All consecutive patients with confirmed IBD attending two Australian tertiary inflammatory bowel disease centres over a 12-year period from January 2005 to March 2017 who were prescribed infliximab and commenced infusions at the study centres were identified via an IBD database and/or pharmacy dispensing records, then prospectively followed. Inpatients receiving infliximab (for example for acute severe colitis) were excluded from this analysis. All patients underwent standard dosing of infliximab 5 mg per kilogram of body weight for induction at week 0, 2 and 6 followed by maintenance infusions, where dosing/dosage interval may have been altered as per the treating clinician’s discretion, predominantly to address secondary loss of response.

Data including baseline demographic data, IBD data including disease distribution duration and complications, therapeutic data including adverse drug reactions (ADRs) and location of infliximab administration, were extracted from medical records. The severity of infliximab infusion reactions were graded retrospectively according to the Common Toxicity Criteria (CTC) version 2.0[17] from 1 to 4, with a CTC score of 1-2 graded arbitrarily defined as “mild” and 3-4 as “severe” reactions respectively.

Inclusion criteria: (1) Aged 18 and above; and (2) Received maintenance therapy infliximab between January 2005 and March 2017 for an IBD indication.

Exclusion criteria: (1) Less than age 18; (2) Received infliximab for a non – IBD indication; and (3) received infliximab as an inpatient.

The primary outcome measure in this study was the safety of infliximab infusions, with the standard infusion protocol as per manufacturer’s guidelines as the reference, compared to (1) a rapid infusion protocol; and (2) a rapid infusion protocol administered via a home-based service, comparing relative incidence of serious adverse events. Secondary outcomes assessed included the relative cost of infusion centre and home-based infliximab infusions and factors associated with a higher risk of infusion reactions in order to risk stratify patients prior to referral for home-based infusions.

Initial standard 2-h infusion data was available from patients infused between January 1, 2005 to December 31, 2013, inclusive. Rapid 30-min infliximab infusion data was available from patients infused between January 1, 2014 and March 31, 2017 inclusive and home-based rapid infliximab infusion data was available from patients infused between October 1, 2017 and December 31, 2019 inclusive. In each case, needle to departure times were collected for each patient for time spent in at an infusion centre and compared between the standard and rapid infusion groups.

Moreover, a cost analysis was performed for infusion centre and home-based delivery of infliximab, comprising study centre staff costs (per unit time) and infusion-related consumables (per unit), per infusion. Total infusion time duration was measured from time of cannula insertion to the patient’s time of departure from the infusion centre, or the time of the nurse’s departure from the home setting (i.e., needle to departure time), given these events were accurately recorded in the medical records for all patients.

Patients who were transitioned to home-based infusions were asked to complete a survey comprising items assessing their satisfaction regarding rapid infusions compared to standard infusions and rapid infusions administered in infusion centre-based vs home-based settings (see Appendix). The items included were customised based on feedback via qualitative interviews of a subgroup of rapid infusion patients (by investigators DvL and QaR), given no suitable, previously validated surveys were found in the literature. Responses to each item were recorded across a numerical scale from 1 (most negative) to 5 (most positive) with 3 denoted as neutral. Furthermore, the short IBD Questionnaire (sIBDQ), to measure concurrent health-related quality of life and the Work Productivity and Activity Impairment in IBD Questionnaire (WPAI-IBD) were also administered to examine perceived effects of rapid infliximab infusions (including home-based) on these domains[18]. Based on the cut-off derived by Swart et al[19], a sIBDQ score of greater than 55 (total 70 indicating excellent quality of life) was deemed to represent a “satisfactory/normal” quality of life[19,20]. Loss of work productivity and daily activity impairment (expressed as a percentage, 100% indicating complete loss/impairment) were derived from the WPAI-IBD as per Reilly et al[20]. The surveys were applied to a seven-day period including a home-based infliximab infusion.

The rapid infusion protocol as applied is shown in Figure 1. Patients underwent their first 3 infusions via a standard 2-h infusion protocol, then progressed onto an “accelerated” 1-h infusion for infusion 4-6 if there were no adverse reactions and from the 7^th infusion onwards then received “rapid” infusions over 30 min thereafter assuming no further reactions. ADRs were treated immediately according to severity and only those graded as mild-moderate had a subsequent re-trial of infliximab at the last tolerated infusion rate. A standardised pre-medication regimen of 200 mg intravenous hydrocortisone, 10 mg oral cetirizine and 1 g oral paracetamol was administered to all patients prior to their first three standard infusions and also immediately in the case of ADRs, as per the nursing and/or medical staff’s discretion at the time.

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Figure 1 Rapid infliximab infusion protocol. BP: Blood pressure; IV: Intravenous; IFX: Infliximab.

Subsequently, those who tolerated at least three rapid infusions without ADRs were offered the opportunity to transition their infusion to home-based infusions. Patients with known active psychiatric comorbidities, unsafe (i.e., for visiting nursing staff) or itinerant living conditions and/or previous poor adherence to medications, infusion and/or clinic visits were deemed unsuitable candidates for home-based infusions and were not offered this option.

The Eastern Health Human Research Ethics Committee approved the study as a low risk audit (LR 64/2017), thus informed consent was deemed not required.

Comparisons between the infusion groups were performed using non-parametric statistics (assuming non-normal distributions) with medians (ranges) presented and Mann-Whitney tests calculated where appropriate. Proportions were expressed as percentages and compared using Fisher exact tests, including relative risks (RR) of infusion reactions/ADRs which were presented for both per infusion and per patient.

In order to determine factors potentially associated with the occurrence of one or more infusion reaction(s) to rapid infliximab infusion(s), univariable analyses [expressed as odds ratios (OR) for categorical variables, with 95% confidence intervals displayed] were performed. Then a multivariable logistic regression analysis was conducted with the occurrence of an infusion reaction(s) due to rapid infusion as the dependent variable. Multiple exploratory models were initially undertaken and forced entry models were always used, with the final model chosen on the basis of effect size and goodness of fit of the overall model. All variables with significant or those trending to significance were included in the multivariable analysis plus other putatively important factors were included, such as age and body mass index (BMI) (dichotomised by cut-off < 22 kg/m² representing the lowest quartile in this cohort). Those factors exerting minimal or no effect size within the model (as per standardised B values) were excluded from the final model. A P value of < 0.05 was deemed to be statistically significant throughout the study.

The standard infusion cohort comprised 169 patients who received a total of 2214 infliximab infusions over an 8-year period (2006 to 2013 inclusive) and the rapid infusion cohort comprised 129 patients who received a total of 1461 infusions over a 4-year period (2014-2017 inclusive). Home-based rapid infusions were administered to 32 patients, with a total of 405 infusions over 2.2 years (October 2017 to December 2019 inclusive). The baseline characteristics of the standard and rapid infusion cohorts are represented in Table 1.

In the standard infusion cohort, a total of 23 patients experienced ADRs directly related to infliximab infusion(s), with 16 of these graded as mild according to CTC. All 16 patients were rechallenged with infliximab of which 15 tolerated the subsequent infusion with the aid of premedications and a slower infusion rate. Seven patients had severe reactions and were not rechallenged.

In the rapid infusion cohort, 8 patients experienced ADRs due to infliximab, all of which (8/8) were mild as per the CTC. Of these, 7 patients were rechallenged with concurrent premedications administered and all seven tolerated the subsequent infusion; four patients returned to rapid infusions, two remained on accelerated infusions and one returned to the standard infusion protocol. All of the eight patients described had previously documented ADRs to standard protocol infusions.

Hence per infliximab infusion administered, the relative risk (RR) for a mild reaction was 0.8% and 0.7% and for a severe reaction was 0.2% and 0.0% in the standard infusion and rapid infusion cohorts respectively. Per patient, the overall RR for a mild reaction was 10.7% and 7.8% and for a severe reaction 3.0% and 0.0% within the standard and rapid infusion cohorts respectively, as shown in Table 2.

Moreover, there was a greater likelihood of patients having an infusion reaction (mild or severe) in the standard protocol cohort than patients receiving rapid protocol infusions, RR 3.0, 95%CI (1.2, 7.7), P = 0.02. The median duration from the commencement of infliximab and the first infusion reaction per patient was 17 d (0, 1401) for standard infusions and 637 d (45, 2122) for rapid infusions respectively.

A univariable logistic regression analysis was performed on all patients in the cohort who received three or more infliximab infusions via the rapid infusion protocol. Factors found to be significantly associated (P < 0.05) and/or trending to significance (0.05 ≤ P ≤ 0.15) with the occurrence(s) of infliximab ADR/s were then included into a multivariable logistic regression analysis, as shown in Table 3. In summary, a lower BMI (< 22 kg/m²), history of one or more extra intestinal manifestations, longer disease duration (> 3 years) and previous exposure to another biologic were each independently associated with a higher likelihood of infusion reaction(s) to rapid infusions (each P < 0.05). There was a non-significant trend to a higher risk also with prior episodic and/or a break in maintenance infliximab dosing.

Median needle to departure time was significantly higher in the standard protocol than the rapid protocol group [108 (70, 253) vs 50 (33, 90) min, P < 0.001] (Figure 2). Based on local costing and consumables, this equated to a median per infusion (per chair) cost of $AUD 49.80 per rapid vs $107.50 per standard protocol infusion (P < 0.001). Hence since inception, rapid infusion protocols resulted in a net cost saving of $AUD 84344 (a net 54% cost reduction) across the whole study centre cohort and follow-up period.

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Figure 2 Needle-to-departure times for standard vs rapid (further subdivided by infusion centre and home based) infliximab protocols.

The baseline characteristics of the rapid home and rapid infusion centrecohorts are represented in Table 4. 32 patients were transitioned to home-based infusions having received at least three rapid infusions in hospital infusion centres with no history of infusion reaction/s to rapid infusions. In total, 405 infliximab infusions had hitherto been administered via the home-based service as of the end of the study follow-up period, with no (0%) reported ADRs. Six patients who subsequently withdrew from the home-based infusion service were due to personal choice (n = 3), change to a different biologic (n = 2) or death (n = 1, unrelated to IBD and/or associated therapies).

Moreover, there was no significant difference in needle to departure times between infusion centre and home-based rapid infusions [median 50 (33, 90) vs 45 (31, 90) min respectively, P = 0.21] (Figure 2). In turn, there were similar costs (incorporating staffing and consumables) between these groups (median $49.80 vs $39.20 per infusion, P = 0.20).

Of the 32 patients who received infliximab via the home-based infusion service, 31 (97% response rate) completed the survey as described. 26 of the 31 were in clinical remission as per CDAI < 150 at the time of survey and the median sIBDQ score in responders was 55 (33, 65) with 57% scoring in the “normal” IBD QoL range as per Swart et al[19].

Only 2 patients (6.4%) reported that their infliximab infusions had a negative impact on their quality of life overall. All 31 (100%) patients preferred the rapid infusion vs the standard infusion protocol, with 17 patients (54.8%) specifically stating this was due to enhanced convenience (Figure 3).

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Figure 3 Results of patient satisfaction survey and preferences regarding standard vs rapid and infusion centre vs home-based infusions.

14 of the 31 responders (45.2%) disagreed with or were neutral about a preference for home-based vs infusion centre-based infusions and 19 (61.3%) found home-based infusions to actually be more inconvenient than those administered in an infusion centre (Figure 3).

Qualitatively, reasons provided for this included a lack of coordination and communication of the timing of infusions, unforeseen delays in nurse arrival at their home, lack of nursing staff (e.g., due to illness or extra demand) on certain days forcing patients to attend the parent hospital for their infusion(s), lack of sufficiently skilled nurses resulting in difficulties obtaining intravenous access and/or administering infusion at slower rates than prescribed. Additionally, others reported a reluctance to “medicalise” their home and/or have infusions in presence of family members (especially their children) or work colleagues. Also, some patients missed the familiarity of the same nursing staff and the camaraderie enabled by attending the same infusion centre, as many had done, for several years.

Responses from the WPAI-IBD showed that in the week including when infliximab was infused at home, there was a median of 0 h per week missed from paid work (range 0, 36.7 h), with only 4 (12.9%) reporting a total of one or more hours of work missed in the same week. Also, the median overall work impairment (incorporating both percentage of work hours missed and impairment of work performance) was 10.0% (0, 81.0).

Infliximab is one of the most commonly used biologic therapies in the management of inflammatory bowel disease (IBD). With the development of infliximab biosimilars and resulting reduction in medication cost, its availability and usage worldwide has seen exponential growth for all therapeutic indications.

Previous studies have suggested rapid 30 min infliximab infusions to be safe in patients with IBD. Despite this, few centres have moved to deliver infliximab therapy for IBD at a patient’s home and there remains a paucity of literature demonstrating the cost benefit of rapid infliximab infusion compared to standard therapy.

The primary aims in this study were to evaluate the safety of transition from standard hospital-based infliximab infusions to rapid infusions and thence to home-based infusions in a protocolised manner, while also assessing efficiency, cost savings and patient satisfaction with this process.

This retrospective study was conducted across two tertiary IBD centres in Australia. Based on pharmacy prescribing records and historic IBD databases, patients who received infliximab over a 12-year period were identified. Data related to infliximab therapy was retrospectively obtained. Patients that were transitioned to at home infliximab were prospectively surveyed for satisfaction and productivity.

Our study reinforced previous findings in showing that rapid 30 min infliximab was safe in patients IBD with minimal side effects. Furthermore, with careful patient selection patients receiving rapid infusion infliximab were able to be safely transitioned to home based therapy. Rapid infliximab infusions resulted in the halving of time patients spent receiving an infusion and resulted in a 54% reduction in delivery related costs. Patients found the transition to rapid infliximab to be highly satisfying but were neutral about receiving infliximab therapy at home.

In our study, rapid 30 min infliximab infusions appeared to be safe and in a protocolised manner could be delivered safely at home. This process has the ability to substantially reduce costs related to delivery of therapy and provides a viable alternative to under resourced infusion centres in the delivery of infusion therapy.

Rapid Infliximab therapy can be delivered safely at home under the supervision of trained health care staff. Our study provides a framework for other centres to selectively transition patients from traditional infusion centres to alternative destinations such as home based. With further safety studies other infusion therapies could potentially be transitioned safety to be delivered at home at the convenience of the patient.