Find a Specialist | Contact Us | For Healthcare Professionals

Please read the Medication Guide for REMICADE® and discuss with your doctor.

Receive the latest news and information from REMICADE®.
Sign Up Now.

REMICADE has been approved for the treatment of pediatric patients with moderate to severe Crohn's disease.

REACH Trial

The FDA approval for REMICADE therapy in pediatric Crohn's disease was based on the results of the REACH clinical trial. REACH stands for "A Randomized, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of Anti-TNF alpha Chimeric Monoclonal Antibody in Pediatric Subjects with Moderate to Severe Crohn's Disease."

REACH trial background

REACH was a multicenter, randomized, open-label, controlled trial, which evaluated the safety and efficacy of REMICADE in 112 pediatric patients (ages 6-17 years) with active CD. The primary objective of this trial was to evaluate the efficacy of a 3-dose induction regimen of REMICADE in reducing signs and symptoms in pediatric patients with moderately to severely active CD. Additionally, the safety profile of REMICADE in these patients was also evaluated. The secondary objective was to compare maintenance of clinical response and remission with REMICADE 5 mg/kg administered every 8 weeks or every 12 weeks.

Patients included in the trial had moderate-severe CD (Pediatric Crohn's Disease Activity Index [PCDAI] >30) and failed to respond to an immunomodulator. Induction of clinical response, the primary endpoint, was evaluated 10 weeks after the initial infusion. At Week 54, clinical response, clinical remission and change from baseline in average daily corticosteroid use were evaluated as secondary efficacy endpoints. Clinical response was defined as a decrease of ≥15 in the PCDAI and a total PCDAI value ≤30. Clinical remission was defined as a PCDAI score of ≤10.

Of the 112 patients enrolled in this study, 103 patients achieved clinical response to induction therapy (REMICADE 5 mg/kg 0, 2 and 6) and were subsequently randomized to REMICADE 5 mg/kg every 8 weeks (n=52) or every 12 weeks (n=51) through Week 46.

REACH study findings

Clinical response at Week 10, the primary endpoint, was achieved in 88% of the patients. Additional response and remission rates are summarized in Table 1.

Table 1. RESPONSE AND REMISSION IN STUDY PEDS CROHN'S

	5 mg/kg REMICADE
	Every 8 Week	Every 12 Week
	Treatment Group	Treatment Group
Patients randomized	52	51
Clinical Response¹
Week 30	73%**	47%
Week 54	64%**	33%
Clinical Remission²
Week 30	60%*	35%
Week 54	56%**	24%

¹Defined as a decrease from baseline in the PCDAI score of ≥15 points and total score of ≤30 points.
²Defined as a PCDAI score of ≤10 points.
*p-value < 0.05
**p-value < 0.01

REMICADE every 8 weeks allowed 75% of kids with Crohn's to eliminate steroid use through Week 54 (P<0.001).

Indications

Plaque Psoriasis
REMICADE is indicated 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 should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Rheumatoid Arthritis
REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.

Psoriatic Arthritis
REMICADE is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.

Adult Crohn's Disease
REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.

REMICADE is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease.

Pediatric Crohn’s Disease
REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.

Ulcerative Colitis
REMICADE is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

Ankylosing Spondylitis
REMICADE is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

IMPORTANT SAFETY INFORMATION

RISK OF INFECTIONS

Patients treated with REMICADE^® 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, 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.

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.

MALIGNANCIES

HEPATOSPLENIC T-CELL LYMPHOMAS

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. All reported REMICADE cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE^® at or prior to diagnosis.

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. 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).

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 at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating REMICADE^®. 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 (e.g., ≥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 with rare cases of new or exacerbated symptoms of demyelinating disorders including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome, seizure, and CNS manifestations of systemic vasculitis. Exercise caution when considering REMICADE^® in all patients with these disorders. Consider discontinuation for significant CNS adverse reactions.

Please see Full Prescribing Information and Medication Guide for REMICADE^®. Provide the Medication Guide to your patients and encourage discussion.

References

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

Full Prescribing Information | Privacy Policy | Legal Notice | Site Map | About Centocor Ortho Biotech Inc.

© Centocor Ortho Biotech Inc. 1999-2009
This site is published by Centocor Ortho Biotech Inc. which is solely responsible for its contents.
It is intended for residents from the United States.
Last Updated: January 19, 2009