Infliximab is a monoclonal human-murine chimeric antibody to tumor necrosis factor-α (TNF-α ) which targets one of the principal mediators of inflammation in inflammatory bowel disease (IBD) (1-3). Infliximab has been shown to be efficacious for the treatment of fistulizing Crohn disease (CD) and for induction and maintenance of remission in adults with moderate to severe CD (1,3,4). This agent has found application in children who are corticosteroid dependent, corticosteroid toxic, refractory to other medications or suffering complications from standard immunosuppression regimens(1,5,6). Effective doses in children, 5 to 10 mg/kg, are similar to those recommended in adults (5). The duration of drug response in children with CD is better when administered early in the course of the disease (7).
Infliximab is given via intravenous infusions that are time consuming and costly. Infusions require hospital or infusion center appointments which require both the parent and child to be present for two to five hours per infusion. This inconvenience threatens compliance. We became interested in looking at alternative settings for infliximab infusions when a well-established pediatric homecare nursing service expressed interest in providing the infusions.
This study was approved by the Colorado Multiple Institutional Review Board. We conducted a retrospective chart review of all children receiving care for IBD at the Center for Pediatric Inflammatory Bowel Diseases at The Children's Hospital, Denver. Those who received home infliximab infusions between September 2001 and October 2003 were included. Children enrolled in the home infusion program had met the following criteria: a minimum of three or more in-patient infliximab infusions without adverse events, clinical remission at the time of entry into home infusion program, good compliance with maintenance medications and insurance approval for pediatric home care nurses to administer infusions.
The pediatric homecare nurses followed infusion protocols similar to those used in the hospital and were present for the entire infusion to monitor for any adverse reactions. The infusion protocol consists of obtaining baseline vital signs followed by monitoring vitals every 30 minutes during the infusion and for 30 minutes post infusion. Resuscitation medications were available at the bedside prior to initiation of the infusion. Children were not routinely premedicated with steroids, diphenhydramine, or acetaminophen. Other requirements included a parent at home, readily available transportation and close proximity to a local emergency room. These children did not routinely see their physician prior to their infusion. They were seen on an individual needed basis.
The cost for the in-home infusions was determined based on the sum of charges for infliximab, nursing services, supplies, laboratory samples and duration of infusion. The in-home cost was then compared with the total hospital cost for each patient. The hospital cost included the patient charge for infliximab, nursing care, supplies, physician visit, laboratory samples and length of hospitalization. To enable comparison, the charge for medication was adjusted for dose and body weight. The wilcoxon signed rank sum test was used to assess differences between the in-hospital costs and the home infusion costs.
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. Each child was asked about the number of infusions received in the hospital versus at home, the duration of infusions in both settings, adverse experiences in either setting, number of hours or days of school missed secondary to infusions in both settings and current medications. The child was then asked to rate his or her overall experience in both settings on a scale of 1 to 10 (10 = most satisfied) to provide a satisfaction score. The parents of each child were also asked to rate their child's experience with the in-home infusions on the same scale.
Between 1999 and 2004, 40 children received infliximab for IBD at our center. Of these, 10 children (8 boys, 2 girls) were enrolled in the home infusion program and received a total of 59 infusions. Nine children had CD and one had indeterminate colitis. Of the patients, 70% had colonic involvement, 50% had small bowel disease and 20% had fistulizing disease. The age range at the time of first in-home infusion was 11.4 to 18.8 years (mean age, 15.6 yrs). Number of infusions per child ranged from 1 to 11 (mean, 5.9) (Table 1).
The individual infusion cost for infliximab given in the hospital ranged from $2,184 to $2,344 per 100 mg infliximab. Single in-home infusion cost ranged from $872 to $938 per 100 mg infliximab, more than $1000 per 100 mg less than in the in-hospital cost, p < 0.001 (Table 2). For example, the estimated cost of an infusion for a 50 kg child receiving 10 mg/kg infliximab was $7,776 if given in the hospital and $3,744 if given at home-an estimated saving of $4,032 per infusion.
The patient in-home infusion satisfaction rating ranged from 6.5 to 10, with a mean satisfaction score of 9.2. The patient hospital satisfaction rating ranged from 5.5 to 9, with mean score of 8.2 (Table 2).
No serious adverse events were reported. There was difficulty with IV access in three infusions and multiple attempts by the pediatric homecare nurse were required to gain adequate access. 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. This patient had his next infusion in the hospital before resuming home infusions.
There is little data on safety and patient satisfaction in children receiving infliximab infusions in either the hospital or clinic setting and no data on in-home infusions. Reported adverse events associated with infliximab include acute and delayed infusion reactions, the development of autoimmunity, and an increased risk of infections(1,3,8). Acute infusion reactions occur in approximately 5% of infusions and include chest pain, shortness of breath, headache, fever, urticaria and hypotension. Delayed systemic reactions occur in <1% of infusions and are characterized by arthralgia, fever and myalgia requiring corticosteroid treatment. Delayed reactions occur more often with episodic infliximab retreatment (9). A recent pediatric study of 111 IBD patients reported outcome of 594 infusions. Seven early and two late reactions were reported in 1.5% of infusions, although none were severe or life threatening (10). All 7 early reactions responded to IV diphenhydramine, and thus would be mangaged successfully by our current home infusion protocol.
Controversy remains as to the safety of infliximab, both in the short and long term. One adult retrospective study of 500 patients reported serious adverse events in 6%, acute reactions in 3.8% and serum sickness-like disease in 2.8% (11). This study also identified two life threatening infusion reactions that required epinephrine and concluded that home administration of infliximab should only be undertaken with great caution if at all (11). There has also been some concern over severe reactions occurring during maintenance therapy with infliximab. Risk factors for these severe reactions include noncompliance with concomitant maintenance immunosuppressive medications, lengthy intervals between infusions and fewer than three prior infusions (8,11). As risk factors for serious adverse events are identified, we suspect that there will be identifiable groups at low and high risk for serious adverse events.
We present data from our home infusion program. We enrolled only what we felt were low-risk patients in our home infliximab infusion program. This group had experienced no reactions when given >3 infusions in the hospital setting. They adhered to their maintenance immunomodulator therapy and were in a state of remission or near remission. This group also complied with a pediatric nursing homecare arrangement for both delivery of and monitoring of their infusions.
Our patients and their families were completely aware of any and all risks that applied to their infusions being provided at home and elected to participate in this program. The majority of our patients and families preferred the in-home infliximab infusion program when compared to in-hospital infusions. This program was associated with significant cost savings and excellent patient and family satisfaction. Further study is needed to clarify the benefits and risks of such programs and to determine at what point home or alternative settings may be recommended for selected groups of patients.
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