)	1 (1.3)	0 (0.0)	1 (7.1)	18 (4.7)
Pharyngitis	4 (2.6)	8 (5.2)	5 (3.2)	2 (2.6)	0 (0.0)	1 (7.1)	16 (4.2)
≥1 Infections	44 (28.2)	60 (39.0)	60 (39.0)	26 (34.2)	10 (40.0)	4 (28.6)	153 (39.8)
Required antimicrobial therapy	24 (15.4)	39 (25.3)	44 (28.6)	14 (18.4)	4 (16.0)	1 (7.1)	101 (26.3)
Discontinuation of study agent for	10 (6.4)	8 (5.2)	14 (9.1)	8 (10.5)	4 (16.0)	0 (0.0)	34 (8.9)
≥1 AE
≥1 Serious AEs	12 (7.7)	13 (8.4)	22 (14.3)	8 (10.5)	5 (20.0)	1 (7.1)	48 (12.5)
Serious infections	3 (1.9)	5 (3.2)	5 (3.2)	1 (1.3)	1 (4.0)	0 (0.0)	12 (3.1)
Neoplasms	1 (0.6)	4 (2.6)	4 (2.6)	0 (0.0)	0 (0.0)	0 (0.0)	8 (2.1)

Values are presented as n (%).

PURSUIT-M, the Program of Ulcerative Colitis Research Studies Utilizing and Investigational Treatment-Maintenance; AE, adverse events.

Table 7.

Approved Golimumab Regimens for Ulcerative Colitis

	EMA		FDA and KFDA
	Body weight ＜80 kg	Body weight ≥80 kg	FDA and KFDA
Induction	200 mg (week 0)		200 mg (week 0)
	100 mg (week 2)		100 mg (week 2)
Maintenance	50 mg every 4 weeks	100 mg every 4 weeks	100 mg every 4 weeks

EMA, European Medicines Agency; FDA, US Food and Drug Administration; KFDA, Korea Food and Drug Administration.

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