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REMICADE - Treatment of Ulcerative Colitis in Adult Patients: Overview of Clinical Trials Data

Last Updated: 01/11/2025

Summary

  • The safety and efficacy of REMICADE in adult patients with ulcerative colitis (UC) were assessed in two randomized, double-blind, placebo-controlled clinical studies in 728 patients with moderately to severely active ulcerative colitis with an inadequate response to conventional oral therapies.1
  • These two Phase 3 trials, ACT (Active Ulcerative Colitis Trial) 1 (a 54-week trial) and ACT 2 (a 30 week-trial), demonstrated that REMICADE induced and maintained clinical response, clinical remission and mucosal healing, and permitted corticosteroid withdrawal while in remission.1
  • Adverse events occurring in ≥10% of any treatment group were worsening ulcerative colitis, abdominal pain, nausea, upper respiratory tract infection, pharyngitis, sinusitis, pain, rash, arthralgia, headache, fever, anemia, and fatigue.1
  • Summarized in this response are data from the pivotal phase 3 trials ACT 1 and ACT 2 which evaluated REMICADE treatment for adults with moderately to severely active UC.

CLINICAL TRIALS DATA

ACT 1 and ACT 2 Trials

Rutgeerts et al1 reported on two placebo-controlled, randomized, double-blind Phase 3 trials (ACT 1 and ACT 2) that were conducted to evaluate The safety and efficacy of REMICADE in adult patients with moderately to severely active ulcerative colitis (UC) with an inadequate response to conventional oral therapies. Other references of data on this topic are also cited within the clinical trials data as appropriate.

  • Study participants in the ACT trials (ACT [Active Ulcerative Colitis Trial]) were randomized to receive REMICADE 5 mg/kg, REMICADE 10 mg/kg, or placebo.
  • To be included in the trial, patients had both clinical and endoscopic evidence of moderate to severe UC (a Mayo score of 6-12 with an endoscopy score ≥2).2
  • Induction of clinical response, the primary endpoint, was evaluated 8 weeks following the initial infusion. Major secondary endpoints were evaluated at Weeks 8 and 30 (response, remission and mucosal healing).2
  • Clinical response was defined by a ≥30% and ≥3-point reduction in the Mayo score accompanied by a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding score of 0 or one. Clinical remission (Mayo score ≤2, with no individual subscores >1) and mucosal healing (endoscopy subscore of 0 or one) were also evaluated.1
  • Concomitant treatment with stable doses of aminosalicylates, corticosteroids and/or immunomodulatory agents was permitted.  Corticosteroid taper was permitted after week 8.

ACT 1

Efficacy
  • A total of 364 active UC patients were randomized to receive REMICADE or placebo at weeks 0, 2, and 6, then every 8 weeks through week 46.2
  • Patients were included if they had failed to respond or were intolerant to oral corticosteroids, azathioprine (AZA), and/or 6-mercaptopurine (6-MP).1
  • The primary and secondary endpoints of clinical response, clinical remission and mucosal healing were achieved in this trial. Also, at week 30, significantly more patients in the combined REMICADE treatment group compared to placebo discontinued the use of corticosteroids while in remission (21.7% vs 10.1%; P=0.039).
  • The data shown in the Table: Summary of ACT 1 Results reflects results through Week 54.

Summary of ACT 1 Results1
 
Treatment Groups
Placebo (%)
(n=121)
REMICADE 5 mg/kg (%)
(n=121)
REMICADE 10 mg/kg (%)
(n=122)
Clinical Responsec
Week 8
37.2
69.4 (P<0.001)
61.5 (P<0.001)
Week 30
29.8
52.1 (P<0.001)
50.8 (P=0.002)
Week 54
19.8
45.5 (P<0.001)
44.3 (P<0.001)
Clinical Remission c
Week 8
14.9
38.8 (P<0.001)
32.0 (P=0.002)
Week 30
15.7
33.9 (P=0.001)
36.9 (P<0.001)
Week 54
16.5
34.7 (P=0.001)
34.4 (P=0.001)
Sustained Response a, c
Week 8 and Week 30
23.1
48.8 (P<0.001)
45.9 (P<0.001)
Week 8, 30 and 54
14
38.8 (P<0.001)
36.9 (P<0.001)
Sustained Remissionb, c
Week 8 and Week 30
8.3
23.1 (P=0.001)
26.2 (P<0.001)
Week 8, 30 and 54
6.6
19.8 (P=0.002)
20.5 (P=0.002)
Mucosal Healing c
Week 8
33.9
62.0 (P<0.001)
59.0 (P<0.001)
Week 30
24.8
50.4 (P<0.001)
49.2 (P<0.001)
Week 54
18.2
45.5 (P<0.001)
46.7 (P<0.001)
Clinical Remission off Corticosteroids
Week 30
10.1
24.3 (P=0.030)
19.2 (P=0.125)
Week 54
8.9
25.7 (P=0.006)
16.4 (P=0.149)
Refractory to corticosteroid therapy
Clinical Response Week 8
35.3
77.4 (P<0.001)
67.7 (P=0.010)
Not refractory to corticosteroid therapy
Clinical Response Week 8
37.9
66.7 (P<0.001)
59.3 (P=0.005)
aResponse at weeks 8 and 30.
bRemission at weeks 8 and 30.
cPatients who had a prohibited change in medication, had an ostomy or colectomy, or discontinued study infusions due to lack of efficacy are considered to not be in clinical response, clinical remission or mucosal healing from the time of the event onward.

Safety

ACT 1 Summary of Safety Through Week 541

Treatment Groups
Placebo
(n=121)
REMICADE 5 mg/kg
(n=121)
REMICADE 10 mg/kg
(n=122)
Mean weeks in study
24.2
34.8
33.3
Any adverse event
85.1%
87.6%
91.0%
Serious adverse events
25.6%
21.5%
23.8%
Discontinued infusions due to adverse event
9.1%
8.3%
9.0%
Acute infusion reactions
10.7%
9.9%
12.3%
Possible delayed hypersensitivity reactions
1.7%
1.7%
0.0%
Serious infections
4.1%
2.5%
6.6%
Patients with antibodies to REMICADE
N/A
7.8%
4.4%
  • Additionally, in ACT 1, there were 3 cases of dysplasia or malignancies, one patient in the 10 mg/kg group (basal cell carcinoma) and 2 patients in the 5 mg/kg group (prostatic adenocarcinoma and colonic dysplasia). The patient with prostate cancer had a 2-year history of elevated prostate specific antigen (PSA).
  • Optic neuritis occurred in one patient in the 5 mg/kg group and tuberculosis developed in a 10 mg/kg group patient.
  • There were no deaths during the study period, however during the trial extension, one placebo-treated patient died.  This patient committed suicide 4 months after their last infusion.3

ACT 2

Efficacy
  • A total of 364 active UC patients were randomized to receive REMICADE or placebo at weeks 0, 2, 6, 14 and 22.4
  • Patients were included if they failed to respond or were intolerant to oral corticosteroids, AZA, 6-MP, or aminosalicylates.1
  • Overall, significantly more patients in the REMICADE treatment groups versus placebo achieved the primary and secondary endpoints of clinical response, clinical remission, and mucosal healing.4
  • Also, a significantly greater proportion of REMICADE treated patients discontinued corticosteroids while in clinical remission. The data shown in Table: Summary of ACT 2 Results outlines the results of the 30 week ACT 2 trial.

Summary of ACT 2 Results1
 
Treatment Groups
Placebo (%)
(n=123)
REMICADE 5 mg/kg (%)
(n=121)
REMICADE 10 mg/kg (%)
(n=120)
Clinical Responsec
Week 8
29.3
64.5 (P<0.001)
69.2 (P<0.001)
Week 30
26
47.1 (P<0.001)
60.0 (P<0.001)
Clinical Remissionc
Week 8
5.7
33.9 (P<0.001)
27.5 (P<0.001)
Week 30
10.6
25.6 (P=0.003)
35.8 (P<0.001)
Sustained Responsea, c
Week 8 and 30
15.4
41.3 (P<0.001)
53.3 (P<0.001)
Sustained Remissionb, c
Week 8 and 30
2.4
14.9 (P<0.001)
22.5 (P<0.001)
Mucosal Healingc
Week 8
30.9
60.3 (P<0.001)
61.7 (P<0.001)
Week 30
30.1
46.3 (P=0.009)
56.7 (P<0.001)
Clinical Remission and Off Steroids
Week 30
3.3
18.3 (P=0.010)
27.3 (P<0.001)
Refractory to corticosteroid therapy
Clinical Response Week 8
37.5
63.3 (P=0.053)
65.5 (P=0.011)
Not refractory to corticosteroid therapy
Clinical Response Week 8
26.4
64.8 (P<0.001)
70.3 (P<0.001)
aResponse at both weeks 8 and 30.
bRemission at both weeks 8 and 30.
cPatients who had a prohibited change in medication, had an ostomy or colectomy, or discontinued study infusions due to lack of efficacy are considered to not be in clinical response, clinical remission or mucosal healing from the time of the event onward.

Safety

ACT 2 Summary of Safety Through Week 301

Treatment Groups
Placebo
(n=123)
REMICADE 5 mg/kg
(n=121)
REMICADE 10 mg/kg
(n=120)
Mean weeks in study
14.4
19.3
18.6
Any adverse events
73.2%
81.8%
80.0%
Serious adverse events
19.5%
10.7%
9.2%
Discontinued infusions due to adverse event
9.8%
1.7%
4.2%
Acute infusion reactions
8.1%
11.6%
11.7%
Possible delayed hypersensitivity reactions
0.0%
0.0%
0.8%
Serious infections
0.8%
1.7%
2.5%
Patients with antibodies to REMICADE
N/A
9.5%
3.2%
  • Additionally, in ACT 2, there were 2 cases of malignancies, one patient in the placebo group (basal cell carcinoma) and 1 patient in the 5 mg/kg group (rectal adenocarcinoma).
  • Optic neuritis occurred in one patient in the 5 mg/kg group and multifocal motor neuropathy developed in a 10 mg/kg group patient.
  • There was one case of lupus-like syndrome reported in a patient in the 5 mg/kg group.
  • Lastly, there were no deaths during the study period, however during the trial extension, one 5 mg/kg patient (due to histoplasmosis) and 1 placebo-treated patient died.3
    • The placebo patient received commercial REMICADE for the treatment of rheumatoid arthritis, approximately 4 months after completing the trial.
    • The patient died due to possible complications of a cerebrovascular accident.

LITERATURE SEARCH

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 22 September 2023.

Summarized in this response are data from the pivotal phase 3 trials ACT 1 and ACT 2 which evaluated REMICADE treatment for adults with moderately to severely active UC.

 

References

1 Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. New Engl J Med. 2005;353(23):2462-2476.  
2 Sandborn WJ, Feagan BG, Olson A, et al. A randomized placebo-controlled trial of infliximab therapy for active ulcerative colitis: ACT I trial results through week 54 [abstract]. Am J Gastroenterol. 2005;100:S313. Abstract 849.  
3 Data on File. (Module 2.7.4), Centocor, Inc; pages 13; 2005.  
4 Sandborn W, Reinisch W, Rachmilewitz D, et al. Infliximab induction and maintenance therapy for ulcerative colitis: the ACT 2 trial [abstract]. Z Gastroenterol. 2005;43(5):V6.