Remicade Information
Remicade (Infliximab)
Remicade (Infliximab) Indications And Usage
Remicade (Infliximab) is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.
Remicade (Infliximab) is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease.
Remicade (Infliximab) 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.
Remicade (Infliximab) Dosage And Administration
The recommended dose of Remicade (Infliximab) 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.
Adverse effects during administration of Remicade (Infliximab) have included flu-like symptoms, headache, dyspnea, hypotension, transient fever, chills, gastrointestinal symptoms, and skin rashes. Anaphylaxis might occur at any time during Remicade (Infliximab) infusion. Approximately 20% of Remicade (Infliximab) -treated patients in all clinical trials experienced an infusion reaction compared with 10% of placebo-treated patients . Prior to infusion with Remicade (Infliximab) , 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, Remicade (Infliximab) should be discontinued.
During or following infusion, patients who have severe infusion-related hypersensitivity reactions should be discontinued from further Remicade (Infliximab) 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.
Remicade (Infliximab) Dosage Forms And Strengths
100 mg vial: 100 mg lyophilized infliximab in a 20 mL vial for injection, for intravenous use.
Remicade (Infliximab) Contraindications
Remicade (Infliximab) at doses >5 mg/kg should not be administered to patients with moderate to severe heart failure. In a randomized study evaluating Remicade (Infliximab) in patients with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), Remicade (Infliximab) treatment at 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure .
Remicade (Infliximab) should not be re-administered to patients who have experienced a severe hypersensitivity reaction to Remicade (Infliximab) . Additionally, Remicade (Infliximab) should not be administered to patients with known hypersensitivity to inactive components of the product or to any murine proteins.
Remicade (Infliximab) Warnings And Precautions
Patients treated with Remicade (Infliximab) are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.
Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease.
Treatment with Remicade (Infliximab) should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients:
Remicade (Infliximab) has been associated with hypersensitivity reactions that vary in their time of onset and required hospitalization in some cases. Most hypersensitivity reactions, which include urticaria, dyspnea, and/or hypotension, have occurred during or within 2 hours of Remicade (Infliximab) infusion.
However, in some cases, serum sickness-like reactions have been observed in patients after initial Remicade (Infliximab) therapy (i.e., as early as after the second dose), and when Remicade (Infliximab) therapy was reinstituted following an extended period without Remicade (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 a marked increase in antibodies to infliximab, loss of detectable serum concentrations of infliximab, and possible loss of drug efficacy.
Remicade (Infliximab) should be discontinued for severe hypersensitivity reactions. Medications for the treatment of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids and/or epinephrine) should be available for immediate use in the event of a reaction .
In rheumatoid arthritis, Crohn's disease and psoriasis clinical trials, re-administration of Remicade (Infliximab) after a period of no treatment resulted in a higher incidence of infusion reactions relative to regular maintenance treatment . In general, the benefit-risk of re-administration of Remicade (Infliximab) after a period of no-treatment, especially as a re-induction regimen given at weeks 0, 2 and 6, should be carefully considered. In the case where Remicade (Infliximab) maintenance therapy for psoriasis is interrupted, Remicade (Infliximab) should be reinitiated as a single dose followed by maintenance therapy.
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse reactions seen with the combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents. Therefore, the combination of Remicade (Infliximab) and anakinra is not recommended.
In clinical studies, concurrent administration of TNF-blocking agents and abatacept have been associated with an increased risk of infections including serious infections compared with TNF-blocking agents alone, without increased clinical benefit. Therefore, the combination of Remicade (Infliximab) and abatacept is not recommended .
Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
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 pediatric patients be brought up to date with all vaccinations prior to initiating Remicade (Infliximab) therapy. The interval between vaccination and initiation of Remicade (Infliximab) therapy should be in accordance with current vaccination guidelines.
Remicade (Infliximab) Adverse Reactions
Adverse reactions have been reported during post approval use of Remicade (Infliximab) in adult and pediatric patients. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Remicade (Infliximab) exposure.
The following adverse reactions, some with fatal outcome, have been reported during post-approval use of Remicade (Infliximab) : neutropenia , interstitial lung disease (including pulmonary fibrosis/interstitial pneumonitis and very rare rapidly progressive disease), idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, pericardial effusion, systemic and cutaneous vasculitis, erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, peripheral demyelinating disorders (such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy), new onset and worsening psoriasis (all subtypes including pustular, primarily palmoplantar), transverse myelitis, and neuropathies (additional neurologic reactions have also been observed) acute liver failure, jaundice, hepatitis, and cholestasis , serious infections and malignancies .
Remicade (Infliximab) Overdosage
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.
Remicade (Infliximab) Description
Infliximab, the active ingredient in Remicade (Infliximab) , is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions) specific for human tumor necrosis factor-alpha (TNFα). It has a molecular weight of approximately 149.1 kilodaltons. Infliximab is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses.
Remicade (Infliximab) is supplied as a sterile, white, lyophilized powder for intravenous infusion. Following reconstitution with 10 mL of Sterile Water for Injection, USP, the resulting pH is approximately 7.2. Each single-use vial contains 100 mg infliximab, 500 mg sucrose, 0.5 mg polysorbate 80, 2.2 mg monobasic sodium phosphate, monohydrate, and 6.1 mg dibasic sodium phosphate, dihydrate. No preservatives are present.
Remicade (Infliximab) Clinical Pharmacology
In adults, single intravenous (IV) infusions of 3 mg/kg to 20 mg/kg showed a linear relationship between the dose administered and the maximum serum concentration. The volume of distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment. Pharmacokinetic results for single doses of 3 mg/kg to 10 mg/kg in rheumatoid arthritis, 5 mg/kg in Crohn's disease, and 3 mg/kg to 5 mg/kg in plaque psoriasis indicate that the median terminal half-life of infliximab is 7.7 to 9.5 days.
Following an initial dose of Remicade (Infliximab) , repeated infusions at 2 and 6 weeks resulted in predictable concentration-time profiles following each treatment. No systemic accumulation of infliximab occurred upon continued repeated treatment with 3 mg/kg or 10 mg/kg at 4- or 8-week intervals. Development of antibodies to infliximab increased infliximab clearance. At 8 weeks after a maintenance dose of 3 to 10 mg/kg of Remicade (Infliximab) , median infliximab serum concentrations ranged from approximately 0.5 to 6 mcg/mL; however, infliximab concentrations were not detectable (
Infliximab pharmacokinetic characteristics (including peak and trough concentrations and terminal half-life) were similar in pediatric (aged 6 to 17 years) and adult patients with Crohn's disease or ulcerative colitis following the administration of 5 mg/kg infliximab.
Population pharmacokinetic analysis showed that in children with juvenile rheumatoid arthritis (JRA) with a body weight of up to 35 kg receiving 6 mg/kg Remicade (Infliximab) and children with JRA with body weight greater than 35 kg up to adult body weight receiving 3mg/kg Remicade (Infliximab) , the steady state area under the concentration curve (AUCss) was similar to that observed in adults receiving 3 mg/kg of Remicade (Infliximab) .
Remicade (Infliximab) Clinical Studies
The safety and efficacy of Remicade (Infliximab) were assessed in a randomized, open-label study (Study Peds Crohn's) in 112 pediatric patients aged 6 to 17 years old with moderately to severely active Crohn's disease and an inadequate response to conventional therapies. The median age was 13 years and the median Pediatric Crohn's Disease Activity Index (PCDAI) was 40 (on a scale of 0 to 100). All patients were required to be on a stable dose of 6-MP, AZA, or MTX; 35% were also receiving corticosteroids at baseline.
All patients received induction dosing of 5 mg/kg Remicade (Infliximab) at Weeks 0, 2, and 6. At Week 10, 103 patients were randomized to a maintenance regimen of 5 mg/kg Remicade (Infliximab) given either every 8 weeks or every 12 weeks.
At Week 10, 88% of patients were in clinical response (defined as a decrease from baseline in the PCDAI score of ≥15 points and total PCDAI score of ≤30 points), and 59% were in clinical remission (defined as PCDAI score of ≤10 points).
The proportion of pediatric patients achieving clinical response at Week 10 compared favorably with the proportion of adults achieving a clinical response in Study Crohn's I. The study definition of clinical response in Study Peds Crohn's was based on the PCDAI score, whereas the CDAI score was used in the adult Study Crohn's I.
At both Week 30 and Week 54, the proportion of patients in clinical response was greater in the every 8-week treatment group than in the every 12-week treatment group (73% vs. 47% at Week 30, and 64% vs. 33% at Week 54). At both Week 30 and Week 54, the proportion of patients in clinical remission was also greater in the every 8-week treatment group than in the every 12-week treatment group (60% vs. 35% at Week 30, and 56% vs. 24% at Week 54), (Table 4).
For patients in Study Peds Crohn's receiving corticosteroids at baseline, the proportion of patients able to discontinue corticosteroids while in remission at Week 30 was 46% for the every 8-week maintenance group and 33% for the every 12-week maintenance group. At Week 54, the proportion of patients able to discontinue corticosteroids while in remission was 46% for the every 8-week maintenance group and 17% for the every 12-week maintenance group.
The safety and efficacy of Remicade (Infliximab) were assessed in 2 randomized, double-blind, placebo-controlled clinical studies in 728 patients with moderately to severely active ulcerative colitis (UC) (Mayo score 6 to 12 [of possible range 0 to 12], Endoscopy subscore ≥2) with an inadequate response to conventional oral therapies (Studies UC I and UC II). Concomitant treatment with stable doses of aminosalicylates, corticosteroids and/or immunomodulatory agents was permitted. Corticosteroid taper was permitted after Week 8. Patients were randomized at week 0 to receive either placebo, 5 mg/kg Remicade (Infliximab) or 10 mg/kg Remicade (Infliximab) at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 46 in Study UC I, and at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 22 in Study UC II. In Study UC II, patients were allowed to continue blinded therapy to Week 46 at the investigator's discretion.
Patients in Study UC I had failed to respond or were intolerant to oral corticosteroids, 6-MP, or AZA. Patients in Study UC II had failed to respond or were intolerant to the above treatments and/or aminosalicylates. Similar proportions of patients in Studies UC I and UC II were receiving corticosteroids (61% and 51%, respectively), 6-MP/AZA (49% and 43%) and aminosalicylates (70% and 75%) at baseline. More patients in Study UC II than UC I were taking solely aminosalicylates for UC (26% vs. 11%, respectively). Clinical response was defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, accompanied by a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1.
The safety and effectiveness of Remicade (Infliximab) for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy are supported by evidence from adequate and well-controlled studies of Remicade (Infliximab) in adults. Additional safety and pharmacokinetic data were collected in an open-label pediatric UC trial in 60 pediatric patients aged 6 through 17 years (median age 14.5 years) with moderately to severely active ulcerative colitis (Mayo score of 6 to 12; Endoscopic subscore ≥ 2) and an inadequate response to conventional therapies. At baseline, the median Mayo score was 8, 53% of patients were receiving immunomodulator therapy (6-MP/AZA/MTX), and 62% of patients were receiving corticosteroids (median dose 0.5 mg/kg/day in prednisone equivalents). Discontinuation of immunomodulators and corticosteroid taper were permitted after Week 0.
All patients received induction dosing of 5 mg/kg Remicade (Infliximab) at Weeks 0, 2, and 6. Patients who did not respond to Remicade (Infliximab) at Week 8 received no further Remicade (Infliximab) and returned for safety follow-up. At Week 8, 45 patients were randomized to a maintenance regimen of 5 mg/kg Remicade (Infliximab) given either every 8 weeks through Week 46 or every 12 weeks through Week 42. Patients were allowed to change to a higher dose and/or more frequent administration schedule if they experienced loss of response.
Clinical response at Week 8 was defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, including a decrease in the rectal bleeding subscore by ≥ 1 points or achievement of a rectal bleeding subscore of 0 or 1.
Clinical remission at Week 8 was measured by the Mayo score, defined as a Mayo score of ≤2 points with no individual subscore >1. Clinical remission was also assessed at Week 8 and Week 54 using the Pediatric Ulcerative Colitis Activity Index (PUCAI) score and was defined by a PUCAI score of
Endoscopies were performed at baseline and at Week 8. A Mayo endoscopy subscore of 0 indicated normal or inactive disease and a subscore of 1 indicated mild disease (erythema, decreased vascular pattern, or mild friability).
Of the 60 patients treated, 44 were in clinical response at Week 8. Of 32 patients taking concomitant immunomodulators at baseline, 23 achieved clinical response at Week 8, compared to 21 of 28 of those not taking concomitant immunomodulators at baseline. At Week 8, 24 of 60 patients were in clinical remission as measured by the Mayo score and 17 of 51 patients were in remission as measured by the PUCAI score.
At Week 54, 8 of 21 patients in the every 8-week maintenance group and 4 of 22 patients in the every 12-week maintenance group achieved remission as measured by the PUCAI score.
During maintenance phase, 23 of 45 randomized patients (9 in the every 8-week group and 14 in the every 12-week group) required an increase in their dose and/or increase in frequency of Remicade (Infliximab) administration due to loss of response. Nine of the 23 patients who required a change in dose had achieved remission at Week 54. Seven of those patients received the 10 mg/kg every 8-week dosing.
The safety and efficacy of Remicade (Infliximab) were assessed in 2 multicenter, randomized, double-blind, pivotal trials: ATTRACT (Study RA I) and ASPIRE (Study RA II). Concurrent use of stable doses of folic acid, oral corticosteroids (≤10 mg/day) and/or non-steroidal anti-inflammatory drugs (NSAIDs) was permitted.
Study RA I was a placebo-controlled study of 428 patients with active rheumatoid arthritis despite treatment with MTX. Patients enrolled had a median age of 54 years, median disease duration of 8.4 years, median swollen and tender joint count of 20 and 31 respectively, and were on a median dose of 15 mg/wk of MTX. Patients received either placebo + MTX or one of 4 doses/schedules of Remicade (Infliximab) + MTX: 3 mg/kg or 10 mg/kg of Remicade (Infliximab) by IV infusion at Weeks 0, 2 and 6 followed by additional infusions every 4 or 8 weeks in combination with MTX.
Study RA II was a placebo-controlled study of 3 active treatment arms in 1004 MTX naive patients of 3 or fewer years' duration active rheumatoid arthritis. Patients enrolled had a median age of 51 years with a median disease duration of 0.6 years, median swollen and tender joint count of 19 and 31, respectively, and >80% of patients had baseline joint erosions. At randomization, all patients received MTX (optimized to 20 mg/wk by Week 8) and either placebo, 3 mg/kg or 6 mg/kg Remicade (Infliximab) at Weeks 0, 2, and 6 and every 8 weeks thereafter.
Data on use of Remicade (Infliximab) without concurrent MTX are limited .
The safety and efficacy of Remicade (Infliximab) were assessed in a randomized, multicenter, double-blind, placebo-controlled study in 279 patients with active ankylosing spondylitis. Patients were between 18 and 74 years of age, and had ankylosing spondylitis as defined by the modified New York criteria for Ankylosing Spondylitis. Patients were to have had active disease as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >4 (possible range 0–10) and spinal pain >4 (on a Visual Analog Scale [VAS] of 0–10). Patients with complete ankylosis of the spine were excluded from study participation, and the use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) and systemic corticosteroids were prohibited. Doses of Remicade (Infliximab) 5 mg/kg or placebo were administered intravenously at Weeks 0, 2, 6, 12 and 18.
At 24 weeks, improvement in the signs and symptoms of ankylosing spondylitis, as measured by the proportion of patients achieving a 20% improvement in ASAS response criteria (ASAS 20), was seen in 60% of patients in the Remicade (Infliximab) -treated group vs. 18% of patients in the placebo group (p
At 24 weeks, the proportions of patients achieving a 50% and a 70% improvement in the signs and symptoms of ankylosing spondylitis, as measured by ASAS response criteria (ASAS 50 and ASAS 70, respectively), were 44% and 28%, respectively, for patients receiving Remicade (Infliximab) , compared to 9% and 4%, respectively, for patients receiving placebo (
The median improvement from baseline in the general health-related quality-of-life questionnaire SF-36 physical component summary score at Week 24 was 10.2 for the Remicade (Infliximab) group vs. 0.8 for the placebo group (
Results of this study were similar to those seen in a multicenter double-blind, placebo-controlled study of 70 patients with ankylosing spondylitis.
The safety and efficacy of Remicade (Infliximab) were assessed in 3 randomized, double-blind, placebo-controlled studies in patients 18 years of age and older with chronic, stable plaque psoriasis involving ≥10% BSA, a minimum PASI score of 12, and who were candidates for systemic therapy or phototherapy. Patients with guttate, pustular, or erythrodermic psoriasis were excluded from these studies. No concomitant anti-psoriatic therapies were allowed during the study, with the exception of low-potency topical corticosteroids on the face and groin after Week 10 of study initiation.
Study I (EXPRESS) evaluated 378 patients who received placebo or Remicade (Infliximab) at a dose of 5 mg/kg at Weeks 0, 2, and 6 (induction therapy), followed by maintenance therapy every 8 weeks. At Week 24, the placebo group crossed over to Remicade (Infliximab) induction therapy (5 mg/kg), followed by maintenance therapy every 8 weeks. Patients originally randomized to Remicade (Infliximab) continued to receive Remicade (Infliximab) 5 mg/kg every 8 weeks through Week 46. Across all treatment groups, the median baseline PASI score was 21 and the baseline Static Physician Global Assessment (sPGA) score ranged from moderate (52% of patients) to marked (36%) to severe (2%). In addition, 75% of patients had a BSA >20%. Seventy-one percent of patients previously received systemic therapy, and 82% received phototherapy.
Study II (EXPRESS II) evaluated 835 patients who received placebo or Remicade (Infliximab) at doses of 3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6 (induction therapy). At Week 14, within each Remicade (Infliximab) dose group, patients were randomized to either scheduled (every 8 weeks) or as needed (PRN) maintenance treatment through Week 46. At Week 16, the placebo group crossed over to Remicade (Infliximab) induction therapy (5 mg/kg), followed by maintenance therapy every 8 weeks. Across all treatment groups, the median baseline PASI score was 18, and 63% of patients had a BSA >20%. Fifty-five percent of patients previously received systemic therapy, and 64% received a phototherapy.
Study III (SPIRIT) evaluated 249 patients who had previously received either psoralen plus ultraviolet A treatment (PUVA) or other systemic therapy for their psoriasis. These patients were randomized to receive either placebo or Remicade (Infliximab) at doses of 3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6. At Week 26, patients with a sPGA score of moderate or worse (greater than or equal to 3 on a scale of 0 to 5) received an additional dose of the randomized treatment. Across all treatment groups, the median baseline PASI score was 19, and the baseline sPGA score ranged from moderate (62% of patients) to marked (22%) to severe (3%). In addition, 75% of patients had a BSA >20%. Of the enrolled patients, 114 (46%) received the Week 26 additional dose.
In Studies I, II and III, the primary endpoint was the proportion of patients who achieved a reduction in score of at least 75% from baseline at Week 10 by the PASI (PASI 75). In Study I and Study III, another evaluated outcome included the proportion of patients who achieved a score of "cleared" or "minimal" by the sPGA. The sPGA is a 6-category scale ranging from "5 = severe" to "0 = cleared" indicating the physician's overall assessment of the psoriasis severity focusing on induration, erythema, and scaling. Treatment success, defined as "cleared" or "minimal," consisted of none or minimal elevation in plaque, up to faint red coloration in erythema, and none or minimal fine scale over
Study II also evaluated the proportion of patients who achieved a score of "clear" or "excellent" by the relative Physician's Global Assessment (rPGA). The rPGA is a 6-category scale ranging from "6 = worse" to "1 = clear" that was assessed relative to baseline. Overall lesions were graded with consideration to the percent of body involvement as well as overall induration, scaling, and erythema. Treatment success, defined as "clear" or "excellent," consisted of some residual pinkness or pigmentation to marked improvement (nearly normal skin texture; some erythema may be present). The results of these studies are presented in Table 12.
In Study I, in the subgroup of patients with more extensive psoriasis who had previously received phototherapy, 85% of patients on 5 mg/kg Remicade (Infliximab) achieved a PASI 75 at Week 10 compared with 4% of patients on placebo.
In Study II, in the subgroup of patients with more extensive psoriasis who had previously received phototherapy, 72% and 77% of patients on 3 mg/kg and 5 mg/kg Remicade (Infliximab) achieved a PASI 75 at Week 10 respectively compared with 1% on placebo. In Study II, among patients with more extensive psoriasis who had failed or were intolerant to phototherapy, 70% and 78% of patients on 3 mg/kg and 5 mg/kg Remicade (Infliximab) achieved a PASI 75 at Week 10 respectively, compared with 2% on placebo.
Maintenance of response was studied in a subset of 292 and 297 Remicade (Infliximab) -treated patients in the 3 mg/kg and 5 mg/kg groups; respectively, in Study II. Stratified by PASI response at Week 10 and investigational site, patients in the active treatment groups were re-randomized to either a scheduled or as needed maintenance (PRN) therapy, beginning on Week 14.
The groups that received a maintenance dose every 8 weeks appear to have a greater percentage of patients maintaining a PASI 75 through week 50 as compared to patients who received the as-needed or PRN doses, and the best response was maintained with the 5 mg/kg every 8-week dose. These results are shown in Figure 4. At Week 46, when Remicade (Infliximab) serum concentrations were at trough level, in the every 8-week dose group, 54% of patients in the 5 mg/kg group compared to 36% in the 3 mg/kg group achieved PASI 75. The lower percentage of PASI 75 responders in the 3 mg/kg every 8-week dose group compared to the 5 mg/kg group was associated with a lower percentage of patients with detectable trough serum infliximab levels. This may be related in part to higher antibody rates . In addition, in a subset of patients who had achieved a response at Week 10, maintenance of response appears to be greater in patients who received Remicade (Infliximab) every 8 weeks at the 5 mg/kg dose. Regardless of whether the maintenance doses are PRN or every 8 weeks, there is a decline in response in a subpopulation of patients in each group over time. The results of Study I through Week 50 in the 5 mg/kg every 8 weeks maintenance dose group were similar to the results from Study II.
Efficacy and safety of Remicade (Infliximab) treatment beyond 50 weeks have not been evaluated in patients with plaque psoriasis.
Remicade (Infliximab) How Supplied/storage And Handling
Each Remicade (Infliximab) 20 mL vial is individually packaged in a carton. Remicade (Infliximab) is supplied in an accumulator carton containing 10 vials.
Each single dose vial contains 100 mg of infliximab for final reconstitution volume of 10 mL.
Remicade (Infliximab) Patient Counseling Information
Manufactured by:Janssen Biotech, Inc. Horsham, PA 19044
U.S. License No. 1864
Remicade (Infliximab)
Remicade (Infliximab)
