Head Toward Symptom Relief With REMICADE®

What is IMPACT 2?*

IMPACT 2 (Induction and Maintenance Psoriatic Arthritis Clinical Trial)

  • A randomized, multicenter, double-blind, placebo-controlled, phase 3 study in 200 adult patients with active psoriatic arthritis (PsA) despite DMARD or NSAID therapy
  • ACR Response – IMPACT 2

    Significant Improvement in Signs and Symptoms as Early as Week 21,2*

    • Significantly more PsA patients treated with REMICADE® achieved ACR 20 response vs placebo at Week 14 (58% vs 11%; P<0.001), and clinical response was maintained through 1 year1-3*
    • Some patients demonstrated improvement, as measured by ACR 20 response, after just 2 weeks (29.6% vs 7%; P<0.001)4

    Click here for a complete study design of IMPACT 2

    SELECTED IMPORTANT SAFETY INFORMATION

    Serious and sometimes fatal side effects have been reported with REMICADE® (infliximab). Infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (e.g., TB, histoplasmosis) have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma, and other malignancies have been reported, including in children and young adult patients. REMICADE® is contraindicated in patients with severe hypersensitivity reactions to REMICADE® and certain patients with congestive heart failure. Other serious side effects reported include melanoma and Merkel cell carcinoma, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity, neurological events, and lupus-like syndrome. Please see related and other Important Safety Information.

     

  • PASI Response – IMPACT 2

    Rapid Improvement in Skin Symptoms1

    Skin improvement was evident as early as Week 2 in some patients with REMICADE® and was generally maintained through Week 541*

    • 64% of patients treated with REMICADE® (n=100) showed at least a 75% improvement from baseline in PASI 75 at Week 14 vs placebo (n=100) at just 2% (P<0.001), regardless of concomitant methotrexate use1,2*
    • 41% of patients treated with REMICADE® (n=100) experienced 90% improvement in PASI from baseline in skin symptoms vs placebo (n=100) (0%) at Week 142*
    • As early as Week 2, 28% of patients treated with REMICADE® 5 mg/kg (n=100) achieved ≥50% improvement from baseline in PASI vs 3.4% with placebo (n=100) (P<0.001)4*

    Click here for a complete study design of IMPACT 2

    SELECTED IMPORTANT SAFETY INFORMATION

    Serious and sometimes fatal side effects have been reported with REMICADE® (infliximab). Infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (e.g., TB, histoplasmosis) have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma, and other malignancies have been reported, including in children and young adult patients. REMICADE® is contraindicated in patients with severe hypersensitivity reactions to REMICADE® and certain patients with congestive heart failure. Other serious side effects reported include melanoma and Merkel cell carcinoma, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity, neurological events, and lupus-like syndrome. Please see related and other Important Safety Information.

     

  • Dactylitis – IMPACT 2

    Significant Improvement in Dactylitis1,2

    IMPACT 2 study results show*

    • 60% reduction from baseline in patients with dactylitis

    Percentage of Patients With Dactylitis Through Week 54

    Click here for a complete study design of IMPACT 2

    SELECTED IMPORTANT SAFETY INFORMATION

    Serious and sometimes fatal side effects have been reported with REMICADE® (infliximab). Infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (e.g., TB, histoplasmosis) have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma, and other malignancies have been reported, including in children and young adult patients. REMICADE® is contraindicated in patients with severe hypersensitivity reactions to REMICADE® and certain patients with congestive heart failure. Other serious side effects reported include melanoma and Merkel cell carcinoma, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity, neurological events, and lupus-like syndrome. Please see related and other Important Safety Information.

     

  • Enthesitis – IMPACT 2

    Significant Improvement in Enthesitis

    IMPACT 2 study results show*

    • 23% of patients treated with REMICADE® 5 mg/kg had enthesopathy at Week 14 vs 33% of patients treated with placebo (P=0.023)1
    • 22% of patients treated with REMICADE® 5 mg/kg had enthesopathy at Week 24 vs 36% of patients treated with placebo (P=0.004)1,2
    • From baseline to Week 54, REMICADE® 5 mg/kg reduced the proportion of patients with enthesitis from 42% to 21%1
    • From Weeks 24 to 54, the placebo group was treated with REMICADE® 5 mg/kg and saw reduction in the proportion of patients with enthesitis from 36% to 20%1,2

    Percentage of Patients with Enthesopathy through Week 54

    Enthesitis is a hallmark feature of PsA and a criterion for diagnosis
    Enthesitis was present in 42% of patients treated with REMICADE® 5 mg/kg upon entry in IMPACT 21,2

    • Enthesitis is inflammation where the tendon, ligament, or joint capsule attaches to bone, commonly seen in the Achilles tendon5,6
    • Unrecognized enthesitis may be a main source of inflammation and widespread pain in PsA7
    • Other common locations of enthesitis include the insertion site of the plantar fascia and other ligamentous attachment sites5

    Click here for a complete study design of IMPACT 2

    SELECTED IMPORTANT SAFETY INFORMATION

    Serious and sometimes fatal side effects have been reported with REMICADE® (infliximab). Infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (e.g., TB, histoplasmosis) have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma, and other malignancies have been reported, including in children and young adult patients. REMICADE® is contraindicated in patients with severe hypersensitivity reactions to REMICADE® and certain patients with congestive heart failure. Other serious side effects reported include melanoma and Merkel cell carcinoma, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity, neurological events, and lupus-like syndrome. Please see related and other Important Safety Information.

     

  • Structural Damage in PsA – IMPACT 2

    Significant Inhibition of Structural Damage

    The IMPACT 2 study showed REMICADE® inhibited progression of structural damage in active PsA as early as 6 months after beginning treatment8*

    Patients treated with REMICADE® demonstrated greater inhibition of structural damage vs placebo at Week 24 (-0.70 vs 0.82; P<0.001), and response was maintained through 1 year.1,8*

    Click here for a complete study design of IMPACT 2

    SELECTED IMPORTANT SAFETY INFORMATION

    Serious and sometimes fatal side effects have been reported with REMICADE® (infliximab). Infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (e.g., TB, histoplasmosis) have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma, and other malignancies have been reported, including in children and young adult patients. REMICADE® is contraindicated in patients with severe hypersensitivity reactions to REMICADE® and certain patients with congestive heart failure. Other serious side effects reported include melanoma and Merkel cell carcinoma, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity, neurological events, and lupus-like syndrome. Please see related and other Important Safety Information.

     

*
IMPACT 2 (Induction and Maintenance Psoriatic Arthritis Clinical Trial 2): a randomized, double-blind, placebo-controlled, multicenter, phase 3 study of REMICADE® in 200 patients with active PsA for at least 6 months who had an inadequate response to DMARDs or NSAIDs. Patients had active articular disease (≥5 swollen and tender joints each), psoriatic target skin lesion (≥2 cm in diameter), and either CRP ≥1.5 mg/dL or morning stiffness lasting ≥45 minutes. Stable methotrexate (MTX) doses of ≤25 mg/week at study entry and stable oral corticosteroid doses equivalent to ≤10 mg/day of prednisone were permitted. During the 24-week, double-blind phase, patients received either REMICADE® 5 mg/kg (n=100) or placebo (n=100) at Weeks 0, 2, 6, 14, and 22. At Week 16, placebo patients with <10% improvement in swollen and tender joint counts were switched to active treatment and received REMICADE® 5 mg/kg at Weeks 16, 18, 22, 30, 38, and 46. At Week 24, all patients receiving placebo crossed over to active treatment and received REMICADE® 5 mg/kg (n=91) at Weeks 24, 26, 30, 38, and 46. Primary endpoints included the proportion of patients with ACR 20 response at Week 14 and the change from baseline in total modified van der Heijde-Sharp (vdH-S) score at Week 24. Improvement in Psoriasis Area and Severity Index (PASI) was evaluated in psoriatic arthritis patients with baseline body surface area (BSA) ≥3% (n=87, placebo; n=83, REMICADE®).
 
References:
  1. REMICADE® (infliximab) Prescribing Information. Janssen Biotech, Inc.
  2. Antoni C, Krueger GG, de Vlam K, et al; for the IMPACT 2 Investigators. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005;64:1150-1157.
  3. Kavanaugh A, Krueger GG, Beutler A, et al; for the IMPACT 2 Study Group. Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann Rheum Dis. 2007;66:498-505.
  4. Data on file. Janssen Biotech, Inc.
  5. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2008;58:851-864.
  6. McGonagle D. Enthesitis: an autoinflammatory lesion linking nail and joint involvement in psoriatic disease. J Eur Acad Dermatol Venereol. 2009;23(suppl 1):9-13.
  7. Leung YY, Tam LS, Kun EW, Li EK. Psoriatic arthritis as a distinct disease entity. J Postgrad Med. 2007;53:63-71.
  8. van der Heijde D, Kavanaugh A, Gladman DD, et al; for the IMPACT 2 Study Group. Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: results from the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2. Arthritis Rheum. 2007;56:2698-2707.

 

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.

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. 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. 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.

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References:
  1. 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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