SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Well-controlled clinical studies have not been performed to evaluate the safety of REMICADE administration in the home-care setting.
• However, pilot studies, a quality improvement project, and retrospective studies have described home-based infusions of REMICADE in patients within the home-care setting.^1-11

CLINICAL DATA

Pilot Studies

Cheng et al (2019)¹ assessed the safety, feasibility, and cost-effectiveness of a REMICADE home-based infusion program during a pilot study in pediatric patients with Crohn’s disease (CD) in the United Kingdom.

• The program ran from October 2014 - April 2018 and was associated with 2 tertiary gastroenterology centers.
• Eligible patients enrolled in this study were >14 years of age, had >5 previous REMICADE infusions in a hospital, and were in clinical remission. Patients with a previous significant infusion reaction or difficult venous access were excluded.
• An infusion nurse obtained blood samples and assessed disease activity by Pediatric Crohn’s Disease Activity Index (PCDAI) score.
• A patient and caregiver satisfaction questionnaire was collected at the end of the program.
• Data were available from 5 patients with a median (range) age at initial diagnosis of 14 (12-15) years and who were treated over 14-33 (median, 28) months.
• All patients received concomitant azathioprine.
• Disease activity during the course of the study is shown in Table: Disease Activity During Home-based REMICADE Infusion.
• The infusion intervals were every 8 weeks (n=3), or every 7 weeks (n=1) or every 6 weeks (n=1) as required for emerging loss of response.
• During the duration of the study, 1 patient had a flare up of disease.
• Four patients were transitioned to adult care and home-based REMICADE was stopped for 1 patient due to the end of the study.
• All 5 patients and caregivers agreed that the program reduced time spent traveling to the hospital, time away from school or work, and fitted in with the patient’s family routine more easily.

Kuin et al (2016)² evaluated REMICADE infusions in a home-based setting during a 1 year pilot study to assess if home-based infusions could be a useful and safe alternative for the management of adult patients with CD in the Amsterdam region.

• Eligible patients enrolled in this study were those who had received REMICADE infusions for at least 1 year without adverse events (AEs) and were in clinical remission (defined as a Harvey Bradshaw Index score ≤ 4) with REMICADE maintenance treatment. Patients with poor venous access were excluded.
• Infusions were given during working hours (no evening or weekend hours) and were administered by home care nurses following standard procedures similar to the infusion clinic. The nurses were present during the entire infusion period and stayed for 1 hour after the infusion was completed. Vital signs were measured prior to and post-infusion. Additionally, emergency equipment and medication were available onsite. AEs were also documented.
• REMICADE treatment was continued at the infusion clinic after completion of the 1 year pilot study.
• For home-based infusions, patient satisfaction and associated costs were studied and compared to hospital-based REMICADE infusions.
• Participants were contacted via telephone to rate their overall experience of whether they would recommend the home-based program to other patients with CD (a score of 10 represented very likely and a score of 1 represented very unlikely), and also satisfaction of infusions given at home and in the hospital were rated based on a scale of 1-10 (a score of 10 represented very satisfied and a score of 1 represented very dissatisfied).
• Thirteen participants (7 female and 6 male patients) received a total of 59 REMICADE home-based infusions.
• Of note, 5 patients discontinued home-based REMICADE infusions before study completion (2 due to infusion planning during working hours; 2 due to the physician discontinuing treatment for clinical, biochemical, and radiological or endoscopic remission; 1 due to REMICADE-induced seborrheic eczema).
• No serious adverse events (SAEs) were reported. However, 1 patient complained of nausea, headache, and palpitations after 1 infusion which were normalized spontaneously during the subsequent infusions, which were administered in 2 hours instead of 1 hour. Additionally, an infusion was delayed in 1 patient due to a cold accompanied by a fever.
• Twelve of thirteen (92%) patients scored 6 points or higher on a scale of 1 to 10 when asked whether they would recommend home-based infusions to other CD patients.
• No difference was detected in the patient satisfaction rate for home versus hospital-based infusions; the median score for both was 8.
• Excluding drug costs, REMICADE home-based infusions costs were €229 per infusion compared with €284 at the infusion clinic.

Retrospective Studies

Gupta et al (2023)³ evaluated adverse outcomes in home vs hospital-based infusions of REMICADE in pediatrics with IBD.

• A retrospective chart review included pediatric patients receiving home- or hospital-based REMICADE infusions between September 2016-2018.
• Pediatric patients receiving home-based infusions of REMICADE were matched to a cohort receiving hospital-based infusions based on age (within 1 year), race (White, Black, other), ethnicity (Hispanic vs not), sex (male/female), and disease type (CD/ ulcerative colitis [UC]).
• Eligible patients enrolled were at least 12 years of age and had received at least 6 infusions (induction, n=3; maintenance, n=3). Patients were excluded if there were concerns for nonadherence, uncontrolled disease, and prior infusion reaction.
• Kaplan-Meier curves and Cox Proportional Hazard (CPH) evaluated the hazard ratio (HR) for adverse outcomes in home vs hospital-based infusions for pediatrics over 2 years of age.
• There were 102 patients (52 patients receiving home-based infusions and hospital-based infusions, respectively) included in this study.
• Infusion reactions were reported by 3 patients receiving home-based infusions.
  • During year 1, one patient experienced fatigue, and another developed hives and lip swelling which was resolved with diphenhydramine and epinephrine treatment. Both patients continued REMICADE without recurrent symptoms.
  • During year 2, one patient experienced shortness of breath during 2 infusions and therapy was changed to ustekinumab due to recurrent symptoms and low drug levels without antibodies.
• Patients receiving home-based infusions experienced the following events:
  • Emergency department visit, n=1; hospitalization, n=1; discontinued therapy, n=5 (due to AEs described above, transition to adult gastroenterology/another institution, secondary loss of response/therapy change, histoplasmosis infection, lymphoma, and pregnancy).
• Patients receiving hospital-based infusions had 8 adverse outcomes:
  • Emergency department visit, n=2; hospitalization, n=3; both emergency department visit and hospitalization, n=2; discontinued therapy, n=1 (due to secondary loss of response/therapy change).
• Disease activity at baseline, year 1, and year 2 among patients who received home- vs hospital-based infusions are shown in Table: Disease Activity Index in Patients with Home- vs Hospital-based infusions.

• At baseline, 94% of home-based infused patients and 88% of hospital-infused patients received 5 mg/kg every 8 weeks as maintenance therapy.
  • After year 1, 23% of patients remained on 5 mg/kg every 8 weeks with a larger proportion of patients receiving hospital-based infusions (33%) vs home-based infusions (14%), P=0.03.
  • After year 2, 19% of patients remained on 5 mg/kg every 8 weeks with no difference between cohorts (18% home-based infusions vs 20% hospital-based infusions).
• Over both years and as expected per site protocols, patients who received home-based infusion had fewer labs drawn (P<0.001) but there were no differences between cohorts for calprotectin, erythrocyte sedimentation rate (ESR), C-reactive protein, albumin, hemoglobin, or the number of clinic visits at each time point.
• The risk for adverse outcomes was similar between cohorts (CPH ratio, 0.89 [0.32- 2.46]).

Viteri et al (2022)⁴ conducted an observational, retrospective study to assess the rate of real-world REMICADE infusion related AEs in patients receiving home-based maintenance infusions.

• Patients receiving home-based infusions of REMICADE were evaluated for the prevalence of AEs, AE types, and the proportion of patients transferred to an emergency room.
• There were 863 patients included in this study, with a total of 8,388 infusions administered between 2020 and 2021.
• On-site AEs during or after infusion occurred in 39 (4.5%) unique patients, with a total of 49 (0.58%) AEs over the study period.
  • The most common AEs were fatigue (22.4%), dermatologic (20.4%), and cardio/pulmonary (16.3%).
• Among the 863 patients receiving REMICADE infusions, 11 (1.3%) experienced fatigue, 10 (1.2%) had skin-related AEs, and 8 (0.9%) experienced cardio/pulmonary-related AEs.
• During the study, 3 (0.35%) patients required emergency room care after infusion.

Baker et al (2021)⁵ conducted a retrospective study to assess if patients receiving home-based biologic infusions, including REMICADE, have increased AEs requiring emergency department (ED) visit or hospital admission vs facility infusions.

• Data was derived from Optum Clinformatics Data Mart, an administrative health claims database from January 2017 to December 2017 and included patients 18 years and older with an ICD-9 or ICD-10 code for an immune-mediated disease and a J-code to identify biologic infusions.
• Hospital-based infusions were excluded from this analysis.
• Patient age, sex, year of infusion, disease and drug were extracted for those who received home-based or facility infusions.
• The primary outcome was an ED visit or hospital admission after administration of the biologic agent at home-based vs facility.
• There were 57,220 patients included in this study with a total of 753,150 infusions.
• Of the 753,150 infusions, 394,638 (52.5%) were REMICADE infusions: home-based infusions, 20,653 and facility infusions, 373,985.
• In the subgroup analysis, the occurrence of an ED visit or hospital admission with REMICADE was 1,085/20,653 (5.3%) with home-based infusions vs 13,191/373,985 (3.5%) with facility infusions.

Fenster et al (2020)⁶ compared adverse outcomes (stopping therapy, IBD-related emergency room visits, and IBD-related hospitalization) in patients with IBD who received REMICADE or vedolizumab at home- or hospital-based infusion center.

• A matched retrospective cohort study included patients treated with REMICADE or vedolizumab at home or at a hospital (control) from January 1, 2016 through July 1, 2017 though a tertiary care IBD center.
• Patients receiving home-based infusions were matched to control patients based on age, gender, IBD type, infusion medication, and time on therapy before home-based infusion or matching.
• The primary endpoint was a composite of stopping biologic therapy, IBD-related emergency room visits, or IBD-related hospitalization.
• The secondary endpoints were degree of monitoring assessed by frequency of IBD outpatient clinic visits and laboratory assessments.
• A total of 69 patients (REMICADE: n=49; vedolizumab: n=23) started receiving home-based infusions during the study period and were similar in baseline characteristics to the matched control patients.
• A total of 89.9% of patients in the home-based infusion cohort transitioned from an infusion center to home-based infusion and 10.1% initiated biologic therapy as home-based infusion.
• Univariable and multivariable CPH analyses were performed to determine the independent effects of variables associated with adverse outcomes.
• The median follow-up time was 672.5 (interquartile range, 134) days for home-based infusion patients and 645 (interquartile range, 121) days in control patients.
• Patients on home-based infusion were more likely to experience adverse outcomes vs control patients (43.5% vs 21.7%; P=0.006).
• In univariable analysis, elevated CRP was associated with time to adverse outcomes at both the start of home-based infusions (HR, 1.91; 95% confidence interval [CI], 1.03-3.52; P=0.039) and receiving home-based infusion (HR, 2.27; 95% CI, 1.22-4.22; P=0.010).
• In multivariable analysis, controlling for elevated CRP at the start of home-based infusion or match and age, home-based infusion was significantly associated with time to adverse outcomes (adjusted HR, 2.30; 95% CI, 1.23-4.31; P=0.009).
• Patients on home-based infusion showed a trend toward stopping therapy within 1 year (20.3% vs 8.7%; P=0.053) and stopping therapy within the complete follow-up period (27.5% vs 15.9%; P=0.099) vs control patients.
• Patients on home-based infusion had significantly more emergency room visits after switching to home-based infusion vs control patients (home-based infusion 30.4% vs control 7.2%; P<0.001) but did not experience more hospitalizations (home-based infusion 17.4% vs control 11.6%; P=0.333).
• Home-based infusion patients receiving therapy for <1 year before the start of home-based infusion were significantly more likely to stop therapy than those who were receiving stable therapy for >1 year (40.6% vs 16.2%; P=0.024).
• In the year following home-based infusion initiation or matching, patients who continued to receive home-based infusion (n=47) had significantly less IBD clinic visits than control patients (n=57) (1.23 vs 1.75; P=0.018).
• Home-based infusion patients were significantly more likely to have ≤2 laboratory assessments in the year after initiating home-based infusion compared with control patients (30.4% vs 0%; P=0.0001).

Checkley et al (2019)⁷ assessed the incidence and management of infusion reactions to REMICADE administered at home or in the ambulatory infusion suite in patients with CD or UC.

• A retrospective chart review included all IBD patients receiving REMICADE at home or in an ambulatory infusion suite via a home-based infusion company from January 1, 2014 through November 23, 2016.
• Infusions were administered and monitored by a nurse.
• The use of premedication (eg, antihistamines, acetaminophen, and/or intravenous steroids) was established by the referring physician.
• Acute reactions were defined as anything occurring during the infusion or within 24 hours following the infusion.
• Delayed reactions were defined as reactions occurring >24 hours after the infusion to 14 days following the infusion.
• Even though delayed and acute immediate reactions were categorized according to severity, in this study, analysis of severity was limited to acute reactions due to the voluntary nature of patient reporting and the difficulty of differentiating delayed reactions from symptoms used in diagnosis.
• Chi-square test was used to compare rates of immediate reactions between maintenance and induction infusions, gender, and administration site.
• During the study, a total of 796 patients (69% with CD and 31% with UC) received 5581 REMICADE infusions.
• A total of 105 new patients (13.2%) received an induction infusion during the study period, totaling 251 infusions (4.5% of all infusions).
• A total of 3052 (54.7%) infusions were administered in patients’ homes and 2529 (45.3%) were administered in the ambulatory infusion suite.
• At the start of the data collection period, the mean patient age was 36 (range, 6-88) years.
• Patients received a mean of 7 infusions during the study and the mean REMICADE dose was 531 (median, 500) mg.
• The mean REMICADE maintenance interval was 7.1 weeks.
• A total of 109 infusion reactions (2% of all infusions) were observed in 62 patients (7.8% of all patients). Table: Infusion Reactions and Proportion for Each Age Range classifies infusion reactions by age.
  • Of these reactions, 87 (79.8%) infusions were assessed as acute (the majority of which were classified as mild [57.5%] or moderate [31.0%]) in severity) and 22 (20.2%) infusions were delayed.
  • Ten infusions were associated with severe reactions (11.5%, 0.2% of all infusions), and of these, 8 (9.2%, 0.1% of all infusions) resulted in emergency room visits.

• Table: Type and Frequency of Acute and Delayed Infusion Reactions to REMICADE notes the types and frequencies of acute reactions (in ≥2% of reactions) and a complete listing of type and frequency of delayed reactions.

• Overall, per-infusion incidence of infusion reactions was 2% in CD patients and 1.9% in UC patients (Table: Infusion Reactions According to Diagnosis).

• Post-infusion reaction management approaches carried out by the infusion nurse are listed in Table: Management Approaches to Acute Infusion Reactions.

• The infusion reactions that did not receive an intervention were assessed as mild in severity and consisted of either headache, pruritus around the infusion site, and/or flushing; these reactions resolved following the completion of the infusion.
• A resolution of acute infusion reactions allowed the continuation of the infusion in most cases.
• There were 14 reactions (16.1% of 87 acute infusion reactions; 0.3% of all infusions) in 14 patients in which the infusion was stopped and not continued; 5 of the 14 patients were able to maintain their scheduled treatment plan and completed their next scheduled infusion, while 9 patients did not return for any additional infusions in the home or ambulatory infusion suite.
• Overall, 69.3% (43/62) of patients who experienced an infusion reaction returned for their next scheduled infusion in the home or ambulatory infusion suite; of these 43 patients, 30 (69.8%) patients did not experience any subsequent reactions and 10 patients experienced 1-5 additional reactions. Two patients experienced 10 infusion reactions, and 1 patient experienced 16 infusion reactions (this patient’s reactions were mild and consisted of repeated headache and pruritus following REMICADE administration).

Goodoory et al (2019)⁸ retrospectively evaluated the safety and patient satisfaction of home-based REMICADE infusions in patients with IBD in the United Kingdom.

• Patients in the analysis were enrolled in a home-based REMICADE infusion program between July 2014 and July 2018.
• Satisfaction survey (rated on a 10-point scale) was evaluated for adequate communication, delivery times, customer service, driver assistance/attitude, nurse support service, clinical waste collection, and overall satisfaction.
• Forty-one patients were included in the analysis.
• The median age of patients was 42 years, 19 (46.3%) patients were women, 9 (22%) patients had UC, and 32 (78%) patients had CD.
• A total of 373 REMICADE infusions were administered at home.
• Patients received a median of 7 REMICADE doses while in the hospital before switching to home-based REMICADE infusions.
• The median duration of follow-up while receiving REMICADE at home was 14 months and the median number of REMICADE doses administered at home was 7.
• There were 3 (0.8%) instances when REMICADE infusions at home were placed on hold or were stopped:
  • Patient 1 (received 8 REMICADE infusions in the hospital and 14 REMICADE infusions at home prior to holding) experienced a skin rash (managed in the community setting). An additional REMICADE dose was administered in the hospital, and REMICADE was halted following a similar skin rash.
  • Patient 2 (received 21 REMICADE infusions in the hospital and 32 REMICADE infusions at home prior to holding) experienced low blood pressure. The next REMICADE dose was administered in the hospital as a precautionary measure.
  • Patient 3 (received 12 REMICADE infusions in the hospital and 19 REMICADE infusions at home prior to holding) became pregnant. Home-based REMICADE was resumed after pregnancy.
• No deaths and no adverse reactions requiring hospital admission occurred.
• Among 18 (69.2%) of 26 patients who received home-based REMICADE in July 2018, the mean and median satisfaction scores were 9.7 and 10 (out of 10), respectively.

Buchman et al (2006)⁹ conducted a review of all consecutive outpatients with IBD who received REMICADE either at an infusion center or at home to compare clinic-based infusions with home-based infusions.

• The following information was recorded: age, gender, number of infusions, acute infusion reactions, and reimbursed charges for infusions.
• The outpatient infusion center population included patients with CD (n=65), UC (n=9), and ankylosing spondylitis (n=1).
• The mean age for the 37 females and 34 males was 36.7 years, and the total number of infusions was 254 (3.4±1.3 per patient).
• The home setting included 13 patients with CD and the mean age was 39.1 years for the 8 females and 36.7 years for the 5 males. The total number of infusion was 54 (4.2±2.0 per patient).
• In the outpatient infusion center, REMICADE was discontinued in 2 cases because acute infusion reactions occurred (pruritis and hives, vasovagal reaction; not reported as SAEs).
• There were no acute infusion reactions in the home setting.
• The mean reimbursed costs (including medication, supplies, nursing, and related charges) was $4554 for the infusion center and $4350 for the patients infused at home (P=not significant). Reimbursed charges did not include medication for Medicaid patients.

Condino et al (2005)¹⁰ conducted a retrospective chart review of pediatric patients receiving REMICADE infusions at home.

• Eligible patients had received ≥3 inpatient REMICADE infusions without AEs, were in clinical remission at the time of entry into the home-based infusion program, maintained good compliance with maintenance medications, and received insurance approval for home-based infusion.
• According to study protocol, home-based infusion nurses were present during the infusion to monitor for adverse reactions every 30 minutes, in addition to 30 minutes after the infusion.
• Medications for resuscitation were readily available prior to initiation of the infusion, and patients were in close proximity to a local emergency room. Patients were not routinely premedicated prior to infusion.
• Each child was contacted via telephone and asked several questions concerning his or her overall experience with infusions given in the hospital setting and at home.
• Both the child and parents then rated their overall experience in both settings on a scale of 1-10 (a score of 10 represented the most satisfied).
• Ten children, 9 with CD and 1 with indeterminate colitis, were enrolled in the home-based infusion program and received a total of 59 infusions. The mean age of patients was 15.6 years, and the mean number of infusions per child was 5.9.
• The patients’ home-based infusion satisfaction scores ranged from 6.5-10 (mean, 9.2), compared to the patients’ hospital satisfaction rating, ranging from 5.5-9 (mean, 8.2).
• No SAEs were reported, however, there was difficulty with intravenous (IV) access during 3 infusions. All of these patients were able to receive their infusions.
• One infusion was stopped when the patient complained of arm pain above the IV site, and this patient had his next infusion in the hospital before resuming home-based infusions.

Valdez et al (2001)¹¹ performed a retrospective chart review of 115 home-based infusion patients who received a total of 172 evaluable REMICADE infusions.

• The vast majority of patients (94%) received REMICADE for the treatment of CD, with the rest of the patients receiving REMICADE for the treatment of rheumatoid arthritis (RA, 4%) or UC (2%).
• REMICADE was infused over an average of 2.12 hours (range, 1-5 hours). Premedications were not routinely administered; however, 29 patients who received a total of 60 infusions were administered premedications, most commonly diphenhydramine with or without acetaminophen.
• Complications were reported in 15 (13%) patients during the infusion or within 30 minutes following 18 (10%) infusions, and all reactions were observed within the first 3 infusions.
• The most common complications were chills, flushing, headache, dizziness, or itching, which occurred in less than 4% of infusions.
• Less than 3% of patients experienced moderate to serious complications that required additional medical management or discontinuation of therapy.
• Chest or back pain, or blood pressure changes occurred with ≤1% of infusions.
• Most complications required minimal management such as slowing/stopping the infusion or adding medications according to standard protocols.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 14 March 2024.