Subject: Infliximab (Remicade®)
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Infliximab, also known as cA2, is the first monoclonal antibody to be approved for the treatment of Crohn’s disease. A single intravenous infusion of infliximab has been shown to induce a clinical response or remission in 65% of patients with moderate-to-severe treatment-resistant Crohn’s disease. The short-term benefits after a single infusion may persist for up to 12 weeks. Long-term maintenance therapy with Infliximab in Crohn’s Disease was evaluated in the ACCENT I trial (A Crohn’s Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen). The results through week 54 of the ACCENT I trial demonstrate that Remicade is safe and well tolerated as a maintenance regimen in patients with moderately to severely active Crohn’s disease. Infliximab has been shown to significantly decrease the number of draining fistulas in patients with Crohn’s disease as compared to placebo. In patients with rheumatoid arthritis, infliximab substantially improves clinical symptoms when given in combination with methotrexate. Infliximab was granted final FDA approval for the treatment of Crohn’s disease on August 24, 1998. The FDA approved infliximab for the treatment of rheumatoid arthritis in combination with methotrexate on November 11, 1999.
On September 20, 2005, the FDA approved infliximab for the treatment of moderate to severe ulcerative colitis in those whose symptoms are not controlled by conventional therapies. A total of 728 patients with moderate to severe ulcerative colitiswere enrolled in the ACT 1 and ACT 2 studies who had uncontrolled disease on aminosalicylates, steroids, and/or immunosuppressant therapies. In the ACT 1 study 20% of the infliximab vs. 10% of the placebo group were in clinical remission and able to discontinue corticosteroids at week 30. The ACT 2 study demonstrated similar effects with 23% infliximab response vs. 3% placebo. The Remicade response was similar in the 5mg/kg and 10mg/kg groups 16. Jarnerot et al. conducted a randomized double-blind trial of infliximab in severe to moderately severe ulcerative colitis not responding to conventional treatment. Forty-five patients were randomized to receive either infliximab 5mg/kg or placebo. There were double the amount of colectomies in the placebo group (7 infliximab vs 14 placebo colectomies, P=0.017, 95%CI) 9.
Infliximab (Remicade®) meets the definition of medical necessity when administered for the following indications (SEE TABLE 1 FOR SPECIFIC CRITERIA):
- Crohn’s Disease
- Fistulizing Crohn’s Disease
- Rheumatoid Arthritis
- Ankylosing Spondylitis
- Psoriatic Arthritis
- Ulcerative Colitis
- Plaque Psoriasis.
|SPECIFIC CRITERIA FOR REMICADE® THERAPY
|1. Crohn’s Disease
- Patient has a history of beneficial clinical response to infliximab therapy for Crohn’s disease OR
- Infliximab is being prescribed for the reduction of signs and symptoms and inducing and maintaining clinical remission in adults and pediatrics with moderately to severely active Crohn’s disease AND
- Patient has had an inadequate response to conventional therapy (i.e., mesalamine substances, corticosteroids, or immunosupprssives agents). AND
- Dosage does not exceed: Adults 10 mg/kg. Children – 5 mg/kg.
|2. Fistulizing Crohn’s Disease
- Patient has a history of beneficial clinical response to infliximab therapy for fistulizing Crohn’s disease OR
- Infliximab is being prescribed for the reduction in the number of draining enterocutaneous fistulas and rectovaginal fistulas and maintaining fistula closure in adult patients. AND
- Dosage does not exceed: Adults 10 mg/kg. Children – 5 mg/kg.
|3. Rheumatoid Arthritis
- Patient has a history of beneficial clinical reponse to infliximab therapy for rheumatoid arthritis OR
- Infliximab is being prescribed for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active rheumatoid arthritis. AND
- Dosage does not exceed: 10 mg/kg. AND
- Remicade® may be used as a first-line agent.
|4. Ankylosing Spondylitis
- Patient has a history of beneficial clinical response to infliximab therapy for ankylosing spondylitis OR
- Infliximab is being prescribed for reducing signs and symptoms in patients with ankylosing spondylitis. AND
- Dosage does not exceed: 5 mg/kg.
|5. Psoriatic Arthritis
- Patient has a history of beneficial clinical response to infliximab therapy for psoriatic arthritis OR
- Infliximab is being prescribed for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with psoratic arthritis. AND
- Dosage does not exceed: 5 mg/kg.
|6. Ulcerative Colitis
- Patient has a history of beneficial clinical response to infliximab therapy for ulcerative colitis OR
- Infliximab is being prescribed for the reduction of signs and symptoms, achieving 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. AND
- Dosage does not exceed: 5 mg/kg.
|7. Plaque Psoriasis
- Patient has a history of beneficial clinical response to infliximab therapy for plaque psoriasis OR
- Infliximab is being prescribed for the treatment of severe plaque-type psoriasis when the following criteria are met:
- Patient is 18 years old or older AND
- Patients has had moderate to severe chronic plaque psoriasis for more than 1 year AND
- Patient has ten percent or more body surface affected by plaque psoriasis AND
- Patient must have failed to adequately respond to or is intolerant to one of the following phototherapies (unless contraindicated):
- psoralens (methoxsalen, trioxsalen) with UVA light (PUVA); OR
- UVB with coal tar or dithranol; OR
- UVB (standard or narrow-band) AND
- Dosage does not exceed: 5 mg/kg.
Infliximab (Remicade®) is considered experimental or investigationalwhen administered for conditions other than those listed above, as there is insufficient clinical evidence to support its use.
DOSAGE AND ADMINISTRATION:
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Crohn’s disease or Fistulizing Crohn’s Disease: The recommended dose of infliximab is 5mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn’s disease or fistulizing Crohn’s disease. For adult patients who respond and then lose their response, consideration may be given to treatment with 10mg/kg. Patients who do not respond by week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue infliximab in these patients.
The recommended dose of infliximab for children with moderately to severely active Crohn’s disease is 5mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5mg/kg every 8 weeks.
Rheumatoid Arthtitis: The recommended dose of infliximab is 3mg/kg given as an intravenous infusion followed with additional similar doses at 2 and 6 weeks after the first infusion then every 8 weeks thereafter. Infliximab should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10mg /kg or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses.
Ankylosing Spondylitis: The recommended dose of infliximab is 5mg/kg given as an intravenous infusion followed with additional similar doses at 2 and 6 weeks after the first infustion, then every 6 weeks thereafter.
Psoriatic arthritis: The recommended dose of infliximab is 5mg/kg given as an intravenous infusion, followed with additional similar doses at 2 and 6 weeks after the first infusion then every 8 weeks thereafter. Remicade can be used with or without methotrexate.
Ulcerative colitis: The recommended dose of infliximab is 5mg/kg given as an induction regimen at 0, 2 and 6 weeks, followed by a maintenance regimen of 5mg/kg every 8 weeks thereafter for the treatment of moderately to severely active ulcerative colitis.
Plaque Psoriasis: The recommended dose of infliximab is 5mg/kg given as an intravenous infusion, followed by additional doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.
|Risk of serious infections:
Patients treated with infliximab are at an 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 infliximab if a patient develops a serious infection or sepsis.
Reported infections include:
- Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before infliximab use and during therapy. Initiate treatment for latent infection prior to infliximab use.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients who develop severe systemic illness.
- Bacterial, viral, and other infections caused by opportunistic pathogens.
Carefully consider the risks and benefits of treatment with infliximab prior to initiating therapy in patients with long-term or recurrent infection.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with infliximab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab. These cases had a very aggressive disease course and have been fatal. All reported infliximab cases have occurred in patients with Crohn disease or ulcerative colitis, and the majority were in adolescent and young adult males. All of these patients received treatment with azathioprine or 6-mercaptopurine concomitantly with infliximab at or prior to diagnosis.
Risk of serious infections: Serious and sometimes fatal infections caused by bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving TNF-blocking agents. Among opportunistic infections, TB, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis were the most commonly reported. Patients have frequently presented with disseminated rather than localized disease, and are often taking concomitant immunosuppressants, such as methotrexate or corticosteroids, with infliximab.
Treatment with infliximab should not be initiated in patients with an active infection, including clinically important localized infections. Consider the risks and benefits of treatment prior to initiating therapy in patients with long-term or recurrent infection; who have been exposed to TB; who have resided or traveled in areas of endemic TB or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or with underlying conditions that may predispose them to infection.
Cases of reactivation of TB or new TB infections have been observed in patients receiving infliximab, including patients who have previously received treatment for latent or active TB. Evaluate patients for TB risk factors and test for latent infection prior to initiating infliximab and periodically during therapy.
Treatment of latent TB infection prior to therapy with TNF-blocking agents has been shown to reduce the risk of TB reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent TB is needed prior to initiating infliximab, even for patients previously vaccinated with Bacille Calmette-Guerin.
Also consider anti-TB therapy prior to initiation of infliximab in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection. Consultation with a health care provider with expertise in the treatment of TB is recommended to aid in the decision of whether initiating anti-TB therapy is appropriate for an individual patient.
Strongly consider TB in patients who develop a new infection during infliximab treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of TB, or who have had close contact with a person with active TB.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with infliximab, including the development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Tests for latent TB infection may also be falsely negative while on therapy with infliximab.
Discontinue infliximab if a patient develops a serious infection or sepsis. Closely monitor a patient who develops a new infection during treatment with infliximab, and undergoes a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Consider appropriate empiric antifungal therapy while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a health care provider with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy.
Serious infections were seen in clinical studies with concurrent use of anakinra and another TNF-alpha–blocking agent, etanercept, with no added clinical benefit compared with etanercept alone. Because of the nature of the adverse reactions seen with combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNF-alpha–blocking agents. Therefore, the combination of infliximab and anakinra is not recommended.
Malignancies: Malignancies, some fatal, have been reported among children, adolescents and young adults who received treatment with TNF-blocking agents (initiation of therapy, 18 years of age or younger), including infliximab. Approximately half of these cases were lymphomas, including Hodgkin and non-Hodgkin lymphomas. 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 (range, 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported postmarketing and were derived from a variety of sources, including registries and spontaneous postmarketing reports.
Postmarketing cases of hepatosplenic T-cell lymphomas, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab. These cases have had a very aggressive disease course and have been fatal. All reported infliximab cases have occurred in patients with Crohn disease or ulcerative colitis, and the majority were in adolescent and young adult males. All of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with infliximab at or prior to diagnosis. It is uncertain whether the occurrence of hepatosplenic T-cell lymphomas is related to infliximab or infliximab in combination with these other immunosuppressants.
In the controlled portions of clinical trials of some TNF-blocking agents, including infliximab, more malignancies (excluding lymphoma and nonmelanoma skin cancer) have been observed in patients receiving TNF blockers, compared with control patients. During the controlled portions of infliximab trials in patients with moderately to severely active RA, Crohn disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and plaque psoriasis, 14 patients were diagnosed with malignancies (excluding lymphoma and nonmelanoma skin cancer) among 4,019 infliximab-treated patients versus 1 among 1,597 control patients (at a rate of 0.52 per 100 patient-years among infliximab-treated patients vs a rate of 0.11 per 100 patient-years among control patients), with median duration of follow-up 0.5 years for infliximab-treated patients and 0.4 years for control patients. Of these, the most common malignancies were breast, colorectal, and melanoma. The rate of malignancies among infliximab-treated patients was similar to that expected in the general population, whereas the rate in control patients was lower than expected.
In the controlled portions of clinical trials of all the TNF-blocking agents, more cases of lymphoma have been observed among patients receiving a TNF blocker, compared with control patients. In the controlled and open-label portions of infliximab clinical trials, 5 patients developed lymphomas among 5,707 patients treated with infliximab (median duration of follow-up, 1 year) versus 0 lymphomas in 1,600 control patients (median duration of follow-up, 0.4 years). In patients with RA, 2 lymphomas were observed for a rate of 0.08 cases per 100 patient-years of follow-up, which is approximately 3-fold higher than expected in the general population. In the combined clinical trial population for RA, Crohn disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and plaque psoriasis, 5 lymphomas were observed for a rate of 0.1 cases per 100 patient-years of follow-up, which is approximately 4-fold higher than expected in the general population. Patients with Crohn disease, RA, or plaque psoriasis, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several-fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronic leukemia have been reported with postmarketing TNF blocker use in RA and other indications. Even in the absence of TNF blocker therapy, patients with RA may be at higher risk (approximately 2–fold) than the general population for the development of leukemia.
In a clinical trial exploring the use of infliximab in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, the majority of lung or head and neck origin, were reported in infliximab-treated patients, compared with control patients. All patients had a history of heavy smoking. Exercise caution when considering the use of infliximab in patients with moderate to severe COPD.
Monitor psoriasis patients for nonmelanoma skin cancers, particularly patients who have had prior prolonged phototherapy treatment. In the maintenance portion of clinical trials for infliximab, nonmelanoma skin cancers were more common in patients with previous phototherapy.
The potential role of TNF-blocking therapy in the development of malignancies is not known. Rates in clinical trials for infliximab cannot be compared with rates in clinical trials of other TNF blockers and may not predict rates observed in a broader patient population. Exercise caution in considering infliximab treatment in patients with a history of malignancy or in continuing treatment in patients who develop malignancy while receiving infliximab.
Hepatitis B virus reactivation: Use of TNF blockers, including infliximab, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which also may contribute to HBV reactivation. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy. Exercise caution in prescribing TNF blockers, including infliximab, for patients identified as carriers of HBV. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with antiviral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Closely monitor patients who are carriers of HBV and require treatment with TNF blockers for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, stop TNF blockers and initiate antiviral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of TNF blocker therapy in this situation, and monitor patients closely.
Hepatotoxicity: Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis, have been reported rarely in postmarketing data in patients receiving infliximab. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between 2 weeks and more than a year after initiation of infliximab; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases. Some of these cases were fatal or necessitated liver transplantation. Evaluate patients with symptoms or signs of liver function impairment for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, 5 times the upper limit of normal [ULN] or more) develop, discontinue infliximab and investigate the abnormality thoroughly. In clinical trials, mild or moderate elevations of ALT and AST have been observed in patients receiving infliximab without progression to severe hepatic injury.
Heart failure: Infliximab has been associated with adverse outcomes in patients with heart failure and use in patients with heart failure only after consideration of other treatment options. The results of a randomized study evaluating the use of infliximab in patients with heart failure (New York Heart Association [NYHA] functional class ΙΙΙ/ΙV) suggested higher mortality in patients who received infliximab 10 mg/kg and higher rates of cardiovascular adverse reactions at doses of 5 and 10 mg/kg. There have been postmarketing reports of worsening heart failure, with and without identifiable precipitating factors, in patients taking infliximab. There have also been rare postmarketing reports of new-onset heart failure, including heart failure in patients without known preexisting cardiovascular disease. Some of these patients were younger than 50 years of age. If a decision is made to administer infliximab to patients with heart failure, closely monitor them during therapy and discontinue infliximab if new or worsening symptoms of heart failure appear.
Hematologic effects: Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients receiving infliximab. The causal relationship to infliximab therapy remains unclear. Although no high-risk group has been identified, exercise caution in patients being treated with infliximab who have ongoing or histories of significant hematologic abnormalities. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (eg, persistent fever) while on infliximab. Consider discontinuation of infliximab therapy in patients who develop significant hematologic abnormalities.
CNS effects: Infliximab and other agents that inhibit TNF have been associated in rare cases with optic neuritis, seizure, and new onset or exacerbation of clinical symptoms and/or radiographic evidence of CNS-demyelinating disorders, including multiple sclerosis and CNS manifestations of systemic vasculitis and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering the use of infliximab in patients with preexisting or recent onset of CNS-demyelinating or seizure disorders. Consider discontinuation of infliximab in patients who develop significant CNS adverse reactions.
Autoimmunity: Treatment with infliximab may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with infliximab, discontinue treatment.
Vaccinations: No data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines in patients receiving anti-TNF therapy. It is recommended that live vaccines not be given concurrently.
It is recommended that all children with Crohn disease be brought up to date with all vaccinations prior to initiating infliximab therapy. The interval between vaccination and initiation of infliximab therapy should be in accordance with current vaccination guidelines.
Immunogenicity: Treatment with infliximab can be associated with the development of antibodies to infliximab. The incidence of antibodies to infliximab in patients given a 3-dose induction regimen followed by maintenance dosing was approximately 10%, as assessed through 1 to 2 years of infliximab treatment. A higher incidence of antibodies to infliximab was observed in patients with Crohn disease receiving infliximab after drug-free intervals greater than 16 weeks. In a study of psoriatic arthritis, in which 191 patients received 5 mg/kg with or without methotrexate, antibodies to infliximab occurred in 15% of patients. The majority of antibody-positive patients had low titers. Patients who were antibody positive were more likely to have higher rates of clearance, and reduced efficacy, and to experience an infusion reaction than were patients who were antibody negative. Antibody development was lower among patients with RA and Crohn disease receiving immunosuppressive therapies, such as 6-mercaptopurine/azathioprine or methotrexate.
In the psoriasis study ΙΙ, which included both the 5 and 3 mg/kg doses, antibodies were observed in 36% of patients treated with 5 mg/kg every 8 weeks for 1 year and in 51% of patients treated with 3 mg/kg every 8 weeks for 1 year. In the psoriasis study ΙΙΙ, which also included both the 5 and 3 mg/kg doses, antibodies were observed in 20% of patients treated with 5 mg/kg induction (weeks 0, 2, and 6), and in 27% of patients treated with 3 mg/kg induction. Despite the increase in antibody formation, the infusion reaction rates in studies Ι and ΙΙ (in patients treated with 5 mg/kg induction followed by every 8 week maintenance for 1 year) and in study ΙΙΙ (in patients treated with 5 mg/kg induction [14.1% to 23%]) and serious infusion reaction rates (less than 1%) were similar to those observed in other study populations. The clinical significance of apparent increased immunogenicity on efficacy and infusion reactions in psoriasis patients compared with patients with other diseases treated with infliximab long-term is not known.
The data reflect the percentage of patients whose test results were positive for antibodies to infliximab in an enzyme-linked immunosorbent assay and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to infliximab with the incidence of antibodies to other products may be misleading.
Hypersensitivity reactions: Infliximab has been associated with hypersensitivity reactions that varied in times of onset and required hospitalization in some cases. Most hypersensitivity reactions, which include urticaria, dyspnea, and/or hypotension, occurred during or within 2 hours of infliximab infusion.
However, in some cases, serum sickness–like reactions have been observed in patients after initial infliximab therapy (as early as after the second dose) and when infliximab therapy was reinstituted following an extended period without infliximab treatment. Symptoms associated with these reactions include fever, rash, headache, sore throat, myalgias, polyarthralgias, hand and facial edema, and/or dysphagia. These reactions were associated with marked increase in antibodies to infliximab, loss of detectable serum concentrations of infliximab, and possible loss of drug efficacy.
For severe hypersensitivity reactions, discontinue infliximab. Have medications for the treatment of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids, epinephrine) available for immediate use in the event of a reaction.
Fertility impairment: It is not known if infliximab can impair fertility in humans. No impairment of fertility was observed in a fertility and general reproduction toxicity study with the analogous mouse antibody used in the 6-month chronic toxicity study.
Children: Infliximab has not been studied in children with Crohn disease younger than 6 years of age. The long-term (more than 1 year) safety and effectiveness of infliximab in children with Crohn disease have not been established in clinical trials.
Safety and efficacy of infliximab in children with ulcerative colitis and plaque psoriasis have not been established.
The safety and efficacy of infliximab in patients with juvenile RA were evaluated in a multicenter, randomized, placebo-controlled, double-blind study for 14 weeks, followed by a double-blind, all-active treatment extension for a maximum of 44 weeks.
The following codes may be used to report these services:
||Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
||Each additional hour (list separately in addition to code for primary)
||Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug
||Chemotherapy administration, intravenous infusion technique; each additional hour (list separately in addition to code for primary procedure)
||Injection, infliximab, 10 mg
||Methotrexate sodium, 5 mg
||Methotrexate sodium, 50 mg
ICD-9 Diagnoses Codes That Support Medical Necessity:
||Crohn’s disease, small intestine
||Crohn’s disease, large intestine
||Crohn’s disease, small intestine with large intestine
||Crohn’s disease, unspecified site
||Ulcerative (chronic) enterocolitis
||Ulcerative (chronic) ileocolitis
||Ulcerative (chronic) proctitis
||Ulcerative (chronic) proctosigmoiditis
||Left-sided ulcerative (chronic) colitis
||Universal ulcerative (chronic) colitis
||Other ulcerative colitis
||Ulcerative colitis, unspecified
||Fistula of intestine, excluding rectum and anus
|714.0 – 714.9
ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/13)
||Unspecified iridocyclitis Uveitis NOS
||Crohn’s disease of small intestine without complications
||Crohn’s disease of large intestine without complications
||Crohn’s disease of both small and large intestine without complications
||Crohn’s disease, unspecified, without complications
||Other ulcerative colitis without complications
||Ulcerative (chronic) proctitis without complications
||Ulcerative (chronic) rectosigmoiditis without complications
||Left sided colitis without complications
||Ulcerative (chronic) pancolitis without complications
||Ulcerative colitis, unspecified, without complications
||Fistula of intestine
||Psoriatic juvenile arthropathy
||Other psoriatic arthropathy
||Rheumatoid arthritis, unspecified
||Felty’s syndrome, unspecified site
||Rheumatoid heart disease with rheumatoid arthritis of unspecified site
||Rheumatoid arthritis of unspecified site with involvement of other organs and systems
||Adult-onset Still’s disease
||Unspecified juvenile rheumatoid arthritis of unspecified site
||Juvenile rheumatoid polyarthritis (seronegative
||Pauciarticular juvenile rheumatoid arthritis, unspecified site
||Chronic postrheumatic arthropathy [Jaccoud], unspecified site
||Rheumatoid lung disease with rheumatoid arthritis of unspecified site
||Ankylosing spondylitis of unspecified sites in spine
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Ankylosing spondylitis: A type of arthritis that causes chronic inflammation of the spine.
Crohn’s Disease: is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. The lower portion of the small intestine (ileum) and the rectum are most commonly affected by this disorder. Symptoms may include watery diarrhea and abdominal pain. The symptoms of Crohn’s Disease can be difficult to manage and diagnosis is often delayed.
Enterocutaneous fistula: a fistula between the intestine and skin of the abdomen.
Mild-Moderate Crohn’s Disease: Mild-moderate Crohn’s disease applies to ambulatory patients able to tolerate oral alimentation without manifestations of dehydration, toxicity (high fevers, rigors, prostration), abdominal tenderness, painful mass, obstruction, or >10% weight loss.
Moderate-Severe Crohn’s Disease: Moderate-severe disease applies to patients who have failed to respond to treatment for mild-moderate disease or those with more prominent symptoms of fevers, significant weight loss, abdominal pain or tenderness, intermittent nausea or vomiting (without obstructive findings), or significant anemia.
Monoclonal antibody: derived from a single cell; pertaining to a single clone. Widely used to measure proteins and drugs in the serum, type tissue and blood, identify infectious agents, identify classification and follow-up therapy of leukemias and lymphomas, and identify tumor antibodies.
Plaque psoriasis: It is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques.
Psoriatic arthritis: Joint inflammation associated with psoriasis. Psoriatic arthritis is a potentially destructive and deforming form of arthritis that affects approximately 10% of persons with psoriasis.
Remission: Remission refers to patients who are asymptomatic or without inflammatory sequelae and includes patients who have responded to acute medical intervention or have undergone surgical resection without gross evidence of residual disease. Patients requiring steroids to maintain well-being are considered to be “steroid-dependent” and are usually not considered to be “in remission.”
Rheumatoid arthritis: usually strikes between ages 20 and 50. Inflammation begins in a joint, usually those of the fingers and hands, resulting in pain, swelling, redness, and eventually joint deformity. It is considered an autoimmune disease, which can affect the entire body, causing fatigue, weight loss, weakness, fever, and loss of appetite. It affects each person differently, with symptoms ranging from mild to debilitating. In many cases, it is difficult to control. In about one in six cases, rheumatoid arthritis becomes severely debilitating and can shorten the life of the person affected.
Severe-Fulminant Disease: Severe-fulminant disease refers to patients with persisting symptoms despite the introduction of steroids as outpatients, or individuals presenting with high fever, persistent vomiting, and evidence of intestinal obstruction, rebound tenderness, cachexia, or evidence of an abscess.
Ulcerative colitis: a chronic inflammatory disease of the colon that is of unknown cause and is characterized by diarrhea with discharge of mucus and blood, cramping abdominal pain, and inflammation and edema of the mucous membrane with patches of ulceration.
Etanercept (Enbrel®), 09-J0000-38
Anakinra (Kineret®), 09-J0000-45
Adalimumab (Humira®), 09-J0000-46
Rituximab (Rituxan®), 09-J0000-59
Abatacept (Orencia®), 09-J0000-67
Certolizumab Pegol (Cimzia®), 09-J0000-77
Golimumab (Simponi™), 09-J1000-11
Natalizumab (Tysabri®) IV, 09-J0000-73
Alefacept (Amevive®), 09-J0000-78
Ustekinumab (Stelara™), 09-J1000-16
Tocilizumab (Actemra®) IV, 09-J1000-21
- American College of Rheumatology. Position Statement: Biologic Agents for Rheumatic Diseases. Approved: 03/03 and 08/09.
- American Gastroenterological Association. Position Statement: Perianal Crohn’s Disease. Gastroenterology 2003; 125: 1503-1507.
- American Medical Association CPT Coding, 2009 professional edition.
- Behm BW, Bickston SJ. Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006893. DOI: 10.1002/14651858.CD006893.
- Data presented at the 2001 American College of Gastroenterology meeting: Las Vegas, NV; October 21-24, 2001.
- Data presented at the 2001 Digestive Disease Week Meeting; Atlanta, GA: May 20-23, 2001.
- DRUGDEX®. Accessed 07/21/10.
- Eidelwein AP, Cuffari C, Abadom V et al. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. March 2005; 11(3): 213-8.
- Facts & Comparisons E Answers. Accessed 07/21/10.
- Garnett WR and Yunker N. Treatment of Crohn’s Disease with Infliximab. Am J Health-Sys Pharm 2001; 58 (4): 307-19.
- Guidelines for the Management of Rheumatoid Arthritis 2002 Update. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Arthritis & Rheumatism Vol. 46, No. 2, February 2002, pp 328-346.
- Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance for Crohn’s disease; the ACCENT I randomized trial. Lancet 2002; 359: 1541-9.
- Harrison MJ, Dixon WG, Watson KD, King Y, Groves R, Hyricdh KL, Symmons DP. Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-TNF (alpha) therapy. Results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2008 Apr 2.
- HAYES, Inc. FDA Approves Long-Term Remicade for Crohn’s Disease. Lansdale, PA: HAYES, Inc. July 2002.
- HAYES, Inc. FDA Approves Remicade® as First-Line Therapy in Patients WITH Moderate to Severe Rheumatoid Arthritis. Lansdale, PA: HAYES, Inc. October 2004.
- HAYES, Inc. Infliximab for Crohn’s Disease. Lansdale, PA: HAYES, Inc. May 2004.
- HAYES, Inc. Infliximab for Rheumatoid Arthritis. Lansdale, PA: HAYES, Inc. April 2004.
- HAYES, Inc. Infliximab Maintenance Therapy for Fistulizing Crohn’s Disease. Lansdale, PA: HAYES, Inc. March 2004.
- HAYES, Inc. Maintenance Infliximab Benefits Select Patients With Crohn’s Disease. Lansdale, PA: HAYES, Inc. May 2002.
- HAYES, Inc. Remicade® Now Indicated to Treat Ulcerative Colitis. Lansdale, PA: HAYES, Inc. September 2005
- HIPAA Space, HCPCS Codes Lookup, Copyright® 2004-2010. Accessed 07/21/10.
- ICD-9 Data.com. Accessed 07/21/10.
- Jarnerot G, Hertervig E, Friis-Liby I et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. June 2005.
- National Guideline Clearinghouse. Management of ulcerative colitis. Society of Surgery of the Alimentary Tract. Accessed October 2005.
- Remicade® (infliximab) Prescribing Information. Revised April 2010.
- The Merck Manual, 16th Edition.
- Wailoo AJ, Bansback N, Brennan A, Michaud K, Nixon RM, Wolfe F. Biologic drugs for rheumatoid arthritis in the medicare program: A cost-effectiveness analysis. Arthritis Rheum. 2008 Mar 27; 58(4): 939-946.
This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 08/11/10.
GUIDELINE UPDATE INFORMATION:
||Medical Coverage Guideline developed.
||Reviewed, revised coverage for Crohn’s disease.
||Revised coverage for Crohn’s disease.
||Revised with updates: Added maintenance therapy to fistulizing crohn’s. Added coverage for psoriatic arthropathy and ankylosing spondylitis. Updated dosing.
||Revised; added coverage for ulcerative colitis, updated dosage and administration, deleted warnings and contraindications section, updated references and Internet links.
||CPT coding update: deleted expired codes 90780, 90781 and added new codes 90765, 90766.
||Scheduled review: added psoriasis indication and ICD-9 code, updated code descriptions and updated references.
||MCG revised to include Medicare Part D as a program exception.
||Revised by adding CPT-4 codes 96413 & 96415.
||Review and revision to guideline; consisting of reformatting, removed ICD-9 codes 557.0 and 619.1, added ICD-9 code 714.2, added statement saying Remicade® is a first line agent and updated references.
||Review and revision to guideline; consisting of reformatting, added black box warning.
||Annual HCPCS coding update: deleted 90765 and 90766; added 96365 and 96366.
||Revision to guideline; consisting of adding maximum dose for each indication.
||Review and revision to guideline; consisting of updating boxed warning, updating the references, and rewording dosing maximums within the position statement.
||Revision to guideline; consisting of adding specific continuation criteria.
||Review and revision to guideline; consisting of updating boxed warnings, precautions and references.
||Revision to guideline; consisting of adding ICD-10 codes.
Data from: http://mcgs.bcbsfl.com/index.cfm