For adult patients with moderately to severely active Crohn's disease (CD) who have had an inadequate response to conventional therapy

BEYOND MILD? REMICADE® RESULTS FOR FISTULIZING DISEASE

ACCENT II: COMPLETE FISTULA CLOSURE AT WEEK 301,2*

ACCENT II: COMPLETE FISTULA CLOSURE AT WEEK 543*

Patients who responded at Week 14 showed significantly higher rates of complete fistula response vs those taking placebo in ACCENT II1,3*

*Results from ACCENT II, a 1-year, randomized, double-blind trial of REMICADE® in 296 patients with at least 1 draining, enterocutaneous fistula. At baseline, approximately 80% of patients were receiving stable doses of 1 or more concomitant Crohn's-related therapies. All patients received an initial 3-dose induction of REMICADE® 5 mg/kg at Weeks 0, 2, and 6. Patients were then randomized based on clinical response at Week 14 to receive REMICADE® 5 mg/kg every 8 weeks or placebo through Week 46. The primary endpoint of the trial was time to loss of fistula response through Week 54 among patients responding at Week 14. Among patients randomized as responders at Week 14, patients receiving REMICADE® maintenance therapy (n=87) had a significantly longer time to loss of fistula response than patients in the control group (n=90) (median >40 weeks vs 14 weeks [P=0.001]). At Week 14, 65% (177/273) of patients were responders. Fistula response was defined as ≥50% reduction in the number of draining fistulas on at least 2 consecutive visits and no increase in CD medication and no surgery for CD.

A complete fistula response was defined as the absence of any draining fistulas.

References: 1. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004;350:876-885. 2. REMICADE® Prescribing Information. Janssen Biotech, Inc. 3. Data on file. Janssen Biotech, Inc. 4. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med. 1999;340:1398-1405.

PRESENT PRIMARY ENDPOINT: REDUCTION OF DRAINING FISTULAS4*

PRESENT SECONDARY ENDPOINT: COMPLETE RESPONSE4*

*Present was a randomized, multicenter, double-bind, placebo-controlled trial of REMICADE® in 94 adult patients with draining abdominal or perianal fistulas of ≥3 months duration as a complication of Crohn’s disease. Patients were randomly assigned to receive one of 3 regimens to be given intravenously at 0, 2, and 6 weeks: placebo, REMICADE® 5 mg/kg, or REMICADE® 10 mg/kg. The primary efficacy endpoint was a ≥50% reduction from baseline in the number of draining fistulas observed at ≥2 consecutive study visits. Secondary efficacy endpoints included closure of all fistulas, the length of time to the beginning of a response, and the duration of the response. Safety was assessed during each infusion and at each study visit. The frequency of adverse events observed was >60% in all 3 treatment groups.

Fifty percent or greater reduction from baseline in the number of draining fistules observed at ≥2 consecutive study visits.

Complete response was defined as the absence of any draining fistula at 2 consecutive visits.

References: 1. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004;350:876-885. 2. REMICADE® Prescribing Information. Janssen Biotech, Inc. 3. Data on file. Janssen Biotech, Inc.
4. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med. 1999;340:1398-1405.

 

REMICADE® is indicated for:

Crohn's Disease
  • 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
Pediatric Crohn's Disease
  • Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age or older with moderately to severely active CD who have had an inadequate response to conventional therapy
Ulcerative Colitis
  • 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
Pediatric Ulcerative Colitis
  • 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
Rheumatoid Arthritis
  • Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate (MTX)
Psoriatic Arthritis
  • Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis (PsA)
Ankylosing Spondylitis
  • Reducing signs and symptoms in patients with active ankylosing spondylitis (AS)
Plaque Psoriasis
  • The treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.
  • REMICADE® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician

 

SERIOUS INFECTIONS

Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE®.1,2 Treatment for latent infection should be initiated prior to treatment with REMICADE®.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.

Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including REMICADE®. These cases have had a very aggressive disease course and have been fatal. The majority of reported REMICADE® cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including REMICADE®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

CONTRAINDICATIONS

REMICADE® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE® if new or worsening CHF symptoms appear. REMICADE® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION

TNF inhibitors, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating REMICADE®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.

HEPATOTOXICITY

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC EVENTS

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY

REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.

NEUROLOGIC EVENTS

TNF inhibitors, including REMICADE®, have been associated in rare cases with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering REMICADE® in patients with these disorders and consider discontinuation if these disorders develop.

AUTOIMMUNITY

Treatment with REMICADE® may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

ADVERSE REACTIONS

In clinical trials, the most common REMICADE® adverse reactions occurring in >10% of patients included infections (eg, upper respiratory, sinusitis, and pharyngitis),
infusion-related reactions, headache, and abdominal pain.

USE WITH OTHER DRUGS

Concomitant use of REMICADE® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as REMICADE® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS

Live vaccines or therapeutic infectious agents should not be given with REMICADE® due to the possibility of clinical infections, including disseminated infections.

Bring pediatric patients up to date with all vaccinations prior to initiating REMICADE®. Exercise caution in the administration of live vaccines to infants born to female patients treated with REMICADE® during pregnancy.

For more information, please see full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion. (Requires Adobe® Reader®. Click here to download.)

References:

1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247.

2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.

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