Abstract
OBJECTIVES
To compare infusion reaction rates between rapid infliximab (REMICADE, Janssen Biotech Inc) infusions and previous standard 2- to 3-hour infusions; additionally, to assess patient satisfaction and reduction in chair time associated with rapid infliximab infusions.
METHODS
Pediatric rheumatology and gastroenterology patients receiving maintenance infliximab therapy using a standard 2- to 3-hour titrated infusion had the opportunity to enroll in the non-titrated rapid 1-hour infusion protocol following tolerance of induction dosing at 0, 2, and 6 weeks. Patients were included from December 1, 2017, to March 31, 2018, via retrospective chart review and patient satisfaction surveys.
RESULTS
Data were collected on 55 patients receiving a total of 160 rapid infliximab infusions. There were 2 infusion reactions during the enrollment and data collection period, resulting in an overall infusion reaction rate of 1.3%. The patient satisfaction survey results showed all patients were at minimum satisfied with the information provided regarding rapid infliximab, decreased time spent in clinic, ease of scheduling, and overall process.
CONCLUSIONS
Our data suggest rapid infliximab infusions are safe in pediatric rheumatology and gastroenterology patients receiving maintenance infliximab infusion therapy. The overall infusion reaction rate of 1.3% in this study is well below the accepted infusion reaction rate of standard-length infliximab infusions of 2% to 3%.
Keywords: gastroenterology, infliximab, infusion, pediatric, reaction, rheumatology
Background
Infliximab is a tumor necrosis factor blocking agent used for the treatment of Crohn's disease, juvenile idiopathic arthritis (JIA), and other inflammatory conditions.1–3 The manufacturer recommends an approximate total infusion time of 2 to 3 hours.3 This extended infusion time, along with a frequency of doses, places a significant burden on patients and health care institutions. Because of the infusion duration, patients experience a sizeable interruption to their daily routine, potentially interfering with school and/or work. Considerations for the health care institution include space, time, and staff availability for the duration of the infusion.2
The main safety concern with administration of infliximab is the potential for acute infusion reactions, which has been associated with 2% to 3% of all infusions.2 Rapid, or 1-hour, infliximab infusions have been implemented at adult infusion centers, including other Fairview/M Health Infusion centers, following the evidence of reduced infusion reactions in adult patients. A total of 16 studies comparing standard to rapid infusion found an overall decreased incidence in infusion reactions in the rapid-infusion groups.1–14 From a pediatric perspective, a recent study published in the Journal of Pediatric Gastroenterology and Nutrition compared standard and rapid infusions in a 16 patient cohort receiving 133 standard infusions followed by 50 rapid infusions.3 The study results were similar to those found in adult patients, with decreased incidence of infusion reactions in the rapid-infusion group.
Based on currently available literature showing safety of decreased infusion duration, the pediatric rheumatology and gastroenterology providers at the University of Minnesota Masonic Children's Hospital elected to implement rapid infliximab infusions for all patients meeting agreed-upon eligibility criteria beginning December 1, 2017, in order to increase patient satisfaction and decrease chair time.
The current study is a single-center retrospective review of the rapid infliximab infusion process. The primary objective was to compare rapid infliximab infusion reaction rates to the established infusion reaction rate of 2% to 3% with standard infliximab infusions. Secondary objectives included an assessment of patient satisfaction and reduction in clinic chair time associated with rapid infliximab infusions.
Methods
All pediatric rheumatology and gastroenterology patients receiving maintenance infliximab infusions at the University of Minnesota Journey Clinic Infusion Center were eligible to enroll in rapid infliximab infusions beginning December 1, 2017. Data was collected on all patients who received at least 1 rapid infliximab infusion during the enrollment period from December 1, 2017, through March 31, 2018.
The following criteria were used for rapid infliximab infusion eligibility: patient may only receive rapid infliximab infusion if 1) receiving treatment from a pediatric rheumatology or gastroenterology provider; 2) tolerate 4 infusions of standard length prior to receiving rapid infusions; 3) be receiving maintenance infliximab infusion therapy; 4) weigh 15 kg or greater (15 kg was used as eligibility criteria in order to ensure patients did not receive greater than a 20 mL/kg bolus, because all infliximab infusions are prepared in 300 mL); 5) if dose increased, patients must receive new dose during 2 hours for 1 dose before resuming rapid infusions. There were no exclusion criteria used.
If a patient was identified as eligible and consented to receive rapid infliximab infusions this information was documented electronically in the patient's chart using the nursing communication shown in Supplemental Table 1. If all options in Supplemental Table 1 were selected as yes, the patient was marked as eligible to receive rapid infliximab infusions. The nursing communication in Supplemental Table 1 also served as notification to providers of the patient's enrollment in the rapid infliximab infusion study.
Following completion of their second rapid infliximab infusion, the patient or patient's caregiver was asked to complete a short, 5-item survey in order to assess overall satisfaction with the rapid infliximab infusion process (questions shown in Supplemental Table 2). They were asked to answer the survey questions using a rating of very dissatisfied, satisfied, very satisfied, or extremely satisfied. All completed, non-duplicate surveys were included in data review. In the event duplicate surveys were completed, only the first survey was included in the results. Data collected from patient charts included: patient age, diagnosis requiring infliximab, number of rapid infliximab infusions received, and number of hours saved compared with previous infusion durations (Supplemental Table 3). If patients experienced an infusion reaction while receiving rapid infliximab, nurses were asked to fill out the form in Supplemental Table 4 (Infliximab Data Collection Form) which, when completed, sent an email to the primary investigator with the reaction information. There is no standard premedication regimen used for all patients receiving infliximab infusions. If patients previously required premedication for standard infusions, this regimen was not changed with transition to rapid infusions. Descriptive statistics were used to evaluation rapid infliximab infusion results.
Results
Of the 58 patients eligible to enroll in rapid infliximab infusions during the study period, 3 patients did not consent. Two of the 3 non-consented patients were offered rapid infusions twice and declined each time, with no reason given in the chart. The third patient was undergoing frequent dose titration to achieve a goal infliximab trough >10, and consented to rapid infusions following dose stabilization. With 3 of 58 not consented to receive rapid infusions, the overall enrollment rate was 94.8%. The remaining 55 patients received a total of 160 rapid infliximab infusions during the study enrollment period. Demographic information for study participants is detailed in Table 1.
Table 1.
Demographic Information (N = 55)
| Parameter | Value |
|---|---|
| Age, mean (range), yr | 14.9 (5–20) |
| Female, n (%) | 30 (54.5) |
| Referring service, n (%) | |
| Gastroenterology | 20 (36.4) |
| Rheumatology | 35 (63.6) |
| Diagnosis, n (%) | |
| Juvenile idiopathic arthritis | 27 (49.1) |
| Crohn’s disease | 15 (27.3) |
| Other | 13 (23.6) |
| Number of rapid infusions | 160 |
| Number of infusion reactions, n/total (%) | 2/160 (1.3) |
Infusion Reactions. During the study process, 2 of 160 patients (1.3%) experienced infusion reactions to infliximab. The infliximab data collection form (Supplemental Table 4) was not used to alert pharmacy following each occurrence, but the information was communicated directly to the infusion center pharmacist if they were not present at the time of reaction.
Patient 1. A 15-year-old male with Crohn's disease and JIA who had been initiated on infliximab therapy in December 2015. The patient had received a total of 24 standard infliximab infusions and was receiving his second rapid infliximab infusion when he experienced a reaction. The patient had arrived to clinic complaining of a sore throat but was evaluated by the provider and determined to be eligible to receive his infusion.
Approximately 15 minutes into his rapid infliximab infusion the patient called out to his nurse that he was feeling dizzy and lightheaded. The nurse practitioner assessed the patient at bedside and noted him to be hypotensive. The infliximab was stopped at 77 mL into the infusion, a 10 mL/kg bolus normal saline was ordered, and the patient's vital signs stabilized. He was then transferred to an inpatient unit to receive the remainder of the infliximab infusion as a standard infusion. He has received 2 subsequent doses of infliximab infused during 2 hours with no infusion reaction and no premedications given to prevent an infusion reaction.
Patient 2. A 5-year-old female with JIA was initiated on infliximab therapy in April 2017 and had received a total of 6 standard infliximab infusions. During her third rapid infliximab infusion she experienced an infusion reaction. Of note, the patient had missed her previous infliximab infusion and had not received any doses in 3 months. Approximately 6 minutes into the infliximab infusion (33 mL had infused) the advanced practice registered nurse was called into the room to assess an infusion reaction. Upon arrival to the room, the patient was vomiting and in distress, with stridor and audible gurgling. She had a muffled voice and was posturing in an effort to maintain her airway. Upon auscultation she was found to be moving good air but tachycardic, with a heart rate of 130 bpm with oxygen saturations in the low 80s.
She was given an intramuscular epinephrine injection and placed on blow-by oxygen. An intravenous fluid bolus was also started at this time. Following the epinephrine administration, the patient's vomiting subsided and breathing eased, and within 5 minutes she was no longer posturing and gurgling had subsided. Oxygen saturations had normalized with blow-by O2, and the patient was transported to the emergency department to be monitored for any rebound symptoms. She has not received any subsequent infliximab infusions at this time with plans to begin therapy with adalimumab.
Survey Results. Survey data was collected on 39 of the 55 patients, and their results are detailed in Table 2 (Results of Satisfaction Survey). Information provided regarding the opportunity to enroll in rapid (1-hour) infliximab (Remicade, Janssen Biotech Inc, Horsham, PA) infusions was given the following ratings: extremely satisfied 23 of 39 (59%), very satisfied 10 of 39 (25.6%), and satisfied 6 of 39 (15.4%). Decreased chair time spent in clinic because of shorter length of infusion received: 28 of 39 (71.8%) had extremely satisfied, 10 of 39 (25.6%) very satisfied, and 1 of 39 (2.6%) satisfied ratings. Ease of appointment scheduling also received positive survey results, with 24 of 39 (61.5%) rating extremely satisfied, 8 of 39 (20.5%) very satisfied, and 7 of 39 (17.9%) satisfied. Overall satisfaction with transition to rapid Remicade infusions received the following ratings: 28 of 39 (71.8%) extremely satisfied, 8 of 39 (20.5%) very satisfied, and 3 of 39 (7.7%) satisfied. As shown by the above results, no items on the satisfaction survey received a rating less than satisfied. Rapid infliximab infusions reduced patient chair time by 162 hours for the 160 total infusions. Of the 39 completed patient surveys, 34 (87%) noted no difference in the feel of rapid Remicade infusions compared with previous infusion.
Table 2.
Results of Satisfaction Survey
| Question and Response, n (%) | ||||
|---|---|---|---|---|
| Q1: Information Provided Regarding Opportunity to Enroll in Rapid (1-hr) Remicade Infusions? | Q2: Decreased Time Spent in Clinic Due to Shorter Length of Infusion? | Q3: Ease of Appointment Scheduling for Rapid (1-hr) Infusions? | Q4: Overall Satisfaction With Transition to Rapid Remicade Infusions? | |
| Extremely satisfied | 23 (59) | 28 (71.8) | 24 (61.5) | 28 (71.8) |
| Very satisfied | 10 (25.6) | 10 (25.6) | 8 (20.5) | 8 (20.5) |
| Satisfied | 6 (15.4) | 1 (2.6) | 7 (17.9) | 3 (7.7) |
| Very dissatisfied | 0 | 0 | 0 | 0 |
Study Limitations. The main limitation of this study was the lack of satisfaction survey results from a subset of 16 patients for whom a survey was not completed or was not given to the infusion center pharmacist. Given the survey results shown from all other patients in this study, we are confident that patients were satisfied with the rapid infliximab process. Despite the positive satisfaction survey results, we also note a potential confounder in the survey scale because questions were skewed towards the positive with no dissatisfied option. We also encountered difficulty with appropriate documentation during the study because the infliximab data collection form (Supplemental Table 4) was not used, and all infusion reaction information was obtained via chart review of physician and nursing notes. Because of the low number of infusion reactions and effective communication of the infusion center nursing staff, we were able to capture the reaction information within 24 hours of the occurrence, allowing for additional face-to-face communication and, if necessary, expansion upon documentation.
Discussion
Our data are consistent with published findings for adult and pediatric patients receiving rapid infliximab infusions, with an overall infusion reaction frequency of 1.3% (95% CI, 0.0172). This is a lower reaction rate than the accepted 2% to 3% infusion reaction rate with standard 2- to 3-hour titrated infusions. When the infusion reaction results are adjusted to exclude patient 2 (who had missed 3 previous infliximab infusion appointments), the infusion reaction rate is reduced to 0.6%. We feel this is a more accurate representation of the true infusion reaction rate during our study period, because by missing the previous 3 infliximab infusions the patient could have been treated as a new patient requiring 3 standard infusions before resuming rapid infusions. Moving forward with rapid infusions at our facility, patients missing 2 or more infliximab infusions will be required to tolerate a minimum of 1 standard infusion prior to resuming rapid, which is consistent with our policy for dose increases.
Conclusions
Infliximab has historically been given as a titrated infusion during 2 to 3 hours based on manufacturing recommendations; however, current practices are beginning to challenge this process. In order to increase patient satisfaction and decrease chair time, many adult infusion centers, including those at the University of Minnesota, have instituted rapid infusions. This study is the first of its kind to show rapid infliximab can be a well-tolerated alternative to standard 2- to 3-hour titrated infusions in both pediatric rheumatology and gastroenterology patients.
Supplementary Material
Acknowledgment
The preliminary findings of this research were presented at The Pediatric Pharmacy Association annual meeting; April 2018; Salt Lake City, UT.
ABBREVIATION
- JIA
juvenile idiopathic arthritis
Footnotes
Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all of the data in the study and take full responsibility for the integrity of the data and accuracy of the data analysis.
Ethical Approval and Informed Consent The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation and have been approved by the appropriate committees at the University of Minnesota. All patients and/or parents/caregiver(s) provided written informed consent and/or assent (as applicable) at enrollment.
Supplemental Material
DOI: 10.5863/1551-6776-25.8.705.S1
DOI: 10.5863/1551-6776-25.8.705.S2
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