The perspective of patients with haemophilia with inhibitors and their care givers: preferences for treatment characteristics

Summary. Treatment preferences of haemophilia patients with inhibitors have not been well documented. This study sought to identify treatment attributes that patients/caregivers consider most important in the USA, inasmuch as those preferences may affect patient adherence to treatment plans. A discrete choice experiment was conducted to elicit treatment preferences. Haemophilia patients with inhibitors, or their caregivers on their behalf, completed a written survey that elicited preferences for treatment features and levels synthesized from the medical literature including: risk of viral transmission, rise in inhibitor titre, reduction in thromboembolic events, number of infusions, preparation time, infusion time/volume, time required to stop bleeding/alleviate pain, use of prophylaxis, use of major surgery and medication cost. Relative importance (RI) of preferences was modelled using a multinomial logit function. Most respondents were male (49 of 51, 96.1%); mean age, 20.7 years (SD = 18.8) and 88.5% of patients had haemophilia type A. The three most important patient‐identified treatment attributes were as follows: time required to stop bleeding (RI = 19.3), possibility that the level of inhibitor may rise (RI = 14.3) and risk of contracting a virus from the product (RI = 13.5). Haemophilia patients with inhibitors and their caregivers appear to be willing to accept treatments that may be more inconvenient and painful as long as the treatments are effective in quickly controlling bleeds, do not increase inhibitor levels and do not pose a risk for viral contraction. Study findings provide meaningful input to the clinical community from patients and caregivers and support the importance of physicians understanding their patients’ treatment preferences.     

Patients', physicians', and pharmacists' preferences towards coagulation factor concentrates to treat haemophilia with inhibitors: results from the COHIBA Study

Summary.  Despite modern highly efficacious technologies, there is still a lack of consensus on how to optimally treat haemophilia patients with inhibitors. The aim of the study was to evaluate preferences towards the characteristics of different coagulation factor concentrates for haemophilia inhibitors patients, from the perspective of patients or their caregivers, haematologists and pharmacists. A discrete choice study was conducted. Potential products were described with eight selected characteristics: perceived viral safety, risk of anamnestic response, possibility of undergoing major surgery, frequency of infusions in prophylaxis, number of infusions to stop bleeding, time to stop bleeding, time to pain recovery and cost. Participants received 16 pairs of potential products and chose from each pair the option they considered better. Data were analysed with a random-effects conditional logistic model. Totally 1614 observations were obtained from 37 patients/caregivers, 39 physicians and 25 pharmacists from Italy. Cost was the most important characteristic to every group. For patients/caregivers, the next most important factors were: risk of anamnestic response, possibility of undergoing major surgery and perceived viral safety. For physicians, the next most important characteristics were: risk of anamnestic response, number of infusions to stop bleeding and possibility of undergoing major surgery. For pharmacists, the next most important factors were: time to stop bleeding, time to pain recovery and possibility of undergoing major surgery. Decisions on treatments must take into account patients' clinical needs; however, preferences can also play an important role in the choice and success of treatments. The results of this study could, therefore, help decision-makers to optimize the overall benefits of treatments.     

Successful treatment of acute subdural haemorrhage with continuous intravenous infusion of factor VIII in a 17 year old with haemophilia A

Intracranial haemorrhage is a common complication of haemophilia, occurring in 2–8% of sufferers [1]. Half of the cases give a history of trauma and despite developments in the management of acute bleeding the condition still carries a mortality of approximately 30% [2]. Surgery may be required, most commonly for evacuation of a subdural haematoma which carries a mortality of up to 40% [3]. We present the case of a 17-year-old haemophiliac with a traumatic subdural haemorrhage, who was treated with a continuous intravenous infusion of factor VIII and made a complete recovery without recourse to surgery. We have found no reference in the world literature of such treatment for acute subdural haemorrhage in a haemophiliac.     

Transplacental transfer of postpartum inhibitors to factor VIII

Summary.  Acquired haemophilia due to antibodies directed against coagulation factor VIII is a well-recognized cause of severe haemorrhage in adults but an uncommon cause of bleeding in children. We present the cases of a mother with a life-threatening postpartum haemorrhage due to an autoantibody to factor VIII and her newborn who developed symptomatic bleeding after a minor surgical intervention as a result of transplacental transfer of the autoantibody. Both patients were treated with infusions of recombinant factor VIIa to control bleeding. The mother required immunosuppressive therapy to decrease inhibitor levels and the infant's levels decreased over time without specific treatment. We also provide a concise review of postpartum haemophilia and transplacental transmission of factor VIII autoantibodies to the neonate – a rare but potentially life-threatening complication of acquired haemophilia in women of childbearing age.     

rVIIa therapy to secure haemostasis during central line insertion in children with high-responding FVIII inhibitors

The provision of adequate haemostasis in children with haemophilia A (HA) who have developed high-responding inhibitors continues to be a great challenge to haematologists and institutional resources. The most exciting development in the management of acute bleeding in these patients, irrespective of inhibitor titre, has been the use of recombinant activated factor VII (rVIIa). Three severe HA children with high-responding inhibitors underwent four central line insertions (two Hickman catheters and two port-a-caths, one replaced because of infection) with rFVIIa cover to enable continuous FVIII infusions. No adverse haemorrhagic events occurred and immune tolerance therapy (ITT) using high-dose FVIII therapy was initiated and inhibitor eradication was achieved in all three patients at 8, 10 and 7 months. A further patient who had a central line in situ prior to the development of a high-responding inhibitor was also successfully ‘tolerized’ at 6 months using the same protocol. Interestingly, all four patients had the IVS 22 mutation.     

Prednisone and low-dose activated prothrombin complex concentrates for FVIII inhibitor in nonhaemophilic patients

Eight nonhaemophilic patients with factor VIII (FVIII) inhibitors were reported. There was no difference in sex distribution. Median age at diagnosis was 62 years (ranging from 14 to 73 years). No associated disorders were revealed and all the patients were presented with severe muscular or arthral bleeding. Inhibitor titre was measured by the Bethesda method, which were 6.4, 126.0, 155.0, 4.8, 56.0, 13.5, 35.0 and 150.0 BU mL⁻¹, respectively, at diagnosis. FVIII:C levels were less than 1 U dL⁻¹ in seven patients and less than 2 U dL⁻¹ in one patient. The median vWF:Ag level was 210% (ranging from 80% to 340%). All the patients had good response to activated prothrombin complex concentrates for acute bleeding episodes and prednisone for inhibitor elimination. Inhibitors completely eliminated in seven patients within a follow-up duration over 1 year, and one patient died of intracranial haemorrhage when her inhibitor titre decreased to 4.5 BU mL⁻¹ and FVIII:C increased to 21 U dL⁻¹.     

Treatment of acquired haemophilia with factor eight inhibitor bypassing activity

Haemorrhagic manifestations in patients with acquired haemophilia can be fatal if not recognized and treated appropriately. A retrospective analysis of the efficacy of factor eight inhibitor bypassing activity (FEIBA) in patients with acquired haemophilia treated in three medical centres in the past 10 years was conducted. The median inhibitor titre at treatment was 128 Bethesda Units (BU) in patients with severe and 34 BU in patients with moderate bleeding; P = 0.001. The majority of patients received FEIBA at a dose of 75 u kg-1 every 8-12 h. The number of FEIBA doses administered was higher in patients with severe compared with moderate haemorrhage, 10 vs. 6 doses per bleeding episode; P = 0.001. Complete response (CR) was achieved in 76% of severe and 100% of moderate bleeding episodes with a total CR of 86%. When compared with patients with human inhibitor titre <50 BU, those with titre >51 BU at treatment had lower median porcine titre, 1 vs. 9.5 BU; P < 0.05, fewer doses of FEIBA, 6 vs. 8.5 doses; P < 0.05, and shorter time to CR, 29 vs. 42 h; P < 0.05. Patients exposed to factor VIII concentrates prior to FEIBA had significantly higher maximum recorded human inhibitor titre compared with patients without such exposure, 273 vs. 38 BU; P = 0.0001. Treatment with FEIBA was very well tolerated and with very few side effects. This study provides evidence that FEIBA is an effective agent in acquired haemophilia and suitable for all types of patients regardless of severity of haemorrhage, underlying disease or inhibitor titre.     

Current practices regarding newborn intracranial haemorrhage and obstetrical care and mode of delivery of pregnant haemophilia carriers: a survey of obstetricians, neonatologists and haematologists in the United States, on behalf of the National Hemophilia Foundation''s Medical and Scientific Advisory Council

We undertook this survey to determine institutional practices of obstetricians, neonatologists and haematologists regarding care of pregnant haemophilia carriers and newborns with haemophilia and intracranial haemorrhage (ICH). Our purpose was also to determine whether institutions had written guidelines to manage such patients. Questionnaires were sent to 1000 obstetricians and through the Haemophilia Treatment Centres (HTC) to 180 paediatric haematologists and 180 neonatologists, each representing an institution. Twenty-three per cent of obstetricians, 22% of neonatologists and 16% of paediatric haematologists returned completed surveys. Over 94% of the respondents had no written guidelines for management of pregnant haemophilia carriers or their newborns or for neurologic assessment of newborns. For known haemophilia carriers, 57% of the obstetricians routinely preferred vaginal delivery and 11% preferred caesarean section. Availability of perinatal services influenced prenatal management (P < 0.05). In term newborns with documented ICH, only 23% of neonatologists would evaluate for haemophilia, whereas in pre-term newborns with ICH, this number dropped even further to 3%. For all newborns with haemophilia, 40% preferred routine administration of clotting factor concentrates (CFC) immediately following birth to offset the trauma of delivery and 89% of paediatric haematologists favoured early prophylaxis with CFC. Guidelines are needed for management of pregnant haemophilia carriers as well as newborns with haemophilia. Physicians need to be made aware that ICH may be a presenting sign of haemophilia in both term as well as pre-term newborns, so that appropriate therapy can be instituted early in the event of a bleed.     

Home treatment with bypassing products in inhibitor patients: a 7.5-year experience

Summary.  The advantages of early treatment of bleeds include minimizing the damage caused by the haemorrhage as well as offering increased convenience and time saved for the patient. The objectives of this prospective, single-centre study were to evaluate the efficacy, safety and feasibility of long-term home treatment with bypassing product in inhibitor patients. Since May 2000, 10 haemophilia A patients with high-titre inhibitors have been included in the study. Nine patients were treated with activated prothrombin complex concentrate (aPCC; factor eight inhibitor bypassing activity, FEIBA™; Baxter AG, Vienna, Austria) and one patient with both aPCC and recombinant activated factor VII (rFVIIa; NovoSeven^®; NovoNordisk A/S, Bagsvaerd, Denmark). A total of 1008 infusions of aPCC and 17 infusions of rFVIIa were given in a home treatment setting. The numbers include 448 infusions of aPCC and 10 infusions of rFVIIa given as prophylactic treatment. During the 7.5 years of follow-up, the patients experienced 431 bleeds. Five hundred and sixty infusions of aPCC and seven infusions of rFVIIa were given to treat these bleeds. Haemostasis was rated as effective in 88% (372/424) and partially effective in 10% (43/424) of the bleeds after a mean number of 1.3 injections. The number of treatments rated as effective was comparable for muscle (90%), joint (85%) and mucocutaneous (86%) bleeds. The safety of the treatment was very good. Only two mild adverse events were reported in total. No thrombotic adverse event has been observed. In conclusion, home treatment with bypassing agents in inhibitor patients is feasible, effective and safe in a long-term perspective.     

rVIIa therapy to secure haemostasis during central line insertion in children with high-responding FVIII inhibitors

The provision of adequate haemostasis in children with haemophilia A (HA) who have developed high-responding inhibitors continues to be a great challenge to haematologists and institutional resources. The most exciting development in the management of acute bleeding in these patients, irrespective of inhibitor titre, has been the use of recombinant activated factor VII (rVIIa). Three severe HA children with high-responding inhibitors underwent four central line insertions (two Hickman catheters and two port-a-caths, one replaced because of infection) with rFVIIa cover to enable continuous FVIII infusions. No adverse haemorrhagic events occurred and immune tolerance therapy (ITT) using high-dose FVIII therapy was initiated and inhibitor eradication was achieved in all three patients at 8, 10 and 7 months. A further patient who had a central line in situ prior to the development of a high-responding inhibitor was also successfully 'tolerized' at 6 months using the same protocol. Interestingly, all four patients had the IVS 22 mutation.     

FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations

Summary.  In patients with severe haemophilia and inhibitors, regular factor VIII inhibitor bypassing activity (FEIBA) prophylaxis has been shown to reduce the frequency of bleeding by up to 85% and to improve patient quality of life. FEIBA is well tolerated; the incidence of thrombotic events and of allergic reactions is extremely low. The concept of prophylaxis in haemophilia patients with inhibitors is relatively new and some clinicians may be unsure of how to use FEIBA in this context. These treatment recommendations, based on published evidence plus the collective experience of a group of haematologists (with practical knowledge of managing inhibitor patients with FEIBA prophylaxis), are intended to provide guidance to clinicians considering initiating and maintaining patients on FEIBA prophylaxis with specific focus on practical aspects of patient selection, dosing, monitoring and stop criteria.     

Porcine factor VIII provides clinical benefit to patients with high levels of inhibitors to human and porcine factor VIII

The development of an inhibitor against Factor VIII is an important complication of haemophilia and occurs in approximately 31% of patients [1]. Despite various approaches to their management, the presence of these inhibitors remains a major cause of morbidity and mortality. Inhibitors may be low level [<5 Bethesda Units (BU)] or high level [>10 BU]. Low-level inhibitors usually remain low and do not respond to administered factor VIII with a rise of the inhibitor titre; high-level inhibitors, in contrast, are characterized by a rapid rise in titre following treatment with factor VIII. Modalities of treatment of acute bleeding episodes in patients with inhibitors include 'overcoming' the inhibitor with very large doses of factor VIII, 'bypassing' the inhibitor blockade with products such as activated prothrombin complex concentrates or recombinant factor VIIa, 'removing' the inhibitor by plasmapheresis or immunoabsorption and 'repressing' it with immunosuppressive drugs and immune tolerance induction. An alternative approach is to use a porcine factor VIII concentrate which does not cross-react with the human factor VIII inhibitor. Following treatment with porcine factor VIII, functional factor VIII can be detected and the therapeutic levels correlate with cessation of bleeding. The use of porcine factor VIII may, however, result in the development of antiporcine factor VIII antibodies, limiting its use. Experience in patients with high-titre inhibitors indicates that porcine factor VIII therapy could be used in the presence of factor VIII inhibitors [2-11], including inhibitors to porcine factor VIII [5,7], and that haemostasis may be obtained in the absence of detectable levels of circulating factor VIII [7,11].     

Concomitant infusion of low doses of rFVIIa and FEIBA in haemophilia patients with inhibitors

Summary.  Patients with severe haemophilia A and an inhibitor may become refractory to FEIBA and/or recombinant factor VIIa (rFVIIa). Sequential therapy with both products has been reported in such patients. In this pilot study, we examined the safety and efficacy of combined rFVIIa and FEIBA therapy in patients with haemophilia A and inhibitors during bleeding episodes. We also tried to evaluate whether thrombin generation (TG), by various mixtures of these agents, can serve as a guide for tailoring therapy. TG was measured in plasma taken from eight haemophilia A patients. Increasing concentrations of rFVIIa, FEIBA or both were added ex vivo to the plasmas, and TG was induced by recalcification. Since low concentrations of rFVIIa and FEIBA had either an additive or a synergistic effect in all patients, the lowest combination, yielding TG comparable or lower than TG achieved with either FEIBA 100 U kg⁻¹ or rFVIIa 160 μg kg⁻¹ alone, was selected for the treatment of bleeding episodes. Five patients with a high titre of an inhibitor (8–1300 BU), including one previously refractory to infusions of rFVIIa at doses up to 400 μg kg⁻¹ X4 daily, were treated with combinations of 30–70 μg kg⁻¹ rFVIIa and 20–30 U kg⁻¹ FEIBA during a total number of 400 bleeding episodes with excellent haemostatic effect. No adverse events and no DIC were observed following these infusions. Concomitant infusion of low-dose rFVIIa and low-dose FEIBA, seems to be safe, efficacious and economical in patients refractory to rFVIIa and probably other haemophilia A patients with an inhibitor.     

Pharmacokinetics,efficacy and safety of BAX326, a novel recombinant factor IX: a prospective,controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level ≤2%) haemophilia B

BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12–65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non‐serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence (n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC_0–72 h per dose. Twice‐weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg^?1 per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on‐demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B.     

A review of immune tolerance induction with Haemate® P in haemophilia A

Immune tolerance induction (ITI) has been shown to successfully eliminate factor VIII (FVIII) inhibitors in haemophilia patients with inhibitors. We performed a literature search to identify reports from January 1980 to October 2012 on the use of the plasma‐derived, von Willebrand factor (VWF)‐containing FVIII concentrate Haemate^® P/Humate‐P^® in the setting of ITI. Six reports were identified that specifically evaluated the use of Haemate^® P/Humate‐P^® including 32 children and 9 adults. Dosing regimens ranged from 20 IU kg⁻¹ every 2–3 days in patients with low‐responding (LR; n = 5) inhibitors to 300 IU kg⁻¹ day⁻¹ in patients with high‐responding (HR; n = 36) inhibitors. Complete success was achieved in all five LR patients, in all three HR patients with good prognostic factors (age ≤7 years, pre‐ITI inhibitor titre <10 BU, historical inhibitor titre <200 BU, time between inhibitor detection and ITI start <2 years), and in 24 of 33 (73%) HR patients with poor prognostic factors. The time to complete success was 0.5–4 months in good‐prognosis patients and 0.5–42 months in poor‐prognosis patients. Few adverse events were observed during ITI, and no cases of inhibitor relapse were reported with follow‐up periods of up to 12 years. On the basis of this retrospective review of a diverse range of studies and case reports, we conclude that Haemate^® P/Humate‐P^® for ITI in patients with inhibitors is effective and produces high rates of ITI success.     

Infection risk and stability of a continuous 8‐h 250 mL rFVIII infusion

This study seeks to identify the delivery method of continuous infusion using a 250 cc IV bag via pump, change every 8 h. Additionally, the study will examine the infection risk with the use of 8 h infusions. Ten hemophilia A patients were identified for the study. Each patient received a bolus factorVIII (FVIII) infusion with a pre FVIII level and 1 h post FVIII level to determine recovery levels for optimal dosing. On the day of 8‐h continuous infusion, the pt received a bolus VIII (Kogenate FS ^?) for correction to 100% followed by individually calculated continuous infusion (Kogenate FS ^?) FVIII. FVIII levels were drawn from the IV bag and peripherally from the patient in the opposite arm at time points: pre infusion, 1, 2, 3, 4, 5, 6 and 8 h. Additionally, blood cultures were drawn from the IV bag and from the IV tubing at time points pre infusion, 4 and 8 h. Fourteen subjects agreed to participate in the study; 4 failed to follow up, hence 10 subjects were included in the analysis of data; 7 severe, 2 moderate, and 1 mild hemophilia A. Age range was 26–62 years. Ethnic breakdown included 5 African American, 4 Caucasian, 1 Hispanic. With all infusions, the range of FVIII was 65–135% (blood) and 62–200% (bag). After the start of infusion, there were no significant differences noted between the hourly FVIII levels in the subjects and the IV values (P‐value range 0.36–0.9). Additionally, given three time points with six cultures per patient, totaling 60 points of cultures drawn for the study, all cultures from the IV bag and patient were negative. The effective delivery method and safety of an 8‐h continuous infusion of FVIII (Kogenate FS ^?) has been confirmed. This method can be helpful given that many hospitals may not carry the required mini‐pumps, allowing a standard safe delivery of FVIII (Kogenate FS ^?) continuous infusion by available means.     

Recombinant factor concentrates may increase inhibitor development: a single centre cohort study

Summary. Recent reports have raised concerns regarding potential risk factors for inhibitor development. In Israel, all haemophilia patients (n = 479) are followed by the National Hemophilia Center. Most children are neonatally exposed to factor concentrate (due to circumcision performed at the age of 8 days). The impact of early exposure and recombinant FVIII products (rFVIII) administration (approved in Israel since 1996) upon inhibitor occurrence in our cohort of haemophilia A (HA) patients was analysed. Two hundred ninety‐two consecutive paediatric cases with a first symptomatic onset of HA were enrolled and followed over a median time of 7 years [min–max: 9 months to 17 years]. Study endpoint was inhibitor development against factor VIII. In addition, the treatment regimens applied, i.e. bolus administration or ‘continuous infusion’ and the family history of inhibitor development were investigated. During the follow‐up period 31/292 children (10.6%) developed high titre inhibitors. Inhibitors occurred in 14/43 (32.5%) HA patients neonatally exposed to rFVIII, as compared to 22/249 previously treated with Plasma Derived (PD) products (8.8%). The odds ratio for inhibitor formation in rFVIII treated HA patients was 3.43 (95% CI: 1.36–8.65). Transient inhibitor evolved among 2/43 paediatric HA patients, only among those treated with rFVIII. The risk of inhibitor detection significantly increased among HA children treated by continuous infusion (P = 0.025). Our experience shows that the risk of inhibitor formation may be increased by early exposure to recombinant concentrates. The multiple variables affecting inhibitor incidence deserve further attention by larger prospective studies.     

Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response

We report the long-term follow-up (median 39·5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 × 10⁹/l at a median 20·2 months from treatment. Kaplan–Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders ( P  = 0·027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88·9% vs. 56·7%, P  = 0·037). Earlier responses (within 20 d from treatment) were significantly associated with both complete ( P  = 0·004) and sustained response ( P  = 0·002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.     

Transitioning patients with inflammatory bowel disease from hospital-based to rapid home-based infliximab: A stepwise,safety and patient-orientated process towards sustainability

BACKGROUND Infliximab and other intravenous biologic infusions are increasingly used for chronic disorders like inflammatory bowel disease(IBD). Rapid infliximab and home-based infusions are attractive solutions to address resource and capacity issues for infusion centres, yet infliximab infusion reactions reportedly occur in up to 25% of patients with IBD, even at the manufacturers' recommended infusion duration of 2 h.AIM To evaluate the safety, cost and patient satisfaction of transitioning from hospitalbased, standard 2 h to rapid home-based, 30-min infliximab infusions.METHODS All patients receiving rapid infliximab infusions for IBD between 2014 to 2017(39 mo) were compared with those who received standard two-hour IFX infusions between 2005-2013(96 mo) at a single IBD centre. Data(per-infusion and perindividual) including adverse drug reactions(ADR), duration(based on needledeparture time) and other clinical data were extracted from electronic medical records. Multivariable logistical regression analysis assessed factors potentially associated with increased risk of ADRs to rapid infusions. The primary outcome was the safety [as per relative risk(RR) of ADR] of(1) rapid 30 m infusions(both hospital-and home-based) vs standard 2 h infliximab infusions. Also, relative cost per infusion and patient satisfaction and productivity were evaluated in rapid infusion recipients who transitioned to home-based infusions.RESULTS Of 129 patients who received 1461 rapid IFX infusions(2014-2017) were compared with 169 patients who received 2214 standard IFX infusions(2005-2013). Within the rapid cohort, 55(42.6%) were males, median age 42 years(range 18, 86), 114(84%) had Crohn's disease(CD) with a median disease duration 5 years(0, 36). Median needle to departure time was higher in the standard than the rapid protocol group, 108(70, 253) vs 50(33, 90) min, P 0.001), with a per infusion cost of $AUD 107.50 vs $49.77, respectively(both P 0.001). There was no difference in median infusion duration or costs between rapid home vs hospital-based infusions(P = 0.21). 8 patients in the rapid infliximab cohort had an ADR compared with 23 standard infliximab recipients(RR 0.55% vs 1.04% respectively), hence a higher likelihood of ADR with standard compared to rapid infusions [RR 3.0, 95%CI(1.2, 7.7), P = 0.02]. No ADRs were observed in 405 rapid home-based infusions. A lower body mass index( 22 kg/m~2), presence 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 reaction(s) to rapid infusions. All(100%) survey respondents preferred the rapid vs standard infusions, however within rapid infusion recipients, 61.3% found home based infusions more inconvenient than hospitalbased infusions despite a median of 0 h per week missed from paid work and no self-reported loss of work productivity.CONCLUSION Transitioning to rapid infliximab infusions appears very safe with significant cost benefit, patient satisfaction and avails the provision of safe, efficient, home-based infliximab infusions by IBD centres worldwide.