INFLIXIMAB-SAIDAL

Infliximab is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions 3.

Infliximab is produced by a recombinant cell line cultured by continuous perfusion.

Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine involved in chronic inflammatory diseases 3.

Its hyperactivity and enhanced signalling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades.

By binding to both the soluble subunit and the membrane-bound precursor of TNF-α 1, infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α 1.

Infliximab was first approved by the

FDA in 1998 under the market name Remicade as an intravenous injection.

It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron's disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondyliti, psoriatic arthritis, and plaque psoriasis Label.

In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder Label.

There are currently two biosilimars of infliximab available in the US market that demonstrate a high degree of similarity to the reference product, Remicade.

They are approved for all eligible indications of the reference product.

Inflectra, a first biosimilar drug product, was approved in 2016.

In December 2017, Ixifi, a second biosimilar that was developed by Pfizer, was granted approval by the FDA.

Infliximab is indicated for the treatment of the following conditions: moderately to severely active ulcerative colitis following treatment with an infliximab product administered Intravenous. 6, 7, 8 Subcutaneous injection of infliximab is used as maintenance therapy in adults who had an inadequate response or were intolerant to conventional therapy. 6 moderately to severely active rheumatoid arthritis in adults in combination with methotrexate. 6, 7 In Europe, it may be used in patients who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs), including methotrexate. 7 moderately to severely active Crohn's disease following treatment with an infliximab product administered Intravenous.

Subcutaneous injection of infliximab is used as maintenance therapy in adults who had an inadequate response or were intolerant to conventional therapy. 6 fistulizing, active Crohn's disease, in adult patients who have not responded despite a full and adequate course of therapy with conventional treatment. 7 severe, active Crohn's disease in children and adolescents aged 6-17 years, who have not responded to conventional therapy; or who are intolerant to or have contraindications for such therapies. 7 severe, active ankylosing spondylitis, in adult patients who have responded inadequately to conventional therapy. 7 active and progressive psoriatic arthritis in adult patients when the response to previous DMARD therapy has been inadequate. 7 moderate to severe plaque psoriasis in adult patients who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy.

Infliximab disrupts the activation of pro-inflammaory cascade signalling.

Infliximab has shown to reduce infiltration of inflammatory cells into sites of inflammation.

It also attenautes the expression of molecules mediating cellular adhesion {including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)}, chemoattraction {[IL-8 and monocyte chemotactic protein (MCP-1)} and tissue degradation {matrix metalloproteinase (MMP) 1 and 3} Label.

Following a single intravenous infusion, infliximab absorption displays a linear relationship between the dose administered and the maximum serum concentration Label.

In patients with

Crohn's disease, the maximum plasma concentration (Cmax) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 75 µg/mL and 181 µg/mL, respectively.

In a maintenance therapy study, multiple infusions of infliximab (at week and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Cmax of 120 µg/mL and 189 µg/mL, respectively 3.

In patients with rheumatoid arthritis, the Cmax of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 192±51 µg/mL, 427±106 µg/mL, and 907±183 µg/mL, respectively 3.

Based on a pharmacokinetic study of adult patients, the distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment Label.

In patients with

Crohn's disease, the apparent volume of distribution at steady state (Vss) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 80 mL/kg and 65 mL/kg, respectively.

In a maintenance therapy study, multiple infusions of infliximab (at week and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Vss of 70 mL/kg and 81 mL/kg, respectively 3.

In patients with rheumatoid arthritis, the Vss of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 4.3±2.5 L, 3.2±0.7 L, and 3.1±0.6 L, respectively 3.

Therapeutic monoclonal antibodies including infliximab are predicted to be nonspecifically metabolized to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or arc excreted by the kidney 4.

The reticuloendothelial system (RES) are phagocytic cells of the immune system such as macrophages and monocytes that play a role in the elimination of endogenous IgG antibodies.

Although administered infliximab accounts for a small fraction of total endogenous IgG and this route is not likely saturated by therapeutic mAbs, infliximab may be removed by opsonization via RES following binding of the Fc part of the antibody to Fcy-receptors expressed on the RES 4.

The median terminal half-life of infliximab is 7.7-9.5 days.

The data is based on a pharmacokinetic study in patients with Crohn's disease, plaque psoriasis and rheumatoid arthritis receiving a single dose of infliximab Label.

In patients with

Crohn's disease, the total body clearance (CL) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 18.4 mL/h and 14.3 mL/h, respectively.

In a maintenance therapy study, multiple infusions of infliximab (at week and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in CL of 15.2 mL/h and 15.2 mL/h, respectively 3.

In patients with rheumatoid arthritis, the CL of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 11±7.5 mL/h, 11.4±5 mL/h, and 11±8.9 mL/h, respectively 3.

Development of antibodies to infliximab increased infliximab clearance Label.

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Single doses up to 20 mg/kg have been administered without any direct toxic effect.

In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

The use of

INFLECTRA at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure.

INFLECTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab products or any of the inactive ingredients of INFLECTRA or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness.

• INFLECTRA doses >5 mg/kg in moderate or severe heart failure.

• Previous severe hypersensitivity reaction to infliximab products or any inactive ingredients of INFLECTRA or to any murine proteins.

Prior to treatment, ensure appropriate personnel and medication are available to treat reactions (e.g., hypersensitivity) that occur during infusion and shortly after infusion INFLECTRA is administered by intravenous infusion for at least 2 hours with an in-line filter Crohn's Disease.

• 5 mg/kg at and 6 weeks, then every 8 weeks.

Some adult patients who initially respond to treatment may benefit from increasing the dose to 10 mg/kg every 8 weeks if they later lose their response.

Crohn's Disease (≥ 6 years old).

Colitis (≥ 6 years old).

• In conjunction with methotrexate, 3 mg/kg at and 6 weeks, then every 8 weeks.

Some patients may benefit from increasing the dose up to 10 mg/kg every 8 weeks or treating as often as every 4 weeks.

• 5 mg/kg at and 6 weeks, then every 6 weeks.

• 5 mg/kg at and 6 weeks, then every 8 weeks. 2.1 Dosage in Adult Crohn's Disease The recommended dosage of INFLECTRA is 5 mg/kg given as an intravenous induction regimen at 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 CD or fistulizing CD.

For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg every 8 weeks.

Patients who do not respond by

Week are unlikely to respond with continued dosing and consideration should be given to discontinue INFLECTRA in these patients. 2.2 Dosage in Pediatric Crohn's Disease The recommended dosage of INFLECTRA for pediatric patients 6 years and older with moderately to severely active CD is 5 mg/kg given as an intravenous induction regimen at and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks. 2.3 Dosage in Adult Ulcerative Colitis The recommended dosage of INFLECTRA is 5 mg/kg given as an intravenous induction regimen at 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 UC. 2.4 Dosage in Pediatric Ulcerative Colitis The recommended dosage of INFLECTRA for pediatric patients 6 years and older with moderately to severely active UC is 5 mg/kg given as an intravenous induction regimen at and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks. 2.5 Dosage in Rheumatoid Arthritis The recommended dosage of INFLECTRA is 3 mg/kg given as an intravenous induction regimen at and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active RA.

INFLECTRA should be given in combination with methotrexate.

For patients who have an incomplete response, consideration may be given to adjusting the dosage up to 10 mg/kg every 8 weeks or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses per infusion or more frequent dosing. 2.6 Dosage in Ankylosing Spondylitis The recommended dosage of INFLECTRA is 5 mg/kg given as an intravenous induction regimen at and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active AS. 2.7 Dosage in Psoriatic Arthritis The recommended dosage of INFLECTRA is 5 mg/kg given as an intravenous induction regimen at and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of PsA.

INFLECTRA can be used with or without methotrexate. 2.8 Dosage in Plaque Psoriasis The recommended dosage of INFLECTRA in adult patients is 5 mg/kg given as an intravenous induction regimen at 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) Ps. 2.9 Assessment for Latent and Active Tuberculosis Prior to initiating INFLECTRA and periodically during therapy, patients should be evaluated for active tuberculosis and tested for latent infection. 2.10 Administration Instructions Regarding Infusion Reactions Prior to treatment, ensure appropriate personnel and medication are available to treat reactions (e.g., hypersensitivity, other reactions) that occur during infusion and shortly after infusion.

Prior to infusion with

INFLECTRA, patient may be premedicated with histamine-1 receptor antagonists, histamine-2 receptor antagonists, acetaminophen, and/or corticosteroids.

For mild to moderate reactions during the infusion, consider slowing or stopping the infusion.

Upon resolution of these reactions, may reinitiate at a lower infusion rate and/or with histamine-1 receptor antagonists, histamine-2 receptor antagonists, acetaminophen, and/or corticosteroids.

Discontinue the infusion if the mild to moderate reactions reoccur.

Discontinue the infusion if severe hypersensitivity reactions occur during the infusion. 2.11 Reconstitution, Dilution, and Administration Instructions INFLECTRA is intended for use under the guidance and supervision of a healthcare provider.

The supplied lyophilized powder must be reconstituted and diluted prior to administration.

The infusion solution should be prepared and administered by a trained medical professional using aseptic technique by the following procedure: 1.

Calculate the dose, total volume of reconstituted INFLECTRA solution required and the number of INFLECTRA vials needed.

More than one vial may be needed for a full dose. 2.

• 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, which has a cake-like appearance.

Avoid prolonged or vigorous agitation.

Foaming of the solution on reconstitution is not unusual.

• Allow the reconstituted solution to stand for 5 minutes.

Visually inspect the reconstituted solution for particulate matter and discoloration.

The reconstituted solution should be colorless to light yellow and opalescent, and the solution may develop a few translucent particles as infliximab-dyyb is a protein.

Do not use if the lyophilized powder has not fully dissolved or if opaque particles, discoloration, or other foreign particles are present.

Do not store unused reconstituted

INFLECTRA solution. 3.

• Withdraw a volume from the 0.9% Sodium Chloride Injection, USP, 250 mL bottle or bag equal to the total volume of reconstituted INFLECTRA required for a dose.

Slowly add the total volume of reconstituted INFLECTRA solution from the vial(s) to the 250 mL infusion bottle or bag.

• Discard any unused portion of the reconstituted INFLECTRA solution remaining in the vial(s).

• Gently invert the bag to mix the solution.

The resulting infusion concentration should range between 0.4 mg/mL (minimum recommended concentration) and 4 mg/mL (maximum recommended concentration) of infliximab-dyyb. 4.

INFLECTRA infusion should begin within 3 hours of reconstitution and dilution.

The infusion must be administered intravenously for at least 2 hours with an infusion set with an in-line, sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 µm or less). 5.

Given that the vials do not contain antibacterial preservatives, discard any unused portion of the infusion solution (do not store for reuse).

No physical biochemical compatibility studies have been conducted to evaluate the co-administration of INFLECTRA with other agents.

INFLECTRA should not be infused concomitantly in the same intravenous line with other agents.

INFLECTRA (infliximab-dyyb) for injection is supplied as one single-dose vial individually packaged in a carton (NDC 0069-0809-01 100 mg vial).

Each single-dose vial contains 100 mg of infliximab-dyyb as a sterile, preservative-free, white lyophilized powder for reconstitution and dilution (more than one vial may be needed for a full dose) .

Storage and Handling Store unopened

INFLECTRA ® vials in a refrigerator at 2°C to 8°C (36°F to 46°F).

If needed, unopened INFLECTRA vials may be stored at room temperature up to a maximum of 30°C (86°F) for a single period up to 6 months but not exceeding the original expiration date.

The new expiration date must be written in the space provided on the carton.

Once removed from the refrigerator, INFLECTRA cannot be returned to the refrigerator.

Not made with natural rubber latex.

For storage condition of the reconstituted and diluted product for administration, see Dosage and Administration.

Storage and Handling Store unopened

INFLECTRA ® vials in a refrigerator at 2°C to 8°C (36°F to 46°F).

If needed, unopened INFLECTRA vials may be stored at room temperature up to a maximum of 30°C (86°F) for a single period up to 6 months but not exceeding the original expiration date.

The new expiration date must be written in the space provided on the carton.

Once removed from the refrigerator, INFLECTRA cannot be returned to the refrigerator.

Not made with natural rubber latex.

For storage condition of the reconstituted and diluted product for administration, see Dosage and Administration.

Available observational studies in pregnant women exposed to infliximab products showed no increased risk of major malformations among live births as compared to those exposed to non-biologics.

However, findings on other birth and maternal outcomes were not consistent across studies of different study design and conduct.

Monoclonal antibodies such as infliximab products are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant.

Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab products.

In a developmental study conducted in mice using an analogous antibody, no evidence of maternal toxicity or fetal harm was observed.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Maternal and/or Embryo/Fetal Risk Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease or rheumatoid arthritis associated with increased disease activity.

Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth.

Fetal/Neonatal Adverse Reactions As with other IgG antibodies, infliximab products cross the placenta.

Infliximab products have been detected in the serum of infants up to 6 months following birth.

Consequently, these infants may be at increased risk of infection, including disseminated infection which can become fatal.

At least a six month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to these infants.

Cases of agranulocytosis in infants exposed in utero have also been reported.

Two prospective cohort studies were conducted assessing birth outcomes as well as the health status of infants up to the age of one year in women exposed to infliximab compared to non-biologic comparators including methotrexate, azathioprine, 6-mercaptopurine and systemic corticosteroids used for the treatment of similar diseases.

The first study was conducted in an IBD pregnancy registry in the United States and assessed pregnancy outcomes in 294 women with inflammatory bowel disease exposed to infliximab during pregnancy compared with 515 women on a non-biologic treatment.

Infliximab exposure was not associated with increased rates of major congenital malformations, miscarriage/stillbirth, infants of low birth weight, small for gestational age, or infection in the first year of life.

The second study among IBD and non-IBD patients in Sweden, Finland, and Denmark compared 97, 7, and 166 women exposed to infliximab to and 1,268 women on non-biologic systemic therapy, respectively.

In this study, comparing pooled data across the three countries, exposure to infliximab was not associated with increased rates of congenital anomalies or infant death.

Infliximab in combination with immunosuppressants (mainly systemic corticosteroids and azathioprine) was associated with increased rates of preterm birth, small for gestational age, low birth weight, and infant hospitalization for infection compared with non-biologic systemic treatment.

Although the study did not show any associations with infliximab monotherapy, the analyses could have been underpowered to detect an association.

There were additional methodological limitations with these studies that may account for the study findings in both studies: the concomitant use of other medications or treatments was not controlled and disease severity was not assessed; in the U.S. study, patient reported outcomes were collected without clinical validation.

These methodological limitations hinder interpretation of the study results.

Animal Data Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab products.

An embryofetal development study was conducted in pregnant mice using cV1q anti-mouse TNFα, an analogous antibody that selectively inhibits the functional activity of mouse TNFα.

This antibody administered in mice, during the period of organogenesis on gestation days (GDs) 6 and 12, at IV doses up to 40 mg/kg produced no evidence of maternal toxicity, fetal mortality, or structural abnormalities.

Doses of to 15 mg/kg in pharmacodynamic animal models with the anti-TNF analogous antibody produced maximal pharmacologic effectiveness.

Analyses of fetal samples on

GD 14 indicated placental transfer of the antibody and exposure of the fetuses during organogenesis.

In a peri-and post-natal development study in mice, no maternal toxicity or adverse developmental effects in offspring were observed when dams were administered IV doses of 10 or 40 mg/kg of the analogous antibody on GDs and 18 and lactation days and 15.

The safety and effectiveness of

INFLECTRA have been established in pediatric patients to 17 years of age for induction and maintenance treatment of CD and UC. .

However, the safety and effectiveness of INFLECTRA in pediatric patients <6 years of age with CD or UC have not been established.

INFLECTRA in the treatment of pediatric patients with Ps and juvenile rheumatoid arthritis (JRA) have not been established.

Crohn's Disease The safety and effectiveness of INFLECTRA have been established 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 CD who have had an inadequate response to conventional therapy.

The use of

INFLECTRA for this indication is supported by evidence from a randomized, open-label pediatric CD study of infliximab in 112 pediatric patients aged 6 years and older.

Infliximab has been studied only in combination with conventional immunosuppressive therapy in pediatric CD.

The longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric CD patients have not been established in clinical trials.

Postmarketing cases of

HSTCL have been reported in pediatric patients treated with TNF blockers including infliximab products.

Due to the risk of

HSTCL, a careful risk-benefit assessment should be made when INFLECTRA is used in combination with other immunosuppressants in pediatric CD patients.

Pediatric Ulcerative Colitis The safety and effectiveness of INFLECTRA for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy have been established.

INFLECTRA for this indication is supported by evidence from adequate and well-controlled studies of infliximab in adults with additional safety and pharmacokinetic data from an open-label pediatric UC Study in 60 pediatric patients aged 6 years and older.

The effectiveness of infliximab in inducing and maintaining mucosal healing in pediatric UC was not established.

Although 41 patients had a Mayo endoscopy subscore of 0 or at the Week 8 endoscopy, the induction phase was open-label and lacked a control group.

Only 9 patients had an optional endoscopy at Week 54.

Approximately half of the patients were on concomitant immunomodulators (AZA, 6-MP, MTX) at study start.

HSTCL, a careful risk-benefit assessment should be made when INFLECTRA is used in combination with other immunosuppressants in pediatric UC patients.

The longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric UC patients have not been established in clinical trials.

Arthritis (JRA) The safety and effectiveness of INFLECTRA in the treatment of pediatric patients with juvenile rheumatoid arthritis (JRA) have not been established.

The safety and efficacy of INFLECTRA in patients with JRA is based on the evaluation of infliximab 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.

Patients with active

JRA between the ages of and 17 years who had been treated with MTX for at least 3 months were enrolled.

Concurrent use of folic acid, oral corticosteroids (≤0.2 mg/kg/day of prednisone or equivalent), NSAIDs, and/or disease modifying antirheumatic drugs (DMARDs) was permitted.

Doses of 3 mg/kg of infliximab or placebo were administered intravenously at Weeks and 6.

Patients randomized to placebo crossed-over to receive 6 mg/kg of infliximab at Weeks 14, 16, and 20, and then every 8 weeks through Week 44.

Patients who completed the study continued to receive open-label treatment with infliximab for up to 2 years in a companion extension study.

The study failed to establish the efficacy of infliximab in the treatment of JRA.

Key observations in the study included a high placebo response rate and a higher rate of immunogenicity than what has been observed in adults.

Additionally, a higher rate of clearance of infliximab was observed than had been observed in adults.

Population pharmacokinetic analysis showed that in pediatric patients with JRA with a body weight of up to 35 kg receiving 6 mg/kg infliximab and pediatric patients with JRA with body weight greater than 35 kg up to adult body weight receiving 3 mg/kg infliximab, the steady state area under the concentration curve (AUCss) was similar to that observed in adults receiving 3 mg/kg of infliximab.

A total of 60 patients with JRA were treated with doses of 3 mg/kg and 57 patients were treated with doses of 6 mg/kg. The proportion of patients with infusion reactions who received 3 mg/kg infliximab was 35% (21/60) over 52 weeks compared with 18% (10/57) in patients who received 6 mg/kg over 38 weeks.

The most common infusion reactions reported were vomiting, fever, headache, and hypotension.

In the 3 mg/kg infliximab group, 4 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions).

In the 6 mg/kg infliximab group, 2 patients had a serious infusion reaction, 1 of whom had a possible anaphylactic reaction.

Two of the 6 patients who experienced serious infusion reactions received infliximab by rapid infusion (duration of less than 2 hours).

Antibodies to infliximab developed in 38% (20/53) of patients who received 3 mg/kg infliximab compared with 12% (6/49) of patients who received 6 mg/kg. A total of 68% (41/60) of patients who received 3 mg/kg of infliximab in combination with MTX experienced an infection over 52 weeks compared with 65% (37/57) of patients who received 6 mg/kg of infliximab in combination with MTX over 38 weeks.

The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was pneumonia.

Other notable infections included primary varicella infection in 1 patient and herpes zoster in 1 patient.

Of the total number of infliximab-treated patients in RA and Ps clinical studies, 256 (9.6%) were 65 years old and over, while 17 (0.6%) were 75 years old and over.

In these trials, no overall differences in safety or effectiveness were observed between geriatric patients (patients ≥65 years old) and younger adult patients (patients to 65 years old).

However, the incidence of serious adverse reactions in geriatric patients was higher in both infliximab and control groups compared to younger adult patients.

Of the total number of infliximab-treated patients in CD, UC, AS, and PsA clinical studies, 76 (3.2%) were 65 years old and over, while 9 (0.4%) were 75 years old and over.

In the

CD, UC, AS, and PsA studies, there were insufficient numbers of geriatric patients to determine whether they respond differently from younger adults.

The incidence of serious infections in infliximab-treated geriatric patients was greater than in infliximab-treated younger adult patients; therefore close monitoring of geriatric patients for the development of serious infections is recommended.