Infliximab BS

Crohn's Disease

Infliximab BS 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.

Infliximab BS 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

Infliximab BS is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.

Ulcerative Colitis

Infliximab BS is indicated for 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 who have had an inadequate response to conventional therapy.

Pediatric Ulcerative Colitis

Infliximab BS is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

Rheumatoid Arthritis

Infliximab BS, 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.

Ankylosing Spondylitis

Infliximab BS is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

Psoriatic Arthritis

Infliximab BS 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.

Plaque Psoriasis

Infliximab BS 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. Infliximab BS should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Infliximab BS injection is a monoclonal antibody. It is used to treat Crohn's disease in children (6 years of age and older) and adults who have not been helped by other medicines, and in adult patients who have a type of Crohn's disease where fistulas form. Infliximab BS injection is used to treat adults with rheumatoid arthritis and ankylosing spondylitis, which is a type of arthritis that affects the joints in the spine. It is used to treat adults with psoriatic arthritis, which is a type of arthritis that causes pain and swelling of the joints and patches of scaly skin on some areas of the body.

Infliximab BS injection is also used to treat children (6 years of age and older) and adults with ulcerative colitis. It is also used to treat chronic severe plaque psoriasis, which is a skin disease with red patches and white scales that don't go away.

Infliximab BS is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Infliximab BS injection is used in certain patients with the following medical conditions:

• Takayasu disease (blood vessel problem), refractory.

Crohn's Disease

The recommended dose of Infliximab BS 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 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 10 mg/kg. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue Infliximab BS in these patients.

Pediatric Crohn's Disease

The recommended dose of Infliximab BS for pediatric patients 6 years and older with moderately to severely active Crohn's disease 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.

Ulcerative Colitis

The recommended dose of Infliximab BS 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 ulcerative colitis.

Pediatric Ulcerative Colitis

The recommended dose of Infliximab BS for pediatric patients 6 years and older with moderately to severely active ulcerative colitis 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.

Rheumatoid Arthritis

The recommended dose of Infliximab BS 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 rheumatoid arthritis. Infliximab BS should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10 mg/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 BS 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 ankylosing spondylitis.

Psoriatic Arthritis

The recommended dose of Infliximab BS 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 psoriatic arthritis. Infliximab BS can be used with or without methotrexate.

Plaque Psoriasis

The recommended dose of Infliximab BS 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.

Monitoring To Assess Safety

Prior to initiating Infliximab BS and periodically during therapy, patients should be evaluated for active tuberculosis and tested for latent infection.

Administration Instructions Regarding Infusion Reactions

Adverse effects during administration of Infliximab BS have included flu-like symptoms, headache, dyspnea, hypotension, transient fever, chills, gastrointestinal symptoms, and skin rashes. Anaphylaxis might occur at any time during Infliximab BS infusion. Approximately 20% of Infliximab BS-treated patients in all clinical trials experienced an infusion reaction compared with 10% of placebo-treated patients. Prior to infusion with Infliximab BS, premedication may be administered at the physician's discretion. Premedication could include antihistamines (anti-H1 +/- anti- H2), acetaminophen and/or corticosteroids.

During infusion, mild to moderate infusion reactions may improve following slowing or suspension of the infusion, and upon resolution of the reaction, reinitiation at a lower infusion rate and/or therapeutic administration of antihistamines, acetaminophen, and/or corticosteroids. For patients that do not tolerate the infusion following these interventions, Infliximab BS should be discontinued.

During or following infusion, patients who have severe infusion-related hypersensitivity reactions should be discontinued from further Infliximab BS treatment. The management of severe infusion reactions should be dictated by the signs and symptoms of the reaction. Appropriate personnel and medication should be available to treat anaphylaxis if it occurs.

General Considerations And Instructions For Preparation And Administration

Infliximab BS is intended for use under the guidance and supervision of a physician. The reconstituted infusion solution should be prepared by a trained medical professional using aseptic technique by the following procedure:

1. Calculate the dose, total volume of reconstituted Infliximab BS solution required and the number of Infliximab BS vials needed. Each Infliximab BS vial contains 100 mg of the Infliximab BS antibody.
2. Reconstitute each Infliximab BS vial with 10 mL of Sterile Water for Injection, USP, using a syringe equipped with a 21-gauge or smaller needle as follows: Remove the flip-top from the vial and wipe the top with an alcohol swab. Insert the syringe needle into the vial through the center of the rubber stopper and direct the stream of Sterile Water for Injection, USP, to the glass wall of the vial. Gently swirl the solution by rotating the vial to dissolve the lyophilized powder. Avoid prolonged or vigorous agitation. DO NOT SHAKE. Foaming of the solution on reconstitution is not unusual. Allow the reconstituted solution to stand for 5 minutes. The solution should be colorless to light yellow and opalescent, and the solution may develop a few translucent particles as Infliximab BS is a protein. Do not use if the lyophilized cake has not fully dissolved or if opaque particles, discoloration, or other foreign particles are present.
3. Dilute the total volume of the reconstituted Infliximab BS solution dose to 250 mL with sterile 0.9% Sodium Chloride Injection, USP, by withdrawing a volume equal to the volume of reconstituted Infliximab BS from the 0.9% Sodium Chloride Injection, USP, 250 mL bottle or bag. Do not dilute the reconstituted Infliximab BS solution with any other diluent. Slowly add the total volume of reconstituted Infliximab BS solution to the 250 mL infusion bottle or bag. Gently mix. The resulting infusion concentration should range between 0.4 mg/mL and 4 mg/mL.
4. The Infliximab BS infusion should begin within 3 hours of reconstitution and dilution. The infusion must be administered over a period of not less than 2 hours and must use an infusion set with an inline, sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 μm or less). The vials do not contain antibacterial preservatives. Therefore, any unused portion of the infusion solution should not be stored for reuse.
5. No physical biochemical compatibility studies have been conducted to evaluate the coadministration of Infliximab BS with other agents. Infliximab BS should not be infused concomitantly in the same intravenous line with other agents.

6. Parenteral drug products should be inspected visually before and after reconstitution for particulate matter and discoloration prior to administration, whenever solution and container permit. If visibly opaque particles, discoloration or other foreign particulates are observed, the solution should not be used.

How supplied

Dosage Forms And Strengths

100 mg vial: 100 mg lyophilized Infliximab BS in a 20 mL vial for injection, for intravenous use.

Storage And Handling

Each Infliximab BS 20 mL vial is individually packaged in a carton. Infliximab BS is supplied in an accumulator carton containing 10 vials.

NDC 57894-030-01 100 mg vial

Each single dose vial contains 100 mg of Infliximab BS for final reconstitution volume of 10 mL.

Storage And Stability

Store unopened Infliximab BS vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not use Infliximab BS beyond the expiration date located on the carton and the vial. This product contains no preservative.

Unopened Infliximab BS vials may also be stored at temperatures up to a maximum of 30°C (86°F) for a single period of up to 6 months but not exceeding the original expiration date. The new expiration date must be written on the carton. Upon removal from refrigerated storage, Infliximab BS cannot be returned to refrigerated storage. [For storage conditions of the reconstituted product, see DOSAGE AND ADMINISTRATION].

Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044. Revised: Nov 2015

See also:
What is the most important information I should know about Infliximab BS?

You should not use this medication if you are allergic to Infliximab BS, or if you are also being treated with anakinra (Kineret) or abatacept (Orencia).

Some people using Infliximab BS have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. This has occurred mainly in teenagers and young adults using Infliximab BS or similar medicines to treat Crohn's disease or ulcerative colitis.

Call your doctor at once if you have any of the following symptoms: fever, night sweats, itching, loss of appetite, weight loss, tiredness, feeling full after eating only a small amount, pain in your upper stomach that may spread to your shoulder, nausea, easy bruising or bleeding, pale skin, feeling light-headed or short of breath, rapid heart rate, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Infliximab BS can lower blood cells that help your body fight infections. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Serious and sometimes fatal infections may occur during treatment with Infliximab BS. Contact your doctor right away if you have signs of infection such as: fever, chills, flu symptoms, or pain, warmth, or redness of your skin.

Before you receive Infliximab BS, tell your doctor if you have heart failure or other heart problems, an active or recent infection, diabetes, liver disease, seizures, chronic obstructive pulmonary disease (COPD), a history of cancer, a weak immune system, numbness or tingling, a nerve or muscle disorder, or if you have recently received a vaccine.

Before you start treatment with Infliximab BS, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Some infections are more likely to occur in certain areas of the world. Tell your doctor where you live and where you have recently traveled or plan to travel to during treatment.

Do not receive a "live" vaccine while you are being treated with Infliximab BS.

Before you start treatment with Infliximab BS, your doctor may perform tests to make sure you do not have tuberculosis or other infections. Some infections are more likely to occur in certain areas of the world. Tell your doctor where you live and where you have recently traveled or plan to travel to during treatment.

Infliximab BS is injected into a vein through an IV. A healthcare provider will give you this injection. You may be watched closely after receiving Infliximab BS, to make sure the medicine has not caused any serious side effects.

While using Infliximab BS, you may need frequent blood tests.

Infliximab BS can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Serious and sometimes fatal infections may occur during treatment with Infliximab BS. Call your doctor right away if you have signs of infection such as: fever, chills, flu symptoms, or pain, warmth, or redness of your skin.

If you need surgery, tell the surgeon ahead of time that you are using Infliximab BS.

If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using Infliximab BS.

Use: Labeled Indications

Ankylosing spondylitis: Treatment of adults with active ankylosing spondylitis (to reduce signs/symptoms).

Crohn disease: Treatment of adults and pediatric patients ≥6 years of age with moderately to severely active Crohn disease who have had inadequate responses to conventional therapy (to reduce signs/symptoms and induce and maintain clinical remission) or to reduce the number of draining enterocutaneous and rectovaginal fistulas and maintain fistula closure in adults.

Plaque psoriasis: Treatment of adults with chronic, severe (extensive and/or disabling) plaque psoriasis as an alternative to other systemic therapy.

Psoriatic arthritis: Treatment of adults with psoriatic arthritis (to reduce signs/symptoms of active arthritis and inhibit progression of structural damage and improve physical function).

Rheumatoid arthritis: Treatment of adults with moderately to severely active rheumatoid arthritis (with methotrexate) (to reduce signs/symptoms of active arthritis and inhibit progression of structural damage and improve physical function).

Ulcerative colitis: Treatment of adults and pediatric patients ≥6 years of age with moderately to severely active ulcerative colitis with inadequate response to conventional therapy (to reduce signs/symptoms and induce and maintain clinical remission and mucosal healing and eliminate corticosteroid use).

Note: Renflexis (Infliximab BS-abda) and Inflectra (Infliximab BS-dyyb) are approved as biosimilars to Infliximab BS (Infliximab BS). In Canada, Remsima is also approved as a biosimilar to Infliximab BS (Infliximab BS).

Off Label Uses

Crohn disease (management after surgical resection)

Data from a small, randomized, double-blind, placebo-controlled trial, a prospective randomized open trial, and a meta-analysis support the use of Infliximab BS in the management of Crohn disease after surgical resection and demonstrated Infliximab BS lowers endoscopic recurrence and possibly histologic and clinical recurrence rates.

See also:
What other drugs will affect Infliximab BS?

Use With Anakinra Or Abatacept

An increased risk of serious infections was seen in clinical studies of other TNFα-blocking agents used in combination with anakinra or abatacept, with no added clinical benefit. Because of the nature of the adverse reactions seen with these combinations with TNF-blocker therapy, similar toxicities may also result from the combination of anakinra or abatacept with other TNFα-blocking agents. Therefore, the combination of Infliximab BS and anakinra or abatacept is not recommended.

Use With Tocilizumab

The use of tocilizumab in combination with biological DMARDs such as TNF antagonists, including Infliximab BS, should be avoided because of the possibility of increased immunosuppression and increased risk of infection.

Use With Other Biological Therapeutics

The combination of Infliximab BS with other biological therapeutics used to treat the same conditions as Infliximab BS is not recommended.

Methotrexate (MTX) And Other Concomitant Medications

Specific drug interaction studies, including interactions with MTX, have not been conducted. The majority of patients in rheumatoid arthritis or Crohn's disease clinical studies received one or more concomitant medications. In rheumatoid arthritis, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics. Concomitant Crohn's disease medications were antibiotics, antivirals, corticosteroids, 6-MP/AZA and aminosalicylates. In psoriatic arthritis clinical trials, concomitant medications included MTX in approximately half of the patients as well as NSAIDs, folic acid and corticosteroids. Concomitant MTX use may decrease the incidence of anti-Infliximab BS antibody production and increase Infliximab BS concentrations.

Immunosuppressants

Patients with Crohn's disease who received immunosuppressants tended to experience fewer infusion reactions compared to patients on no immunosuppressants. Serum Infliximab BS concentrations appeared to be unaffected by baseline use of medications for the treatment of Crohn's disease including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.

Cytochrome P450 Substrates

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as Infliximab BS, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of Infliximab BS in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

Live Vaccines /Therapeutic Infectious Agents

It is recommended that live vaccines not be given concurrently with Infliximab BS. It is also recommended that live vaccines not be given to infants after in utero exposure to Infliximab BS for at least 6 months following birth.

It is recommended that therapeutic infectious agents not be given concurrently with Infliximab BS.

See also:
What are the possible side effects of Infliximab BS?

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not predict the rates observed in broader patient populations in clinical practice.

Adverse Reactions In Adults

The data described herein reflect exposure to Infliximab BS in 4779 adult patients (1304 patients with rheumatoid arthritis, 1106 patients with Crohn's disease, 202 with ankylosing spondylitis, 293 with psoriatic arthritis, 484 with ulcerative colitis, 1373 with plaque psoriasis, and 17 patients with other conditions), including 2625 patients exposed beyond 30 weeks and 374 exposed beyond 1 year. [For information on adverse reactions in pediatric patients see Clinical Trials Experience] One of the mostcommon reasons for discontinuation of treatment was infusion-related reactions (e.g., dyspnea, flushing, headache and rash).

Infusion-Related Reactions

An infusion reaction was defined in clinical trials as any adverse event occurring during an infusion or within 1 hour after an infusion. In Phase 3 clinical studies, 18% of Infliximab BS-treated patients experienced an infusion reaction compared to 5% of placebo-treated patients. Of Infliximab BS-treated patients who had an infusion reaction during the induction period, 27% experienced an infusion reaction during the maintenance period. Of patients who did not have an infusion reaction during the induction period, 9% experienced an infusion reaction during the maintenance period.

Among all Infliximab BS infusions, 3% were accompanied by nonspecific symptoms such as fever or chills, 1% were accompanied by cardiopulmonary reactions (primarily chest pain, hypotension, hypertension or dyspnea), and < 1% were accompanied by pruritus, urticaria, or the combined symptoms of pruritus/urticaria and cardiopulmonary reactions. Serious infusion reactions occurred in < 1% of patients and included anaphylaxis, convulsions, erythematous rash and hypotension. Approximately 3% of patients discontinued Infliximab BS because of infusion reactions, and all patients recovered with treatment and/or discontinuation of the infusion. Infliximab BS infusions beyond the initial infusion were not associated with a higher incidence of reactions. The infusion reaction rates remained stable in psoriasis through 1 year in psoriasis Study I. In psoriasis Study II, the rates were variable over time and somewhat higher following the final infusion than after the initial infusion. Across the 3 psoriasis studies, the percent of total infusions resulting in infusion reactions (i.e., an adverse event occurring within 1 hour) was 7% in the 3 mg/kg group, 4% in the 5 mg/kg group, and 1% in the placebo group.

Patients who became positive for antibodies to Infliximab BS were more likely (approximately two- to three-fold) to have an infusion reaction than were those who were negative. Use of concomitant immunosuppressant agents appeared to reduce the frequency of both antibodies to Infliximab BS and infusion reactions.

Infusion Reactions Following Re-administration

In a clinical trial of patients with moderate to severe psoriasis designed to assess the efficacy of longterm maintenance therapy versus re-treatment with an induction regimen of Infliximab BS following disease flare, 4% (8/219) of patients in the re-treatment therapy arm experienced serious infusion reactions versus < 1% (1/222) in the maintenance therapy arm. Patients enrolled in this trial did not receive any concomitant immunosuppressant therapy. In this study, the majority of serious infusion reactions occurred during the second infusion at Week 2. Symptoms included, but were not limited to, dyspnea, urticaria, facial edema, and hypotension. In all cases, Infliximab BS treatment was discontinued and/or other treatment instituted with complete resolution of signs and symptoms.

Delayed Reactions/Reactions Following Re-administration

In psoriasis studies, approximately 1% of Infliximab BS-treated patients experienced a possible delayed hypersensitivity reaction, generally reported as serum sickness or a combination of arthralgia and/or myalgia with fever and/or rash. These reactions generally occurred within 2 weeks after repeat infusion.

Infections

In Infliximab BS clinical studies, treated infections were reported in 36% of Infliximab BS-treated patients (average of 51 weeks of follow-up) and in 25% of placebo-treated patients (average of 37 weeks of follow-up). The infections most frequently reported were respiratory tract infections (including sinusitis, pharyngitis, and bronchitis) and urinary tract infections. Among Infliximab BS-treated patients, serious infections included pneumonia, cellulitis, abscess, skin ulceration, sepsis, and bacterial infection. In clinical trials, 7 opportunistic infections were reported; 2 cases each of coccidioidomycosis (1 case was fatal) and histoplasmosis (1 case was fatal), and 1 case each of pneumocystosis, nocardiosis and cytomegalovirus. Tuberculosis was reported in 14 patients, 4 of whom died due to miliary tuberculosis. Other cases of tuberculosis, including disseminated tuberculosis, also have been reported post-marketing. Most of these cases of tuberculosis occurred within the first 2 months after initiation of therapy with Infliximab BS and may reflect recrudescence of latent disease. In the 1-year placebo-controlled studies RA I and RA II, 5.3% of patients receiving Infliximab BS every 8 weeks with MTX developed serious infections as compared to 3.4% of placebo patients receiving MTX. Of 924 patients receiving Infliximab BS, 1.7% developed pneumonia and 0.4% developed TB, when compared to 0.3% and 0.0% in the placebo arm respectively. In a shorter (22-week) placebo-controlled study of 1082 RA patients randomized to receive placebo, 3 mg/kg or 10 mg/kg Infliximab BS infusions at 0, 2, and 6 weeks, followed by every 8 weeks with MTX, serious infections were more frequent in the 10 mg/kg Infliximab BS group (5.3%) than the 3 mg/kg or placebo groups (1.7% in both). During the 54-week Crohn's II Study, 15% of patients with fistulizing Crohn's disease developed a new fistula-related abscess.

In Infliximab BS clinical studies in patients with ulcerative colitis, infections treated with antimicrobials were reported in 27% of Infliximab BS-treated patients (average of 41 weeks of follow-up) and in 18% of placebo-treated patients (average 32 weeks of follow-up). The types of infections, including serious infections, reported in patients with ulcerative colitis were similar to those reported in other clinical studies.

The onset of serious infections may be preceded by constitutional symptoms such as fever, chills, weight loss, and fatigue. The majority of serious infections, however, may also be preceded by signs or symptoms localized to the site of the infection.

Autoantibodies/Lupus-like Syndrome

Approximately half of Infliximab BS-treated patients in clinical trials who were antinuclear antibody (ANA) negative at baseline developed a positive ANA during the trial compared with approximately one-fifth of placebo-treated patients. Anti-dsDNA antibodies were newly detected in approximately one-fifth of Infliximab BS-treated patients compared with 0% of placebo-treated patients. Reports of lupus and lupus-like syndromes, however, remain uncommon.

Malignancies

In controlled trials, more Infliximab BS-treated patients developed malignancies than placebo-treated patients.

In a randomized controlled clinical trial exploring the use of Infliximab BS in patients with moderate to severe COPD who were either current smokers or ex-smokers, 157 patients were treated with Infliximab BS at doses similar to those used in rheumatoid arthritis and Crohn's disease. Of these Infliximab BS-treated patients, 9 developed a malignancy, including 1 lymphoma, for a rate of 7.67 cases per 100 patient-years of follow-up (median duration of follow-up 0.8 years; 95% CI 3.51 - 14.56). There was 1 reported malignancy among 77 control patients for a rate of 1.63 cases per 100 patientyears of follow-up (median duration of follow-up 0.8 years; 95% CI 0.04 - 9.10). The majority of the malignancies developed in the lung or head and neck.

Patients With Heart Failure

In a randomized study evaluating Infliximab BS in moderate to severe heart failure (NYHA Class III/IV; left ventricular ejection fraction ≤ 35%), 150 patients were randomized to receive treatment with 3 infusions of Infliximab BS 10 mg/kg, 5 mg/kg, or placebo, at 0, 2, and 6 weeks. Higher incidences of mortality and hospitalization due to worsening heart failure were observed in patients receiving the 10 mg/kg Infliximab BS dose. At 1 year, 8 patients in the 10 mg/kg Infliximab BS group had died compared with 4 deaths each in the 5 mg/kg Infliximab BS and the placebo groups. There were trends toward increased dyspnea, hypotension, angina, and dizziness in both the 10 mg/kg and 5 mg/kg Infliximab BS treatment groups, versus placebo. Infliximab BS has not been studied in patients with mild heart failure (NYHA Class I/II).

Immunogenicity

Treatment with Infliximab BS can be associated with the development of antibodies to Infliximab BS. An enzyme immunoassay (EIA) method was originally used to measure anti-Infliximab BS antibodies in clinical studies of Infliximab BS. The EIA method is subject to interference by serum Infliximab BS, possibly resulting in an underestimation of the rate of patient antibody formation. A separate, drug-tolerant electrochemiluminescence immunoassay (ECLIA) method for detecting antibodies to Infliximab BS was subsequently developed and validated. This method is 60-fold more sensitive than the original EIA. With the ECLIA method, all clinical samples can be classified as either positive or negative for antibodies to Infliximab BS without the need for the inconclusive category.

The incidence of antibodies to Infliximab BS was based on the original EIA method in all clinical studies of Infliximab BS except for the Phase 3 study in pediatric patients with ulcerative colitis where the incidence of antibodies to Infliximab BS was detected using both the EIA and ECLIA methods.

The incidence of antibodies to Infliximab BS in patients given a 3-dose induction regimen followed by maintenance dosing was approximately 10% as assessed through 1 to 2 years of Infliximab BS treatment. A higher incidence of antibodies to Infliximab BS was observed in Crohn's disease patients receiving Infliximab BS after drug-free intervals > 16 weeks. In a study of psoriatic arthritis in which 191 patients received 5 mg/kg with or without MTX, antibodies to Infliximab BS 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, reduced efficacy and to experience an infusion reaction than were patients who were antibody negative. Antibody development was lower among rheumatoid arthritis and Crohn's disease patients receiving immunosuppressant therapies such as 6-MP/AZA or MTX.

In the psoriasis Study II, which included both the 5 mg/kg 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 III, which also included both the 5 mg/kg 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 I and II in patients treated with 5 mg/kg induction followed by every 8 week maintenance for 1 year and in Study III in patients treated with 5 mg/kg induction (14.1%-23.0%) and serious infusion reaction rates ( < 1%) were similar to those observed in other study populations.

Upon reconstitution, each mL of powder for concentrate for solution for infusion contains Infliximab 10 mg.

Infliximab BS also contains the following excipients: Sucrose, polysorbate 80, monobasic sodium phosphate and dibasic sodium phosphate.

Infliximab BS is a chimeric immunoglobulin G1 (IgG1) monoclonal antibody manufactured from a recombinant cell line cultured by continuous perfusion.