Remicade (infliximab) - 6 indications

Scroll down for information on each indication:

• for the treatment of Crohn's disease in adults and pediatrics; approved August 1998, May 2006
• for use in combination with methotrexate for the treatment of rheumatoid arthritis; approved November 1999
• for the treatment of ankylosing spondylitis; approved December 2004
• for the treatment of psoriatic arthritis; approved May 2005
• for the treatment of ulcerative colitis in adults and pediatrics; approved September 2005, September 2011
• for the treatment of plaque psoriasis; approved September 2006

General Information

Remicade (infliximab) works by blocking the activity of human tumor necrosis factor alpha (TNFa), a protein that mediates inflammation and cellular immune response. 

Remicade is specifically indicated for the following conditions:

Crohn's disease

• Adults: 
  • reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease (CD) who have had an inadequate response to conventional therapy
  • reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD
• Pediatrics: 
  • reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active CD who have had an inadequate response to conventional therapy

Rheumatoid Arthritis

• for use in combination with methotrexate to reduce signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis

Ankylosing Spondylitis

• for reducing signs and symptoms in adult patients with active ankylosing spondylitis

Psoriatic Arthritis

• for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis

Ulcerative Colitis

• Adults
  • reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy
• Pediatrics
  • reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active UC who have had an inadequate response to conventional therapy

Plaque Psoriasis

• for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate

Remicade is supplied as an injection for intravenous administration. Scroll down for dosing/administration for each indication.

Mechanism of Action

Remicade (infliximab) neutralizes the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibits binding of TNFα with its receptors. Infliximab does not neutralize TNFβ (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNFα. Biological activities attributed to TNFα include: induction of pro-inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Cells expressing transmembrane TNFα bound by infliximab can be lysed in vitro or in vivo.

Side Effects

Adverse effects associated with the use of Remicade may include, but are not limited to, the following:

• infections (e.g. upper respiratory, sinusitis, and pharyngitis)
• infusion-related reactions
• headache
• abdominal pain

The Remicade drug label comes with the following Black Box Warning: SERIOUS INFECTIONS and MALIGNANCY Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens. Discontinue Remicade if a patient develops a serious infection. Perform test for latent TB; if positive, start treatment for TB prior to starting Remicade. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including Remicade. Post-marketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers including Remicade. Almost all had received azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. The majority of Remicade cases were reported in patients with Crohn’s disease or ulcerative colitis, most of whom were adolescent or young adult males.

Indication 1 - Crohn's disease in adults and pediatrics

approved August 1998, May 2006

Dosing/Administration

Adults:

• The recommended dosage is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active CD or fistulizing CD. For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg every 8 weeks. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue Remicade in these patients.

Pediatrics:

• The recommended dosage for pediatric patients 6 years and older with moderately to severely active CD is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

Clinical Trial Results

Adults

The safety and efficacy of single and multiple doses of Remicade were assessed in 2 randomized, double-blind, placebo-controlled clinical studies in 653 adult patients with moderate to severely active CD [Crohn’s Disease Activity Index (CDAI) ≥220 and ≤400] with an inadequate response to prior conventional therapies.

In the single-dose trial of 108 adult patients, 16% (4/25) of placebo patients achieved a clinical response (decrease in CDAI ≥70 points) at Week 4 vs. 81% (22/27) of patients receiving 5 mg/kg Remicade. Additionally, 4% (1/25) of placebo patients and 48% (13/27) of patients receiving 5 mg/kg Remicade achieved clinical remission (CDAI<150) at Week 4.

In a multi-dose trial (ACCENT I [Study Crohn’s I]), 545 adult patients received 5 mg/kg at Week 0 and were then randomized to one of three treatment groups; the placebo maintenance group received placebo at Weeks 2 and 6, and then every 8 weeks; the 5 mg/kg maintenance group received 5 mg/kg at Weeks 2 and 6, and then every 8 weeks; and the 10 mg/kg maintenance group received 5 mg/kg at Weeks 2 and 6, and then 10 mg/kg every 8 weeks. Patients in response at Week 2 were randomized and analyzed separately from those not in response at Week 2. Corticosteroid taper was permitted after Week 6. At Week 2, 57% (311/545) of patients were in clinical response. At Week 30, a significantly greater proportion of these patients in the 5 mg/kg and 10 mg/kg maintenance groups achieved clinical remission compared to patients in the placebo maintenance group. Additionally, a significantly greater proportion of patients in the 5 mg/kg and 10 mg/kg Remicade maintenance groups were in clinical remission and were able to discontinue corticosteroid use compared to patients in the placebo maintenance group at Week 54.

Pediatrics

Remicade was evaluated in a randomized, open-label study (Study Peds Crohn’s) in 112 pediatric patients aged 6 to 17 years old with moderately to severely active CD and an inadequate response to conventional therapies. All patients received induction dosing of 5 mg/kg Remicade at Weeks 0, 2, and 6. At Week 10, 103 patients were randomized to a maintenance regimen of 5 mg/kg Remicade given either every 8 weeks or every 12 weeks. At Week 10, 88% of patients were in clinical response (defined as a decrease from baseline in the PCDAI score of ≥15 points and total PCDAI score of ≤30 points), and 59% were in clinical remission (defined as PCDAI score of ≤10 points). 

Fistulizing Crohn’s Disease

The safety and efficacy of Remicade were assessed in 2 randomized, double blind, placebo-controlled studies in adult patients with fistulizing CD with fistula(s) that were of at least 3 months duration. In the first trial, 94 adult patients received 3 doses of either placebo or Remicade at Weeks 0, 2 and 6. Fistula response (≥50% reduction in number of enterocutaneous fistulas draining upon gentle compression on at least 2 consecutive visits without an increase in medication or surgery for CD) was seen in 68% (21/31) of patients in the 5 mg/kg Remicade group and 56% of patients in the 10 mg/kg Remicade group vs. 26% of patients in the placebo arm. The median time to onset of response and median duration of response in Remicade-treated patients was 2 and 12 weeks, respectively. Closure of all fistulas was achieved in 52% of Remicade-treated patients compared with 13% of placebo-treated patients. In the second trial (ACCENT II [Study Crohn’s II]), adult patients who were enrolled had to have at least 1 draining enterocutaneous (perianal, abdominal) fistula. All patients received 5 mg/kg Remicade at Weeks 0, 2 and 6. Patients were randomized to placebo or 5 mg/kg Remicade maintenance at Week 14. Patients received maintenance doses at Week 14 and then every 8 weeks through Week 46. Patients who were in fistula response (fistula response was defined the same as in the first trial) at both Weeks 10 and 14 were randomized separately from those not in response. The primary endpoint was time from randomization to loss of response among those patients who were in fistula response. 

At Week 14, 65% (177/273) of patients were in fistula response. Patients randomized to Remicade maintenance had a longer time to loss of fistula response compared to the placebo maintenance group. At Week 54, 38% (33/87) of Remicade-treated patients had no draining fistulas compared with 22% (20/90) of placebo-treated patients. Compared to placebo maintenance, patients on Remicade maintenance had a trend toward fewer hospitalizations.

Indication 2 - for use in combination with methotrexate for the treatment of rheumatoid arthritis

approved November 1999

Dosing/Administration

The recommended dosage is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active RA. Remicade should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dosage up to 10 mg/kg every 8 weeks or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses per infusion or more frequent dosing.

Clinical Trial Results

Remicade was evaluated in a multicenter phase III trial called ATTRACT (Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy), which included 428 subjects at 34 centers in North America and Europe. The double-blind, placebo-controlled, randomized trial was designed to compare the effectiveness of Remicade in combination with methotrexate versus treatment with methotrexate plus placebo.

Changes in joint-space narrowing and bone erosion were measured on a five-point scale using the van der Heijde modified Sharp system. Fifty-four-week data demonstrated an overall median change from baseline for radiographic scores of 0.0 among subjects treated with the combination of Remicade plus methotrexate, compared to a median change of 4.0 for subjects treated with methotrexate alone. This result was maintained through two years. The methotrexate-only findings represent a 7-8% deterioration in radiographic scores. Additionally, after 54 weeks of therapy, approximately 52% of subjects who received Remicade and methotrexate experienced a reduction in the signs and symptoms of rheumatoid arthritis as measured by ACR 20, compared to 17% of subjects receiving methotrexate alone.

Indication 3 - ankylosing spondylitis

approved December 2004

Dosing/Administration

The recommended dosage is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active AS.

Clinical Trial Results

Remicade was assessed in a randomized, multicenter, double-blind, placebo-controlled study in 279 adult patients with active AS. Patients were between 18 and 74 years of age, and had AS, as defined by the modified New York criteria for Ankylosing Spondylitis. Patients were to have had active disease as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >4 (possible range 0-10) and spinal pain >4 (on a Visual Analog Scale [VAS] of 0-10). Patients with complete ankylosis of the spine were excluded from study participation, and the use of Disease Modifying AntiRheumatic Drugs (DMARDs) and systemic corticosteroids were prohibited. Doses of Remicade 5 mg/kg or placebo were administered intravenously at Weeks 0, 2, 6, 12 and 18. At 24 weeks, improvement in the signs and symptoms of AS, as measured by the proportion of patients achieving a 20% improvement in ASAS response criteria (ASAS 20), was seen in 60% of patients in the Remicade-treated group vs. 18% of patients in the placebo group. Improvement was observed at Week 2 and maintained through Week 24. At 24 weeks, the proportions of patients achieving a 50% and a 70% improvement in the signs and symptoms of AS, as measured by ASAS response criteria (ASAS 50 and ASAS 70, respectively), were 44% and 28%, respectively, for patients receiving Remicade, compared to 9% and 4%, respectively, for patients receiving placebo. A low level of disease activity (defined as a value <20 [on a scale of 0-100 mm] in each of the 4 ASAS response parameters) was achieved in 22% of Remicade-treated patients vs. 1% in placebo-treated patients.

Indication 4 - psoriatic arthritis

approved May 2005

Dosing/Administration

The recommended dosage is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of PsA. Remicade can be used with or without methotrexate.

Clinical Trial Results

Remicade was assessed in a multicenter, double-blind, placebo-controlled study in 200 adult patients with active PsA despite DMARD or NSAID therapy. During the 24-week double-blind phase, patients received either 5 mg/kg Remicade or placebo at Weeks 0, 2, 6, 14, and 22 (100 patients in each group). At Week 16, placebo patients with <10% improvement from baseline in both swollen and tender joint counts were switched to Remicade induction (early escape). At Week 24, all placebo-treated patients crossed over to Remicade induction. Dosing continued for all patients through Week 46. Treatment with Remicade resulted in improvement in signs and symptoms, as assessed by the ACR criteria, with 58% of Remicade-treated patients achieving ACR 20 at Week 14, compared with 11% of placebo-treated patients. The response was similar regardless of concomitant use of methotrexate. Improvement was observed as early as Week 2. At 6 months, the ACR 20/50/70 responses were achieved by 54%, 41%, and 27%, respectively, of patients receiving Remicade compared to 16%, 4%, and 2%, respectively, of patients receiving placebo. 

Indication 5 - the treatment of ulcerative colitis in adults and pediatrics

approved September 2005, September 2011

Dosing/Administration

Adults:

• The recommended dosage is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adult patients with moderately to severely active UC. 

Pediatrics:

• The recommended dosage for pediatric patients 6 years and older with moderately to severely active UC is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

Clinical Trial Results

Adults

Remicade was assessed in 2 randomized, double-blind, placebo-controlled clinical studies in 728 adult patients with moderately to severely active UC (Mayo score 6 to 12 [of possible range 0 to 12], Endoscopy subscore ≥2) with an inadequate response to conventional oral therapies (Studies UC I and UC II). Concomitant treatment with stable doses of aminosalicylates, corticosteroids and/or immunomodulatory agents was permitted. Corticosteroid taper was permitted after Week 8. Patients were randomized at week 0 to receive either placebo, 5 mg/kg Remicade or 10 mg/kg Remicade at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 46 in Study UC I, and at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 22 in Study UC II. In Study UC II, patients were allowed to continue blinded therapy to Week 46 at the investigator’s discretion. Adult patients in Study UC I had failed to respond or were intolerant to oral corticosteroids, 6-MP, or AZA. Adult patients in Study UC II had failed to respond or were intolerant to the above treatments and/or aminosalicylates. In both Study UC I and Study UC II, greater percentages of patients in both Remicade groups achieved clinical response, clinical remission and mucosal healing than in the placebo group. Each of these effects was maintained through the end of each trial (Week 54 in Study UC I, and Week 30 in Study UC II). In addition, a greater proportion of patients in Remicade groups demonstrated sustained response and sustained remission than in the placebo groups. Of patients on corticosteroids at baseline, greater proportions of adult patients in the Remicade treatment groups were in clinical remission and able to discontinue corticosteroids at Week 30 compared with the patients in the placebo treatment groups (22% in Remicade treatment groups vs. 10% in placebo group in Study UC I; 23% in Remicade treatment groups vs. 3% in placebo group in Study UC II). In Study UC I, this effect was maintained through Week 54 (21% in Remicade treatment groups vs. 9% in placebo group).

Pediatrics

Approval for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy are supported by evidence from adequate and well controlled studies of Remicade in adults.

Indication 6 - the treatment of plaque psoriasis

approved September 2006

Dosing/Administration

The recommended dosage in adult patients is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of chronic severe (i.e., extensive and/or disabling) plaque psoriasis.

Clinical Trial Results

Three randomized, double-blind, placebo-controlled studies were conducted in patients 18 years of age and older with chronic, stable Ps involving ≥10% BSA, a minimum PASI score of 12, and who were candidates for systemic therapy or phototherapy. 

Study I (EXPRESS) evaluated 378 patients who received placebo or Remicade at a dose of 5 mg/kg at Weeks 0, 2, and 6 (induction therapy), followed by maintenance therapy every 8 weeks. At Week 24, the placebo group crossed over to Remicade induction therapy (5 mg/kg), followed by maintenance therapy every 8 weeks. Patients originally randomized to Remicade continued to receive Remicade 5 mg/kg every 8 weeks through Week 46.

Study II (EXPRESS II) evaluated 835 patients who received placebo or Remicade at doses of 3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6 (induction therapy). At Week 14, within each Remicade dose group, patients were randomized to either scheduled (every 8 weeks) or as needed (PRN) maintenance treatment through Week 46. At Week 16, the placebo group crossed over to Remicade induction therapy (5 mg/kg), followed by maintenance therapy every 8 weeks. 

Study III (SPIRIT) evaluated 249 patients who had previously received either psoralen plus ultraviolet A treatment (PUVA) or other systemic therapy for their psoriasis. These patients were randomized to receive either placebo or Remicade at doses of 3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6. At Week 26, patients with a sPGA score of moderate or worse (greater than or equal to 3 on a scale of 0 to 5) received an additional dose of the randomized treatment.

In Studies I, II and III, the primary endpoint was the proportion of patients who achieved a reduction in score of at least 75% from baseline at Week 10 by the PASI (PASI 75). Rates (% of patients) for each study are as follows (Remicade 3mg/kg, Remicade 5mg/kg vs. placebo, respectively).

• Study I: NA vs. 80% vs. 3%
• Study II: 70% vs. 75% vs. 4%
• Study III: 71% vs. 87% vs. 3%